Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042510 (ventricular fibrillation)
 10,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies in cats suggest alpha-adrenergic contributions to arrhythmias during myocardial ischemia and reperfusion. The validity of this concept in other species, however, remains uncertain. Thus, 106 chloralose-anesthetized open-chest dogs undergoing a 25 min coronary artery occlusion followed by reperfusion received saline (n = 52), prazosin (1 mg/kg, n = 26), phentolamine (5 mg/kg, n = 18), or phentolamine (same dose) + propranolol (1 mg/kg, n = 10). Alpha-blockade was confirmed by alpha-agonist dose-response studies. In phentolamine-treated dogs, arterial pressure and heart rate were kept constant to prevent exacerbation of ischemia. Control and treated groups were comparable with respect to variables known to affect arrhythmias, such as size of occluded and reperfused vascular beds, coronary collateral flow, severity of ischemia estimated from intramyocardial CO2 tension, and peak reactive hyperemia. During coronary occlusion, the number of single premature ventricular complexes was reduced by phentolamine (P less than 0.01), but not by prazosin or phentolamine + propranolol; no treatment affected the total number of couplets, ventricular tachycardia episodes and ventricular ectopic complexes, or the incidence of ventricular tachycardia and ventricular fibrillation. During coronary reperfusion, arrhythmias did not differ in control and treated groups. Thus, selective alpha 1-(prazosin), nonselective alpha 1- and alpha 2-(phentolamine), and combined alpha- and beta-blockade (phentolamine + propranolol) failed to attenuate complex arrhythmias induced by acute myocardial ischemia and reperfusion. Alpha-adrenergic mechanisms appear unimportant in the genesis of these arrhythmias in the canine model.
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PMID:Effect of alpha-adrenergic blockade on arrhythmias induced by acute myocardial ischemia and reperfusion in the dog. 615 73

Recent experimental and clinical data have stimulated interest in the use of alpha-adrenergic antagonists in acute myocardial infarction. We evaluated nicergoline, a new relatively selective alpha 1-antagonist which uniquely lowers heart rate. Open-chest dogs, randomized to control (n = 25) or intravenously treated group (n = 20; 0.5 mg/kg bolus, then 0.10 to 0.15 mg/kg/min), underwent coronary artery occlusion (CAO) followed after 25 minutes by coronary artery reperfusion (CAR). Nicergoline decreased heart rate by 47 +/- 5 bpm and mean aortic pressure by 39 +/- 4 mm Hg. Following CAO, nicergoline reduced total coronary collateral resistance (radiolabeled microspheres; 698 +/- 75 vs 2167 +/- 530 mm Hg/ml/min/gm, p less than 0.05), increased the ischemic zone/nonischemic zone flow ratio (0.14 +/- 0.04 vs 0.06 +/- 0.02, p less than 0.05), and reduced the rise in intramyocardial CO2 tension in the ischemic zone (mass spectrometry, p less than 0.001). Furthermore, the drug decreased the rate of ventricular tachycardia (VT; 191 +/- 13 vs 243 +/- 3 bpm, p less than 0.001) and the incidence of ventricular fibrillation (VF; 1 of 20 [5%] vs 7 of 25 [28%], p less than 0.05). Following CAR, nicergoline did not significantly reduce the incidence of VF but did lower rate (154 +/- 8 vs 212 +/- 10 bpm, p less than 0.001) and incidence (p less than 0.05) of VT. Thus nicergoline reduced severity of ischemia and afforded protection against arrhythmias induced by myocardial ischemia and reperfusion. The observed reduction in heart rate may have contributed importantly to these beneficial effects. Clinical investigation of this potentially useful vasodilator seems warranted.
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PMID:Beneficial effects of the alpha-adrenergic antagonist nicergoline during acute myocardial ischemia and reperfusion in the dog. 641 40

To evaluate the role of left ventricular distention in the pathophysiology of myocardial injury during cardiac surgery, 40 isolated, perfused feline hearts were subjected to 1 hour of either hypothermic potassium arrest (groups 1, 2 and 3) or 1 hour of hypothermic ventricular fibrilation (groups 4 and 5). During this period, intracavitary left ventricular pressure was maintained at 0 mm Hg in groups 1 and 4, at 30 mm Hg in groups 2 and 5 and 45 mm Hg in group 3. After either reperfusion of defibrillation, myocardial gas tensions, left ventricular function, coronary blood flow, the ration of endocardial to epicardial blood flow, and myocardial water content were measured to evaluate the degree of myocardial injury incurred. In addition, structural changes in the myocardium were assessed using light and electron microscopy. No differences in these parameters were seen in hearts that underwent ischemic arrest, regardless of the presence or absence of significant left ventricular distention. In fibrillating hearts, however, dilatation decreased ventricular performance, impaired subendocaridal blood flow and elevated myocardial CO2 tensions. These results suggest that left ventricular distention per se is not harmful during periods of ischemia. During periods of ventricular fibrillation, howevr, distention produces impaired subendocardial blood flow, resulting increased ischemia and decreased recovery of ventricular performance.
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PMID:Comparison of the effects of left ventricular distention during cardioplegic-induced ischemic arrest and ventricular fibrillation. 677 38

We provided total cardiopulmonary support for 1-18 hours in unanesthetized tethered lambs by peripheral vascular cannulation, using a roller pump and the spiral membrane lung. Respirations were allowed to remain spontaneous and unaided. A Swan-Ganz catheter was placed for retrograde pulmonary artery blood flow sampling. Within a few minutes following induced ventricular fibrillation the PCO2 of sampled blood flowing retrograde through the lungs fell below 10 mm Hg, the PO2 rose to near 150 mm Hg, the pH rose to above 7.8, and the glucose level fell to less than 20 mg %. All of these values later gradually shifted, approaching mixed venous blood values within minutes. After 1-18 hrs of perfusion the animals went into shock and were sacrificed. At autopsy, the lungs of animals breathing room air were beefy and hemorrhagic. In lambs that were "breathing" CO2 enriched air the retrograde pulmonary artery blood pH and PCO2 was usually maintained close to the mixed venous blood values. The observed pulmonary changes were considerably less abnormal, and the microscopic abnormalities were at times nonexistent. We believe the integrity of pulmonary blood flow is vital to the survival of the lungs as a functioning organ. Cessation of total forward pulmonary blood flow (unlike partial cardiopulmonary bypass), combined with spontaneous pulmonary ventilation, rapidly leads to massive, pulmonary infarctions, shock, and death.
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PMID:Massive pulmonary infarction during total cardiopulmonary bypass in unanesthetized spontaneously breathing lambs. 679 84

The process of CO2 euthanasia on mouse, rat, guinea pig and rabbit was observed using a CO2 euthanasia cabinet. The cabinet was filled with CO2 gas and the caged animal was placed into the cabinet. These animals quietly collapsed and their respiratory movement ceased within 25--225 seconds. A-V block was the first arrhythmia recognized on ECG in all cases. The arrhythmia recorded on ECG included complete A-V block, A-V dissociation, ventricular escape rhythm, atrial fibrillation, ventricular flutter and ventricular fibrillation. It could be concluded that euthanasia was satisfactorily performed on these species by means of the CO2 euthanasia cabinet.
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PMID:[Use of CO2 euthanasia cabinet for experimental animals (author's transl)]. 679 31

The halothane-diethyl ether azeotrope was evaluated in dogs as the anesthetic agent for deep surface hypothermia with total circulatory arrest for open-heart operation. All 10 animals given azeotrope in 100% oxygen (O2) experienced atrial arrhythmias during cooling, and 1 had ventricular fibrillation prior to the completion of cooling at 18 degrees to 20 degrees C. After only 30 minutes' arrest, 8 of the 10 dogs had postoperative motor disturbances. Administering the azeotrope in 95% O2 and 5% carbon dioxide (CO2) yielded markedly improved results characterized by a rapid, smooth cooling course, easy resuscitation following circulatory arrest, and rapid rewarming, and 3 out of 10 dogs experienced mild motor disturbance after 60 minutes of circulatory arrest. This method, when compared with our standard method of ether in 100% O2, resulted in reduced blood lactates and a striking improvement in clinical status on the first postoperative morning. In limited clinical trials, infants undergoing repair of congenital cardiac defects have done well and responded as expected based on the laboratory experience. Since the results with the azeotrope in 95% O2 and 5% CO2 were at least as good as, and in several instances better than, those with the standard method employing either, the nonexplosive characteristic of the azeotrope warrants continued evaluation of this agent.
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PMID:Improved anesthesia for deep surface-induced hypothermia: the halothane-diethyl ether azeotrope. 735 62

During the global myocardial ischemia of cardiac arrest and during regional myocardial ischemia due to local impairment of coronary blood flow, intramyocardial carbon dioxide tensions (Pmco2) of ischemic myocardium increase to levels exceeding 400 Torr. The mechanism of such myocardial hypercarbic acidosis is as yet incompletely understood, specifically whether these increases in Pmco2 are due to increased oxidative metabolism, decreased CO2 removal, or buffering of metabolic acids. We therefore measured Pmco2 and the total CO2 content of rat hearts harvested before, during, and after resuscitation from cardiac arrest. Pmco2 significantly increased from an average of 63 to 209 Torr during a 4-min interval of untreated ventricular fibrillation. This was associated with concurrent decreases in intracellular pH from an average of 7.03 to 6.02 units. The total CO2 content of the myocardium simultaneously decreased from 17.0 to 16.5 mmol/kg. Accordingly, increases in Pmco2 and [H+] were observed in the absence of increases in the total CO2 content and therefore the calculated myocardial bicarbonate. These observations in the rat model implicate buffering of metabolic acids by bicarbonate rather than increases in CO2 production or decreases in CO2 removal as the predominant mechanism accounting for myocardial hypercarbia.
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PMID:Mechanisms of myocardial hypercarbic acidosis during cardiac arrest. 761 73

We investigated the effects of the ATP-dependent K+ channel antagonist glyburide and the ATP-dependent K+ channel agonist pinacidil in a Langendorff-perfused rabbit isolated heart subjected to a period of global hypoxia. A class III antiarrhythmic drug, E-4031, also was studied in this model. These studies aimed to define the mechanism of action of putative profibrillatory actions of pinacidil and the mechanism for the antifibrillatory effect of the class III antiarrhythmic drug, E-4031, in the hypoxic heart. After stabilization and determination of baseline functional parameters under normoxic perfusion conditions (95% O2/5% CO2), hearts were subjected to global hypoxia by switching to a 95% N2/5% CO2 saturated perfusion medium for a period of 12 min. After the hypoxic period, normoxia was re-established by switching to the oxygen-carbon dioxide saturated buffer medium for a period of 40 min. The oxygen tension of the perfusion buffer was reduced from approximately 400 mm Hg to below 50 mm Hg during the hypoxic period. All hearts subjected to hypoxia had reduced function: the left ventricular developed pressure and +/- dP/dt were reduced significantly. Myocardial tissue ATP concentrations were reduced (> 50%) in hearts subjected to hypoxia. Under conditions of hypoxic/reoxygenation and in the presence of a low (2.5 mM) potassium concentration ([K+]0), pinacidil (1.25 microM) facilitated the induction of ventricular fibrillation (80% fibrillation in the presence of pinacidil vs. 20% in the absence of pinacidil). Glyburide (10 microM) and E-4031 (1 and 10 microM) significantly reduced the incidence of ventricular fibrillation associated with pinacidil (20% fibrillation in the presence of hypoxia, pinacidil, and glyburide or 10 microM E-4031). Opening of the ATP-dependent K+ channel by pinacidil under normoxia and low K+ also facilitated the induction of ventricular fibrillation (60% ventricular fibrillation). Pinacidil failed to induce ventricular fibrillation under either normoxic or conditions of hypoxic/reoxygenation when the [K+]0 was increased to 5.1 mM. The results of this study demonstrate that K+ channel activators facilitate the induction of ventricular fibrillation under both normoxic conditions and conditions of hypoxic/reoxygenation when the perfusion buffer K+ concentration is reduced.
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PMID:Actions of pinacidil at a reduced potassium concentration: a direct cardiac effect possibly involving the ATP-dependent potassium channel. 767 50

We wished to examine selected class I antiarrhythmic agents for their potential to exhibit proarrhythmic or antifibrillatory actions. Quinidine, lidocaine, aprindine, and flecainide were evaluated in an experimental model that made use of rabbit isolated perfused heart. Hearts were stabilized with oxygenated buffer (95% O2/5% CO2) with or without pinacidil (1.25 microM) and then were subjected to hypoxia (95% N2/5% CO2) for 12 min, followed by 40-min normoxic perfusion (95% O2/5% CO2). Test drugs were added to the perfusion medium 5 min before hypoxia was induced. Prevention of spontaneous ventricular fibrillation (VF) was determined. To characterize the electrophysiologic effects of the selected antiarrhythmic agents, we determined the changes in threshold current and effective refractory period (ERP) before and after drug treatment. Addition of the potassium channel agonist, pinacidil, to the perfusion medium invariably resulted in VF during the hypoxic interval or shortly after reoxygenation. Pretreatment of the heart with glibenclamide prevented pinacidil-induced VF. Quinidine, aprindine, lidocaine, and flecainide each were studied at a single concentration. The respective drug concentrations were selected to produce comparable changes in ventricular refractory period. Of the class I agents selected for study, only quinidine prolonged the ventricular ERP and provided significant protection against pinacidil-induced VF. In contrast, aprindine and lidocaine decreased ventricular ERP and did not prevent VF induced by the combination of pinacidil and hypoxia. Quinidine, aprindine, and lidocaine did not exhibit proarrhythmic effects in the presence of hypoxia when pinacidil was not added to the perfusion medium. Flecainide, when added to the perfusion medium without pinacidil elicited proarrhythmic activity leading to VF when the hearts were made hypoxic. Flecainide-induced VF was antagonized by glibenclamide. The data suggest that VF can be provoked by the potassium channel agonist pinacidil or by flecainide under conditions that reduce intracellular ATP concentration. Glibenclamide, a selective antagonist of the KATP channel prevented the profibrillatory actions of pinacidil and flecainide. Quinidine, but not lidocaine and aprindine, prevented VF induced by pinacidil and hypoxia.
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PMID:Antifibrillatory and profibrillatory actions of selected class I antiarrhythmic agents. 768 39

Using 14 mongrel dogs, we investigated the correlation between arteriovenous differences of PCO2 (AVD-CO2) and cardiac output (CO) during CPR. Ventricular fibrillation was induced by an electrical current and the respirator was stopped for 5 min. Cardiopulmonary resuscitation (CPR) was performed during the next 10 min and CO was measured with simultaneous arterial and venous blood gas analysis. CO was measured 26 times during CPR. The animals were divided into two groups according to the values of CO during CPR: low-CO group (CO < 0.3 l/min) and high-CO group (CO > or = 0.3 l/min). AVD-CO2 in the low CO group was 39.8 +/- 5.7 mmHg and that of the high group was 27.4 +/- 14.8 mmHg (mean +/- S.D., P < 0.05). In conclusion, AVD-CO2 showed an inverse result with the degree of CO during CPR.
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PMID:Arteriovenous differences in PCO2 and cardiac output during CPR in the dog. 807 59


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