cardiovascular-agents and Hypoxia

This is the first scientific statement from the American Heart Association on maternal resuscitation. This document will provide readers with up-to-date and comprehensive information, guidelines, and recommendations for all aspects of maternal resuscitation. Maternal resuscitation is an acute event that involves many subspecialties and allied health providers; this document will be relevant to all healthcare providers who are involved in resuscitation and specifically maternal resuscitation.

Topics: Airway Management; Cardiopulmonary Resuscitation; Cardiovascular Agents; Critical Care; Early Medical Intervention; Electric Countershock; Emergency Medical Services; Female; Fetal Death; Heart Arrest; Humans; Hypotension; Hypoxia; Infant, Newborn; Oxygen Inhalation Therapy; Patient Positioning; Pregnancy; Pregnancy Complications, Cardiovascular

Leukotrienes are biologically active lipid mediators of inflammation involved in atherogenesis. Obstructive sleep apnoea (OSA) patients exhibit early atherosclerosis and activation of the leukotriene pathway. In OSA patients, the production of leukotrienes is increased in relation to OSA severity and in vitro exposure of immune cells to intermittent hypoxia increases leukotriene pathway transcription. Moreover, the leukotriene transcriptional pathway is associated with early vascular remodelling. Lastly, obesity is a major confounding factor for leukotriene activation in OSA. The aim of this review was to focus on the intricate network of leukotrienes, chronic intermittent hypoxia, and atherosclerosis, with an emphasis on the role of leukotrienes in the early atherosclerosis observed in OSA patients.

Topics: Animals; Atherosclerosis; Cardiovascular Agents; Confounding Factors, Epidemiologic; Gene Expression Regulation; Humans; Hypoxia; Inflammation Mediators; Leukotrienes; Obesity; Risk Factors; Signal Transduction; Sleep Apnea, Obstructive; Transcription, Genetic

The obstructive sleep apnoea syndrome (OSAS) had become a major public health concern in modern society due to its high prevalence but, above all, to its associated morbidity, especially cardiovascular.. Untreated OSAS is associated with an increased incidence of fatal (myocardial infarction and stroke) (odds ratio: 2.87) and non-fatal cardiovascular events (myocardial infarction, stroke, coronary artery bypass surgery and coronary angiography) (odds ratio: 3.17). Moreover, the prevalence of hypertension in patients with OSAS is high, between 35 and 80%. The pathophysiological mechanisms leading to these complications are mainly due to intermittent hypoxia secondary to repeated episodes of apnoea/hypopnoea during sleep. These mechanisms include sympathetic hyperactivation, impairment of vasomotor reactivity, vascular inflammation, oxidative stress and metabolic disorders. In patients with OSAS, the impact of continuous positive pressure is proven in terms of prevention of cardiovascular events although blood pressure reduction is limited. Obviously these effects are proportional to observance.. OSAS does increase the cardiovascular risk, independently of other risk factors. Although the impact of treatment is relatively low in decreasing blood pressure, it seems essentially effective in preventing cardiovascular morbidity. Therefore, OSAS screening, and the association of specific treatments in cardio-metabolic patients and OSAS patients respectively, should be included in clinical strategies.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Comorbidity; Continuous Positive Airway Pressure; Endothelium, Vascular; Glucose Intolerance; Humans; Hypertension; Hypoxia; Metabolic Syndrome; Nitric Oxide; Obesity; Oxidative Stress; Prevalence; Sleep Apnea, Obstructive; Sympathetic Nervous System; Vasculitis

Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease.

Topics: Acute Disease; Cardiovascular Agents; Combined Modality Therapy; Diagnosis, Differential; Diuresis; Heart Failure; Humans; Hypotension; Hypoxia; Myocardial Infarction; Myocardial Revascularization; Narcotics; Oxygen Inhalation Therapy; Pulmonary Edema; Respiration, Artificial; Sepsis; Shock; Shock, Cardiogenic; Sodium Potassium Chloride Symporter Inhibitors; Vasoconstrictor Agents; Vasodilator Agents; Ventricular Dysfunction, Left

Venous hypoxia has long been postulated as a potential cause of varicosity formation. This article aimed to review the development of this hypothesis, including evidence supporting and controversies surrounding it. Vein wall oxygenation is achieved by oxygen diffusing from luminal blood and vasa vasorum. The whole media of varicosities is oxygenated by vasa vasorum as compared to only the outer two-thirds of media of normal veins. There was no evidence that differences exist between oxygen content of blood from varicose and non-varicose veins, although the former demonstrated larger fluctuations with postural changes. Studies using cell culture and ex vivo explants demonstrated that hypoxia activated leucocytes and endothelium which released mediators regulating vein wall remodelling similar to those observed in varicosities. Venoactive drugs may improve venous oxygenation, and inhibit hypoxia activation of leucocytes and endothelium. The evidence for hypoxia as a causative factor in varicosities remains inconclusive, mainly due to heterogeneity and poor design of published in vivostudies. However, molecular studies have shown that hypoxia was able to cause inflammatory changes and vein wall remodelling similar to those observed in varicosities. Further studies are needed to improve our understanding of the role of hypoxia and help identify potential therapeutic targets.

Topics: Animals; Cardiovascular Agents; Evidence-Based Medicine; Humans; Hypoxia; Oxygen; Risk Assessment; Risk Factors; Treatment Outcome; Varicose Veins; Veins

Over decades, anesthesiologists have used intravenous adenosine as mainstay therapy for diagnosing or treating supraventricular tachycardia in the perioperative setting. More recently, specific adenosine receptor therapeutics or gene-targeted mice deficient in extracellular adenosine production or individual adenosine receptors became available. These models enabled physicians and scientists to learn more about the biologic functions of extracellular nucleotide metabolism and adenosine signaling. Such functions include specific signaling effects through adenosine receptors expressed by many mammalian tissues; for example, vascular endothelia, myocytes, hepatocytes, intestinal epithelia, or immune cells. At present, pharmacological approaches to modulate extracellular adenosine signaling are evaluated for their potential use in perioperative medicine, including attenuation of acute lung injury; renal, intestinal, hepatic and myocardial ischemia; or vascular leakage. If these laboratory studies can be translated into clinical practice, adenosine receptor-based therapeutics may become an integral pharmacological component of daily anesthesiology practice.

Topics: Adenosine; Anesthesia; Animals; Cardiovascular Agents; Extracellular Space; Humans; Hypoxia; Intraoperative Complications; Perioperative Care; Signal Transduction; Tachycardia, Supraventricular

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries inducing increased pulmonary arterial resistance. Conventional treatment is based on life style modification and nonspecific treatment (warfarine, diuretics, oxygen). Calcium channel blockers are vasodilatators that have been shown to be of great efficacy in a very specific subpopulation of patients with PAH. For the majority of patients, specific PAH therapies are still lacking. Numerous studies evaluating prostacyclin agonists, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors are now available to guide therapeutic choices. Despite those important advances there is still no cure for PAH. Fortunately, research is ongoing and many drugs show promises.

Topics: Algorithms; Altitude; Anticoagulants; Cardiovascular Agents; Contraception; Contraindications; Diuretics; Enzyme Inhibitors; Female; Humans; Hypertension, Pulmonary; Hypnotics and Sedatives; Hypoxia; Lung Transplantation; Pregnancy; Vasoconstrictor Agents

The hepatopulmonary syndrome is characterized as the triad of liver disease, pulmonary gas exchange abnormalities leading to arterial deoxygenation and evidence of intrapulmonary vascular dilatations. This review summarizes the pathological mechanisms leading to pulmonary vascular changes in hepatopulmonary syndrome. The role of the three currently used diagnostic imaging modalities of contrast-enhanced echocardiography, perfusion lung scanning and pulmonary arteriography that identify the presence of intrapulmonary vascular abnormalities are reviewed. Liver transplantation is considered to be the definitive treatment of hepatopulmonary syndrome with often successful reversal of hypoxemia, however other treatments have been trialed. This review further appraises the evidence for the use of pharmacological agents and the role of radiological interventions in hepatopulmonary syndrome.

Topics: Cardiovascular Agents; Disease Progression; Hepatopulmonary Syndrome; Humans; Hypoxia; Liver Transplantation; Portasystemic Shunt, Transjugular Intrahepatic; Pulmonary Artery; Radiography, Interventional; Treatment Outcome; Vasodilation

Topics: Abnormalities, Drug-Induced; Animals; Antioxidants; Cardiovascular Agents; Constriction; Embryo, Mammalian; Female; Humans; Hypoxia; Organ Culture Techniques; Pregnancy; Pregnancy Outcome; Reactive Oxygen Species; Reperfusion Injury

Topics: Acidosis; Adrenal Cortex Hormones; Arteriovenous Anastomosis; Blood Coagulation Disorders; Blood Transfusion; Cardiovascular Agents; Child; Child, Preschool; Hemodynamics; Hormones; Humans; Hypoxia; Infant; Infant, Newborn; Microcirculation; Receptors, Adrenergic; Shock; Shock, Hemorrhagic; Shock, Septic

To further our understanding of central sleep apnea (CSA) at high altitude during acclimatization, we tested the hypothesis that pharmacologically altering cerebral blood flow (CBF) would alter the severity of CSA at high altitude.. The study was a randomized, placebo-controlled single-blind study.. A field study at 5,050 m in Nepal.. We studied 12 normal volunteers.. Between days 5 to 10 at high altitude, CBF velocity (CBFv) was increased by intravenous (IV) acetazolamide (10 mg/kg) and reduced by oral indomethacin (100 mg).. Arterial blood gases, hypoxic and hypercapnic ventilatory responses, and CBFv and its reactivity to carbon dioxide were measured awake. Overnight polysomnography was performed. The central apnea-hypopnea index was elevated following administration of indomethacin (89.2 ± 43.7 to 112.5 ± 32.9 events/h; mean ± standard deviation; P < 0.05) and was reduced following IV acetazolamide (89.2 ± 43.7 to 47.1 ± 48.1 events/h; P < 0.001). Intravenous acetazolamide elevated CBFv at high altitude by 28% (95% confidence interval [CI]: 22-34%) but did not affect ventilatory responses. The elevation in CBFv was partly mediated via a selective rise in partial pressure of arterial carbon dioxide (PaCO2) (28 ± 4 to 31 ± 3 mm Hg) and an associated fall in pH (P < 0.01). Oral indomethacin reduced CBFv by 23% (95% CI: 16-30%), blunted CBFv reactivity, and increased the hypercapnic ventilatory response by 66% (95% CI: 30-102%) but had no effect on PaCO2 or pH.. Our findings indicate an important role for cerebral blood flow regulation in the pathophysiology of central sleep apnea at high altitude.

Topics: Acclimatization; Acetazolamide; Administration, Intravenous; Administration, Oral; Adult; Altitude; Carbon Dioxide; Cardiovascular Agents; Cerebrovascular Circulation; Female; Humans; Hypercapnia; Hypoxia; Indomethacin; Male; Middle Aged; Polysomnography; Single-Blind Method; Sleep Apnea, Central; Wakefulness; Young Adult

The origin of dyspnea in chronic heart failure (HF) is multifactorial, and excessive ventilation is thought to play a role in inducing this symptom. Chemosensivity is augmented in HF, correlates with increased pulmonary ventilation (VE), and is an adverse prognostic marker. Despite increased blood levels of natriuretic peptides in clinical conditions associated with dyspnea, their effect on pulmonary VE and chemoreceptor activity remains unexplored.. We tested in a prospective, placebo-controlled, three-way cross-over, double-blind randomized study the effects of the recombinant form of the natural human B-type natriuretic peptide (R-BNP) in comparison with placebo and levosimendan on chemoreflex sensitivity at rest, as well as their effects on pulmonary VE, systemic blood pressure, heart rate and sympathetic serum activity both at rest and during exercise.. Eleven stable chronic HF patients were randomized to sessions of 6-min treadmill-walking tests during placebo, or levosimendan or R-BNP intravenous infusion in the following conditions: room air, hypoxia, and hypercapnia. R-BNP administration determined higher pulmonary ventilatory response at rest and during exercise (P < 0.001) consequent to a boost of respiratory rate (P < 0.001) under room air and hypoxia conditions. Norepinephrine blood levels increased from rest to exercise in all conditions without differences among placebo, levosimendan, and R-BNP effects. BNP blood levels remained unchanged.. The novelty of the present findings is that R-BNP infusion in HF patients can boost pulmonary ventilatory response at rest and during exercise.

Topics: Adult; Brazil; Cardiovascular Agents; Chemoreceptor Cells; Chronic Disease; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure; Hemodynamics; Humans; Hydrazones; Hypercapnia; Hyperventilation; Hypoxia; Infusions, Intravenous; Lung; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pyridazines; Recombinant Proteins; Respiratory Rate; Simendan; Time Factors; Treatment Outcome

Trifluoperazine (TFP), an antipsychotic drug approved by the Food and Drug Administration, has been show to exhibit anti-cancer effects. Pulmonary arterial hypertension (PAH) is a devastating disease characterized by a progressive obliteration of small pulmonary arteries (PAs) due to exaggerated proliferation and resistance to apoptosis of PA smooth muscle cells (PASMCs). However, the therapeutic potential of TFP for correcting the cancer-like phenotype of PAH-PASMCs and improving PAH in animal models remains unknown. PASMCs isolated from PAH patients were exposed to different concentrations of TFP before assessments of cell proliferation and apoptosis. The in vivo therapeutic potential of TFP was tested in two preclinical models with established PAH, namely the monocrotaline and sugen/hypoxia-induced rat models. Assessments of hemodynamics by right heart catheterization and histopathology were conducted. TFP showed strong anti-survival and anti-proliferative effects on cultured PAH-PASMCs. Exposure to TFP was associated with downregulation of AKT activity and nuclear translocation of forkhead box protein O3 (FOXO3). In both preclinical models, TFP significantly lowered the right ventricular systolic pressure and total pulmonary resistance and improved cardiac function. Consistently, TFP reduced the medial wall thickness of distal PAs. Overall, our data indicate that TFP could have beneficial effects in PAH and support the view that seeking new uses for old drugs may represent a fruitful approach.

Topics: Animals; Antipsychotic Agents; Cardiovascular Agents; Cell Proliferation; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Repositioning; Female; Forkhead Box Protein O3; Gene Expression Regulation; Hemodynamics; Humans; Hypertension, Pulmonary; Hypoxia; Indoles; Monocrotaline; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Primary Cell Culture; Proto-Oncogene Proteins c-akt; Pulmonary Artery; Pyrroles; Rats; Rats, Sprague-Dawley; Survivin; Trifluoperazine

Endothelial injury is considered as a trigger of pulmonary vascular lesions in the pathogenesis of hypoxic pulmonary hypertension (HPH). Although endothelial colony-forming cells (ECFCs) have vascular regeneration potential to maintain endothelial integrity, hypoxia-induced precise alteration in ECFCs function remains controversial. This study investigated the impact of hypoxia on human ECFCs function in vitro and the underlying mechanism. We found that hypoxia inhibited ECFCs proliferation, migration and angiogenesis. Compared with no treatment, the expression of hypoxia inducible factor-1α (HIF-1α) in hypoxia-treated ECFCs was increased, with an up-regulation of p27 and a down-regulation of cyclin D1. The over-secreted vascular endothelial growth factor (VEGF) was detected, with the imbalanced expression of fetal liver kinase 1 (flk-1) and fms related tyrosine kinase 1 (flt-1). Hypoxia-induced changes in ECFCs could be reversed by HIF-1α inhibitor KC7F2. These data suggest that HIF-1α holds the key in regulating ECFCs function which may open a new perspective of ECFCs in HPH management.

Topics: Adult; Cardiovascular Agents; Cell Cycle; Cell Movement; Cell Proliferation; Cells, Cultured; Cyclin D1; Disulfides; Endothelial Cells; Humans; Hypertension, Pulmonary; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Middle Aged; Receptors, Vascular Endothelial Growth Factor; Signal Transduction; Sulfonamides; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Young Adult

Skin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies. However, outcomes of these studies remain controversial. We previously demonstrated that transcutaneous CO. Six-week-old male Sprague-Dawley rats were divided into two equal groups: the control group (n = 6) and CO. A statistically significant difference was found in the percentage of the flap survival area between the two groups on postoperative days 3 and 5 (p < 0.05). Furthermore, the expression of VEGF and bFGF was significantly higher and that of HIF-1α was significantly lower in the CO. Transcutaneous CO

Topics: Administration, Cutaneous; Animals; Carbon Dioxide; Cardiovascular Agents; Graft Survival; Hypoxia; Ischemia; Male; Necrosis; Plastic Surgery Procedures; Postoperative Complications; Rats; Rats, Sprague-Dawley; Skin; Surgical Flaps; Treatment Outcome

Salvianolic acid A (Sal A), a bioactive compound isolated from the Chinese medicinal herb Danshen, is used for the prevention and treatment of cardiovascular diseases. However, the protective function of Sal A on preserving the role of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) is unclear. The present study investigated the effects and mechanisms of Sal A (2.5, 5, 10mg/kg, i.p.) on BSCB permeability at different time-points after compressive SCI in rats. Compared to the SCI group, treatment with Sal A decreased the content of the Evans blue in the spinal cord tissue at 24h post-SCI. The expression levels of tight junction proteins and HO-1 were remarkably increased, and that of p-caveolin-1 protein was greatly decreased after SCI Sal A. The effect of Sal A on the expression level of ZO-1, occluding, and p-caveolin-1 after SCI was blocked by the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP). Also, Sal A inhibited the level of apoptosis-related proteins and improved the motor function until 21days after SCI. In addition, Sal A significantly increased the expression of microRNA-101 (miR-101) in the RBMECs under hypoxia. AntagomiR-101 markedly increased the RBMECs permeability and the expression of the Cul3 protein by targeting with 3'-UTR of its mRNA. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 was significantly increased after agomiR-101 treatment. Therefore, Sal A could improve the recovery of neurological function after SCI, which could be correlated with the repair of BSCB integrity by the miR-101/Cul3/Nrf2/HO-1 signaling pathway.

Topics: Animals; Caffeic Acids; Capillary Permeability; Cardiovascular Agents; Caveolin 1; Cullin Proteins; Disease Models, Animal; Drug Evaluation, Preclinical; Heme Oxygenase (Decyclizing); Hypoxia; Lactates; Male; MicroRNAs; Motor Activity; Neuroprotective Agents; NF-E2-Related Factor 2; Random Allocation; Rats, Sprague-Dawley; Spinal Cord; Spinal Cord Injuries; Tight Junctions; Zonula Occludens-1 Protein

Our previous study in vitro showed that hydrogen sulfide (H2S) could protect the medullary respiratory centers from injury induced by acute hypoxia in brainstem slices of neonatal rats. The present study was carried out to determine if H2S could exhibit similar protective effects in adult rats and to explore the underlying mechanisms of its protection. It was observed that hypoxia induced a diphasic respiratory response, an excitatory phase followed by an inhibitory one, as indicated by an increase followed by a decrease in frequency of rhythmic discharge of the diaphragm. Nissl staining revealed that some of the neurons in the medullary respiratory related nuclei were impaired in hypoxia rats. Hypoxia led to increases in the content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as a decrease in the level of Bcl-2 mRNA of the medulla oblongata. Intracerebroventricular injection of 2.5mM NaHS (a donor of H2S) or L-cysteine (L-Cys, a substrate for H2S) could prevent inhibitory respiratory effect occurred in the rats with hypoxia. Exogenous application of NaHS and L-Cys could also reduce the content of MDA and the activities of SOD and GSH-Px, and increase the level of Bcl-2 mRNA expression of medulla oblongata caused by hypoxia. These results indicate that H2S could protect the medullary respiratory centers against injury induced by acute hypoxia in adult rats partly due to its anti-oxidant and anti-apoptotic effects.

Topics: Anesthesia; Animals; Antioxidants; Cardiovascular Agents; Cysteine; Glutathione Peroxidase; Hydrogen Sulfide; Hypoxia; Malondialdehyde; Medulla Oblongata; Neurons; Neuroprotective Agents; Rats, Sprague-Dawley; Respiration; Superoxide Dismutase

Central hydrogen sulfide (H2S) has been reported to act as a gaseous neuromodulator involved in the ventilatory and cardiovascular control of normotensive rats, whereas no information is available in spontaneously hypertensive rats (SHR). We recorded minute ventilation (VE), mean arterial pressure (MAP) and heart rate (HR) before and after blocking of enzyme Cystathionine β-synthase (CBS) producing H2S in neural tissue by microinjection of aminooxyacetate (inhibitor of CBS) into the fourth ventricle of Wistar normotensive rats (WNR) and SHR followed by 30min of normoxia (21% inspired O2) or hypoxia (10% inspired O2) exposure. Microinjection of AOA or saline (1μL) did not change VE, MAP and HR during normoxia in both WNR and SHR. In WNR, hypoxia caused an increase in VE, HR and a decrease in MAP and these responses were unaltered by AOA. In SHR, hypoxia produced a higher increase of VE, and decrease in MAP and HR when compared to WNR, and these responses were all blunted by AOA. In conclusion, endogenous H2S plays important modulatory roles on hypoxia-induced ventilatory and cardiovascular responses, inhibiting the cardiovascular and stimulating the respiratory systems in SHR.

Topics: Animals; Arterial Pressure; Cardiovascular Agents; Cardiovascular System; Disease Models, Animal; Fourth Ventricle; Heart Rate; Hydrogen Sulfide; Hypertension; Hypoxia; Male; Rats, Inbred SHR; Rats, Wistar; Respiration; Tidal Volume

Therapeutic hypothermia has become a standard neuroprotective treatment in term newborn infants following perinatal asphyxia. Hypothermia-induced changes in the reactivity of the vessels supplying the brain might play a role in its therapeutic or side effects. We investigated the putative age-related changes and the effect of clinically relevant cooling (33°C) on the reactivity of the newborn rat carotid artery. Carotid artery rings from 2-3 days old and 9-10 days old rats were mounted in myographs and studied at 33°C and 37°C. Hypothermia did not significantly affect the contractions induced by KCl and U46619, nor the relaxations induced by acetylcholine (ACh), the nitric oxide (NO) donor sodium nitroprusside (SNP), the NO-independent stimulator of soluble guanylate cyclase (sGC) BAY 41-2272, the β -adrenoceptor agonist isoproterenol, the adenylate cyclase activator forskolin, and acute hypoxia (PO2 3 kPa). The relaxations induced by ACh, isoproterenol, the β 2-adrenoceptor agonist salbutamol, the β 3-adrenoceptor agonist CL-316243 and acute hypoxia increased with postnatal age and were impaired by endothelium removal or by inhibition of NO synthase (L-NAME) or sGC (ODQ). In contrast, the relaxations induced by SNP, BAY 41-2272 and forskolin were endothelium-independent and did not change with age. In conclusion, mild hypothermia (33°C) does not affect the reactivity of neonatal rat carotid arteries. Our data suggest a reduced NO bioavailability in the carotid artery during the first days of life. This transient reduction in endothelium-dependent relaxation might play a role in the adaptation of the circulatory system to birth and in the neonatal vascular response to insults such as hypoxia.

Topics: Aging; Animals; Animals, Newborn; Cardiovascular Agents; Carotid Arteries; Dose-Response Relationship, Drug; Enzyme Inhibitors; Female; Hypothermia, Induced; Hypoxia; In Vitro Techniques; Male; Muscle Contraction; Myography; Pregnancy; Rats; Rats, Sprague-Dawley; Temperature; Time Factors

Topics: Arrhythmias, Cardiac; Cardiac Surgical Procedures; Cardiovascular Agents; Cyanosis; Diagnostic Techniques, Cardiovascular; Female; Humans; Hypoxia; Infant, Newborn; Male; Pacemaker, Artificial; Postoperative Complications; Pulmonary Valve Insufficiency; Respiration, Artificial; Tetralogy of Fallot

Previous research has shown an inconsistent effect of hypoxia on dynamic cerebral autoregulation (dCA), which may be explained by concurrent CO2 control. To test the hypothesis that hypoxic dCA is mediated by CO2, we assessed dCA (transcranial Doppler) during and following acute normobaric isocapnic and poikilocapnic hypoxic exposures. On 2 separate days, the squat-stand maneuver was used to determine dCA in healthy subjects (n = 8; 3 women) in isocapnic and poikilocapnic hypoxia exposures (end-tidal oxygen pressure 50 Torr for 20 min). In isocapnic hypoxia, the amplitude of the cerebral blood flow response to increases and decreases in mean arterial blood pressure were elevated (i.e., increases in gain of +35 and +28%, respectively; P < 0.05). However, dCA gain to increases in pressure was reduced compared with baseline (-32%, P < 0.05) following the isocapnic hypoxia exposure. Similarly, intravenous bolus injections of sodium nitroprusside and phenylephrine in a separate group of subjects (n = 8; 4 women) also demonstrated a reduction in dCA gain to hypertension following isocapnic hypoxia. In contrast, dCA gain with the squat-stand maneuver did not significantly change from baseline during or following poikilocapnic hypoxia (P > 0.05). Our results demonstrate that dCA impairment in isocapnic hypoxia can be prevented with hypocapnia, and highlight the integrated nature of hypoxic cerebrovascular control, which is under strong CO2 influence.

Topics: Acute Disease; Adult; Blood Pressure; Carbon Dioxide; Cardiovascular Agents; Cerebrovascular Circulation; Female; Homeostasis; Humans; Hypocapnia; Hypoxia; Male; Nitroprusside; Phenylephrine; Posture; Young Adult

Cerebrovascular pathology has long moved from the category of a single medical problem in the social problem. Progression of vascular lesions of the brain results in significant disability, and in the later stages interfere with the ability to self-service and significantly reduces the quality of life. The key link is ischemic brain damage, or glutamate cascade, which many researchers believe trigger excitotoxic damage and a major cause of neuronal death. One important component of effective control of the effects of ischemic disorders is complex neuro-cytoprotective therapy. To correct for the effects of both acute and chronic ischemia of the brain need to effectively act in several directions simultaneously, normalizing metabolic changes, eliminating the cytokine imbalance transcription violations, reducing the severity of oxidative stress and excitotoxicity.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Cerebrovascular Circulation; Cerebrovascular Disorders; Energy Metabolism; Humans; Hypoxia; Ischemia; Methylhydrazines; Randomized Controlled Trials as Topic

This study sought to determine the effect of combined treatment of hypoxia plus indomethacin on pulmonary vascular remodeling in fetal rats.. Hypoxia and indomethacin were used to treat pregnant rats during 19-21 days of gestation. The adventitia, media, and intima of pulmonary arteries from fetal rats were assessed. Western blots were used for determining the abundance of smooth muscle specific alpha-actin protein (α-SMA), elastin, and endothelial nitric oxide synthase (eNOS) in lung tissues. Plasma brain-type natriuretic peptide (BNP) levels, reflecting the increased right ventricular load or pulmonary arterial pressure, were detected.. The ratio of left ventricular free wall plus septum to right ventricular weight significantly increased in hypoxia plus indomethacin-treated group. The medial thickness percentage of pulmonary arteries of < 100 μm and ≥100 μm in diameter from hypoxia plus indomethacin-treated group was higher than that from control or single treatment group. Vascular elastin area percentage and immunostaining density of eNOS from the combined-treated group were higher than other groups. The relative abundance of α-SMA, elastin, and eNOS and plasma BNP levels in hypoxia plus indomethacin-treated group also significantly increased compared with other groups.. Hypoxia and indomethacin had synergistic effect on fetal pulmonary vascular remodeling. This rat model induced by combined treatments can mimic human persistent pulmonary hypertension of the newborn.

Topics: Actins; Animals; Animals, Newborn; Blotting, Western; Cardiovascular Agents; Disease Models, Animal; Elastin; Female; Humans; Hypoxia; Indomethacin; Infant, Newborn; Lung; Myocardium; Natriuretic Peptide, Brain; Nitric Oxide Synthase Type III; Persistent Fetal Circulation Syndrome; Pulmonary Artery; Rats; Rats, Sprague-Dawley

Although hypoxia and ischemia are known to be involved in the pathogenesis of cardiovascular disease, specific therapeutic targets still remain elusive. To address this important issue, we have performed 2 series of experimental studies, aiming at erythropoietin (Epo)/Epo receptor (EpoR) based on the following backgrounds. Epo has long been regarded as a hematopoietic hormone that acts exclusively in the proliferation and differentiation of erythroid progenitors. Although recent studies have demonstrated that EpoR is expressed in the cardiovascular system, the potential protective role of the vascular Epo/EpoR system in vivo remains to be examined. We hypothesized that the vascular Epo/EpoR system plays an important protective role against the development of cardiovascular disease. Using vascular EpoR-deficient mouse, we demonstrated that the vascular Epo/EpoR system plays a crucial role for endothelial function and vascular homeostasis. The vascular Epo/EpoR system is important for the activation of the vascular endothelial growth factor/vascular endothelial growth factor receptor-2 system, inhibits hypoxia-induced pulmonary endothelial damage and promotes ischemia-induced angiogenesis in vivo. These results indicate that the vascular Epo/EpoR system plays an important protective role against hypoxia/ischemia, demonstrating that this system is a novel therapeutic target in cardiovascular medicine.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Drug Delivery Systems; Endothelium, Vascular; Erythropoietin; Homeostasis; Humans; Hypoxia; Mice; Mice, Knockout; Myocardial Ischemia; Receptors, Erythropoietin

Hypoxic pulmonary hypertension is a disease of the lung vasculature that is usually quantified by pulmonary vascular resistance (PVR). However, a more complete description of lung vascular function and right ventricular afterload is provided by pulmonary vascular impedance (PVZ) from spectral analysis of pulsatile pressure-flow relationships. We studied pulsatile pressure-flow relationships in isolated, perfused lungs of mice in normoxia, after induction of hypoxic pulmonary hypertension by 10 days of hypoxic exposure, and after the administration of the vasoactive agents sodium nitroprusside and serotonin in order to gain insight into the effects of disease and vasoactive agents on afterload. Chronic hypoxia exposure increased 0 Hz impedance (Z(0)) from 2.0 +/- 0.2 to 3.3 +/- 0.2 mmHg min/mL but decreased characteristic impedance (Z(C)) from 0.21 +/- 0.02 to 0.18 +/- 0.01 mmHg min/mL (both p < 0.05). Sodium nitroprusside only slightly decreased Z(0) but increased Z(C) in normal lungs (p < 0.05) and did not affect Z(C) and decreased Z(0) in hypertensive lungs (p < 0.05). Serotonin increased Z(C) in normal and hypertensive lungs but decreased Z(0) in hypertensive lungs (p < 0.05). There was an inverse correlation between mean pulmonary artery pressure and Z(C) in all circumstances. These findings demonstrate that vasoactive interventions can have different sites of action (i.e., proximal vs. distal segments) in the normal and chronically hypoxic pulmonary vasculature, and the pressure-dependency of Z(C) and R(W). The measurement of PVZ in isolated lungs allows for an improved understanding of the modes of action of drugs and hypoxia on the pulmonary circulation.

Topics: Animals; Blood Vessels; Cardiovascular Agents; Electric Impedance; Hypertension, Pulmonary; Hypoxia; Lung; Male; Mice; Mice, Inbred C57BL; Nitroprusside; Pulmonary Circulation; Pulsatile Flow; Vascular Resistance

To investigate the cardioprotective potential of Syringa pinnatifolia Hems1. var. alashanensis essential oil (SPEO) against experimental acute myocardial ischemia (AMI), hydrogen peroxide (H(2)O(2))-induced myocyte injury and activities against hypoxia and platelet aggregation.. Wistar rats, Kunming mice and primary cultured rat neonatal myocytes were used in this study. AMI in rats was induced by ligation of the left anterior descending (LAD) coronary artery, and deviation of ST-segment, as well as changes of myocardial enzyme activities were observed. Hypoxia test in Kunming mice was performed to evaluate the effect of SPEO against hypoxia. The protective effect of SPEO on H(2)O(2)-induced cell injury was evaluated in terms of cell viability assay. The in vitro effect of SPEO against platelet aggregation was studied using adenosine 5'-diphosphate (ADP) as agonist.. Administration of SPEO reduced deviation of ST-segment, decreased the levels of lactate dehydrogenase (LDH), creatine kinase (CK) and Troponin T (TnT) while increased the activities of superoxide dismutase (SOD). The protective role of SPEO was further confirmed by histopathological examination. In the hypoxia test, both 8 and 32 mg/kg of SPEO could prolong survival time of mice under hypoxia condition. At the meantime SPEO showed remarkable protective effect on cultured rat myocyte death induced by H(2)O(2). SPEO also inhibited ADP-induced rat platelet aggregation by 47.4%, 37.0% and 32.9% at the dose of 5, 2.5 and 1.25 microg/mL, respectively.. These results suggest that SPEO possessing activities against hypoxia, oxidative stress and platelet aggregation has a significant protective effect against experimental myocardial ischemia.

Topics: Animals; Cardiovascular Agents; Cell Death; Creatine Kinase; Disease Models, Animal; Electrocardiography; Female; Hydrogen Peroxide; Hypoxia; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred Strains; Muscle Cells; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Oils, Volatile; Phytotherapy; Plant Extracts; Plant Stems; Platelet Aggregation; Rats; Rats, Wistar; Superoxide Dismutase; Syringa; Troponin T

The estimation of fluid deficits in camelids is challenging. However, early recognition and treatment of shock and hypovolemia is instrumental to improve morbidity and mortality of critically ill camelids. Early goal-directed fluid therapy requires specific knowledge of clinical indicators of hypovolemia and assessment of resuscitation endpoints, but may significantly enhance the understanding, monitoring, and safety of intravenous fluid therapy in South American camelids (SAC). It is important to recognize that over-aggressive fluid resuscitation is just as detrimental as under resuscitation. Nonetheless, a protocol of conservative fluid management is often indicated in the treatment of camelids with pulmonary inflammation, to counteract edema formation. The early recognition of lung dysfunction is often based on advanced diagnostic techniques, including arterial blood gas analysis, diagnostic imaging, and noninvasive pulmonary function testing.

Topics: Animals; Blood Pressure; Camelids, New World; Cardiovascular Agents; Colloids; Critical Illness; Crystalloid Solutions; Emergency Medical Services; Fluid Therapy; Hypovolemia; Hypoxia; Injections, Intravenous; Isotonic Solutions; Lung Diseases

Topics: Algorithms; Biomarkers; Cardiovascular Agents; Diagnostic Techniques, Cardiovascular; Exercise Tolerance; Heart Diseases; Humans; Hypertension, Pulmonary; Hypoxia; Lung Transplantation; Prognosis; Pulmonary Veno-Occlusive Disease; Referral and Consultation; Risk Factors; Terminal Care; Thromboembolism

Preload parameters in postresuscitation phase are not sufficiently sensitive to guide fluid therapy in critically ill patients. We analyzed modifications in the fluid therapy and vasoactive drugs of critically ill patients that were produced by inclusion of extravascular lung water (EVLW) data in the treatment protocol and evaluated the short-term response.. This observational and prospective study included consecutive patients with hypotension or hypoxemia, comparing the therapeutic plan for fluid and vasoactive drug treatment between before and after knowing the EVLW value.. We studied 42 patients. After knowing the EVLW, 52.4% (n = 22) of initial therapeutic plans were changed, modifying fluid therapy in all of these cases and vasoactive therapy in 22% of them. EVLW value was 13.91 +/- 5.62 in patients with change of therapeutic plan versus 10 +/- 4.52 in those with no change (p < 0.05). No differences were found in preload parameters as a function of change/no change. The most frequent decision change (n = 13) was to fluid reduction plus diuretic administration, and patients with this modification had significantly (p < 0.05) higher EVLW values compared with the remaining patients with a change in fluid therapy. Out of the 22 patients with a modified therapeutic decision, the therapy proved effective in 18 patients. Quantification of EVLW in patients who can be considered euvolemic induces important modifications in fluid and vasoactive therapy. These changes generally resulted in a lower volume loading and a positive outcome for the patient.

Topics: Analysis of Variance; Cardiovascular Agents; Chi-Square Distribution; Critical Illness; Extravascular Lung Water; Female; Fluid Therapy; Hemodynamics; Humans; Hypotension; Hypoxia; Indicator Dilution Techniques; Male; Prospective Studies; Respiration, Artificial; Respiratory Distress Syndrome; Sepsis

Every cell needs energy, i.e., adenosine triphosphate (ATP), to carry out its function. Decreased oxygen levels, decreased blood flow, and other stressful conditions can drastically effect the intracellular concentrations of these energy compounds. Skeletal muscle, unlike the heart, can address this drop in ATP by employing the myokinase reaction, ultimately producing ATP with a subsequent elevation in adenosine monophosphate (AMP). Ribose, a naturally occurring 5-carbon monosaccharide, is a key component of RNA, DNA (which has deoxyribose), acetyl coenzyme A, and ATP. Each cell produces its own ribose, involved in the pentose phosphate pathway (PPP), to aid in ATP production. States of ischemia and/or hypoxia can severely lower levels of cellular energy compounds in the heart, with an associated compromise in cellular processes, ultimately reflected in altered function. Ribose appears to provide a solution to the problem in replenishing the depressed ATP levels and improving functional status of patients afflicted with cardiovascular diseases.

Topics: Adenosine Triphosphate; Cardiovascular Agents; Cardiovascular Diseases; Dietary Supplements; Energy Metabolism; Heart; Humans; Hypoxia; Ischemia; Myocardium; Ribose

Topics: Adult; Altitude; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Contraceptives, Oral; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Dehydration; Drug-Eluting Stents; Exercise; Female; Genetic Predisposition to Disease; Humans; Hypoxia; Myocardial Infarction; Paclitaxel; Risk Factors; Time Factors; Treatment Outcome

Topics: Acute Disease; Brain Edema; Brain Ischemia; Cardiovascular Agents; Case Management; Combined Modality Therapy; Decompression, Surgical; Fever; Humans; Hyperglycemia; Hypertension; Hypoxia; Intracranial Hypertension; Pneumonia; Thrombolytic Therapy; Urinary Tract Infections; Water-Electrolyte Imbalance

The goal of this study was to determine the effect of angiotensin type 1 (AT(1)) receptor antagonism on vasodilator responses in isolated skeletal muscle resistance arteries. Normotensive Sprague-Dawley rats were fed normal rat chow with the AT(1) receptor antagonist losartan (1mg/ml) in the drinking water for 7 days and compared with untreated control rats. Changes in the diameter of isolated resistance arteries supplying the gracilis muscle were assessed with a video micrometer. Arteriolar responses to acetylcholine, iloprost, and sodium nitroprusside were unaffected by losartan administration, whereas dilation to reduced Po(2) was converted into a constriction. Hypoxia-induced constriction of vessels from losartan-treated rats was inhibited by endothelium removal or indomethacin (1 microM). Blockade of the PGH(2)-thromboxane A(2) receptor with SQ-29548 (10 microM), thromboxane synthase inhibition with dazoxiben (10 microM), or the addition of the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL, 100 microM) converted hypoxic vasoconstriction to a dilation that was blocked by inhibiting nitric oxide synthase with N(omega)-nitro-l-arginine methyl ester (100 microM). These data suggest that AT(1) receptor activation has an important role in maintaining the vascular release of prostaglandins responsible for mediating hypoxic dilation in skeletal muscle microvessels.

Topics: Acetylcholine; Angiotensin II Type 1 Receptor Blockers; Animals; Arteries; Cardiovascular Agents; Enzyme Inhibitors; Epoprostenol; Hypoxia; In Vitro Techniques; Indomethacin; Losartan; Male; Muscle, Skeletal; NG-Nitroarginine Methyl Ester; Oxygen; Partial Pressure; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane A2, Prostaglandin H2; Thromboxane A2; Thromboxanes; Time Factors; Vascular Resistance; Vasoconstriction; Vasodilation; Vasodilator Agents

Dexrazoxane is a cardioprotective antioxidant that is clinically used to reduce the cardiotoxicity of the chemotherapeutic drug doxorubicin. We examined the hypothesis that dexrazoxane also may be able to protect neonatal rat cardiac myocytes from hypoxia-reoxygenation damage. Hypoxia-reoxygenation damage is thought to involve oxidative stress on the heart muscle, possibly by the production of hydroxyl radicals mediated by iron. The results of this study showed that dexrazoxane was highly effective in protecting myocytes from hypoxia-reoxygenation-induced lactate dehydrogenase release. The metal chelating hydrolysis product of dexrazoxane, ADR-925, also protected myocytes from hypoxia-reoxygenation damage, although it was less effective than dexrazoxane. This study also showed that ADR-925 and dexrazoxane rapidly entered myocytes and displaced iron from a fluorescence-quenched trapped intracellular iron-calcein complex. These results suggest that dexrazoxane may protect myocytes against hypoxia-reoxygenation-induced damage by chelating free or loosely bound iron, thus preventing site-specific iron-based oxygen radical damage. Thus, dexrazoxane or its analogs may have some clinical utility in preventing tissue damage that occurs after a stroke or heart attack.

Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Ethylenediamines; Extracorporeal Membrane Oxygenation; Fluoresceins; Fluorescent Dyes; Glycine; Hypoxia; Ion Transport; L-Lactate Dehydrogenase; Models, Cardiovascular; Myocytes, Cardiac; Rats; Rats, Sprague-Dawley; Razoxane; Time Factors; Treatment Failure

Heart failure (HF) is considered a putative factor predisposing to acute renal failure (ARF). Since outer medullary hypoxic injury may play an important role in the pathogenesis of acute tubular necrosis, we explored the impact of experimental HF on the propensity to develop ARF with hypoxic medullary injury following the inhibition of prostaglandin and nitric oxide synthesis.. Compensated, high-output HF was induced in Sprague-Dawley rats by aorto-caval fistula. At the eighth to ninth postoperative day, the rats were injected with indomethacin and N(omega) nitro-L-arginine methyl ester (L-NAME; ARF protocol) and were sacrificed 24 hours later for morphologic evaluation.. Kidney function comparably declined in HF-ARF rats and in control sham operated animals (CTR-ARF). Nevertheless, outer medullary hypoxic damage with medullary thick ascending limb (mTAL) necrosis occurred almost exclusively in the HF-ARF group (11 +/- 4% vs. 0.2 +/- 0.2% of tubules in CTR-ARF, P < 0.03). In a third group of HF animals subjected to vehicles only (HF-Nil), kidney function was preserved and renal morphology remained intact. Papillary-tip necrosis was consistently found in all animals subjected to indomethacin and L-NAME, irrespective of preconditioning. Morphometric evaluation disclosed that HF was not associated with mTAL hypertrophy.. Incipient HF predisposes to hypoxic outer medullary injury, probably reflecting the impact of regional vasoconstrictive stimuli rather than tubular hypertrophy when protective local vasodilating mechanisms are hampered. The presence and extent of outer medullary hypoxic damage cannot be predicted from the functional derangement, which in the experimental settings may also represent prerenal azotemia or papillary damage.

Topics: Acute Kidney Injury; Animals; Cardiomegaly; Cardiovascular Agents; Disease Models, Animal; Enzyme Inhibitors; Heart Failure; Hypoxia; Indomethacin; Kidney Medulla; Kidney Tubular Necrosis, Acute; Loop of Henle; NG-Nitroarginine Methyl Ester; Rats; Rats, Sprague-Dawley; Renal Circulation; Vasoconstriction; Vasodilation

After birth, the full-term ductus arteriosus actively constricts and undergoes extensive histologic changes that prevent subsequent reopening. These changes are thought to occur only if a region of intense hypoxia develops within the ductus wall after the initial active constriction. In preterm infants, indomethacin-induced constriction of the ductus is often transient and is followed by reopening. Prostaglandins and nitric oxide both play a role in inhibiting ductus closure in vitro. We hypothesized that combined inhibition of both prostaglandin and nitric oxide production (with indomethacin and N-nitro-L-arginine (L-NA), respectively) may be required to produce the degree of functional closure that is needed to cause intense hypoxia. We used preterm (0.67 gestation) newborn baboons that were mechanically ventilated for 6 d: 6 received indomethacin alone, 7 received indomethacin plus L-NA, and 16 received no treatment (control). Just before necropsy, only 25% of control ductus and 33% of indomethacin-treated ductus were closed on Doppler examination; in contrast, 100% of the indomethacin-plus-L-NA-treated ductus were closed. Control and indomethacin-treated baboons developed negligible-to-mild ductus hypoxia (EF5 technique). Similarly, there was minimal evidence of ductus remodeling. In contrast, indomethacin-plus-L-NA-treated baboons developed intense hypoxia in regions where the ductus was most constricted. The hypoxic muscle strongly expressed vascular endothelial growth factor, and proliferating luminal endothelial cells filled and occluded the lumen. In addition, cells in the most hypoxic regions were undergoing DNA fragmentation. In conclusion, preterm newborns are capable of remodeling their ductus, just like the full-term newborn, if they can reduce their luminal blood flow to a point that produces intense ductus wall hypoxia. Combined prostaglandin and nitric oxide inhibition may be necessary to produce permanent closure of the ductus and prevent reopening in preterm infants.

Topics: Animals; Animals, Newborn; Bisbenzimidazole; Blood Pressure; Cardiovascular Agents; DNA Fragmentation; Ductus Arteriosus; Endothelial Growth Factors; Enzyme Inhibitors; Etanidazole; Fetus; Fluorescent Dyes; Hydrocarbons, Fluorinated; Hypoxia; Immunohistochemistry; In Situ Nick-End Labeling; Indicators and Reagents; Indomethacin; Lymphokines; Nitric Oxide; Nitroarginine; Papio; Prostaglandins; Respiratory Physiological Phenomena; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

The objective of this study was to characterize the effects of acute anoxia on contractile and electrical activity in the heart of an anoxia-tolerant fish species, the crucian carp (Carassius carassius L.). Responses of atrial and ventricular tissue or isolated cells to NaCN, adenosine, and carbachol were determined to examine the effects of anoxia on cardiac performance and to clarify the possible role of local purinergic modulation and parasympathetic nervous control in the function of the anoxic fish heart. The contractility of the crucian carp heart is strongly decreased by acute anoxia. A rapid reduction in cardiac contractility is attained by reflex bradycardia and suppression of atrial contractility. These responses are mediated by muscarinic cholinergic receptors through the opening of inwardly rectifying potassium channels and are likely to protect the cardiac muscle from hypoxic/anoxic damage. The depletion of tissue oxygen content also directly depresses heart rate and cardiac force. Ultimately, an increase in cytosolic Ca(2+) concentration occurs that activates sarcolemmal Ca(2+) extrusion through the Na(+)-Ca(2+)-exchange and generates an inward exchange current with consequent depolarization of the resting membrane potential and possible cell death. At physiological concentration, the effects of adenosine on contractile and electrical activity were relatively weak, suggesting that the purinergic system is not involved in the acute anoxia response of the crucian carp heart.

Topics: Acute Disease; Adenosine; Animals; Atrial Function; Carbachol; Cardiotonic Agents; Cardiovascular Agents; Carps; Electrophysiology; Heart Rate; Hypoxia; In Vitro Techniques; Muscarine; Muscarinic Agonists; Myocardial Contraction; Purines; Sodium Cyanide; Ventricular Function

3-(2,2,2-trimethylhydrazinium) propionate (MET-88) is an inhibitor of carnitine synthesis. This study was carried out to investigate whether or not reduction of carnitine content could attenuate hypoxic damage in isolated perfused rat hearts. Rats were divided into four groups: 1) vehicle control; 2) pretreatment with MET-88 (MET-88); 3) application of insulin (500 muU/mL) in the perfusate (insulin); and 4) pretreatment with MET-88 and application of insulin (MET-88 + insulin). MET-88 (100 mg/kg) was orally administered once a day for 10 days until the day before the experiments. Hearts were initially perfused for a 10 min period under normoxia, followed by a 30 min period under hypoxia. Hearts were frozen at the end of hypoxia for the measurement of high-energy phosphates, carnitine derivatives, and glycolysis intermediates. In a separate series of untreated and MET-88 treated hearts, exogenous glucose and palmitate oxidation was measured. MET-88 decreased the extent of the depression of cardiac contractility (+dP/dt), and aortic flow during the hypoxic state. Insulin also improved cardiac function, and co-treatment of MET-88 and insulin additionally improved cardiac function during hypoxia. MET-88 prevented the decrease of high-energy phosphate and the increase of long-chain acylcarnitine after 30 min of hypoxic perfusion. In addition, MET-88 increased the steady state of glucose oxidation in hypoxic perfused rat hearts. These results indicate that MET-88 has cardioprotective effects on contractile function and energy metabolism of isolated perfused rat hearts in a hypoxic condition. Preventing the accumulation of long-chain acylcarnitine may serve to protect hypoxic hearts.

Topics: Administration, Oral; Animals; Cardiovascular Agents; Carnitine; Coronary Circulation; Glucose; Glycolysis; Heart; Hypoglycemic Agents; Hypoxia; In Vitro Techniques; Insulin; Lactic Acid; Male; Methylhydrazines; Myocardial Contraction; Oxidation-Reduction; Palmitates; Phosphates; Rats; Rats, Sprague-Dawley

To characterize KC 12291 (1-(5-phenyl-1,2, 4-thiadiazol-3-yl-oxypropyl)-3-[N-methyl-N-[2-(3,4-dimethoxy phenyl) ethyl] amino] propane hydrochloride), a newly synthezised inhibitor of voltage-gated Na+ channels, the effects of the agent on Na+ current and ischemia-induced Na+ overload were investigated in isolated cardiomyocytes, atria and saline-perfused hearts. As measured by the patch clamp technique, KC 12291 (1 microM) significantly reduced peak Na+ current after activation of voltage-gated Na+ channels in rat cardiomyocytes. Partial depolarization enhanced the inhibitory effects during steady state conditions of the channel. In isolated guinea pig atria, 1 microM KC 12291 had no effect on contractility under basal conditions but effectively delayed the onset and reduced the extent of anoxic contracture. The concentration-response curve was clearly shifted to the left when atria were partially depolarized by increased extracellular K+. As measured by 23Na NMR spectroscopy in isolated perfused guinea pig hearts, intracellular Na+ rose more than four-fold in a linear fashion during 60 min of low-flow ischemia. KC 12291 (1 microM) prevented Na+ overload within the initial 12 min of ischemia; thereafter the slope of Na+ accumulation was identical to controls. Electrical excitability of hearts, evaluated by intracardial ECG, completely ceased within 15 min after the onset of ischemia. KC 12291 (1 microM) accelerated this process by more than 6 min. The data provide first evidence that KC 12291 reduces Na+ influx through voltage-gated Na+ channels during ischemia and thus delays Na+ overload by enhancing the inexcitability of the heart.

Topics: Animals; Cardiovascular Agents; Electric Stimulation; Electrocardiography; Female; Guinea Pigs; Heart; Heart Atria; Heart Ventricles; Hypoxia; In Vitro Techniques; Ion Channel Gating; Male; Membrane Potentials; Myocardial Contraction; Myocardial Ischemia; Myocardium; Oxygen; Patch-Clamp Techniques; Perfusion; Rats; Rats, Wistar; Sodium; Sodium Channels; Thiadiazoles

Angiopeptin is an analog of somatostatin-14, which has been found to inhibit cellular proliferation in several models of systemic vascular injury. As proliferation plays a major role in pulmonary hypertension, we examined the hypothesis that angiopeptin would inhibit the development of chronic hypoxic pulmonary hypertension in the rat. Angiopeptin was infused intravenously (90-100 microg/kg/day) by minipumps in 10 rats during a 3-week exposure to hypobaric hypoxia and in six normoxic rats. Normal saline was infused in six hypoxic control rats and in seven normoxic control rats. Angiopeptin produced no significant difference in mean pulmonary arterial pressure and resistance, right ventricular weight, or medial thickness of small pulmonary vessels. Vasoconstrictor responses of isolated lungs to acute hypoxia were not affected by angiopeptin. We conclude that angiopeptin, at the high intravenous dose used, does not significantly reduce the development of chronic hypoxic pulmonary hypertension in rats.

Topics: Animals; Cardiovascular Agents; Chronic Disease; Heart Ventricles; Hematologic Tests; Hemodynamics; Hypertension, Pulmonary; Hypoxia; Lung; Male; Oligopeptides; Organ Size; Peptides, Cyclic; Perfusion; Pulmonary Circulation; Rats; Rats, Sprague-Dawley; Somatostatin

Repetitive episodic (18-24 s twice per minute) hypocapnic hypoxia (HH) administered chronically (7 h/day, 35 days) to Sprague-Dawley or Wistar-Kyoto rats results in a sustained increase in daytime blood pressure (BP). We examined acute and chronic BP response to episodic HH and eucapnic hypoxia (EH) in borderline hypertensive rats [first generation (F1) cross between spontaneously hypertensive and Wistar-Kyoto rats]. We hypothesized that episodic HH and EH would create a greater increase in acute and chronic BP in this breed of rat than in previously studied strains. We also examined neural mechanisms by which BP changes from hypoxia are induced. BP and heart rate were examined acutely in nine F1 rats during baseline, HH, EH, EH with prazosin, and EH with prazosin and atropine. Five groups of male F1 rats were studied after 35-day exposure to the following: Unhandled (n = 8): no treatment; Sham (n = 10): episodic compressed air; HH (n = 14): daily episodic hypoxia (2.7%); EH1 (n = 12); hypoxia 2.9%, CO2 8.4%; and EH2 (n = 11): hypoxia 2.8% and CO2 10.5%. Under acute conditions, HH caused a 34.2-mmHg and EH a 77.9-mmHg increase in mean BP. Prazosin partially blocked the increase in BP. Under chronic conditions, HH caused a 10.3-mmHg increase in daytime mean BP, whereas EH caused a fall in mean BP of 16.6 and 9.3 mmHg in the two separately studied groups. In the F1 rat, acute EH causes an elevation of BP but chronic EH causes a fall in BP. The acute response to EH is not predictive of what occurs after chronic exposure in the hypertension-prone F-1 rat.

Topics: Animals; Antihypertensive Agents; Arousal; Atropine; Blood Pressure; Cardiovascular Agents; Heart Rate; Hypertension; Hypocapnia; Hypoxia; Male; Prazosin; Rats; Rats, Inbred WKY; Rats, Sprague-Dawley; Stress, Psychological

The present study was undertaken to elucidate the effects of sodium tanshinone VI 1-phenolate (1), 1'-O-hydrogen succinyltanshinone VI 1-O-hydrogen succinate (2), and disodium 1'-O-succinyltanshinone VI 1-O-succinate (3), water-soluble derivatives of tanshinone VI, on post-hypoxic contractile recovery of isolated perfused rat hearts. The effects were compared with those of tanshinone VI as tested previously. The hearts were perfused for 20 min under hypoxic conditions, followed by 45 min reoxygenation, and their cardiac performance was determined. Changes in tissue sodium, potassium, calcium, and magnesium contents after reoxygenation, and release of creatine kinase and purines and bases (ATP metabolites) during hypoxia/reoxygenation were also examined. The derivatives were dissolved in a Krebs-Henseleit buffer and administered at concentrations of 42 nM into the buffer. Hypoxia/reoxygenation resulted in slight recovery of cardiac contractile force, significant alterations in tissue ion concentrations, and pronounced release of creatine kinase and ATP metabolites, suggesting hypoxia/reoxygenation-induced functional and morphological damage. The tanshinone VI derivatives improved post-hypoxic contractile recovery, which was associated with restoration of tissue ionic concentrations, and diminishment of the release of creatine kinase and ATP metabolites from the hypoxic/reoxygenated hearts. The efficacy of these compounds was similar to that of tanshinone VI. The results suggest that water-soluble tanshinone VI derivatives, like tanshinone VI itself, are beneficial for hypoxia/reoxygenation injury.

Topics: Adenosine Triphosphate; Animals; Cardiovascular Agents; Creatine Kinase; Drugs, Chinese Herbal; Heart; Hypoxia; In Vitro Techniques; Male; Myocardial Contraction; Myocardium; Phenanthrenes; Rats; Rats, Wistar

The method of the study of medical agent influence and biological active substances on duration of small laboratory animals swimming has been worked out excluding the air. For this purpose the animals were placed into altitude chamber, filled with water by 1/3 (one-third) of its volume being in antiorthostatic position on dipping into water. It has been established that at the altitude of 4000 (four thousand) meters high the rat swimming duration became shorter in comparison with their work under normal pressure in 2.5-4 times. Bemitil stimulating work in hypobaric hypoxia depresses it sharply. Bemitil stimulating influence on the rat efficiency did not appear with rising. Antioxidant substance ionol increased efficiency in normal conditions and in hypoxia AKS-85 adaptogenic compound increased swimming in the height duration to a greater degree, mildronat substance for efficiency restoration produced actoprotective influence.

Topics: Amphetamine; Animals; Antioxidants; Atmosphere Exposure Chambers; Atmospheric Pressure; Benzimidazoles; Butylated Hydroxytoluene; Cardiovascular Agents; Hypoxia; Methylhydrazines; Mice; Physical Endurance; Posture; Swimming

The present study was undertaken to elucidate the possible effects of tanshinone VI, one of the extracts from the root of Salvia, on post-hypoxic recovery of cardiac contractile force. For this purpose, rat hearts were perfused for 45 min under reoxygenated conditions following 20-min hypoxic perfusion, and changes in tissue high-energy phosphates and calcium contents, and release of ATP metabolites and creatine kinase were examined. Post-hypoxic recovery of cardiac contractile force was augmented when hearts were treated with 42 nM tanshinone VI during hypoxia. This beneficial recovery was accompanied by enhanced restoration of myocardial high-energy phosphates, depression of hypoxia- and reoxygenation-induced increase in tissue calcium content, and suppression of release of ATP metabolites such as adenosine, inosine and hypoxanthine from the perfused heart. The results suggest that tanshinone VI is beneficial for the recovery of cardiac contractility after a certain period of oxygen-deficiency, possibly through mechanisms involving improvement of myocardial energy production upon oxygen-replenishment and/or inhibition of calcium accumulation in the cardiac cell.

Topics: Abietanes; Adenosine Triphosphate; Animals; Calcium; Cardiovascular Agents; Creatine Kinase; Hypoxia; Male; Myocardial Contraction; Myocardial Reperfusion; Phenanthrenes; Phosphates; Rats; Rats, Inbred Strains

Vasodilator therapy in pulmonary hypertension is limited by the lack of an agent selective for the pulmonary circulation. The effects of intravenous prostacyclin and two stable prostaglandin analogs, ZK 36-374 and CL 115,347, were assessed on the preconstricted pulmonary vasculature of the anesthetized dog. During hypoxic vasoconstriction ZK 36-374 (0.4 micrograms/kg per min) markedly reduced pulmonary artery pressure (26 +/- 3 to 13 +/- 1 mm Hg) (p less than 0.05) and pulmonary vascular resistance (6.2 +/- 1.1 to 2.8 +/- 0.2 mm Hg/liter per min) (p less than 0.01). There was no significant effect on cardiac output, aortic pressure or arterial blood gases. Pulmonary vasoconstriction induced by prostaglandin F2 alpha was similarly affected by ZK 36-374, and in this instance the aortic pressure was also reduced (158 +/- 11 to 129 +/- 11 mm Hg) (p less than 0.01). ZK 36-374 (0.2 micrograms/kg per min) was more effective in lowering hypoxic pulmonary vascular resistance (from 6.5 +/- 0.6 to 3.0 +/- 0.3 mm Hg/liter per min) than was prostacyclin (0.75 micrograms/kg per min) (from 6.3 +/- 0.6 to 4.2 +/- 0.4 mm Hg/liter per min) (p less than 0.05) and resulted in a smaller fall in aortic pressure (p less than 0.05). CL 115,347 (1.0 micrograms/kg per min) had no effect on the pulmonary vasculature during normoxia or when preconstricted by prostaglandin F2 alpha or hypoxia, but reduced aortic pressure and total systemic resistance (p less than 0.05). It appears to be a selective systemic vasodilator with no pulmonary vascular activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cardiovascular Agents; Dinoprost; Dogs; Drug Evaluation, Preclinical; Epoprostenol; Female; Hypertension, Pulmonary; Hypoxia; Iloprost; Male; Prostaglandins F; Pulmonary Circulation; Vascular Resistance

Topics: Animals; Benzoquinones; Cardiovascular Agents; Citric Acid Cycle; Coronary Circulation; Coronary Disease; Electron Transport; Hypoxia; Malates; Mice; Myocardium; Quinones; Rats; Succinates; Ubiquinone

Topics: Cardiovascular Agents; Coronary Vessels; Dipyridamole; Hypoxia; Vasodilator Agents

Topics: Cardiovascular Agents; Coronary Artery Disease; Electrocardiography; Ergot Alkaloids; Humans; Hypoxia; Sclerosis