naloxone and Arrhythmias--Cardiac

Pharmacologic agents are used to improve conditions that may contribute to the development of cardiac arrest such as dysrhythmias, hypotension, shock, or anoxia. The authors review the clinical application of several specific agents in resuscitation.

Topics: Adrenal Cortex Hormones; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atropine; Bretylium Tosylate; Calcium Channel Blockers; Cardiotonic Agents; Dobutamine; Dopamine; Heart Arrest; Humans; Isoproterenol; Lidocaine; Naloxone; Norepinephrine; Resuscitation; Vasoconstrictor Agents

Topics: Acid-Base Imbalance; Arrhythmias, Cardiac; Blood Circulation; Blood Pressure; Child; Digestive System Diseases; Fluid Therapy; Glucocorticoids; Heart Rate; Heparin; Humans; Infection Control; Kidney Diseases; Naloxone; Nutrition Disorders; Respiratory Therapy; Shock

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

The opioid system plays a role in the regulation of the cardiovascular system. Endogenic as well as egzogenic administration of opioids influences the heart rhythm. This work was undertaken in order to assess the influence of crossover activity of the heart opioid system on the heart conduction system in patients with various disturbances of rhythm having an efficient circulatory system and a normal 12-lead stationary ECG. Subjects were 20 patients (9 men and 11 women of mean age of 38.7 years) reporting sudden heart palpitations. They were subjected to invasive programmable electrophysiological studies (PES). Naloxone was administered intravenously to 10 patients. Pentazocine was administered in the same way. In the remaining 10 patients the order of drug administration was reversed. PES was done in the basic state and after the administration of each drug. Study results were subjected to statistical analysis with no-parameter Wilcoxon test assuming differences to be significant at p less than 0.05. Blocking of the opioid system resulted in significant lengthening of the sinoatrial (SACT), intra-atrial (PA), and atrioventricular node (AH) conduction times, while no changes were induced in conduction in the His-Purkinje system (HV) and automation of the sinus node. Naloxone lengthened the atrial (ERPA) and atrioventricular node (ERPA AVN) effective refractory periods. Stimulation of the opioid system resulted in decreases of the following values: SACT, PA, AH, ERPA, ERPA AVN, while no effect was exerted on the SNRT, HV, ERPV. Neither drug influenced the QRS time, although naloxone lengthened QTc period significantly. Opioids did not influence the time of conduction in concealed extranodal atrioventricular pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arrhythmias, Cardiac; Blood Pressure; Electric Stimulation; Electrocardiography; Electrophysiology; Female; Heart Conduction System; Heart Rate; Hemodynamics; Humans; Injections, Intravenous; Male; Naloxone; Pentazocine; Receptors, Opioid

After administration of fentanyl, 0.15 mg naloxone or levallorphan or placebo were given several times and in increased doses and at same intervals of time to six volunteers. The experiment has been done after the rules of a double blind study. Naloxone has shown its superiority to levallorphan. The study demonstrated a faster and better action of naloxone in the way of a return to initial conditions of respiratory frequency, blood gases, and EEG. The concentration and attention faculties after naloxone have become clearly better in contrary to the results after levallorphan. At the end of an anaesthetic procedure, the greatest care should be given to the patient. First of all effective antagonism of the respiratory depression should be obtained without concomitant sedative and psychomimetic effects. The use of antagonists with agonist properties to reverse respiratory depression due to a morphinomimetic drug is not justified and so naloxone should supplant levallorphan.

Topics: Adult; Arrhythmias, Cardiac; Blood Gas Analysis; Double-Blind Method; Fentanyl; Humans; Levallorphan; Male; Naloxone; Psychological Tests; Respiration Disorders

Benzonatate is a local anesthetic-like sodium channel antagonist that is widely prescribed as an antitussive. While it may be reasonable to assume that patients would present with a prolonged QRS interval following benzonatate overdose, the published literature does not support this. We report a case of a patient presenting following a benzonatate overdose with a prolonged QRS on her initial electrocardiograph (ECG) rhythm strip with rapid normalization of QRS duration.. A 14-year-old girl presented in cardiac arrest following a benzonatate overdose. The patient was found in cardiac arrest within minutes of last being known well. Bystanders immediately provided cardiopulmonary resuscitation (CPR), and she was in asystole on emergency medical services (EMS) arrival. Return of spontaneous circulation (ROSC) was obtained following administration of intraosseous epinephrine and naloxone. EMS obtained an ECG rhythm strip following ROSC demonstrating a sinus rhythm with a QRS duration of 160 ms. Over the ensuing 30 minutes, there was progressive narrowing of the QRS. A 12-lead ECG obtained on arrival in the emergency department (ED) 44 minutes later demonstrated a QRS duration of 94 ms. Initially, EMS ECG rhythm strips were unavailable and an isolated benzonatate ingestion was considered less likely as ECG intervals were normal. Benzonatate exposure was later confirmed with a urine benzonatate concentration, which was 8.5 mcg/mL. The patient made a full recovery.. Cases of pediatric benzonatate overdose with rapid development of cardiac arrest and full recovery have been previously reported. In this case, evidence of cardiac sodium channel blockade was demonstrated with a prolonged QRS interval on initial ECG rhythm strip analysis. However, unlike previous cases, rapid resolution of QRS prolongation occurred in this case. While transient QRS prolongation may be observed, finding a normal QRS interval should not discount the possibility of benzonatate overdose.

Topics: Adolescent; Anesthetics, Local; Antitussive Agents; Arrhythmias, Cardiac; Butylamines; Child; Drug Overdose; Epinephrine; Female; Heart Arrest; Humans; Naloxone; Sodium Channels

This study characterized the antiarrhythmic effects of the opioid receptor antagonist naloxone in rats subject to electrically induced and ischemic arrhythmias. Naloxone (2, 8 and 32 μmol/kg/min) was examined on heart rate, blood pressure, and the electrocardiogram (EKG) as well as for effectiveness against arrhythmias produced by occlusion of the left anterior descending coronary artery or electrical stimulation of the left ventricle. Naloxone reduced blood pressure at the highest dose tested while heart rate was dose-dependently reduced. Naloxone dose-dependently prolonged the P-R and QRS intervals and increased the RSh amplitude indicative of effects on cardiac sodium (Na) channels. Naloxone prolonged the Q-T interval suggesting a delay in repolarization. Naloxone effects were comparable to the comparator quinidine. Naloxone (32 μmol/kg/min) reduced ventricular fibrillation (VF) incidence to 38% (from 100% in controls). This same dose significantly increased the threshold for induction of ventricular fibrillation (VFt), prolonged the effective refractory period (ERP) and reduced the maximal following frequency (MFF). The patterns of ECG changes, reduction in ischemic arrhythmia (VF) incidence and changes in electrically induced arrhythmia parameters at high doses of naloxone suggest that it directly blocks cardiac Na and potassium (K) ion channels.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Blood Pressure; Coronary Vessels; Dose-Response Relationship, Drug; Electric Stimulation; Electrocardiography; Heart Rate; Heart Ventricles; Male; Myocardial Ischemia; Naloxone; Quinidine; Rats; Rats, Sprague-Dawley; Refractory Period, Electrophysiological; Sodium Channels; Ventricular Dysfunction; Ventricular Fibrillation

Augmentation of cardiac sympathetic tone during myocardial ischemia has been shown to increase myocardial O(2) demand and infarct size as well as induce arrhythmias. We have previously demonstrated that electroacupuncture (EA) inhibits the visceral sympathoexcitatory cardiovascular reflex. The purpose of this study was to determine the effects of EA on left ventricular (LV) function, O(2) demand, infarct size, arrhythmogenesis, and in vivo cardiac norepinephrine (NE) release in a myocardial ischemia-reperfusion model. Anesthetized rabbits (n = 36) underwent 30 min of left anterior descending coronary artery occlusion followed by 90 min of reperfusion. We evaluated myocardial O(2) demand, infarct size, ventricular arrhythmias, and myocardial NE release using microdialysis under the following experimental conditions: 1) untreated, 2) EA at P5-6 acupoints, 3) sham acupuncture, 4) EA with pretreatment with naloxone (a nonselective opioid receptor antagonist), 5) EA with pretreatment with chelerythrine (a nonselective PKC inhibitor), and 6) EA with pretreatment with both naloxone and chelerythrine. Compared with the untreated and sham acupuncture groups, EA resulted in decreased O(2) demand, myocardial NE concentration, and infarct size. Furthermore, the degree of ST segment elevation and severity of LV dysfunction and ventricular arrhythmias were all significantly decreased (P < 0.05). The cardioprotective effects of EA were partially blocked by pretreatment with naloxone or chelerythrine alone and completely blocked by pretreatment with both naloxone and chelerythrine. These results suggest that the cardioprotective effects of EA against myocardial ischemia-reperfusion are mediated through inhibition of the cardiac sympathetic nervous system as well as opioid and PKC-dependent pathways.

Topics: Animals; Arrhythmias, Cardiac; Benzophenanthridines; Electroacupuncture; Models, Animal; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Naloxone; Narcotic Antagonists; Norepinephrine; Oxygen; Protein Kinase C; Rabbits; Signal Transduction; Sympathetic Nervous System; Ventricular Function, Left

We investigated the involvement of central and peripheral opioid receptors (OR) in the cardioprotective effects of fentanyl (FENT) in a model of myocardial ischemia/reperfusion injury associated with pharmacologically induced sympathetic overactivity in anesthetized rabbits.. Central sympathetic stimulation was achieved through intracerebroventricular injection of l-glutamate in animals submitted to 35 min of coronary occlusion followed by 120 min of reperfusion. Rabbits received naloxone HCl intracerebroventricularly or naloxone methiodide IV, a quaternary compound that does not cross the blood-brain barrier, 5 min before FENT treatment (5 or 50 microg/kg, IV).. Infarct area was reduced only by FENT 50 (from 51% +/- 2% to 24% +/- 2%). This protective effect was abolished by peripheral (42% +/- 4%), but not central, OR blockade (32% +/- 3%). The number of premature ventricular complexes during the ischemic period (54 +/- 3) was reduced by FENT 50 (19 +/- 7), an effect blunted by central (40 +/- 3) but not peripheral (18 +/- 7) blockade of OR. During reperfusion, the number of premature ventricular complexes (134 +/- 50) was reduced to 9 +/- 5 by FENT 50 and was prevented by central (42 +/- 4) as well as peripheral (20 +/- 11) OR blockade. The mortality rate (50%) and incidence of ventricular tachycardia (55%) were completely abolished by FENT 50.. We conclude that fentanyl's effects for limiting myocardial ischemic injury are mediated via peripheral ORs while opioid's antiarrhythmic actions are mediated via central OR agonism.

Topics: Animals; Arrhythmias, Cardiac; Cardiotonic Agents; Dose-Response Relationship, Drug; Female; Fentanyl; Hemodynamics; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Naloxone; Narcotic Antagonists; Rabbits; Receptors, Opioid

It was found that pretreatment of rats with selective agonist of kappa1-opioid receptors (OR) (-)--U--50.488 decreased the incidence of ischemic (10 min) and reperfusion (10 min) ventricular arrhythmias. The selective kappa2-OR agonist GR-89696 had no effect on the incidence of ventricular arrhythmias during a 10-min coronary artery occlusion and following reperfusion in anesthetized rats. The effect of (-)--U-50.488 was abolished by the selective kappa1-OR antagonist of non-binaltorphimine and the non-selective peripheral OR antagonist naloxone methiodide. Perfusion of isolated rat heart with (-)--U-50.488 did not affect arrhythmias during ischemia and reperfusion. The authors suggest that stimulation of kappa1-opioid receptors located outside the central nervous system increases heart resistance against arrhythmogenic action of ischemia/reperfusion, antiarrhythmic action of (-)--U-50.488 being mediated through extracardiac opioid receptors.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Myocardial Reperfusion Injury; Myocardium; Naloxone; Naltrexone; Piperazines; Pyrrolidines; Quaternary Ammonium Compounds; Rats; Rats, Wistar; Receptors, Opioid, kappa

It has been found that stimulation of delta-1 opioid receptors by intravenous administration of DPDPE (0.5 mg/kg) decreases the incidence of ischemic and reperfusion-induced arrhythmias and also increases myocardial tolerance to the arrhythmogenic action of epinephrine in rats. Pretreatment with a selective delta-2 agonist, DSLET, had no antiarrhythmic effect. The inhibition of the enzymatic breakdown of endogenous enkephalins by intravenous administration of acetorphan decreased the incidence of epinephrine-induced arrhythmias. Pretreatment with a selective delta opioid receptor antagonist, ICI-174.868, completely abolished this antiarrhythmic effect. Adaptation of rats to repeated immobilization stress during 12 days increased myocardial tolerance to the arrhythmogenic action of coronary artery occlusion (10 min) and reperfusion (10 min). Pretreatment with a selective delta opioid receptor antagonist, TIPP(Psy), did not abolish the antiarrhythmic effect of adaptation to immobilization stress. It seems that endogenous agonists of delta opioid receptors are not involved in the antiarrhythmic effect resulting from adaptation to stress.

Topics: Adaptation, Physiological; Animals; Arrhythmias, Cardiac; Enkephalin, D-Penicillamine (2,5)-; Enkephalin, Leucine; Ligands; Male; Myocardial Reperfusion Injury; Naloxone; Naltrexone; Narcotic Antagonists; Oligopeptides; Rats; Rats, Wistar; Receptors, Opioid, delta; Tetrahydroisoquinolines; Thiorphan

The effect of kappa receptors agonists and antagonists was studied in the model of epinephrine induced arrhythmias. Kappa receptor agonists U-50,488 and [D-Ala2]-Dynorphin A (1-13) administered I.C.V. potentiate the arrhythmogenic effect of epinephrine. The effect of U-50,488 was completely blocked by kappa receptor antagonist, nor-binaltorphine. Administration of N-cholinergic receptor inhibitor, hexamethonium, prevented pro-arrhythmic effects of U-50,488 and [D-Ala2]-Dynorphin A (1-13). The data support the hypothesis that central kappa opioid receptors play an important role in the arrhythmogenesis.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Arrhythmias, Cardiac; Dynorphins; Epinephrine; Hexamethonium; Male; Naloxone; Naltrexone; Narcotic Antagonists; Peptide Fragments; Pyrrolidines; Rats; Rats, Wistar; Receptors, Opioid, kappa

Topics: Animals; Arrhythmias, Cardiac; Blood-Brain Barrier; Brain; Dynorphins; Ganglionic Blockers; Heart; Hexamethonium; Injections, Intraventricular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Parasympathetic Nervous System; Rats; Rats, Wistar; Receptors, Opioid, kappa

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Creatine Kinase; In Vitro Techniques; Myocardial Reperfusion Injury; Myocardium; Naloxone; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar; Receptors, Opioid, delta; Receptors, Opioid, mu

The effects of the opioid-type stressor, immobilization, on severity of ouabain-induced cardiac arrhythmias and the possible involvement of serum catecholamines were investigated in rats. Immobilization significantly reduced the number of ventricular premature beats and the incidence of ventricular tachycardia episodes. The arterial serum catecholamine levels (A, NA and DA), measured immediately after the stressor application, were increased significantly and were in negative correlation with the arrhythmia parameters. Both changes were reversed by naloxone (5 mg/kg) treatment after application of immobilization. The effects observed in this study may be attributed to the actions of endogenous opioid peptides released during stress.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Dopamine; Epinephrine; Heart Rate; Immobilization; Male; Naloxone; Narcotic Antagonists; Norepinephrine; Opioid Peptides; Ouabain; Rats; Rats, Wistar; Stress, Physiological

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atropine; Autonomic Nervous System; Electrocardiography; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Epinephrine; Ganglionic Blockers; Hexamethonium; Male; Muscarinic Antagonists; Naloxone; Narcotic Antagonists; Oligopeptides; Rats; Rats, Wistar; Receptors, Opioid, mu

Endogenous opioid peptides subserve regulatory roles in cardiovascular function and are released upon myocardial ischemia contributing to the development of ischemic arrhythmias and cardiogenic shock, which are reversed by the opioid antagonist naloxone. Since the hallmark of myocardial infarction is the impairment of hemodynamics and ventricular function, we evaluated further if blockade of opioids reverses the ischemia induced hemodynamic compromise, and if the effects are mediated by opioid receptors. Thirty-two mongrel dogs were anesthetized and artificially ventilated. Median thoracotomy was performed, the heart exposed, and the left anterior descending coronary artery isolated for subsequent occlusion and reperfusion. All cardiac parameters were recorded on an Electronics for Medicine recorder through the intracardiac catheters advanced from femoral vessels. Results indicate that naloxone significantly reversed the ischemic and reperfusion induced reduction in aortic, left ventricular and pulmonary arterial pressures, and left ventricular dp/dt. The inactive (+) stereoisomer of naloxone was without effect. These data demonstrate that opioids may have a role in the pathophysiology of myocardial infarction, mediated by opioid receptors, and provide new insight and strategies for the understanding and treatment of ischemic heart disease.

Topics: Animals; Arrhythmias, Cardiac; Dogs; Female; Hemodynamics; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Naloxone; Narcotic Antagonists; Opioid Peptides; Receptors, Opioid; Shock, Cardiogenic; Stereoisomerism

Dextropropoxyphene overdose may be complicated by serious cardiovascular manifestations, including conduction abnormalities and collapse. We report two patients in whom cardiac toxicity developed. Cardiovascular depression seemed to be improved after naloxone infusion in these two cases. Possible mechanisms are briefly discussed.

Topics: Adult; Arrhythmias, Cardiac; Dextropropoxyphene; Drug Overdose; Female; Heart Block; Humans; Male; Middle Aged; Naloxone

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

The effects of fentanyl at a dose of 100 micrograms.kg-1 on cardiac automaticity, refractoriness and conduction have been studied in a model of heterotopic heart transplantation which combines a denervated heart (donor) and a non-denervated heart (recipient) in each of 20 dogs employed. Once the surgical procedure had been completed, cycle length, sinoatrial conduction time, antegrade and retrograde A-V node block points, cycle length at which 1:1 conduction ceases to exist and the antegrade effective refractory period of the A-V node and ventricles were measured. These parameters were determined in hearts both in the basal situation and 10 min after fentanyl injection. In the recipient organs, fentanyl produced statistically significant prolongation of cycle length, sinoatrial conduction time, antegrade block point and antegrade effective refractory periods of the A-V node and ventricles, with respect to the basal situation (P less than 0.01 for all these parameters); in 20% of cases, a complete A-V block was produced. In the donor hearts (denervated), prolongations of cycle length (P less than 0.01) and the antegrade block point (P less than 0.05), as compared with the basal situation, were recorded, but no other modifications were detected. To test whether these effects were due to the action of fentanyl, 10 animals were subsequently injected with naloxone, an agent which reverted the reported changes, although in the recipient organs, there persisted a slight prolongation of the cycle length with respect to basal measurements (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arrhythmias, Cardiac; Denervation; Dogs; Electrocardiography; Fentanyl; Heart; Heart Block; Heart Conduction System; Heart Transplantation; Hemodynamics; Models, Cardiovascular; Naloxone; Transplantation, Heterotopic

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

The effects of the stereoisomers of naloxone during myocardial ischemia were studied. (-)-Naloxone (but not the (+)-isomer naloxone) attenuated the ischemia-induced cardiac arrhythmias, hypotension, and bradycardia that result from coronary artery occlusion in anesthetized rats. From these findings, it may be inferred that endogenous opioid peptides may play a role in the pathophysiology of myocardial ischemia. It is also suggested that naloxone may have therapeutic value in the prevention and treatment of ischemic heart disease.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Coronary Disease; Coronary Vessels; Endorphins; Female; Heart Rate; Male; Naloxone; Rats; Rats, Inbred Strains; Stereoisomerism; Time Factors

The antiarrhythmic properties of the opiate antagonist naloxone have been reported in a variety of models of arrhythmia. To determine the generality and the possible central involvement of its antiarrhythmic activity, the effects of naloxone were assessed against cardiac arrhythmias induced by intravenous bolus injections of picrotoxin. Naloxone at doses of 0.33 and 1 mg/kg significantly reduced the incidence and severity of picrotoxin-induced arrhythmias in a dose-related manner, without alteration of blood pressure and heart rate. The results demonstrate the antiarrhythmic efficacy of naloxone in an additional animal model. They further suggest that the antiarrhythmic actions of naloxone may be mediated by the central nervous system via both the autonomic and GABAergic pathways.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Chi-Square Distribution; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Electrocardiography; Female; Incidence; Male; Naloxone; Picrotoxin; Rats; Rats, Inbred Strains

The purpose of this study was to examine the hypothesis that the calcium channel blocker, diltiazem, modulates catecholamine-induced arrhythmias through CNS mechanisms. Rats, that had catheters previously inserted into the lateral cerebral ventricle and femoral artery, received diltiazem, 10 or 50 micrograms/kg or the diluent, into the lateral cerebral ventricle (i.c.v.). Epinephrine was infused to produce arrhythmias. The onset of ventricular arrhythmias, premature ventricular complexes, occurred at a significantly (P less than 0.05) greater dose of epinephrine, after diltiazem, compared to the control group and in a dose-dependent manner, with the mean (+/- 1 SEM) dose of epinephrine being 198 +/- 5, 175 +/- 13 and 115 +/- 15 micrograms/kg in the groups treated with 50 and 10 micrograms/kg of diltiazem and the control groups, respectively. The development of fatal arrhythmias, mainly ventricular tachyarrhythmias, occurred at significantly (P less than 0.05) greater concentrations of epinephrine with diltiazem, 50 and 10 micrograms/kg, 225 +/- 5 and 183 +/- 13 micrograms/kg, respectively, compared to controls, 131 +/- 15 micrograms/kg. Endogenous opioids of the mu-type were implicated in this action of diltiazem, because the mu opioid antagonist naloxone, 1 mg/kg (i.v.), significantly (P less than 0.05) antagonized the antiarrhythmic effects of centrally administered diltiazem and the mu opioid agonist DAGO (i.c.v.), did not further enhance the suppression of epinephrine-induced arrhythmias, produced by diltiazem, 50 micrograms/kg. Atropine sulfate, which crosses the blood-brain barrier and atropine methylnitrate, which does not enter the brain, each at 1 mg/kg (i.v.), produced an equal and significant antagonism of the effect of diltiazem, 50 micrograms/kg, that was less than that of naloxone. The combination of naloxone plus atropine sulfate completely prevented the effect of diltiazem, 50 micrograms/kg, on arrhythmias. The antiarrythmic action of diltiazem could not be explained by alteration of the blood pressure or heart rate response to epinephrine. The results suggest that: (a) calcium channels on neurons in the CNS play an important role in the modulation of epinephrine-induced cardiac arrhythmias, (b) diltiazem can suppress arrhythmias through CNS mechanisms, (c) activation of the parasympathetic nervous system mediates some of the effect of diltiazem, but (d) the mechanism of action of diltiazem is modulated through endogenous opioids.

Topics: Acetylcholine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atropine; Blood Pressure; Brain; Diltiazem; Endorphins; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalins; Epinephrine; Heart Rate; Injections, Intraventricular; Naloxone; Rats; Rats, Inbred Strains

The antiarrhythmic actions of low and high doses of U-50,488H, a selective kappa-receptor agonist, were examined in pentobarbitone-anaesthetized rats subjected to occlusion of the left anterior descending coronary artery. At a high dose (16 mumol/kg) U-50,488H reduced blood pressure, heart rate and prolonged the P-R and QRS intervals of the electrocardiogram. This dose reduced the incidence of ventricular arrhythmias produced by occlusion. The blood pressure, heart rate, ECG and antiarrhythmic actions of a high dose of U-50,488H were not antagonized by 8 mumol/kg naloxone, a dose which had no cardiovascular or ECG actions. Naloxone alone reduced arrhythmia incidence but to a lesser extent than U-50,488H. A low dose (0.2 mumol/kg) of U50,488H in the absence or presence of naloxone had no effect on arrhythmias. Thus, U-50,488H had antiarrhythmic actions at a high dose which were independent of opioid receptors.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atenolol; Blood Pressure; Coronary Disease; Dose-Response Relationship, Drug; Drug Interactions; Electrocardiography; Heart Rate; Male; Naloxone; Potassium; Pyrrolidines; Rats; Rats, Inbred Strains

The aim was to evaluate the effects of an opiate agonist (U50,488H) and an opiate antagonist (naloxone) in myocardial ischaemia.. A left thoracotomy was performed and the left coronary artery was ligated in adult Sprague-Dawley rats of either sex (350-400 g). Blood pressure, heart rate and electrocardiogram were measured before and after injections of U50,488H or naloxone and throughout the 30 min postligation period.. Following coronary artery occlusion, all rats in the control group developed arrhythmias, bradycardia, and hypotension. U50,488H potentiated and naloxone attenuated the ischaemia induced arrhythmias, bradycardia, and hypotension.. The potentiating and blocking effects of U50,488H and naloxone, respectively, suggest that endogenous opioid peptides are involved in the pathophysiology of myocardial ischaemia and play an important role in ischaemic heart disease.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Arrhythmias, Cardiac; Blood Pressure; Coronary Disease; Disease Models, Animal; Female; Heart Rate; Male; Naloxone; Pyrrolidines; Rats; Rats, Inbred Strains

It was found, that injection of delta-receptors agonist dalargin before the occlusion of left anterior coronary artery in rats prevented the decrease of ventricular fibrillation threshold (VFT). An injection of naloxone in dose 0.5 mg/kg (for the blockade of mu-receptors only) had no influence on the VFT. Naloxone in dose 1 mg/kg (for the blockade peripheric mu- and delta-receptors) decreased VFT. An intraventricular infusion of dalargin (10 mkg) induced bradycardia and an increase of VFT. It was assumed that anti-arrhythmic effects of enkephalins in acute myocardial ischemia could be realized by an activation of peripheric delta-receptors and central mu-receptors.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Enkephalin, Leucine-2-Alanine; Enkephalins; Male; Myocardial Infarction; Naloxone; Rats; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu; Ventricular Fibrillation

The aim was to investigate the antiarrhythmic effects of (+)- and (-)-naloxone in various arrhythmia models in vivo.. Naloxone (1-40 mg.kg-1), naltrexone (20-40 mg.kg-1), or standard antiarrhythmic drugs (quinidine, lignocaine, phenytoin, (+)-sotalol) were injected intravenously. Ventricular extrasystoles were then elicited by infusion of either ouabain (guinea pigs) or aconitine (rats), or by electrical stimulation (guinea pigs).. Male Wistar rats and guinea pigs (n = 6-10) were used. Arterial blood pressure and ECG were recorded continuously.. Naloxone and naltrexone decreased the heart rate. The effect of naloxone was not stereospecific and is apparently not mediated by opioid receptors. Naloxone had no influence on ouabain induced arrhythmias or fibrillation threshold in guinea pigs. The appearance of aconitine induced extrasystoles was accelerated by 20 mg.kg-1 (-)-naloxone but delayed by 40 mg.kg-1. No effects were seen with (+)-naloxone or (-)-naltrexone.. The results show that naloxone does not possess prominent antiarrhythmic properties.

Topics: Aconitine; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Depression, Chemical; Guinea Pigs; Heart Rate; Male; Naloxone; Naltrexone; Ouabain; Rats; Stereoisomerism

Acute experiments on cats have shown that the naloxone blocks of opiate receptors increased essentially the incidence of idioventricular arrhythmias in myocardial ischemia. These results may evidence of the endogenous opioid peptides involvement in the body response on the acute myocardial ischemia.

Topics: Acute Disease; Animals; Arrhythmias, Cardiac; Cats; Coronary Disease; Electrocardiography; Female; Heart Rate; Male; Naloxone; Receptors, Opioid

1. The effects of a range of opioid receptor agonists and antagonists with differing opioid receptor selectivities on ischaemia-induced arrhythmias in anaesthetised rats was investigated. 2. Naloxone was antiarrhythmic only at doses expected to antagonise kappa- and delta-receptors in addition to mu-receptors. 3. The opioid receptor antagonist Mr 2266, which is twice as potent at kappa-receptors as at mu-receptors dose-dependently reduced the incidence and severity of the arrhythmias resulting from coronary artery occlusion. 4. The opioid receptor antagonist M 8008 (1 mg kg-1), which is twice as potent at delta-receptors as at mu-receptors but has very little affinity for the kappa-receptor, did not exhibit any beneficial antiarrhythmic properties. 5. MrZ 2593, a quarternary complex of naloxone which does not readily cross the blood brain barrier, was antiarrhythmic which implies that the antiarrhythmic actions of opioid receptor antagonists may be mediated via peripheral opioid receptors. 6. The agonists, diamorphine, [Leu] enkephalin and U-50,488H exhibited no significant arrhythmogenic effects under the present experimental conditions. 7. It is tentatively suggested that blockade of peripheral kappa-receptors during acute myocardial ischaemia may result in an antiarrhythmic effect.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Blood Pressure; Coronary Disease; Coronary Vessels; Enkephalin, Leucine; Heart Rate; Heroin; Male; Naloxone; Pyrrolidines; Rats; Rats, Inbred Strains; Receptors, Opioid; Time Factors

The opiate antagonist naloxone reduced the incidence and severity of cardiac arrhythmia induced in rats by intracarotid administration of adrenaline. Naloxone also reversed the adrenaline-induced arrhythmia in isolated heart preparations, suggesting a local antiarrhythmic action of the opiate antagonist. Similar effects were obtained with the (+) stereoisomer of naloxone which is inactive as an opiate antagonist. Thus, the direct action of naloxone at the rat heart is probably not mediated by opiate receptors.

Topics: Animals; Arrhythmias, Cardiac; Electrocardiography; Epinephrine; In Vitro Techniques; Naloxone; Rats; Stereoisomerism

The effect of intravenous administration of the opioid antagonist naloxone in rats with acute left coronary artery ligation was studied. The results demonstrated that naloxone in a dose 2 mg/kg b. w. affords its protection on infarcted animals by two mechanisms: Reduces by 22% the incidence of early arrhythmias that occur within 15-20 minutes of acute myocardial ischaemia, and are responsible for the early (up to the 30th minutes) postligation death; Reverses the hypotension that results from the development of cardiogenic shock after 30 minutes myocardial infarction. The total mortality after naloxone treatment was significantly reduced by 22%. Naloxone does not influence significantly the size of the infarcted area but the incidence of left ventricle wall perforations was decreased by 38%. Both effects of naloxone are attributed to the antagonism of opioid receptors either directly on the myocardium or through blocking the central action of beta-endorphin. A direct effect of naloxone on the cardiac muscle action potential cannot be excluded.

Topics: Acid-Base Equilibrium; Animals; Arrhythmias, Cardiac; Coronary Vessels; Ligation; Male; Myocardial Infarction; Naloxone; Rats; Rats, Inbred Strains

The effects of pre- and post-treatment with naloxone on the cardiotoxicity of ouabain in the guinea-pig were studied. After pretreatment with naloxone, the dose of ouabain required to induce ventricular arrhythmias and cardiac arrest were significantly increased, in a dose-dependent manner, compared with the control, indicating a protective effect of naloxone against digitalis intoxication. Administration of naloxone at the onset of cardiac arrhythmias induced by a lethal dose of ouabain restored the cardiac rhythm and consequently saved life in seven out of eight animals, indicating an antiarrhythmic effect of naloxone in digitalis-intoxicated guinea-pigs. The protective and antiarrhythmic effects of naloxone against digitalis intoxication have clinical implications.

Topics: Animals; Arrhythmias, Cardiac; Digitonin; Dose-Response Relationship, Drug; Drug Interactions; Female; Guinea Pigs; Heart; Heart Arrest; Naloxone; Ouabain

To test the hypothesis that the endogenous opioid system is operative in digitalis arrhythmias, guinea pigs anesthetized with pentothal and breathing spontaneously were allocated to a control group or four naloxone groups: 0.1 mg/kg i.v., 1.0 mg/kg i.v., 2 mg/kg i.v. or 4 mg/kg i.v. after the induction of arrhythmias by digoxin 100 micrograms/kg i.v. every 15 min. Naloxone at higher doses resulted in a rapid development of fatal arrhythmias with high degree AV block being more frequent than ventricular tachycardiac or fibrillation. Survival was significantly and inversely related to naloxone dose. The role of the autonomic nervous system was studied using cervical cord transection at the C7 level or bilateral cervical vagotomy, or atropine 1.2 mg/kg pretreatment. Cord transection, but not vagotomy, was associated with a significantly higher digoxin dose to produce arrhythmias. Naloxone 4 mg/kg i.v. shortened survival in cord transected animals, but less than in intact animals. Naloxone did not alter survival in vagotomized animals or animals that were pretreated with atropine. Thus, naloxone accelerates the development of fatal cardiac arrhythmias suggesting that endogenous opioids are involved in digitalis toxic arrhythmias an effect interrelated to the autonomic, mainly parasympathetic, nervous system.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Digitalis Glycosides; Digoxin; Electrocardiography; Guinea Pigs; Male; Naloxone; Sympathetic Nervous System

The intravenous administration of naloxone 2 min before coronary artery occlusion in anaesthetized dogs reduced the incidence and severity of cardiac arrhythmias during coronary occlusion (20 min) and reperfusion (120 min) in a dose-related manner. It also reduced the mortality. At a dose of 1 mg kg-1 (the maximum dose used in this study) naloxone abolished the appearance of the life threatening ventricular fibrillation (VF) and ventricular tachycardia (VT) and as a consequence all dogs in this group survived. The results suggest a possible involvement of endogenous opioid peptides in arrhythmogenesis during coronary occlusion and reperfusion in the dog.

Topics: Anesthesia; Animals; Arrhythmias, Cardiac; Blood Pressure; Coronary Circulation; Coronary Disease; Dogs; Female; Heart Rate; Male; Naloxone

Rabbits were used to study the inhibitory effect of analogous electro-acupuncture on the experimental arrhythmias, i.e. hypothalamic stimulation-induced ventricular extrasystole (HVE). The result revealed that HVE, which was due to an increased cardiac sympathetic activity, could be inhibited by deep peroneal nerve stimulation with an electrical current of low frequency and low intensity. Such effect is related to endogenous opioid peptides and serotonin in the arcuatus area, the periaqueductal gray and and the medial medulla. The acupuncture correction of arrhythmias may have the same mechanism.

Topics: Acupuncture Therapy; Animals; Arrhythmias, Cardiac; Blood Pressure; Cardiac Complexes, Premature; Chemoreceptor Cells; Cinanserin; Electric Stimulation Therapy; Electrocardiography; Heart; Hypothalamus; Medulla Oblongata; Microinjections; Morphine; Naloxone; Norepinephrine; Periaqueductal Gray; Pressoreceptors; Rabbits; Serotonin; Sympathetic Nervous System; Vagus Nerve

Certain basic principles are applicable to most drug overdose emergencies. These include emptying the stomach, administering activated charcoal, supporting vital functions, protecting target organs and using specific antidotes in appropriate cases. There are certain steps to be taken automatically in an unconscious patient with an unknown overdose. Drug screens rarely affect management. Special situations involve overdoses of acetaminophen, salicylates, tricyclic antidepressants, anticholinergics and narcotics.

Topics: Acetaminophen; Acetylcysteine; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Cathartics; Charcoal; Humans; Hypnotics and Sedatives; Ipecac; Naloxone; Narcotics; Parasympatholytics; Poisoning; Salicylates

Topics: Animals; Arrhythmias, Cardiac; Buprenorphine; Coronary Vessels; Dogs; Dose-Response Relationship, Drug; Female; Ligation; Male; Morphinans; Myocardial Infarction; Naloxone

Intoxicated persons appear frequently in substance abuse centers and in general hospital settings. The severity of their condition ranges from mild impairment to coma or delirium. The prominent features of intoxication with the major classes of abused drugs are described. Staff responses to intoxication are discussed. Guidelines are presented for systematic management of this condition.

Topics: Arrhythmias, Cardiac; Delusions; Diazepam; Hallucinations; Hallucinogens; Humans; Hypnotics and Sedatives; Naloxone; Narcotics; Nonprescription Drugs; Phencyclidine; Poisoning; Seizures; Solvents; Stimulation, Chemical

Twenty patients undergoing microlaryngoscopy were anaesthetised with thiopentone and nitrous oxide. Half of the patients received 1.0-1.5 mg of fentanyl during anaesthesia, the effect of which was antagonised by naloxone 0.4 mg intravenously and 0.4 mg subcutaneously. The other patients served as controls and received saline instead of fentanyl and naloxone. Fentanyl markedly reduced mean arterial pressure and the heart rate-systolic arterial pressure product during microlaryngoscopy. Conversely, there were significant increases in these measurements after naloxone had been given. However, there were no significant differences between patients given fentanyl with naloxone, and those given saline, in respect of arterial pressure, heart rate or dysrhythmia during recovery. No patient vomited, or appeared nauseated when observed afterwards in the operating room. One patient vomited several hours after naloxone.

Topics: Aged; Anesthesia, General; Arrhythmias, Cardiac; Blood Pressure; Female; Fentanyl; Heart Rate; Humans; Laryngoscopy; Male; Middle Aged; Naloxone; Time Factors

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

Naloxone pretreatment (1.0, 3.0 and 10.0 mg/kg i.v.) failed to protect anesthetized pigs from cardiac arrhythmias including ventricular fibrillation (VF) and death following acute occlusion (20 min) or reperfusion of the left anterior descending coronary artery. These findings suggest that opiate-like substances possibly released by the ischemic myocardium do not contribute significantly to the etiology of cardiac arrhythmias, or sudden death associated with the early stages of myocardial infarction in pigs. The effectiveness of naloxone in preventing acute ischemia-induced arrhythmias in rats may be due to mechanisms other than opiate-receptor blockade.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Coronary Disease; Female; Heart Rate; Hemodynamics; Male; Morphine; Naloxone; Swine; Ventricular Fibrillation

The intravenous administration of naloxone 15 min before acute coronary artery ligation in both anesthetized and conscious male rats markedly reduced the incidence and severity of the ventricular arrhythmias that occur within 30 min of the onset of myocardial ischaemia. The incidence of ventricular fibrillation was especially reduced and, in conscious rats, the survival 16 h after ligation was increased from 27% (in the controls) to 58 and 73% after 2 and 4 mg/kg naloxone respectively. One possible explanation of these results implies a detrimental effect of released endorphin in the early stages of myocardial ischaemia.

Topics: Anesthesia; Animals; Arrhythmias, Cardiac; beta-Endorphin; Coronary Vessels; Endorphins; Ligation; Male; Naloxone; Rats; Rats, Inbred Strains; Time Factors

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

Immediate attention must be given to the respiratory system of the heroin abuser; then he should be given naloxone HCl. Search for evidence of use of additional drugs, which may compound problems. Pulmonary edema, aspiration pneumonia and pulmonary embolization are the most common complications. Infections, particularly endocarditis, and cardiac arrhythmia also occur with heroin overdose. Hepatitis is common. Treatment must include not only attention to the presenting symptoms but also referral to a rehabilitation center when possible.

Topics: Arrhythmias, Cardiac; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Emergency Service, Hospital; Endocarditis; Female; Genital Diseases, Female; Heroin; Heroin Dependence; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infections; Male; Methadone; Naloxone; Pulmonary Edema; Respiratory Insufficiency