naloxone and Hypotension

Substance abuse is a significant health problem in the adolescent population. Prevention is a formidable challenge, but attempts at discouraging experimentation in early adolescence and the promotion of healthy adult role models may be effective strategies. Questions that may elicit a history suggestive of abuse should be a routine part of the adolescent medical history. Pediatricians should be familiar with the important clinical findings resulting from intoxication with the various substances of abuse and should be able to recognize the "telltale" signs of abuse. Effective management is based on attention to the basics of life support, careful attention to the physical findings, and judicious use of specific therapeutic agents. Above all, a compassionate attitude should prevail if acute-phase recovery and long-term rehabilitation are to be successful.

Topics: Absorption; Adolescent; Adult; Alcoholic Intoxication; Amphetamines; Anti-Anxiety Agents; Benzodiazepines; Cocaine; Diagnosis, Differential; Female; Fever; Glucose; Hallucinogens; Humans; Hypotension; Illicit Drugs; Lysergic Acid Diethylamide; Marijuana Abuse; Mescaline; Methaqualone; Mushroom Poisoning; Naloxone; Narcotics; Nitrites; Poisoning; Solvents; Substance-Related Disorders

Endogenous opioid peptides are released in response to stressful situations, such as circulatory shock, both as hormones and as central and peripheral neurotransmitters. Naloxone, an opiate antagonist, improves cardiovascular function in a variety of animal models of shock caused by endotoxemia, hemorrhage, anaphylaxis, or spinal trauma. Administration of thyrotropin-releasing hormone (TRH) in supraphysiologic doses also has pressor effects in these shock models. Given acutely after injury, TRH improves recovery in models of spinal trauma; however, the experimental effects of TRH do not involve action at the opiate receptor. Clinical evaluation of the use of naloxone in patients with shock has been largely limited to treatment of sepsis. The paucity of prospective, randomized trials makes these clinical data difficult to evaluate, but in septic patients the use of naloxone does not seem to improve survival. The use of naloxone in shock of other etiologies has not been clinically investigated, and may hold greater promise. Acute-phase treatment of spinal trauma victims with TRH is currently undergoing clinical trials.

Topics: Adult; Animals; Blood Pressure; Endorphins; Humans; Hypotension; Ischemia; Naloxone; Shock, Hemorrhagic; Shock, Septic; Shock, Traumatic; Thyrotropin-Releasing Hormone

Topics: Animals; Blood Pressure; Brain Stem; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dogs; Endorphins; Humans; Hypotension; Morphine; Naloxone; Nitroprusside; Rabbits; Receptors, Opioid; Shock; Sleep

The recent evolution of our understanding of endogenous OPs has led to important new insights into the pathophysiology of many disease states. Opiate antagonism may provide the critical care physician with yet another lifesaving weapon. Opiate antagonists are not approved for human use in the various conditions discussed in this article; their use is strictly experimental and should be restricted to controlled trials. We look forward to continued research and clinical trials involving these agents.

Topics: Animals; Body Temperature Regulation; Cardiovascular System; Clonidine; Endorphins; Halothane; Humans; Hypotension; Naloxone; Narcotic Antagonists; Rats; Receptors, Opioid; Respiration; Shock, Hemorrhagic; Shock, Septic; Shock, Surgical; Spinal Cord; Thyrotropin-Releasing Hormone

Topics: Animals; Brain; Brain Ischemia; Cardiovascular Physiological Phenomena; Cardiovascular System; Endorphins; Enkephalins; Humans; Hypertension; Hypotension; Morphine; Naloxone; Pressoreceptors; Receptors, Opioid; Reflex; Shock; Shock, Hemorrhagic; Shock, Septic; Spinal Cord Injuries; Thyrotropin-Releasing Hormone

Topics: Animals; Blood Pressure; Hemodynamics; Humans; Hypotension; Naloxone; Pressoreceptors; Rats; Shock, Hemorrhagic; Shock, Septic

Topics: Acidosis; Adult; Alcohol Drinking; Alkalosis; Animals; Child, Preschool; Circadian Rhythm; Dogs; Electrolytes; Female; Humans; Hypercapnia; Hypertension; Hypotension; Hypoxia; Infant; Lung; Male; Mice; Naloxone; Narcotics; Neurotransmitter Agents; Rats; Temperature; Thyroid Gland; Time Factors

The specific opiate-antagonist naloxone rapidly reverses hypotension caused by endotoxin, hypovolemia, and spinal transection. In endotoxin shock in rats, naloxone's effects were stereospecific and were observed with intravenous (iv) doses as low as 0.1 mg/kg. In endotoxin shock in dogs, naloxone treatment significantly improved both cardiovascular parameters and survival. Naloxone, given iv, similarly improved blood pressure and survival in rat and canine models of hypovolemic shock. Moreover, intracerebroventricular (ivt) naloxone at a dose of 10 micrograms restored blood pressure after hypovolemia; this effect was blocked by hypophysectomy. In addition naloxone, given ivt, stereospecifically restored blood prssure after spinal shock. From these findings it is suggested that (1) pituitary endorphins are pathophysiologic factors in shock; (2) endorphins' cardiodepressant effects are mediated by opiate receptors within the central nervous system; and (3) use of opiate antagonists may be of therapeutic benefit in the treatment of shock in humans.

Topics: Animals; Blood Pressure; Cardiac Output; Cardiovascular System; Dogs; Dose-Response Relationship, Drug; Endorphins; Heart Rate; Humans; Hypotension; Naloxone; Rats; Receptors, Opioid; Shock, Septic; Vascular Resistance

Topics: Administration, Oral; Administration, Rectal; Adolescent; Adult; Aged; Arrhythmias, Cardiac; Colic; Constipation; Dizziness; Dose-Response Relationship, Drug; Female; Humans; Hypertension; Hypotension; Infusions, Intravenous; Injections, Intravenous; Injections, Subcutaneous; Intubation, Gastrointestinal; Male; Middle Aged; Naloxone; Narcotic Antagonists; Nausea; Neostigmine; Parasympathomimetics; Retrospective Studies; Treatment Outcome

One hundred and forty-one investigators from 45 institutions across Canada participated in the phase 4 clinical trial of sufentanil citrate involving 616 patients. All patients were ASA physical status class I, II, or III, undergoing elective, non-cardiac, major surgical procedures. The average duration of surgery was 1.98 hr and mean dosage of sufentanil was 1.24 micrograms.kg-1.hr-1. Supplemental inhalational anaesthesia was administered to 266 patients (43 per cent). Eighty-six patients required naloxone in the immediate postoperative period. Eighty per cent of these patients had received in excess of 1.0 microgram.kg-1.hr-1 of sufentanil. One hundred and twenty-nine adverse reactions were reported as disturbing and possibly drug-related. Profound bradycardia or sinus arrest was reported in four cases and disturbing hypotension in 37. None of these events required termination of the procedure. The induction, maintenance and recovery phases were rated as good or satisfactory by the participating investigators in 94, 92 and 93 per cent of cases respectively.

Topics: Anesthesia, Inhalation; Anesthesia, Intravenous; Anesthetics; Blood Pressure; Clinical Trials as Topic; Female; Fentanyl; Heart Rate; Humans; Hypotension; Male; Middle Aged; Multicenter Studies as Topic; Naloxone; Sufentanil

Angiotensin-converting enzyme (ACE) inhibitor overdose is an uncommonly presenting toxicologic emergency. Management is primarily supportive care, but a small body of evidence exists to support naloxone for management of hypotension.. We present a case of accidental ACE inhibitor overdose. The patient took approximately 300 mg lisinopril over 48 h and presented for evaluation of syncope. He was hypotensive and unresponsive to fluids. We administered naloxone with immediate and sustained resolution in hypotension. The mechanism of action is briefly discussed. WHY SHOULD AN EMERGENCY MEDICINE PHYSICIAN BE AWARE OF THIS?: Naloxone is a rapid, low-risk, low-cost, and effective intervention for hypotension due to ACE inhibitor toxicity. It is supported by basic science research and clinical experience.

Topics: Angiotensin-Converting Enzyme Inhibitors; Drug Overdose; Humans; Hypotension; Lisinopril; Male; Naloxone

We aimed to describe the severity of clonidine poisonings in a paediatric population referred to a tertiary toxicology service.. We undertook a retrospective review of all presentations of clonidine poisoning in children or adolescents reported to a tertiary toxicology service from March 2014 to February 2020. Cases were divided into young children (0-6 years), older children (7-11 years) and adolescents (12-17 years). We report clinical effects: bradycardia, hypotension and abnormal Glasgow coma score (GCS), based on standard paediatric observation charts, interventions, length of emergency department stay, proportion admitted to a medical ward or paediatric intensive care unit.. We identified 111 clonidine poisonings, 41 young children, 9 older children and 61 adolescents. There were more females in the adolescent group and slightly more males in the younger age groups. The median dose ingested was 13 mcg/kg (interquartile range: 7-38 mcg/kg), which varied across ages. Clonidine alone was ingested in 78 cases (70%) and co-ingestion was more common in adolescents (24/61; 39%). Thirty-seven patients (33%) were admitted and 23 (21%) were admitted to paediatric intensive care unit. Median length of emergency department stay was 16.4 h, longer for adolescents. At least one abnormal observation occurred in 101 of 111 (91%) cases: 76 of 106 (72%) bradycardia, 76 of 110 (69%) hypotension and 4 of 99 (4%) GCS < 9. Thirteen (12%) had severe bradycardia, more common in young children and 23 (21%) had severe hypotension, more common in adolescents. For 27 children (0-11 years) ingesting 5-10 mcg/kg, 3 (11%) had severe bradycardia or severe hypotension and 1 received naloxone (4%). No cases ingesting <5 mcg/kg developed moderate/severe bradycardia or hypotension. Four cases received naloxone with no significant change, two patients got atropine with a transient response. One patient was intubated to facilitate safe inter-hospital transfer.. Paediatric clonidine poisoning commonly results in bradycardia, hypotension and decreased GCS, but rarely severe or requiring major interventions. Children ingesting <5 mcg/kg do not require admission.

Topics: Adolescent; Atropine; Bradycardia; Child; Child, Preschool; Clonidine; Female; Humans; Hypotension; Male; Naloxone; Poisoning; Retrospective Studies

The pedunculopontine tegmental nucleus (PPT) is involved in cardiovascular regulation. The presence of mu (μ) opioid receptors in the PPT nucleus has been determined. In the present study, the role of this nucleus in normotensive conditions and then the role of these receptors on cardiovascular function in hypotension induced by hemorrhage (HEM) were investigated.. Animals were divided into the following groups: Group 1: control, Group 2: HEM, Group 3: morphine at dose 100 nmol (a general opioid receptor agonist), Group 4: naloxone at dose 100 nmol (a general opioid receptor antagonist), Group 5: morphine + HEM, and Group 6: naloxone + HEM. After anesthesia, two femoral arteries were cannulated to record the cardiovascular parameters and blood withdrawal. Two minutes after induction of HEM, drugs were injected into the nucleus, and cardiovascular parameters were measured. Changes (Δ) in cardiovascular responses due to drug injection and HEM were calculated and compared to control and HEM groups.. HEM significantly reduced changes in systolic and mean arterial pressures and increased heart rate changes compared to control. Morphine microinjection in normotensive and HEM rats significantly decreased systolic blood pressure, mean arterial pressure, and heart rate, and naloxone significantly increased all these parameters.. This study showed that the PPT nucleus plays a role in modulating the cardiovascular responses induced by HEM. The µ opioid receptor of the PPT nucleus in the normotensive and HEM rats have inhibitory effects on blood pressure and heart rate mainly, and these effects are eliminated by naloxone microinjection.

Topics: Animals; Blood Pressure; Femoral Artery; Hemorrhage; Hypotension; Morphine Derivatives; Naloxone; Pedunculopontine Tegmental Nucleus; Rats; Receptors, Opioid; Receptors, Opioid, mu

Brimonidine is a topical ophthalmic alpha-2 adrenergic agonist solution used to treat glaucoma. The toxidrome includes drowsiness, lethargy, hypotension, bradycardia, and respiratory depression when ingested in infants. We report a case of intentional subcutaneous injection of brimonidine in an elderly patient resulting in hypotension and CNS depression that responded to naloxone. A 73-year-old female with a past medical history significant for glaucoma, hypertension, and indwelling pacemaker presented to the emergency department after injecting her brimonidine tartrate ophthalmic solution subcutaneously (SQ). The patient was not taking any antihypertensive medications or opioids. Initial presentation consisted of lethargy, a paced rhythm of 60 bpm, and blood pressure of 91/24 mmHg with a MAP of 46. Due to central nervous system depression, 3 mg of intranasal naloxone was administered. The patient was treated with intravenous fluids and escalating doses of naloxone and required a continuous infusion. Mental status and vital signs subsequently improved. The patient was admitted to the ICU and naloxone was subsequently weaned over 12 h. Systemic central alpha-2 adrenergic agonist toxicity resulted from SQ brimonidine injection. Central alpha-2 adrenergic agonist overdoses present as sympatholytic effects including CNS depression, bradycardia, hypotension, and may mimic the opioid toxidrome. Brimonidine SQ injection has not previously been reported and this case has similar findings to other central alpha-2 adrenergic agonist poisonings. Naloxone has previously shown variable reversal of CNS depression in central alpha-2 overdose. In this case, high-dose naloxone was useful for reversing CNS depression and hemodynamic instability.

Topics: Adrenergic alpha-Agonists; Aged; Analgesics, Opioid; Bradycardia; Brimonidine Tartrate; Drug Overdose; Female; Glaucoma; Humans; Hypotension; Infant; Injections, Subcutaneous; Lethargy; Naloxone; Ophthalmic Solutions; Quinoxalines

Morphine is an opiate alkaloid characterized by various clinical effects, among which the most prominent are its analgesic and psychoactive effects. It also has a prominent depressive effect on the respiratory and cardiovascular system. Because of its psychoactive effect, morphine is very addictive and often used as a recreational narcotic. As a medication, it has found its use as an analgesic agent in chronic pain treatment, in hemorrhagic shock, and in acute heart failure with pulmonary edema. Albeit, morphine use in heart failure is controversial, based on many observational studies showing the negative effect on the outcomes of the patients treated with morphine during acute cardiovascular incidents. In this report, the authors present a case of cardiogenic shock (CS) with transient left ventricular ejection fraction reduction, occurring in a patient attempting suicide using a high dose of intravenous morphine sulphate administration. Other CS causes were ruled out. To the best of the authors' knowledge, this is the second case of a morphine-related CS reported in literature. Int J Occup Med Environ Health. 2021;34(1):133-8.

Topics: Administration, Intravenous; Adult; Analgesics, Opioid; Humans; Hypotension; Male; Morphine; Naloxone; Narcotic Antagonists; Norepinephrine; Shock, Cardiogenic; Suicide, Attempted; Ventricular Dysfunction, Left; Ventricular Function, Left

The presence of opioid receptors in the cuneiform nucleus (CnF), which is a mesencephalic area, and their involvement in the central cardiovascular responses have been shown. Therefore, this study is designed to examine the possible role of mu- (μ) and delta- (δ) opioid receptors in the CnF in the cardiovascular responses in normotensive and hemorrhagic hypotensive rats. Following anesthesia and the recording of the blood pressure, the agonist and antagonist of μ- (morphine and naloxone) and δ- (D-Pen 2, 5]-Enkephalin hydrate (DPDPE) and naltridole) receptors were microinjected into the CnF. In the hemorrhagic groups, the drugs were microinjected into the nucleus 2 min after withdrawing 15 % of the total blood volume (TBV). Time-course changes (Δ) in the mean arterial pressure (MAP), systolic blood pressure (SBP), and heart rate (HR) were obtained and compared with the control and hemorrhage groups. Microinjecting morphine in both normotensive and hemorrhagic rats significantly decreased ΔSBP, ΔMAP, and ΔHR; also, naloxone significantly increased all these parameters. The cardiovascular effects of DPDPE and naltridole were not significant in the normotensive rats; however, DPDPE attenuated only the tachycardia induced by the hypotensive hemorrhage. The findings of this study revealed that the opioid receptors in the CnF had an inhibitory effect on the cardiovascular parameters in both normotensive and hypotensive hemorrhagic conditions and these effects were mostly mediated by μ-opioid receptors.

Topics: Analgesics, Opioid; Animals; Blood Pressure; Heart Rate; Hemorrhage; Hypotension; Male; Microinjections; Midbrain Reticular Formation; Morphine; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid

We report here the case of a patient with perindopril intoxication inducing severe bradycardia together with a profound hypotension. Initiation of a naloxone infusion completely resolved those symptoms. As a consequence, we could recommend as a first step the use of naloxone in order to prevent the use of more invasive therapeutic tools.

Topics: Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Bradycardia; Humans; Hypotension; Male; Middle Aged; Naloxone; Perindopril

Moderate sedation has been standard for noninvasive gastrointestinal procedures for decades yet there are limited data on reversal agent use and outcomes associated with need for reversal of sedation.. To determine prevalence and clinical significance of reversal agent use during endoscopies and colonoscopies.. Individuals with adverse events requiring naloxone and/or flumazenil during endoscopy or colonoscopy from 2008 to 2013 were identified. A control group was obtained by random selection of patients matched by procedure type and date. Prevalence of reversal agent use and statistical comparison of patient demographics and risk factors against controls were determined.. Prevalence of reversal agent use was 0.03% [95% confidence interval (CI), 0.02-0.04]. Events triggering reversal use were oxygen desaturation (64.4%), respiration changes (24.4%), hypotension (8.9%), and bradycardia (6.7%). Two patients required escalation of care and the majority of patients were stabilized and discharged home. Compared with the control group, the reversal group was older (61±1.8 vs. 55±1.6, P=0.01), mostly female (82% vs. 50%, P<0.01), and had lower body mass index (24±0.8 vs. 27±0.7, P=0.03) but received similar dosages of sedation. When adjusted for age, race, sex, and body mass index, the odds of reversal agent patients having a higher ASA score than controls was 4.7 (95% CI, 1.7-13.1), and the odds of having a higher Mallampati score than controls was 5.0 (95% CI, 2.1-11.7) with P<0.01.. Prevalence of reversal agent use during moderate sedation is low and outcomes are generally good. Several clinically relevant risk factors for reversal agent use were found suggesting that certain groups may benefit from closer monitoring.

Topics: Age Factors; Anti-Arrhythmia Agents; Antidotes; Atropine; Body Mass Index; Bradycardia; Case-Control Studies; Colonoscopy; Conscious Sedation; Female; Fentanyl; Flumazenil; Health Status; Humans; Hypnotics and Sedatives; Hypotension; Hypoxia; Male; Midazolam; Middle Aged; Naloxone; Narcotic Antagonists; Sex Factors; Treatment Outcome

MCRT (YPFPFRTic-NH(2)) is a chimeric opioid peptide based on morphiceptin and PFRTic-NH(2). In order to assess the cardiovascular effect of MCRT, it was administered by intravenous (i.v.) injection targeting at the peripheral nervous system and by intracerebroventricular (i.c.v.) injection targeting at the central nervous system. Naloxone and L-NAME were injected before MCRT to investigate possible interactions with MCRT. Results show that administration of MCRT by i.v. or i.c.v. injection could induce bradycardia and decrease in mean arterial pressure (MAP) at a greater degree than that with morphiceptin and PFRTic-NH(2). When MCRT and NPFF were coinjected, we observed a dose-dependent weakening of these cardiovascular effects by MCRT. Because naloxone completely abolished the cardiovascular effects of MCRT, we conclude that opioid receptors are involved in regulating the MAP of MCRT regardless of modes of injection. The effect of MCRT on heart rate is completely dependent on opioid receptors when MCRT was administered by i.c.v. instead of i.v. The central nitric oxide (NO) pathway is involved in regulating blood pressure by MCRT under both modes of injection, but the peripheral NO pathway had no effect on lowering blood pressure mediated by MCRT when it was administered by i.c.v. Based on the results from different modes of injection, the regulation of heart rate by MCRT mainly involves in the central NO pathway. Lastly, we observed that the cardiovascular effects of MCRT such as bradycardia and decrease of blood pressure, were stronger than that of its parent peptides. Opioid receptors and the NO pathway are involved in the cardiovascular regulation by MCRT, and their degree of involvement differs between intravenous and intracerebroventricular injection.

Topics: Analgesics, Opioid; Animals; Blood Pressure; Bradycardia; Endorphins; Heart Rate; Hypotension; Injections, Intravenous; Injections, Intraventricular; Male; Morphinans; Naloxone; Naltrexone; Narcotic Antagonists; NG-Nitroarginine Methyl Ester; Rats; Rats, Wistar

Some of the benefits of exercise appear to be mediated through modulation of neuronal excitability in central autonomic control circuits. Previously, we identified that six weeks of voluntary wheel running had a protective effect during hemorrhage (HEM), limiting both the hypotensive phase of HEM and enhancing recovery. The present study was undertaken to evaluate the role of opioid release in the lateral parabrachial nucleus (LPBN) on the response to severe HEM in chronically exercised (EX, voluntary) versus sedentary (SED) controls. Male Sprague Dawley rats were allowed either free access to running wheels (EX) or normal cage conditions (SED). After 6 weeks of "training" animals were instrumented with a bilateral cannula directed toward the dorsolateral pons and arterial catheters. After a recovery period, animals underwent central microinjection of either vehicle (VEH; n=3/group) or the opioid receptor antagonist naloxone (NAL; n=6/group) followed by withdrawal of 30% of their total estimated blood volume. Following VEH injection, the drop in MAP during and following HEM was significantly attenuated in the EX vs SED animals. Alternatively, NAL microinjection in the dorsolateral pons (20 μM, 200-500 nl) reversed the beneficial effect of EX on the HEM response. NAL microinjection in SED rats did not significantly alter the response to HEM. These data suggest chronic voluntary EX has a beneficial effect on the autonomic response to severe HEM which is mediated, in part, via EX-induced plasticity of the opioid system within the dorsolateral pons.

Topics: Animals; Blood Pressure; Heart Rate; Hemorrhage; Hypotension; Male; Microinjections; Naloxone; Narcotic Antagonists; Physical Conditioning, Animal; Pons; Rats; Rats, Sprague-Dawley; Receptors, Opioid

Propofol is an intravenous anesthetic that is widely used to anesthetize patients during neurosurgical procedures. Although propofol is considered to be an essential component of contemporary management of acute brain injury in the operating room and in critical care settings, propofol-induced hypotension (PIH) remains a frequent and undesirable side effect. After 3 decades of clinical use, multiple proposed causes of PIH, and conflicting experimental results, the mechanism of PIH is still a puzzle for neuroscience and anesthesiology. This study evaluated the role of opioid receptors in PIH.. Pentobarbital-anesthetized rats were subjected to systemic or central pretreatment with naloxone followed by intravenous or central administration of propofol.. In the absence of pretreatment with naloxone, intravenous (7.5 mg/kg) and intracistenal propofol (10 µg) injection induced 45% and 35% reductions in the mean arterial pressure, respectively (P<0.05). Both systemic (5 mg/kg) and central (100 µg) pretreatment with naloxone prevented PIH without independently affecting mean arterial pressure.. This experiment in anesthetized rats indicates that central and peripheral opioid receptor blockade prevents PIH, suggesting that these receptors are involved in the cardiovascular alterations elicited by propofol administration.

Topics: Anesthetics, Intravenous; Animals; Blood Pressure; Hypotension; Naloxone; Narcotic Antagonists; Propofol; Rats; Rats, Wistar; Receptors, Opioid

We describe a 4-year-old boy who presents to the emergency department with lethargy, bradycardia, and initial hypertension followed by hypotension due to guanfacine toxicity after ingestion of standard doses of the extended release formulation. This is the first case report to describe the use of naloxone to treat these symptoms and document improvements in level of consciousness, blood pressure, and heart rate associated with this therapy.

Topics: Antihypertensive Agents; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Child, Preschool; Electrocardiography; Follow-Up Studies; Guanfacine; Humans; Hypotension; Male; Naloxone; Narcotic Antagonists

The aim of the present work was to investigate the role of brain μ, κ and δ opioid receptors in the central serotonergic mechanisms regulating blood pressure in rats. The data obtained show that: (1) pharmacological activation of central 5-HT(3) receptors yields a significant decrease in blood pressure; (2) the blockade of those receptors by a selective antagonist induces an acute hypertensive response; (3) the pharmacological blockade of central opioid receptors by three different opioid antagonists exhibiting variable degrees of selectivity to μ, κ and δ opioid receptors always suppressed the hypotensive response induced by central 5-HT(3) receptor stimulation; (4) the blockade of opioid receptors by the same opioid antagonists that impaired the hypotensive effect of central 5-HT(3) receptor stimulation failed to modify blood pressure in animals not submitted to pharmacological manipulations of central 5-HT(3) receptor function. It is shown that a 5-HT(3) receptor-dependent mechanism seems to be part of the brain serotonergic system that contributes to cardiovascular regulation since the hypertensive response observed after ondansetron administration indicates that central 5-HT(3) receptors exert a tonic inhibitory drive on blood pressure. Furthermore, the data obtained here clearly indicate that the hypotensive response observed after pharmacological stimulation of central 5-HT(3) receptors depends on the functional integrity of brain μ, κ and δ opioid receptors, suggesting that a functional interaction between serotonergic and opiatergic pathways in the brain is part of the complex, multifactorial system that regulates blood pressure in the central nervous system.

Topics: Animals; Biguanides; Blood Pressure; Heart Rate; Hypotension; Male; Naloxone; Naltrexone; Narcotic Antagonists; Ondansetron; Rats; Rats, Wistar; Receptors, Opioid; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Agonists; Serotonin 5-HT3 Receptor Antagonists

The concept of opioid-induced hyperalgesia has recently gained prominence as a contributing factor for long-term treatment failure.. To evaluate possible differences of opioids used in anaesthesia, cumulative doses of sufentanil and remifentanil were compared with escalating doses of the oripavine derivative etorphine, in awake and trained canines. This was followed by naloxone unmasking a possible hyperalgesic state, which had developed during opioid administration. Heart rate, blood pressure and propagation of nociceptive volleys in somatosensory-evoked potentials as well as the skin-twitch reflex were evaluated.. Opioid-related hypotension and bradycardia were reversed by naloxone with a late (30 min) overshoot of R43 and R17% after remifentanil and sufentanil, respectively. Following etorphine, overshoot in mean blood pressure was R9%, whereas heart rate still remained below S9% when compared with control. Peak hyperalgesia, as detected in the somatosensory-evoked potential and skin-twitch, increased by R70% after remifentanil and by R43% after sufentanil. This reflected a significant (P<0.005) increase in propagation of nociceptive afferents as late as 30 min after naloxone reversal. Such potentiation was not observed in the etorphine group, as peak somatosensory-evoked potential deflection and skin-twitch remained below S80% when compared with control.. The pure mu-agonists sufentanil or remifentanil seem to induce a 'bimodal' inhibitory followed by an excitatory effect. The latter is unmasked by naloxone in the postadministration period. In contrast, this is not seen with etorphine, a close congener of buprenorphine. The proposed mode of action of such hyperexcitatory effects may involve second-messenger-mediated G-protein activation, originally proposed by others. Ligands of the oripavine series may present an alternative for prevention of opioid-induced hyperalgesia in patients.

Topics: Afferent Pathways; Analgesics, Opioid; Animals; Blood Pressure; Bradycardia; Dogs; Dose-Response Relationship, Drug; Etorphine; Evoked Potentials, Somatosensory; Heart Rate; Hyperalgesia; Hypotension; Naloxone; Narcotic Antagonists; Piperidines; Remifentanil; Substance Withdrawal Syndrome; Sufentanil

Severe haemorrhage leads to a reflex bradycardia and hypotension. This is thought to be protective, but is attenuated by both concomitant musculoskeletal injury and exogenous morphine. The aim of this study was to determine whether the injury-induced attenuation of the response to severe haemorrhage could be blocked by naloxone. Male Wistar rats, terminally anaesthetized with alphadolone/alphaxalone (19-20 mg kg(-1) h(-1)I.V.), were randomly allocated to one of four groups. In groups I and IV, haemorrhage was simple [40% of estimated total blood volume (BV)], while in groups II and III it was initiated 10 min after the onset of bilateral hindlimb ischaemia (a model of musculoskeletal injury). Groups I and II received 20 microl of 0.9% saline intracerebroventricularly (I.C.V.) immediately before haemorrhage, while groups III and IV received 20 microg of naloxone I.C.V., in the same volume. In group I, the bradycardia reached its peak after the loss of 32.8 +/- 0.3% BV (mean +/- S.E.M.). Blood pressure did not fall significantly until the loss of 15.0 +/- 3.0% BV. The response in group IV was not significantly different from group I. By contrast, the bradycardia was absent after similar blood losses in groups II and III, while hypotension was attenuated. These results indicate that naloxone, at a dose known to be effective in blocking mu-opioid receptors and preventing other aspects of the response to injury, does not prevent the injury-induced attenuation of the response to severe haemorrhage. Thus the attenuation of the response to blood loss by injury is unlikely to be mediated via the mu-opioid receptors.

Topics: Animals; Blood Pressure; Blood Volume; Bradycardia; Heart Rate; Hemorrhage; Hindlimb; Hypotension; Ischemia; Male; Musculoskeletal System; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid, mu

Compared to other calcium channel blockers (CCBs), overdose with dihydropyridine CCBs are considered relatively benign due to their vascular selectivity. Although not a sustained-release preparation, amlodipine's prolonged duration of effect is concerning following overdose. In addition, angiotensin II receptor blocker blunting of vasoconstrictive and sympathetic compensatory responses could exacerbate calcium channel blocker toxicity. We describe severe toxicity associated with an overdose of amlodipine and valsartan.. A 75-year-old woman presented to the ED 45 minutes after a witnessed suicidal ingestion of a "handful" of amlodipine and valsartan tablets. Hypotension, which appeared two hours after ingestion, was refractory to crystalloids and colloids, calcium gluconate, epinephrine, norepinephrine, phenylephrine, and vasopressin infusions. High-dose insulin euglycemia (HIE) therapy, and treatment with glucagon and naloxone were successful in improving her hemodynamic status. In this combined overdose, right heart catheterization demonstrated both negative inotropic effects and decreased systemic vascular resistance.. Co-ingestion of amlodipine with valsartan produced profound toxicity. Early institution of HIE therapy may be beneficial to reverse these effects.

Topics: Aged; Amlodipine; Antidotes; Antihypertensive Agents; Blood Glucose; Calcium Channel Blockers; Cardiac Catheterization; Drug Interactions; Drug Overdose; Female; Glucagon; Humans; Hypotension; Insulin; Naloxone; Severity of Illness Index; Suicide, Attempted; Tetrazoles; Time Factors; Valine; Valsartan

After an initial compensatory phase, hemorrhage reduces blood pressure due to a widespread reduction of sympathetic nerve activity (decompensatory phase). Here, we investigate the influence of intracerebroventricular naloxone (opioid-receptor antagonist) and morphine (opioid-receptor agonist) on the two phases of hemorrhage, central and peripheral hemodynamics, and release of vasopressin and renin in chronically instrumented conscious sheep. Adult ewes were bled (0.7 ml x kg(-1) x min(-1)) from a jugular vein until mean arterial blood pressure (MAP) reached 50 mmHg. Starting 30 min before and continuing until 60 min after hemorrhage, either artificial cerebrospinal fluid (aCSF), naloxone, or morphine was infused intracerebroventricularly. Naloxone (200 microg/min but not 20 or 2.0 microg/min) significantly increased the hemorrhage volume compared with aCSF (19.5 +/- 3.2 vs. 13.9 +/- 1.1 ml/kg). Naloxone also increased heart rate and cardiac index. Morphine (2.0 microg/min) increased femoral blood flow and decreased hemorrhage volume needed to reduce MAP to 50 mmHg (8.9 +/- 1.5 vs. 13.9 +/- 1.1 ml/kg). The effects of morphine were abolished by naloxone at 20 microg/min. It is concluded that the commencement of the decompensatory phase of hemorrhage in conscious sheep involves endogenous activation of central opioid receptors. The effective dose of morphine most likely activated mu-opioid receptors, but they appear not to have been responsible for initiating decompensation as 1) naloxone only inhibited an endogenous mechanism at a dose much higher than the effective dose of morphine, and 2) the effects of morphine were blocked by a dose of naloxone, which, by itself, did not delay the decompensatory phase.

Topics: Acute Disease; Analgesics, Opioid; Animals; Arginine Vasopressin; Blood Pressure; Central Venous Pressure; Consciousness; Dose-Response Relationship, Drug; Female; Heart Rate; Hemorrhage; Hypotension; Hypovolemia; Injections, Intraventricular; Morphine; Naloxone; Narcotic Antagonists; Receptors, Opioid; Recovery of Function; Renin; Sheep; Species Specificity; Vascular Resistance

Topics: Aged; Analgesia, Epidural; Analgesics, Opioid; Anesthetics, Local; Antihypertensive Agents; Bupivacaine; Carcinoma; Cardiotonic Agents; Dobutamine; Enalapril; Female; Humans; Hypertension; Hypotension; Liver Neoplasms; Metoprolol; Morphine; Naloxone; Narcotic Antagonists; Norepinephrine; Thoracic Vertebrae; Time Factors; Vasoconstrictor Agents

Endogenous opioid peptides like endomorphins, met-enkephalin and NPFF/FMRFamide family of neuropeptides, besides playing a role in modulation of antinociception, also affect cardiovascular system. Based on MERF, which consists of overlapping sequences of FMRFa and met-enkephalin, two chimeric peptides YGGFMKKKFMRFamide (YFa) and [D-Ala2] YAGFMKKKFMRFamide ([D-Ala2] YFa) were designed and synthesized. In this study, effect of YFa and [D-Ala2] YFa on arterial blood pressure and heart rate was evaluated in anaesthetized rats. Both YFa and [D-Ala2] YFa showed a dose-dependent fall in mean arterial pressure in dose-range of 13-78 micromol/kg. After naloxone treatment (5 mg/kg), vasodepressor effect of [D-Ala2] YFa and YFa was only partially blocked as compared to met-enkephalin. Partial blockade of vasodepressive effect of YFa and [D-Ala2] YFa by naloxone may be attributed to interaction of these chimeric peptides with receptors other than naloxone-sensitive receptors such as anti-opioid receptors, adrenergic receptors and D-analogue receptors.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Enkephalin, Methionine; Enkephalins; FMRFamide; Heart Rate; Hypotension; Male; Naloxone; Neuropeptides; Peptides; Rats; Rats, Wistar; Receptors, Adrenergic; Receptors, Opioid; Vasodilator Agents

High CO(2)-sensitivity, one of the major characteristics of the cerebrovascular bed, has been shown to be influenced by a variety of factors. There are no reports, however, on the involvement of the endogenous opioid peptides in the modulation of the CO(2)-sensitivity of the cerebral and spinal cord vessels, either in normotensive or, in hypotensive conditions. The effect of general opiate receptor blockade (1.0mg/kg naloxone, i.v.) on regional cerebrovascular CO(2)-sensitivity was studied with radiolabeled microspheres in 10 distinct brain and spinal cord regions of the anesthetized cat. The CO(2)-induced flow changes were investigated in normotensive, in moderately hypotensive (MAP=80 mmHg) and in deep hypotensive cats (MAP=40 mmHg). The systemic arterial pressure was lowered by hemorrhage. In the normotensive cats, opiate receptor blockade caused no changes in the vascular CO(2)-sensitivity in the investigated cerebral and spinal cord regions. In moderate hypotension, cerebral and spinal CO(2)-sensitivity was significantly reduced by the hemorrhage itself, but remained unaffected by the naloxone administration. In deep hemorrhagic hypotension, however, general opiate receptor blockade resulted not only in a further reduction of the already impaired CO(2)-sensitivity, but even in a reversal of the effect of CO(2) from flow increase to flow decrease. These results indicate that endogenous opioid peptides, which do not seem to influence cerebrovascular reactions in steady-state, normotensive conditions, may contribute significantly to the maintenance of the normal vasodilatory response of the cerebral and spinal cord vessels to CO(2) during hemorrhage-induced deep arterial hypotension.

Topics: Animals; Blood Pressure; Brain; Carbon Dioxide; Cats; Cerebrovascular Circulation; Female; Hemorrhage; Hypotension; Male; Naloxone; Narcotic Antagonists; Opioid Peptides; Spinal Cord

This study was conducted to more clearly delineate the possible role of endogenous opioid receptors and opioid peptides in general anesthesia-associated hypotension in rats. Exposure to 2% isoflurane in oxygen produced a triphasic change in mean arterial pressure (MAP), including an early phase in which MAP fell by -28.4 +/- 2.2%. The magnitude of this early-phase hypotension was attenuated in rats pretreated with intravenous (i.v.) mu-subtype-selective doses of either naloxone or methylnaloxone but not central doses of the selective mu-opioid antagonist beta-funaltrexamine. This early hypotensive phase was also reduced following i.v. pretreatment with antiserum against methionine-enkephalin but not beta-endorphin. These findings suggest that early-phase isoflurane-induced hypotension may be due to activation of peripheral mu-opioid receptors by an endogenous opioid peptide, possibly related to methionine-enkephalin.

Topics: Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Antibodies, Blocking; beta-Endorphin; Blood Pressure; Endorphins; Enkephalin, Methionine; Hot Temperature; Hypotension; Injections, Intraventricular; Isoflurane; Male; Naloxone; Naltrexone; Narcotic Antagonists; Pain Measurement; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, Opioid; Urethane

Endogenous opioids target noradrenergic locus ceruleus (LC) neurons and potently inhibit LC activity. Nonetheless, it has been difficult to demonstrate functional regulation of the LC-noradrenergic system by endogenous opioids because of the lack of effect of opiate antagonists. The present findings provide evidence that endogenous opioids regulate LC neuronal activity during the termination of a stressor. LC neuronal discharge was recorded from halothane-anesthetized rats before, during, and after hypotensive stress elicited by intravenous nitroprusside infusion. In naive rats, mean arterial blood pressure was temporally correlated with LC activity such that hypotension was associated with increased LC discharge and a return to the normotensive state was associated with a decrease in LC discharge below pre-stress values. After microinfusion of an antagonist of the stress neuropeptide corticotropin-releasing factor (CRF) into the LC, the increase in LC discharge associated with hypotension was prevented, whereas LC inhibition associated with termination of the challenge occurred at an earlier time and was of a greater magnitude. In contrast, microinfusion of naloxone into the LC completely abolished LC inhibition associated with termination of the stressor. Naloxone microinfusion did not prevent LC inhibition associated with hypertension produced by intravenous vasopressin administration, suggesting that endogenous opioids may be selectively engaged during the termination of hypotensive stress. These results provide evidence for a functional release of endogenous opioids within the LC. This action of endogenous opioids may serve to counterbalance excitatory effects of CRF on the LC-norepinephrine system, thereby limiting its activation by stress.

Topics: Animals; Blood Pressure; Corticotropin-Releasing Hormone; Hypotension; Injections, Intravenous; Locus Coeruleus; Male; Microinjections; Naloxone; Narcotic Antagonists; Neural Inhibition; Neurons; Nitroprusside; Opioid Peptides; Peptide Fragments; Rats; Rats, Sprague-Dawley; Stress, Physiological; Vasopressins

Topics: Animals; Endotoxemia; Humans; Hypotension; Mice; Naloxone; Narcotic Antagonists; Sheep; Shock, Hemorrhagic

Opioid receptors are activated during severe hemorrhage, resulting in sympathoinhibition and a profound fall in blood pressure. This study examined the location and subtypes of opioid receptors that might contribute to hypotension after hemorrhage. Intrathecal naloxone methiodide (100 nmol) abolished the fall in blood pressure after hemorrhage (1.5% of body wt; mean arterial pressure 122 +/- 8 mmHg after naloxone methiodide vs. 46 +/- 5 mmHg in controls, P < 0. 001). Intracisternal naloxone methiodide was less effective than intrathecal naloxone methiodide, whereas intravenous naloxone methiodide, which does not cross the blood-brain barrier, did not alter the fall in blood pressure after hemorrhage. These results demonstrate that spinal opioid receptors contribute to hypotension after hemorrhage but do not exclude supraspinal effects. In separate experiments, the subtype-specific opioid antagonists ICI-174864 (delta-antagonist), norbinaltorphimine (nor-BNI; kappa-antagonist), and H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP; mu-antagonist) were each administered intrathecally to determine the minimum dose that would attenuate hypotension during severe hemorrhage. These antagonists were effective at similar doses (3 nmol for CTOP, 6 nmol for ICI-174864, and 10 nmol for nor-BNI), although the binding affinities of these three different agents for their target receptors varied >1600-fold. Comparisons of the minimum effective doses of these antagonists in relation to their binding affinities provides strong evidence for the participation of delta-receptors in mediating hypotension after hemorrhage. In contrast, the dose at which nor-BNI was effective suggests an effect at delta-receptors but not kappa-receptors. The efficacy of CTOP, albeit at a high dose, also suggests an effect at mu-receptors.

Topics: Animals; Blood Pressure; Consciousness; Dynorphins; Endorphins; Enkephalin, Leucine; Heart Rate; Hemorrhage; Hypotension; Male; Naloxone; Narcotic Antagonists; Neural Inhibition; Rats; Rats, Inbred WKY; Receptors, Opioid, kappa; Receptors, Opioid, mu; Somatostatin; Spinal Cord; Sympathetic Nervous System

The possible involvement of the L-arginine-nitric oxide pathway and endogenous opioid mechanisms in the hemorrhagic hypotension- (HH) induced changes of hepatic arterial blood flow and vascular resistance was studied in cats. During HH hepatic arterial blood flow was significantly higher both in L-arginine- and naloxone-treated animals than in controls. Furthermore, HH induced a significant increase of the hepatic vascular resistance in the control group, which was prevented by L-arginine or naloxone treatment. Because inhibition of the nitric oxide synthesis by N(G)-nitro-L-arginine in normotensive cats induced a similar increase of the hepatic vascular resistance to that observed during HH in the control group, our results indicate that impairment of the endothelial function may be responsible for the hemorrhage-induced L-arginine- and naloxone-reversible hepatic arterial vasoconstriction. This hypothesis is consistent with our previous observations demonstrating the development of endothelial dysfunction in the feline hepatic artery during HH.

Topics: Animals; Arginine; Cats; Drug Evaluation, Preclinical; Hemorrhage; Hypotension; Liver; Male; Naloxone; Nitroarginine; Regional Blood Flow; Vasoconstriction

Our goal was to test directly whether the vasoconstrictor action of naloxone during hypovolemic hypotension is centrally mediated. In eight chronically instrumented rabbits, progressive central hypovolemia and fall in cardiac output (CO) were produced by gradually inflating a cuff on the thoracic vena cava. Central hypovolemia was then sustained for 8 min by holding CO constant. In the main experiment (n = 4), each rabbit was studied eight times over 4 experimental days. Saline or naloxone treatment commenced 10 min before progressive hypovolemia (early treatment) or 2 min after the onset of sustained hypovolemia (late treatment), given by intravenous infusion or into the fourth ventricle (V4). With saline treatment, there was spontaneous recovery of systemic vasoconstriction and arterial pressure during sustained hypovolemia. Late treatment with naloxone (4 mg/kg i.v.; 4-37 micrograms/kg V4) accelerated and exaggerated these changes. Thus, under conditions of constant CO and central blood volume, the vasodilatation of the decompensatory phase of acute hypovolemia is not sustained, and intravenous nalox one's vasoconstrictor action is via a brain stem mechanism.

Topics: Animals; Blood Volume; Female; Hemodynamics; Hypotension; Injections, Intravenous; Injections, Intraventricular; Naloxone; Narcotic Antagonists; Rabbits; Time Factors

Neuropeptide FF (NPFF), a morphine modulatory peptide, is localized within discrete autonomic regions including the brainstem nucleus tractus solitarius (NTS) and the parabrachial nucleus (PBN). We investigated the activation of NPFF neurons in the NTS of rats induced by cardiovascular challenge and centrally generated opiate withdrawal. For hypotensive stimulation, we used systemic infusions of sodium nitroprusside (NP) or hemorrhage (HEM), and hypertension was achieved by intravenous phenylephrine (PHENYL) or angiotensin II (AII). In rats that received continuous intracerebroventricular injections of morphine, intraperitoneal injections of naloxone precipitated behavioural signs of opioid withdrawal. Activated NTS neurons were identified by using a combined immunohistochemistry for Fos and NPFF, and neurons projecting to the PBN were determined with a retrograde tracer. HEM, administration of vasoactive drugs, and opiate withdrawal produced a very robust activation of NTS neurons. In NP and HEM groups, 25.6+/-3.2% and 7.6+/-1.3% of NPFF neurons were activated, respectively. Lesser numbers of NPFF neurons were activated in the PHENYL (4.6+/-1.6%) and AII (2.4+/-0.8%) groups. However, following opiate withdrawal, virtually no Fos expression was observed in NPFF neurons. NPFF neurons activated during NP infusion constituted the largest number of cells projecting to the PBN. This study shows that NPFF neurons in NTS that project to the PBN respond selectively to NP as opposed to other cardiovascular challenges or opiate withdrawal. These data support an emerging and important role for NPFF in the context of central cardiovascular regulation.

Topics: Angiotensin II; Animals; Hemodynamics; Hypertension; Hypotension; Male; Morphine; Morphine Dependence; Naloxone; Neurons; Nitroprusside; Oligopeptides; Phenylephrine; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic; Solitary Nucleus; Substance Withdrawal Syndrome

Endogenous opioids are known to mediate some of the cardiovascular sequelae of sepsis. Inhibition of adrenergic action has been implicated as a physiological path by which endogenous opioids cause deleterious changes in cardiovascular function during endotoxin shock, but where and to what extent this accounts for changes in regional vascular resistance remains unclear. In this study, we addressed this question by examining the role of alpha-adrenergic actions in cardiovascular performance and the regional perfusion changes caused by naloxone during endotoxin shock. Rats had catheters inserted into the tail artery, left cardiac ventricle, and jugular vein. Twenty-four hours later, rats received saline or endotoxin (2 mg/kg) challenge intravenously over 30 min, followed at 40 min by intravenous naloxone (or saline) treatment (4 mg/kg + 2 mg/kg x h) in the presence or absence of phentolamine (100 micrograms/kg + 600 micrograms/kg x h) or yohimbine (40 micrograms/kg + 4 micrograms/kg x h). Radiolabeled microspheres were used to determine cardiac outputs and blood flows at 0, 30, 60, and 120 min after beginning endotoxin infusion. Naloxone attenuated the endotoxin-induced decline in mean arterial pressure (MAP) and cardiac output (CO), but had no effect on increased systemic vascular resistance (SVR). Phentolamine blocked naloxone's ability to increase MAP and CO, but permitted an increase in SVR by naloxone. In the presence of yohimbine, naloxone still increased MAP, but not CO nor SVR. Regional vascular responses varied, with naloxone demonstrating a vasoconstrictive effect despite alpha-adrenergic receptor blockade in some beds, and no effect in others. The response of individual organs in the hepatosplanchnic circulation was heterogenous as well. These data suggest that some effects of endogenous opioids during endotoxin shock are mediated via inhibition of alpha-adrenergic effects, but that some cardiovascular effects of endogenous opioids are independent of adrenergic control during endotoxin shock.

Topics: Adrenergic alpha-Antagonists; Animals; Blood Flow Velocity; Blood Pressure; Cardiac Output; Endotoxins; Hemodynamics; Hypotension; Male; Naloxone; Narcotic Antagonists; Phentolamine; Rats; Rats, Sprague-Dawley; Shock, Septic; Vascular Resistance; Vasoconstriction; Yohimbine

Several procedures performed in the electrophysiology laboratory (EP lab) require surgical manipulation and are lengthy. Patients undergoing such procedures usually receive general anesthesia or deep sedation administered by an anesthesiologist. In 536 consecutive procedures performed in the EP lab, we assessed the safety and efficacy of deep sedation administered under the direction of an electrophysiologist and in the absence of an anesthetist. Patients were monitored with pulse oximetry, noninvasive blood pressure recordings, and continuous ECGs. The level of consciousness and vital signs were evaluated at 5-minute intervals. Deep sedation was induced in 260 patients using midazolam, phenergan, and meperidine, then maintained with intermittent dosing of meperidine at the following mean doses: midazolam 0.031 +/- 0.024 mg/kg; phenergan 0.314 +/- 0.179 mg/kg; and meperidine 0.391 +/- 0.167 mg/kg per hour. In the remaining 276 patients, deep sedation was induced with midazolam and fentanyl and maintained with a continuous infusion of fentanyl at a mean dose of 2.054 +/- 1.43 micrograms/kg per hour. Fourteen patients experienced a transient reduction in oxygen saturation that was readily reversed following administration of naloxone. An additional 11 patients desaturated secondary to partial airway obstruction, which resolved after repositioning the head and neck. Fourteen patients experienced hypotension with fentanyl. All but one returned to baseline blood pressures following an infusion of normal saline. No patient required intubation and no death occurred. Only three patients had recollection of periprocedure events. No patient remembered experiencing pain with the procedure. Hospital stays were not prolonged as a result of the sedation used.. (1) deep sedation during EP procedures can be administered safely under the guidance of the electrophysiologist without an anesthetist present; (2) the drugs used should be readily reversible in case of respiratory depression; and (3) this approach may reduce the overall cost of the procedures in the EP lab, maintaining adequate patient comfort.

Topics: Adjuvants, Anesthesia; Airway Obstruction; Anesthesia, Intravenous; Anesthesiology; Anesthetics, Intravenous; Blood Pressure; Consciousness; Cost Control; Electrocardiography; Electrophysiology; Evaluation Studies as Topic; Female; Fentanyl; Heart Rate; Humans; Hypnotics and Sedatives; Hypotension; Laboratories; Length of Stay; Male; Memory; Meperidine; Midazolam; Middle Aged; Monitoring, Physiologic; Naloxone; Narcotic Antagonists; Oximetry; Oxygen; Promethazine; Safety

The profound hypotension caused by acute hemorrhage is thought to involve opioid peptide neurons. In this study, we tested whether glycyl-L-glutamine [Gly-Gln; beta-endorphin-(30-31)], a nonopioid peptide derived from beta-endorphin processing, prevents the cardiovascular depression induced by hemorrhage in conscious and anesthetized rats. Previously, we found that Gly-Gln inhibits the hypotension and respiratory depression produced by beta-endorphin and morphine but does not affect opioid antinociception. Hemorrhage (2.5 ml/100 g body wt over 20 min) lowered arterial pressure in conscious rats (from 120.1 +/- 2.9 to 56.2 +/- 4.7 mmHg) but did not change heart rate significantly. Intracerebroventricular Gly-Gln (3, 10, or 30 nmol) pretreatment inhibited the fall in arterial pressure and increased heart rate significantly. The response was dose related and was sustained during the 35-min posthemorrhage interval. Pentobarbital sodium anesthesia potentiated the hemodynamic response to hemorrhage and attenuated the effect of Gly-Gln. Gly-Gln (10 or 100 nmol icv) did not influence arterial pressure or heart rate in normotensive rats. These data indicate that Gly-Gln is an effective antagonist of hemorrhagic hypotension.

Topics: Animals; Blood Pressure; Cerebral Ventricles; Dipeptides; Heart Rate; Hemorrhage; Hypotension; Injections, Intraventricular; Male; Naloxone; Neural Inhibition; Pulse; Rats; Rats, Sprague-Dawley; Stereoisomerism

The influence of naloxone-induced general opiate receptor blockade on hypothalamic blood flow autoregulation was investigated in anaesthetized, artificially ventilated, temperature controlled cats. In order to study the changes of the hypothalamic blood flow (H2-gas clearance technique) at the lower limit of autoregulation systemic arterial pressure was reduced in a stepwise manner to 100, 80, 60 and 40 mmHg, by haemorrhage. Autoregulatory mechanisms of the hypothalamic vessels remained effective and hypothalamic blood flow showed no significant reduction until the arterial pressure was reduced to 60 mmHg in the vehicle-treated control cats. General opiate receptor blockade by 1 mg kg-1 mL-1 i.v. injected naloxone resulted in a significant reduction of the autoregulatory capacity of the hypothalamic vessels: the blood flow followed passively the arterial pressure fall already from 100 mmHg mean arterial pressure. The effect of opiate receptor blockade on the upper limit of the autoregulation was studied during acute arterial hypertension, induced by angiotensin-II infusion (25 micrograms 0.1 mL-1 min-1 i.v.). Hypothalamic blood flow remained remarkably steady following angiotensin-II infusion in the saline-treated control animals. Naloxone pretreatment (1 mg kg-1 mL-1 i.v.), however, induced a significant downward shift of the upper limit of the autoregulation, and hypothalamic blood flow started to increase in the 125-145 mmHg arterial pressure range. The narrowing of the autoregulatory range following general opiate receptor blockade suggests an important role of endogenous opioid peptides in hypothalamic blood flow autoregulatory mechanisms both in hypotensive and in hypertensive conditions.

Topics: Angiotensin II; Animals; Carbon Dioxide; Cats; Central Venous Pressure; Cerebrovascular Circulation; Female; Hemorrhage; Homeostasis; Hypertension; Hypotension; Hypothalamus; Male; Naloxone; Narcotic Antagonists; Receptors, Opioid

Previous data have shown that apomorphine-induced respiratory depression can be reversed by the opiate antagonist, naloxone. The present study investigates the influence of naloxone on cardiovascular changes and vomiting elicited by apomorphine in dogs. In chloralose-anaesthetized animals, naloxone (0.02 mg/kg i.v.) failed to modify either the decrease in blood pressure and the biphasic changes (bradycardia followed by a long-lasting tachycardia in heart rate or the characteristics (occurrence, latency, duration) of the emesis elicited by apomorphine (200 micrograms/kg i.v.). In contrast, in conscious animals, naloxone (0.02 mg/kg i.v.) increased both the number and the duration (but not latency) of vomiting induced by a lower dose of apomorphine (30 micrograms/kg i.v.). These data show that apomorphine-induced vomiting and arterial hypotension do not involve opiate receptors.

Topics: Anesthetics; Animals; Apomorphine; Blood Pressure; Chloralose; Dogs; Female; Heart Rate; Hypotension; Male; Naloxone; Vomiting

The endogenous opioid peptide (EOP) dynorphin and opioid receptors have been found in the heart. This opioid system plays important roles in cardiovascular regulation and is involved in the pathophysiology of shock, heart failure and myocardial ischaemia. The aim of this study was to evaluate whether the EOP dynorphin modulates or potentiates ischaemia-induced arrhythmias and whether its effects are prevented by the opiate antagonist naloxone. Following coronary artery occlusion, all rats in the control group developed ischaemia-induced arrhythmias, bradycardia and hypotension, which were significantly potentiated by pre-treatment with dynorphin and attenuated by treatment with naloxone. The results clearly indicate that EOPs may be released when myocardial ischaemia occurs, thus causing arrhythmias, bradycardia and hypotension. Dynorphin and naloxone, by virtue of their opioid agonistic and antagonistic actions, respectively, potentiate and attenuate these fatal complications secondary to myocardial ischaemia. This suggests that EOPs play an important part in ischaemic heart disease.

Topics: Animals; Arrhythmias, Cardiac; Bradycardia; Dynorphins; Female; Heart Conduction System; Hypotension; Male; Myocardial Ischemia; Naloxone; Rats; Rats, Sprague-Dawley; Shock, Cardiogenic

It has been shown that endogenous opioid peptides (EOP) subserve important roles in cardiovascular regulation and are involved in the pathophysiology of myocardial ischemia, contributing to the deleterious effects. The aim of this study was to evaluate the effects of the opiate antagonist naloxone on the hemodynamics and ventricular function following coronary artery occlusion and reperfusion in the dog, utilizing the technique of cardiac catheterization. During myocardial ischemia and reperfusion, it was found that in the control group, there was reduction in the aortic, left ventricular, right atrial, pulmonary arterial and wedge pressures, and in the left ventricular dP/dt. The reduction in the aortic, left ventricular and pulmonary arterial pressures, and left ventricular dP/dt were significantly attenuated by pretreatment with naloxone. The results indicate a regulatory role of EOP in the cardiovascular function and suggest a possible involvement of EOP in myocardial ischemia and reperfusion causing detrimental effects such as arrhythmias, bradycardia, hypotension and, as shown in this study, impaired hemodynamics and ventricular function. The beneficial effects of naloxone on circulatory dynamics may have clinical implications in the prevention and treatment of ischemic heart disease.

Topics: Animals; Arrhythmias, Cardiac; Bradycardia; Dogs; Endorphins; Female; Hemodynamics; Hypotension; Male; Myocardial Ischemia; Myocardial Reperfusion; Naloxone; Ventricular Function, Left

We tested the hypothesis that the pressor effect of naloxone during acute hemorrhagic hypotension is mediated in part at peripheral sites. Experiments were performed in conscious, chronically prepared rabbits. First, we compared the hemodynamic response to peripheral injections of naloxone and naloxone methobromide during acute hemorrhagic hypotension. Naloxone methobromide, which does not enter the central nervous system, produced a lesser pressor effect than naloxone. Second, we looked for peripheral effects of naloxone after close-arterial injection into the hindquarter vasculature. Unlike i.v. injections, close-arterial injection of naloxone did not produce any significant hemodynamic changes during hemorrhagic hypotension. Finally, we compared the capacities of naloxone and naloxone methobromide to block the peripherally mediated cardiovascular response to i.v. methionine-enkephalin in nonhemorrhaged animals. The potency of the two compounds, in terms of their blockade of this peripherally mediated response, was similar. The results of the present study do not support a predominant peripheral role for naloxone during acute hemorrhagic hypotension in conscious rabbits.

Topics: Animals; Blood Pressure; Endorphins; Enkephalin, Methionine; Heart Rate; Hemodynamics; Hemorrhage; Hypotension; Male; Naloxone; Oxymorphone; Rabbits; Vascular Resistance

Previous studies of both hypertensive and normotensive individuals have indicated a prolonged reduction in blood pressure for several hours after aerobic exercise. In related studies of spontaneously hypertensive rats, this postexercise hypotension has been prevented with naloxone. The purpose of the present investigation was to examined whether the postexercise hypotension may be reversed by antagonism of opioid sensitive receptors with naloxone in normotensive humans. Eight males 22-34 yr of age, participated in two 60-min cycling trials at 60% of VO2 peak, followed by 29 min of recovery. Beginning at 7-min recovery, naloxone or saline (control) was administered intravenously through an indwelling catheter. Blood pressure and heart rate were monitored every 15 min during exercise and every 2 min during recovery. Heart rate was significantly elevated (P < 0.05) over basal levels for the first 11 min of recovery, but from 13 to 29 min was not different from that measured at rest. In both trials, after 11 min of recovery, systolic and mean arterial blood pressures were significantly (P < 0.05) lower than pre-exercise levels (9 +/- 1 mm Hg and 4 +/- 1 mm Hg, respectively). Injection of naloxone (0.1 mg.kg-1) reversed the hypotensive response. However, the reversal was transient, lasting from minutes 15 to 27. Since naloxone reverses postexercise hypotension, opioid sensitive receptors appear to be involved in the reduction in systolic blood pressure following a single bout of submaximal exercise in normotensive humans.

Topics: Adult; Blood Pressure; Exercise; Heart Rate; Humans; Hypotension; Male; Naloxone; Oxygen Consumption; Receptors, Opioid; Time Factors

1. The effects of both the (-)- and (+)-stereoisomers of naloxone in anaesthetized dogs with arrhythmias induced by acute coronary artery occlusion followed by reperfusion were investigated. 2. Following coronary artery occlusion and reperfusion, all dogs in the control group developed ischaemia- and reperfusion-induced cardiac arrhythmias, bradycardia and hypotension. 3. The opiate antagonist (-)-naloxone prevented the arrhythmias, bradycardia and hypotension due to myocardial ischaemia and reperfusion. 4. The (+)-stereoisomer of naloxone, which is inactive as an opiate antagonist, was without beneficial effects. 5. These results indicate a possible involvement of endogenous opioid peptides in the cardiac effects due to myocardial ischaemia and reperfusion, mediated by opiate receptors through opiate antagonism.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Bradycardia; Dogs; Female; Heart Rate; Hypotension; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Naloxone; Stereoisomerism

In the present study, the role of the endogenous opioid peptide systems in the regulation of blood pressure during standardized, stepwise hemorrhagic hypotension was investigated in anesthetized rats. Central as well as peripheral administration of naloxone resulted in an increase in the bleeding volumes required to reduce blood pressure. Bleeding volumes also increased after the peripheral injection of naloxone methobromide, an analog of naloxone that does not readily cross the blood-brain barrier. Following central administration of antisera against beta- and alpha-endorphin and dynorphin A(1-13), the amount of blood that had to be withdrawn to induce hypotension was elevated. In rats treated with an antiserum against [Met5] enkephalin or gamma-endorphin, bleeding volumes did not differ from those of rats treated with control serum. These data indicate that activation of central and possibly also of peripheral opiate receptors plays a role in the control of blood pressure during blood loss. Dynorphin A(1-13), beta- and alpha-endorphin, or closely related peptides might be the endogenous ligands for the receptors that are blocked by naloxone.

Topics: alpha-Endorphin; Animals; beta-Endorphin; Blood Pressure; Dynorphins; Endorphins; Enkephalin, Methionine; gamma-Endorphin; Hemorrhage; Hypotension; Immunization, Passive; Male; Naloxone; Oxymorphone; Peptide Fragments; Rats; Rats, Inbred Strains

We investigated possible interactions between arginine vasopressin (AVP) and endogenous opioid peptides during rapid hypotensive hemorrhage and subsequent opioid receptor blockade in conscious rabbits. Plasma AVP concentration did not change after normotensive hemorrhage but increased after hypotensive hemorrhage. Blockade of V1-AVP receptors (AVPX) did not affect prehemorrhage arterial pressure, heart rate, or hindquarter blood flow and vascular resistance. AVPX did not alter the hemodynamic response to hemorrhage or the blood loss required to reduce mean arterial pressure to less than 40 mmHg. However, hindquarter blood flow was higher and mean arterial pressure and hindquarter resistance lower after hypotensive hemorrhage in AVPX-treated animals. These differences were maintained after naloxone or saline injection. Naloxone increased mean arterial pressure and hindquarter resistance and decreased heart rate with or without AVPX. At 2 min postinjection, plasma AVP values were greater after saline than after naloxone. When naloxone's pressor response was reduced by alpha-adrenergic blockade, plasma AVP values were higher after naloxone than after saline. Thus AVP was not vital to maintenance of blood pressure during rapid normotensive hemorrhage or to the abrupt decrease in arterial blood pressure and resistance after rapid hypotensive hemorrhage. AVP release was important to spontaneous recovery from acute hypotensive hemorrhage but only of minor importance to naloxone's pressor response. Finally, AVP release appeared to be inhibited by endogenous opioids during acute hemorrhagic hypotension.

Topics: Animals; Arginine Vasopressin; Drug Interactions; Endorphins; Hemodynamics; Hemorrhage; Hypotension; Naloxone; Narcotic Antagonists; Rabbits; Rest

The interaction between opioid and prostanoid mechanisms in the control of cerebral hemodynamics was investigated in the conscious hypotensive piglet. Radiomicrospheres were used to determine regional cerebral blood flow (rCBF) in piglets pretreated with the opioid receptor antagonist, naloxone, or its vehicle, saline, during normotension, hypotension, and after the administration of indomethacin, a cyclooxygenase inhibitor, during hypotension. Hemorrhage (30 ml/kg) decreased systemic arterial pressure from 68 +/- 12 to 40 +/- 10 mm Hg but did not decrease blood flow to any brain region. Indomethacin treatment (5 mg/kg) of hypotensive piglets decreased blood flow to all brain regions within 20 min; this decrease in CBF resulted from increases in cerebral vascular resistance of 65 and 281% at 20 and 40 min after treatment, respectively. In hypotensive piglets, cerebral oxygen consumption was reduced from 2.62 +/- 0.71 to 0.53 +/- 0.27 ml 100 g-1 min-1 and to 0.11 +/- 0.04 ml 100 g-1 min-1 at 20 and 40 min following indomethacin, respectively. Treatment with naloxone (1 mg/kg) had no effect on rCBF, calculated cerebral vascular resistance, or cerebral oxygen consumption of normotensive or hypotensive piglets. However, decreases in CBF and oxygen consumption and increases in cerebral vascular resistance upon treatment of hypotensive piglets with indomethacin were attenuated in animals pretreated with naloxone. These data indicate that the removal of prostanoid modulation of an opioid-mediated constrictor influence on the cerebral circulation is a potential mechanism for the increase in cerebral vascular resistance that follows indomethacin treatment of hypotensive piglets.

Topics: Animals; Arteries; Blood Flow Velocity; Blood Pressure; Carbon Dioxide; Cardiac Output; Cerebrovascular Circulation; Cyclooxygenase Inhibitors; Endorphins; Hemorrhage; Hydrogen-Ion Concentration; Hypotension; Indomethacin; Microspheres; Naloxone; Oxygen; Prostaglandins; Swine; Vascular Resistance; Vasoconstriction

The hemodynamic effects of captopril and other angiotensin-converting enzyme inhibitors may be mediated by the endogenous opioid system. The opioid antagonist naloxone has been shown to block or reverse the hypotensive actions of captopril. We report a case of an intentional captopril overdose, manifested by marked hypotension, that resolved promptly with the administration of naloxone. To our knowledge, this is the first reported case of captopril-induced hypotension treated with naloxone. Our experience demonstrates a possible role of naloxone in the reversal of hypotension resulting from captopril.

Topics: Adult; Blood Pressure; Captopril; Drug Overdose; Female; Humans; Hypotension; Naloxone; Suicide, Attempted

Growth-hormone-releasing peptide (GH-RP-6) is a synthetic hexapeptide that selectively releases growth hormone (GH) when administered to a number of animals species. In the rat, maximal GH release occurs after intravenous administration of 100 micrograms/kg GH-RP-6. Intravenous administration of 5 mg/kg GH-RP-6 produced 100% lethality within 2-5 min of drug administration. Further investigative studies demonstrated that the lethal effect of GH-RP-6 was preceded by an initial hypertensive episode, followed by a rapid, profound hypotension and bradycardia. The rise and fall in blood pressure also were observed in pithed rats treated with GH-RP-6, suggesting that the central nervous system was not responsible for the changes in blood pressure. However, the GH-RP-6-induced bradycardia was not observed in pithed rats, indicating the fall in heart rate was mediated through a central reflex mechanism. No direct effects of GH-RP-6 were seen in the isolated rat aorta or canine saphenous vein. Pretreatment of conscious rats with naloxone (10 mg/kg, iv), an opiate receptor antagonist, did not prevent the hypertensive response to GH-RP-6, but the hypotension and lethality were attenuated. Pretreatment with cyproheptadine (2.5 mg/kg, iv), a dual serotonin/histamine antagonist, or ketanserin (3 mg/kg, iv), a selective serotonin antagonist, prevented the GH-RP-6-induced hypotension and lethality. Cyproheptadine unmasked a 40 mm Hg rise in mean arterial pressure which persisted for over 10 min. In addition, degranulation of mast cells with compound 48/80 inhibited the toxicity of GH-RP-6, suggesting that mast cell degranulation and the subsequent release of autocoids is responsible for the cardiovascular effects of GH-RP-6. In vitro, GH-RP-6 (10(-5) - 10(-3) M) produced a concentration-related release of histamine from rat peritoneal mast cells. However, the histamine release by GH-RP-6 (10(-4) M) was not inhibited by naloxone (10(-4) M) in isolated mast cells, suggesting either that peritoneal mast cells are not responsible or that the mast cell degranulation in vitro is not opiate mediated. In conclusion, it appears that GH-RP-6 degranulates mast cells releasing serotonin, which produces hypotension, bradycardia, and death. This degranulation of mast cells is apparently inhibited by naloxone in vivo, suggesting that opiate receptors are involved in the hypotension and lethality associated with the administration of GH-RP-6.

Topics: Analysis of Variance; Animals; Cimetidine; Cyproheptadine; Dose-Response Relationship, Drug; Drug Synergism; Growth Hormone-Releasing Hormone; Histamine H2 Antagonists; Histamine Release; Hormones; Hypotension; Injections, Intravenous; Ketanserin; Male; Mast Cells; Naloxone; Oligopeptides; Pyrilamine; Rats; Rats, Inbred Strains; Serotonin

Reduction of renal perfusion is followed by increases in plasma renin activity (PRA) and arterial pressure. The present experiments were designed to determine if an opiate antagonist would alter pressor or renin responses to acute reduction of renal arterial pressure (RAP) in anesthetized rats. Male Sprague-Dawley rats were anesthetized with Inactin, and an adjustable constrictor device was placed around the abdominal aorta proximal to the renal arteries. One-half of the animals were pretreated with the opiate antagonist naloxone (2 mg/kg iv), and the other one-half were pretreated with saline vehicle. The abdominal aorta was then constricted to reduce RAP by 25% (measured as femoral arterial pressure) in one-half of the animals in each pretreatment group. Compared with vehicle pretreatment, naloxone pretreatment did not alter the PRA response to aortic constriction; however, naloxone did attenuate the pressor response. We conclude that 1) the PRA response to acute reduction of renal arterial pressure is not dependent on an opiate mechanism in the rat, and 2) attenuation of the pressor response to aortic constriction by naloxone in intact rats is not secondary to a suppression of the PRA response.

Topics: Analysis of Variance; Animals; Blood Pressure; Body Weight; Heart Rate; Hypotension; Male; Morphine; Naloxone; Rats; Rats, Inbred Strains; Renal Circulation; Renin

We performed a retrospective review to investigate the safety of prehospital naloxone administration by paramedics as part of a protocol for all patients presenting with an acutely depressed level of consciousness (LOC). The prevalence of naloxone-induced vomiting, seizures, hypotension, hypertension, and cardiac arrest was sought from the prehospital records of 813 patients treated during a 12-month period. The mean age of the treated patients was 42.4 +/- 9.7 years. The initial dose of naloxone was 0.4 to 0.8 mg, and the mean total dose was 0.9 +/- 0.6 mg. No patients lost a pulse within ten minutes of receiving naloxone. Two patients (0.2%) experienced a significant drop in systolic blood pressure, and one patient (0.1%) demonstrated a significant rise in systolic blood pressure within five minutes of naloxone administration. Vomiting occurred in two patients (0.2%), and one patient (0.1%) suffered a tonic-clonic seizure within five minutes of naloxone administration. Of the 813 patients treated, 60 patients (7.4%: mean age, 32.3 +/- 6.7 years) were judged to have an improved LOC after naloxone, with 27 (3.3%) regaining a normal LOC. We conclude that in the above doses, naloxone is safe as part of prehospital protocols for paramedics treating patients with an acutely depressed LOC. However, the vast majority of patients treated empirically with naloxone in the field demonstrated no benefit.

Topics: Adult; Emergencies; Emergency Medical Services; Female; Heart Arrest; Humans; Hypotension; Male; Middle Aged; Naloxone; Pennsylvania; Retrospective Studies; Safety; Seizures; Unconsciousness; Vomiting

The present study investigated the question of whether peripheral or central opiate receptors are activated during controlled haemorrhagic hypotension. In anaesthetized Wistar rats, blood pressure was reduced by steps, by bleeding, to 80, 60 and 40 mmHg. Subcutaneous administration of 1 mg/kg of naloxone and of methyl naloxone-Br, an analogue of naloxone, which does not readily cross the blood-brain barrier, significantly elevated the bleeding volume at the 40-mmHg blood pressure level. A dose of 10 mg/kg of methyl naloxone-Br had no effect on the bleeding volume. We therefore conclude that during haemorrhage, endogenous opioid peptides activate both central and peripheral opiate receptors, thereby exerting a hypotensive influence.

Topics: Animals; Central Nervous System; Hemorrhage; Hypotension; Male; Naloxone; Oxymorphone; Peripheral Nerves; Rats; Rats, Inbred Strains; Receptors, Opioid

Effects of hemorrhage on renal nerve activity and of subsequent opiate receptor blockade with naloxone were studied in conscious rabbits. Mean arterial pressure remained constant at 77 +/- 2 mm Hg through 17 +/- 2 ml/kg hemorrhage, while renal nerve activity increased by 159 +/- 16%. After 25 +/- 1 ml/kg hemorrhage, mean arterial pressure fell by 42 +/- 3 mm Hg, and renal nerve activity decreased below the prehemorrhagic control level by 41 +/- 15%. Bolus injection of naloxone (3 mg/kg i.v.) increased mean arterial pressure to 79 +/- 2 mm Hg, not significantly different from the prehemorrhagic control level. Renal nerve activity increased by 171 +/- 28%, comparable to the peak increase during nonhypotensive hemorrhage. On a different day, hemorrhage was repeated, and phenylephrine was infused during the subsequent hypotension. Phenylephrine increased mean arterial pressure to the prehemorrhagic control level. With increasing mean arterial pressure, renal nerve activity increased from its level during hypotensive hemorrhage and recovered toward the prehemorrhagic control level (-26 +/- 11%), but it did not return to the peak value reached during nonhypotensive hemorrhage. To further examine the blocking effects of naloxone on changes in mean arterial pressure and renal nerve activity induced by exogenous opiate peptides, methionine-enkephalin was injected both in the control state and after treatment with naloxone. A bolus injection of methionine-enkephalin (10 micrograms/kg) decreased mean arterial pressure (-8.1 +/- 2.0 mm Hg) and renal nerve activity (-95 +/- 1%). Pretreatment with naloxone (0.5 mg/kg) effectively blocked this depressor effect and reduction in renal nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Consciousness; Enkephalins; Hemorrhage; Hypotension; Kidney; Naloxone; Rabbits; Receptors, Opioid; Sympathetic Nervous System

Intracerebroventricular injections of nicardipine (10 micrograms/kg) to SHR induced hypotension which was suppressed by pretreatment with 6-OHDA. This hypotension was also inhibited by a previous injection of naloxone (100 micrograms/kg i.c.v.) whereas the hypotension induced by intravenously injected nicardipine (10 micrograms/kg) was not changed. It is suggested that the release of endogenous opioids is involved in the sympatho-inhibitory effect of centrally administered dihydropyridine calcium channel antagonists.

Topics: Animals; Blood Pressure; Dihydropyridines; Endorphins; Hydroxydopamines; Hypotension; Male; Naloxone; Nicardipine; Oxidopamine; Rats; Rats, Inbred SHR; Receptors, Opioid; Sympathetic Nervous System

The possible role of the endogenous opioid system in the central hypotensive mechanism of action of alpha-methyldopa was investigated. Conscious normotensive Wistar rats were used in this study and all treatments were given intracisternally. Pretreatment with the opiate receptor antagonist naltrexone resulted in a parallel shift to the right of the dose-response curve for alpha-methyldopa, both for blood pressure and heart rate. In addition, when increasing doses of naltrexone and a constant dose of alpha-methyldopa were used the opiate receptor antagonist inhibited dose-dependently alpha-methyldopa-induced hypotension but not the bradycardia. Administration of naltrexone after the injection of alpha-methyldopa failed to reverse or inhibit alpha-methyldopa-induced hypotension, indicating that the interaction between alpha-methyldopa and the endogenous opioid system occurs at the start of the action of alpha-methyldopa. An antiserum against endorphins also inhibited the fall in blood pressure after alpha-methyldopa. These findings indicate that stimulation of opiate receptors, probably by an endorphin, is involved in the mechanism of action of alpha-methyldopa and that this stimulation seems to occur at the start of the action of alpha-methyldopa.

Topics: Animals; beta-Endorphin; Bradycardia; Dose-Response Relationship, Drug; Heart Rate; Hypotension; Immune Sera; Male; Methyldopa; Naloxone; Naltrexone; Rats; Rats, Inbred Strains

Topics: Adult; Clonidine; Humans; Hypotension; Male; Naloxone; Substance Withdrawal Syndrome

Naloxone reverses hemorrhagic hypotension in the conscious guinea-pig. Captopril and saralasin impede this naloxone effect, suggesting that angiotensin II is involved in naloxone action. This is compatible with previous work which has shown that B-endorphin inhibits the centrally mediated pressor action of angiotensin II, and that naloxone blocks this effect. Naloxone may be interacting with the postulated brain renin-angiotension II system or may be blocking the action of shock-induced circulating angiotensin II on a centrally located area such as the hypothalamus.

Topics: Animals; Blood Pressure; Captopril; Guinea Pigs; Hemorrhage; Hypotension; Hypothalamus; Naloxone; Neural Inhibition; Receptors, Opioid; Renin-Angiotensin System; Saralasin

The purpose of the study was to examine the effects of naloxone on signs of cerebral ischaemia during hypotensive haemorrhage in unanaesthetized spontaneously hypertensive rats. Mean arterial blood pressure (MAP), heart rate (HR) and somatosensory evoked potentials (SEP) were recorded. Arousal tests were also performed and the behavioural responses quantified. The SEP alone were a poor indicator of cerebral function in these unanaesthetized rats, because they were markedly influenced by changes in activity and arousal of the animals. Hypotensive haemorrhage resulted in a biphasic tachycardia response, an attenuation of the first SEP component and a reduction of the behavioural response score. Naloxone, 5 mg kg-1 i.v., induced transient bradycardia and a dramatic improvement in arousal test responses, while SEP were not clearly altered. The MAP was kept constant after naloxone injection by adjustments of bleeding and transfusion. Injection of naloxone in unbled control SHR also induced bradycardia but without any changes in SEP and the behavioural responses. The results indicate that naloxone can have beneficial effects in cerebral ischaemia. Possible mechanisms are discussed.

Topics: Animals; Arousal; Behavior, Animal; Brain Ischemia; Depression; Evoked Potentials, Somatosensory; Hemodynamics; Hemorrhage; Hypotension; Male; Naloxone; Rats; Rats, Inbred SHR

The effect of opiate antagonist therapy with naloxone on hemorrhagic shock was examined. An equivalent intravenous bolus of naloxone or normal saline had the same pressor effect in conscious, unrestrained, hypovolemic hypotensive rats. The proposal that opiate antagonists are of therapeutic value in the treatment of hemorrhage is questioned.

Topics: Animals; Blood Pressure; Hemorrhage; Hypotension; Male; Naloxone; Rats; Rats, Inbred Strains; Sodium Chloride

Clonidine is a centrally acting antihypertensive agent used in the management of essential hypertension. Oral clonidine loading is now used frequently in the management of hypertensive urgencies (ie, increases in arterial pressure not associated with acute, life-threatening end-organ injury). We report the case of a patient with an acute inferior myocardial infarction associated with blunt chest trauma who developed an abrupt and unexplained increase in arterial pressure 24 hours after admission and who was treated with oral clonidine (0.5 mg in divided doses over two hours). Drug therapy was followed by prolonged (four hours) systemic arterial hypotension (mean arterial pressure less than 70 mm Hg). Four milligrams of naloxone in two divided doses was given. Each naloxone bolus was followed by a 15-mm-Hg increase in mean arterial pressure and a return to values that were normal for this patient. Naloxone may be of value in reversing clonidine toxicity when clonidine is given to treat an acute rise in arterial pressure.

Topics: Accidents, Traffic; Aged; Clonidine; Female; Humans; Hypertension; Hypotension; Myocardial Infarction; Naloxone; Wounds, Nonpenetrating

The apneic laryngeal chemoreflex (QRL), elicited by water on the vocal cords and by mechanical stimulation (MRL) has been compared in dog. Both stimuli cause apnea, bradycardia, hypotension and constriction of the glottis. In QRL apnea predominates white in MRL bradycardia is more intense. All the components of the response decrease with naloxone at a 400 micrograms X kg-1 doses, suggesting that the reflex inhibition depends on endogenous opioids located in the respiratory centre.

Topics: Animals; Apnea; Bradycardia; Dogs; Hypotension; Larynx; Naloxone; Physical Stimulation; Reflex

The purpose of this study was to examine the effects of naloxone on signs of relative cerebral ischaemia induced by hypotensive haemorrhage. Mean arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (rSNA) and somatosensory evoked potentials (SEP) were recorded in chloralose-anaesthetized spontaneously hypertensive rats exposed to graded bleeding. Hypotensive haemorrhage resulted, after a very brief sympathetic excitation, in marked sympathetic inhibition and bradycardia and a considerable reduction of SEP, indicating relative cerebral ischaemia. However, after 25-30 min this sympatho-inhibitory response was reversed to pronounced sympathetic excitation and tachycardia, which was accompanied by a further attenuation of SEP. A single bolus of naloxone (10 mg kg-1) caused transient sympathetic inhibition and bradycardia, which was accompanied by an improvement of SEP. A bolus injection (5-10 mg kg-1) followed by a 30 min infusion of naloxone (25-35 mg kg-1 h-1) caused a sustained SEP improvement despite the fact that MAP was kept constant during naloxone administration. We conclude that naloxone can have beneficial effects on brain function during cerebral ischaemia, effects that are probably due to blockade of opioid receptors. Our model of relative cerebral ischaemia might be useful for evaluating the mechanisms behind the naloxone effects during this condition.

Topics: Animals; Blood Pressure; Brain; Brain Ischemia; Evoked Potentials, Somatosensory; Heart Rate; Hemorrhage; Hypotension; Male; Naloxone; Rats; Rats, Inbred SHR; Sympathetic Nervous System

Anaphylaxis results from the generation and release of a variety of mediators and their effects on various organs. Involvement of the respiratory and cardiovascular systems is of primary importance to the attending physician. Prompt recognition and initial therapy directed to maintenance of an effective airway and circulatory system is critical. Cardiovascular collapse may involve the parallel operation of several mechanisms including hypovolemia, alterations in pulmonary or systemic vascular resistance, depressed myocardial contractility, dysrhythmias, and exogenous drug administration. Although epinephrine is the mainstay of therapy, improvement in cardiovascular status may require aggressive fluid administration, and additional pharmacologic and non-pharmacologic aids.

Topics: Anaphylaxis; Blood Pressure; Epinephrine; Fluid Therapy; Gravity Suits; Histamine H1 Antagonists; Humans; Hypotension; Naloxone

In 5 uremic patients the role of opioid peptides in dialysis-induced hypotension was investigated through the administration of naloxone. An intravenous bolus injection of 1 mg of naloxone was administered immediately before starting a routine hemodialysis session and was repeated when the patients' systolic arterial pressure sank below 90 mm Hg. In our patients, naloxone had no effect on the resting arterial pressure or on dialysis-induced hypotension.

Topics: Blood Pressure; Female; Humans; Hypotension; Kidney Failure, Chronic; Male; Naloxone; Renal Dialysis; Uremia

Topics: Animals; Diprenorphine; Hematocrit; Hypotension; Male; Morphinans; Naloxone; Nitroprusside; Rats; Rats, Inbred Strains; Saline Solution, Hypertonic; Shock; Vasopressins

We evaluated the effectiveness and safety of iv naloxone in 12 septic patients who remained hypotensive despite volume replacement, appropriate antibiotics, and vasopressor therapy. Only four patients responded positively to naloxone, by increases in mean arterial pressure of between 10 to 15 mm Hg that lasted for 15 to 60 min. These patients could not be distinguished from the others on the basis of underlying illness, laboratory or physical findings, length of preceding hypotension, or glucocorticoid therapy. Four patients had adverse reactions: one developed pulmonary edema, one patient had a grand-mal seizure, and two patients became severely hypotensive. We conclude that in patients with well-established septic shock, naloxone does not reliably improve mean arterial pressure or other physiologic variables, and may cause severe adverse reactions.

Topics: Aged; Analysis of Variance; Blood Pressure; Critical Care; Drug Evaluation; Female; Hemodynamics; Humans; Hypotension; Injections, Intravenous; Male; Middle Aged; Naloxone; Shock, Septic

Topics: Atropine; Bradycardia; Child, Preschool; Dopamine; Female; Fluid Therapy; Guanabenz; Guanidines; Humans; Hypotension; Middle Aged; Naloxone; Sleep Stages

Topics: Animals; Humans; Hypotension; Naloxone; Narcotic Antagonists; Postoperative Complications; Respiratory Insufficiency; Spinal Cord Injuries

Naloxone, an opiate antagonist, is reported to reverse hypotension and to improve survival in hemorrhaged and septic animals. We have found recently that naloxone also blunts the hyperglycemic response to hemorrhage. This could result from a naloxone-induced diminution of the hypotensive stimulus to hyperglycemia, from a naloxone-induced diminution of hormonal secretion or action, from a naloxone-mediated decrease in glucose production, or from a direct action of naloxone on glucose uptake in skeletal muscle and other peripheral tissues. In order to examine the direct effect of naloxone on glucose uptake in skeletal muscle, male Sprague-Dawley rats were perfused in a standardized isolated perfused hindlimb system with or without naloxone (0.5 microgram/ml of perfusate). No insulin was added to the perfusate. Glucose uptake in animals treated with naloxone was 30.2% greater than that of control animals (p less than 0.05). This increase was not dependent on insulin. Although no significant differences were noted in the individual products of glucose utilization, the total tissue glucose that could be accounted for by these intermediates was increased in naloxone-treated hindlimbs (p less than 0.05). Thus the increase in glucose uptake by skeletal muscle noted in these experiments may explain, in part, the blunted hyperglycemic response to hemorrhage that occurs after naloxone administration. These results also suggest the possibility that endogenous opiates may be important in regulating glucose metabolism after hemorrhage.

Topics: Animals; Glucose; Hemorrhage; Hindlimb; Hyperglycemia; Hypotension; Male; Naloxone; Perfusion; Rats; Rats, Inbred Strains

Topics: Humans; Hypotension; Ischemic Attack, Transient; Naloxone; Steroids; Thromboxanes

Sixteen anesthetized foxhounds were instrumented for hemodynamic measurements. The adrenolumbar vein was cannulated, and hemorrhagic hypotension (MAP = 40 mmHg for 3h) was induced by bleeding. The plasma levels of beta-endorphin (beta-END), methionine-enkephalin (M-ENK), and leucine-enkephalin (L-ENK) were determined in systemic and adrenal venous blood by specific RIA. Five dogs received an i.v. bolus of naloxone (2 mg/kg) and a subsequent naloxone infusion of 2 mg/kg per hour 1 h after onset of hypovolemia. Eleven dogs served as controls and received equivalent volumes (1 ml/kg per hour) of saline. Hemorrhage resulted in a sharp increase in plasma concentrations of all measured opioid peptides, particularly of M-ENK (26-fold) and L-ENK (24-fold) in the adrenal effluent. Systemic beta-END levels remained 3-fold increased, whereas the ENK release decreased spontaneously. Naloxone treatment inhibited the spontaneous fall of adrenal ENK release during the hypotensive phase; the ENK values remained elevated 20- to 35-fold. Reinfusion of the autologous blood resulted in a normalization of the concentrations of all peptides in both groups. These data demonstrate that hemorrhagic hypotension will cause stimulation of release of endogenous opioid peptides. The high levels of ENK in the adrenal effluent indicate that the adrenal gland is the main source of these peptides in the circulation. In addition to beta-END, the ENK have therefore to be considered as possible factors perpetuating circulatory shock.

Topics: Adrenal Glands; Animals; beta-Endorphin; Dogs; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Female; Hemorrhage; Hypotension; Male; Naloxone

The central and peripheral hemodynamic effects of rapid hemorrhage and subsequent opiate receptor blockade were studied in conscious rabbits. With hemorrhage of less than 12 ml/kg, mean arterial blood pressure (BP) was maintained by an increase in total peripheral resistance (TPR). Cardiac output (CO) declined in spite of an increase in heart rate (HR). Blood loss greater than 13 ml/kg resulted in an abrupt decrease in BP that was largely due to a decline in TPR. CO continued to decline gradually as it did early in hemorrhage. HR also decreased at the transition to hypotension. Subsequent opiate receptor blockade with naloxone (3 mg/kg) produced a prompt increase in BP and a decrease in HR. An increase in TPR accounted for the rise in BP. CO did not change significantly after naloxone. Therefore the hypotension associated with hemorrhage results from a decline in peripheral vascular resistance that is reversible by opiate receptor blockade with naloxone. These results are consistent with the involvement of opiate receptors and endogenous opiate peptides centrally and/or peripherally in control of vascular resistance during acute hemorrhagic hypotension.

Topics: Animals; Consciousness; Hemodynamics; Hemorrhage; Hypotension; Male; Naloxone; Rabbits; Receptors, Opioid; Time Factors; Vascular Resistance

Previous studies established that naloxone reverses hypotension in endotoxin, hemorrhagic, and spinal shock. We studied endotoxin shock in hypophysectomized (Hx) rats, which have little circulating beta-endorphin. Hx or intact rats received surgically implanted jugular catheters for drug injection and aortic catheters for arterial blood pressure (MAP) recording. On the second day after implantation, rats were pretreated with either naloxone or saline. Two minutes later each rat received endotoxin. Following endotoxin, all rats showed a brief biphasic hypertensive-hypotensive response followed by stabilization of MAP near baseline. Within 20 min, all Hx rats, regardless of pretreatment, and the saline-treated intact rats, showed progressive hypotension (P less than 0.005). Only the naloxone-pretreated intact rats maintained a stable MAP. Plasma endorphin measured at 20 min was undetectable in Hx rats in contrast to intact rats (P less than 0.001); plasma corticosterone levels were likewise suppressed in the Hx rats (P less than 0.01). Thus (1) naloxone protected only the rats with an intact pituitary-adrenal-sympathetic system, and (2) pituitary endorphin is not required to generate endotoxin shock in hypophysectomized rats.

Topics: Animals; beta-Endorphin; Blood Pressure; Corticosterone; Endorphins; Hypophysectomy; Hypotension; Male; Naloxone; Pituitary Gland; Rats; Rats, Inbred Strains; Shock, Septic

Platelet-activating factor (PAF), a vasoactive phospholipid implicated in anaphylactic reactions, causes severe hypotension in experimental animals that is highly resistant to pharmacological therapy. In the present studies, we showed that PAF (1 nmol/600 g body weight, IV) produced profound hypotension in unanesthetized guinea pigs that was promptly and completely reversed by thyrotropin-releasing hormone (TRH) (2 mg/kg, IV) or by the synthetic TRH analog MK771 (2 mg/kg, IV). TRH also reversed this hypotension when administered intracerebroventricularly (ICV) at a dose (0.02 mg/kg) that was systemically ineffective. The opiate receptor antagonist naloxone (5 mg/kg) was less effective than TRH in reversing the cardiovascular consequences of PAF administration. These data suggest that TRH reverses PAF-induced shock through central receptor-mediated mechanisms. This therapeutic action of TRH may partially account for the beneficial cardiovascular effects of this peptide in anaphylactic shock.

Topics: Animals; Blood Pressure; Guinea Pigs; Hypotension; Male; Naloxone; Platelet Activating Factor; Thiazolidines; Thyrotropin-Releasing Hormone; Time Factors

Naloxone clorhidrate was administered intravenously to 15 patients with endotoxic shock and refractary hypotension, following meningococcal sepsis. Doses used were between 0.01-0.2 mg/kg. Three patients (two of them with moderate shock) showed an increase in sistolic arterial pressure, which was maintained and above 20 mm/Hg. Among the rest of them (except one with severe shock) naloxone action was non-existent in nine cases, or with short action and without answer to next doses in other three. Eleven patients died. A blood pressure increase was maintained only in two of the four survivors. Usefulness of naloxone in this kind of patients is not clear. Presence in endotoxin shock of a variety of refractory factors besides beta endorphins, greatly limits therapeutic efficiency of this drug.

Topics: Adolescent; Child; Child, Preschool; Endorphins; Humans; Hypotension; Infant; Meningococcal Infections; Naloxone; Shock, Septic

Topics: Anaphylaxis; Dextrans; Humans; Hypotension; Male; Middle Aged; Naloxone

Topics: Drug Tolerance; Gastric Lavage; Glucose; Humans; Hypotension; Malaria; Naloxone; Narcotics; Opioid-Related Disorders; Plasma Substitutes; Receptors, Opioid; Sexually Transmitted Diseases; Substance Withdrawal Syndrome; Substance-Related Disorders; Tetanus; Tuberculosis

The effects of naloxone on sympathetic nerve activity during E coli endotoxin hypotension were studied in alpha-chloralose anesthetized cats. Blood pressure and left preganglionic splanchnic nerve (PSN) activity were measured. Naloxone (2 mg/kg) was injected intravenously 30 min after endotoxin. In control group, 30 min after endotoxin, both mean blood pressure (MBP) and PSN activity decreased by 68 +/- 7% and 47 +/- 10%, respectively, and were followed by a gradual decline, so that after 60 min MBP and PSN activity were 54 +/- 8% and 48 +/- 7% of the pre-endotoxin level. The reduced blood pressure recovered to 81 +/- 4% of the pre-endotoxin level 5 min after naloxone. However, the naloxone-induced recovery of blood pressure was transient and there was a decline to the pre-naloxone level within 30 min after the injection. At the end of the experiment (60 min after endotoxin), the level of MBP was significantly higher than in the control group. Similarly, there was a modest recovery in PSN activity (61 +/- 7% of the pre-endotoxin level 5 min after naloxone) that was maintained for 20 min only to decline again. Three of five cats treated with an intermittent bolus injection (2 mg/kg, 30 min and 6 h after endotoxin) of naloxone survived, compared to only one of five nontreated cats. These observations suggest that at least part of the beneficial cardiovascular actions of naloxone in endotoxin shock involves activation of the efferent sympathetic system. To improve longterm survival it may be necessary to continuously administer naloxone.

Topics: Animals; Blood Pressure; Cats; Endotoxins; Escherichia coli; Hypotension; Naloxone; Shock, Septic; Splanchnic Nerves; Stimulation, Chemical

1. Male Wistar rats were either bilaterally adrenalectomized or sham-operated, and given 1% sodium chloride solution instead of tap water to drink. Seven days later, arterial blood pressures were recorded directly from conscious freely moving rats. 2. Systolic and diastolic blood pressures were significantly lower in the adrenalectomized rats, whereas heart rates were significantly higher than in sham-operated animals. The tachycardia was due to a combination of sympathetic hyperactivity and reduced vagal tone, which may have been reflex responses to a reduction in effective blood volume. 3. Baroreflex control of the sinus node was assessed from the pulse interval responses to rises (induced by methoxamine) or falls (induced by glyceryl trinitrate or sodium nitroprusside) in systemic arterial blood pressure. The relation between pulse interval and systolic blood pressure was described by the same curve in sham-operated and adrenalectomized rats, indicating that, in the latter, there was no change in baroreflex setting or sensitivity. 4. Intravenous administration of naloxone (2 mg/kg) had no effect on systemic arterial blood pressure in adrenalectomized rats, suggesting that endogenous opiates were not contributing to the hypotension.

Topics: Adrenalectomy; Animals; Atropine; Blood Pressure; Heart Rate; Hypotension; Male; Naloxone; Nitroglycerin; Potassium; Pressoreceptors; Propranolol; Rats; Rats, Inbred Strains; Reflex; Sodium

Leukotriene D4 (LTD4), a component of slow reacting substance of anaphylaxis (SRS-A)1, produces marked hypotension in laboratory animals2,3, implicating it as a potential mediator of anaphylactic shock. It has been demonstrated that naloxone reverses the hypotension associated with endotoxaemia4-6, hypovolaemia7,8 and spinal injury9,10, presumably through blockade of endogenous opioid systems11. More recently, it has also been shown that thyrotropin releasing hormone (TRH) improves experimental shock12 and spinal injury13, and it has been postulated that TRH acts by 'physiological' antagonism of endogenous opioid systems in these conditions. Here we report that TRH both blocked and reversed leukotriene-induced hypotension in the unanaesthetized guinea pig, whereas naloxone had no effect. LTD4 hypotension was also reversed by intracerebroventricular (i.c.v.) administration of TRH at a dose that had no effect when given systemically. LTD4 administration was associated with sympatho-adrenomedullary activation, and TRH further augmented this response. Peripheral cholinergic blockade with methylatropine did not alter the leukotriene hypotension. These data demonstrate the first dissociation of TRH and naloxone in experimental shock and suggest that the beneficial effects of TRH in this model result from central interactions which are not mediated by endogenous opioids. The findings further provide a potential link between the physiological (that is, cardiovascular) effects of a peptide (TRH) and those of a leukotriene; this may have implications with regard to the pathophysiology and therapy of anaphylaxis.

Topics: Animals; Blood Pressure; Drug Interactions; Guinea Pigs; Hypotension; Kinetics; Male; Naloxone; SRS-A; Thyrotropin-Releasing Hormone

Naloxone or physiological solution were injected in different doses to 11 baboons (Papio hamadryas) weighing 7-8 kg after bloodletting in a volume of 40% of the total amount of the blood. Naloxone effectively raised (in all the doses) the arterial blood pressure which dropped after bloodletting. The action of naloxone injected in small doses was more pronounced and had unique time parameters. Besides, the respiratory rate was also increased. Injection of nalorphine in a dose of 1 mg/kg produced a similar but a more demonstrable action as compared with naloxone in a dose of 1 mg/kg. A conclusion is made about the possibility of using the antagonists of opioid peptides on a clinical basis for the treatment of shock conditions. An assumption of an inconclusive role played by the subtypes of opiate receptors in the formation of shock conditions is also confirmed.

Topics: Acute Disease; Animals; Blood Pressure; Hemorrhage; Hypotension; Male; Nalorphine; Naloxone; Papio; Respiration

Topics: Aged; Humans; Hypotension; Male; Naloxone; Shock, Septic

Acute ingestions of imidazoline compounds, including clonidine hydrochloride, are a recognized clinical entity. The signs and symptoms of this overdose superficially resemble those of opiate intoxication, leading to attempts to reverse this poisoning with naloxone hydrochloride. Despite previous descriptions of success using naloxone in acute clonidine poisoning, five cases of acute pediatric ingestions of clonidine ranging from mild to severe occurred in which naloxone hydrochloride in doses up to 0.1 mg/kg was unsuccessful in reversing the signs and symptoms of this intoxicant. Although naloxone can be safely administered to children who ingest clonidine to distinguish them from those who are intoxicated by opiates, it is not therapeutically useful to use naloxone to reverse poisoning with this class of agents.

Topics: Bradycardia; Child, Preschool; Clonidine; Female; Humans; Hypotension; Infant; Male; Monitoring, Physiologic; Naloxone; Respiration; Time Factors

This study examined the effects of bolus injections of naloxone hydrochloride, a specific narcotic antagonist, on systemic cardiovascular function, intracranial and cerebral perfusion pressures, blood gas status, and cortical encephalograms (EEG's) in 38 cats after two different grades of experimental brain injury. Naloxone had no prolonged effects on uninjured control animals. However, as compared to a saline-injected control group, naloxone significantly reversed the hypotension and reduction in pulse pressure seen after higher grades of injury. These changes persisted for at least 60 minutes after injection and were accompanied by increased intracranial and perfusion pressures. More severely injured hypotensive cats injected with naloxone also had higher values of arterial pO2 and pH, lower pCO2, as well as higher EEG amplitudes. In less severely injured normotensive cats, naloxone produced greater effects on cardiovascular variables and intracranial pressure when injected 15 minutes rather than 45 minutes after injury. These data suggest that endogenous opiates may contribute to some instances of hypotension seen after concussive brain injury. Levels of endogenous opiates may also increase transiently even with lesser degrees of injury not associated with hypotension. The possible clinical application of narcotic antagonists to the treatment of head injury is discussed.

Topics: Animals; Blood Gas Analysis; Brain Concussion; Cats; Cerebrovascular Circulation; Endorphins; Female; Hypotension; Male; Naloxone; Shock; Time Factors

Topics: Humans; Hypotension; Naloxone; Shock, Septic

Topics: Aged; Heart Failure; Humans; Hypotension; Infusions, Parenteral; Male; Naloxone; Respiration, Artificial; Respiratory Insufficiency

A patient who ingested 1.5 g pentazocine developed status epilepticus, coma, respiratory depression, acidosis, profound hypotension, and ventricular arrhythmias. Although this patient survived after institution of general supportive measures, she did not respond to usual doses of naloxone. We describe the clinical symptoms and course of recovery of a patient with pentazocine overdose. Our case suggests that pentazocine overdose may require higher doses of naloxone (5 to 20 mg) than are customarily used for narcotic overdoses.

Topics: Acidosis; Arrhythmias, Cardiac; Coma; Critical Care; Electrocardiography; Female; Humans; Hypotension; Middle Aged; Naloxone; Pentazocine; Respiratory Insufficiency; Status Epilepticus; Substance-Related Disorders

Adult respiratory distress syndrome (ARDS) is a serious complication of trauma and sepsis. We have earlier shown naloxone, an opiate antagonist, and cyproheptadine, an antiserotonin drug, to be effective in reducing pulmonary platelet trapping (PPT), which is thought to play an important role in the evolution of ARDS in endotoxin-shocked dogs. Endorphins are implicated as pathophysiologic factors in shock, and serotonin is a possible mediator of their action. The present study shows naloxone and cyproheptadine to be equally effective in protecting against PPT in dogs subjected to trauma, and when naloxone is given before the trauma it also obviates the hypotension associated with trauma. In addition, the naloxone- and cyproheptadine-treated animals did not show the increased platelet aggregability usually seen in traumatized dogs.

Topics: Animals; Blood Platelets; Blood Pressure; Chromium Radioisotopes; Cyproheptadine; Dogs; Female; Hindlimb; Hypotension; In Vitro Techniques; Isotope Labeling; Lung; Male; Naloxone; Organ Size; Platelet Aggregation; Respiratory Distress Syndrome; Wounds and Injuries

Topics: Animals; Body Temperature; Dogs; Endotoxins; Escherichia coli; Female; Hypotension; Male; Naloxone; Receptors, Opioid; Shock, Septic; Temperature

Opiate receptor blockade with naloxone reverses the hypotension associated with severe hemorrhage in a variety of animal models. In the present study, we examined the mechanisms of naloxone's actions in conscious rabbits made hypotensive by hemorrhage. This was accomplished through pharmacological blockade of the efferent limbs of the sympathetic or parasympathetic nervous systems prior to naloxone injection. In addition, we examined the effects of naltrexone in the same model. Naloxone treatment in hypotensive-hypovolemic, conscious rabbits results in an increase in mean arterial blood pressure (BP) and a decrease in heart rate (HR). The bradycardia appears to be due to a reduction in beta-adrenergic and an increase in muscarinic-cholinergic activity. The pressor effect is apparently due to increased alpha-adrenergic receptor activation, and is accompanied by an increase in cardiac output, stroke volume, and total peripheral resistance. Naltrexone did not significantly affect BP but it did reduce HR. The results from the present study suggest that naloxone's effects are mediated by an integrated response of the sympathetic and parasympathetic nervous systems. The actions of naloxone may be mediated through antagonism of endogenous opiates.

Topics: Adrenergic Fibers; Animals; Atropine; Blood Pressure; Efferent Pathways; Heart Rate; Hemodynamics; Hemorrhage; Hypotension; Male; Naloxone; Naltrexone; Parasympathetic Nervous System; Phentolamine; Propranolol; Rats; Receptors, Adrenergic; Receptors, Cholinergic; Receptors, Opioid

Topics: Animals; Blood Pressure; Female; Humans; Hypotension; Middle Aged; Naloxone; Rats; Shock, Septic; Stimulation, Chemical

Naloxone was given intravenously to thirteen patients with prolonged hypotension. Eight patients with sepsis who were not receiving corticosteroids had a 45% increase in systolic blood-pressure within minutes of receiving 0.4--1.2 mg of naloxone. The increase in blood-pressure lasted for at least 45 min. In two patients a second dose, given after recurrence of hypotension, resulted in another increase in blood-pressure. Four patients with hypoadrenocorticotropism had no pressor response to naloxone. These observations suggest that endorphins may contribute to the hypotension of sepsis and that naloxone may have therapeutic value in the treatment of septic shock.

Topics: Adrenal Insufficiency; Adult; Aged; Blood Pressure; Cardiac Output; Endorphins; Female; Humans; Hypotension; Male; Middle Aged; Naloxone; Shock, Septic

Topics: Aged; Humans; Hypnotics and Sedatives; Hypotension; Male; Naloxone; Shock

These studies have demonstrated that the opiate-antagonist naloxone improves blood pressure and functional neurologic recovery after spinal injury. From these findings we suggest that endorphins are released in response to spinal injury and contribute to the hypotension and to the ultimate neurologic deficit. Naloxone's ability to reverse the presumed endorphin-mediated hypotension in this model supports the hypothesis that its therapeutic effects may be secondary to its improvement of spinal cord blood flow, thereby reducing the ischemic damage caused by spinal cord trauma.

Topics: Animals; Cats; Endorphins; Female; Hypotension; Male; Naloxone; Rats; Shock; Spinal Cord Injuries

Topics: Adult; Aged; Female; Humans; Hypotension; Male; Middle Aged; Myocardial Infarction; Naloxone; Shock, Septic

The effects of naloxone on blood pressure and heart rate were studied in conscious, chronically prepared rabbits. In addition, the effects of barbiturate anesthesia on the response to naloxone were investigated. Initial surgery to implant arterial and venous catheters was performed under halothane anesthesia. Experiments were begun 10 days to 2 weeks later. The rabbits were divided into two groups: a normotensive group and a group made hypotensive by hemorrhage. In the normotensive rabbits, naloxone (2 mg/kg i.v.) did not alter mean arterial blood pressure (BP), pulse pressure, (PP), or heart rate (HR). However, a 5 mg/kg dose increased BP and PP, and decreased HR. In the hypotensive group, naloxone in a dose of 2, 3, or 5 mg/kg i.v. significantly increased BP and PP while decreasing HR in a dose-related manner. A dose of 0.2 mg/kg did not significantly alter any of the measured parameters. Pentobarbital anesthesia significantly reduced the effects of the 3 mg/kg naloxone dose in the hypotensive group. These actions of naloxone may be mediated through antagonism of endogenous opiates.

Topics: Animals; Blood Pressure; Dose-Response Relationship, Drug; Heart Rate; Hemorrhage; Hypotension; Male; Naloxone; Pentobarbital; Rabbits

Topics: Animals; Blood Pressure; Body Temperature; Body Temperature Regulation; Hypotension; Hypothermia; Laminectomy; Male; Naloxone; Rats; Receptors, Opioid; Respiration; Spinal Cord

The endogenous opiate ligand, beta-endorphin, is released during stress. We tested the hypothesis that endorphins may be involved in the pathophysiology of hemorrhagic shock by using the opiate receptor blocking agent, naloxone. Two groups of five anesthetized dogs were instrumented to monitor cardiovascular performance and subjected to a protocol in which they were bled into a reservoir to lower mean arterial pressure to 45 mmHg and maintained at that pressure for one hour. At that time the reservoir was clamped and on group of dogs received an intravenous bolus of naloxone (2 mg/kg) and an infusion at 2 mg/kg-hr. These dogs demonstrated a prompt increase in arterial pressure, left ventricular dp/dtmax and cardiac output. The shed blood was returned at t = 2 hr and drug infusion continued for 2 hours. The control group of dogs received saline in equivalent volume. The control dogs died within 30 minutes of clamping the reservoir while all five treated dogs survived beyond 72 hours (P less than 0.02). These data suggest the involvement of endorphins acting on opiate receptors as part of the pathophysiology in this shock model.

Topics: Animals; Blood Pressure; Blood Volume; Dogs; Heart Rate; Hypotension; Naloxone; Receptors, Opioid; Shock; Vascular Resistance

Topics: Animals; Blood Pressure; Dogs; Hypotension; Injections, Intraventricular; Naloxone; Shock, Septic

The opiate antagonist naloxone has been used to treat shock following acute blood loss in conscious rats. Naloxone treatment rapidly increased mean arterial pressure and pulse pressure in this new shock model. More importantly, these blood pressure changes were sustained and survival was significantly increased with maloxone as compared with placebo treatment. From these findings, it may be inferred that endorphins may play a role in the pathophysiology of hypovolemic shock. It is suggested that narcotic antagonists may prove to be of therapeutic value in the treatment of shock.

Topics: Animals; Blood Pressure; Hypotension; Male; Naloxone; Rats; Shock

We have operated upon 446 consecutive patients in the office, using the controlled titrated method of sedation which we have described. We believe the results are superior to the methods in more common use. A major factor in choosing a narcotic as our one basic drug was the availability of a safe, swift, and effective antidote to it.

Topics: Adolescent; Adult; Aged; Anesthesia, Local; Arrhythmias, Cardiac; Bradycardia; Humans; Hypotension; Injections, Intravenous; Male; Meperidine; Middle Aged; Morphine; Naloxone; Respiratory Insufficiency; Surgery, Plastic; Vomiting

In 70 patients (maxillo-facial-, neurosurgical-, abdominal- and gynaecological operations) the technique of "analgetic anaesthesia" using high doses of fentanyl (0.025 mg/kg body weight) and naloxone as its antagonist (0.02 mg/kg body weight) has been employed. All patients were artificially ventilated with N2O/O2 in a 3:1 ratio. Muscle relaxation was achieved with pancuronium-bromide (0.08 mg/kg). The patients had no apparent heart or lung disease. The youngest patient was 4 years of age, the oldest 82 years of age (average age 48.9). The necessity for a reinjection of fentanyl (half the initial dose) was determined by continously monitoring heart rate. This variable appeared to be the most subtle index indicating a reduction in analgesia. Sufficient analgesia was maintained once the heart rate stayed 20% below preanaesthetic levels. At the end of the operation naloxone reversed the respiratory depression. There was no evidence indicating postoperative pain, which may have required administration of additional analgesics. If deep analgesia was maintained up to the last surgical procedures no emesis appeared in the post operative period. The incidence of emesis was higher 10% compared to the classical neuroleptanalgesia with droperidol this was often noted in cases where blood accumulated in the stomach (maxillo-facial operations) (70%). In 3% of all cases psychomotor agitation with delirium appeared right after the injection of naloxone. This lasted for about 15 minutes. We suspect that due to the sudden and powerful effect of naxolone, in replacing fentanyl from its receptor site, acute withdrawal symptoms may be precipitated.

Topics: Adolescent; Adult; Aged; Analgesia; Autonomic Nervous System; Child; Child, Preschool; Female; Fentanyl; Genital Diseases, Female; Humans; Hypertension; Hypotension; Male; Maxilla; Middle Aged; Naloxone; Nausea; Neurosurgery; Tachycardia; Vomiting