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)

This study examines the arrhythmogenic action of alpha 1 and alpha 2-adrenoceptor stimulation in the isolated perfused rat heart. The alpha 1-agonist methoxamine in the presence of the beta 1-antagonist atenolol 10(-6) M decreased the ventricular fibrillation threshold in the normoxic rat ventricular myocardium: VFT values (mA): Control 11.2 +/- 0.5; methoxamine 10(-6) M 4.9 +/- 0.9 (P less than 0.01 vs control); methoxamine 10(-5) M 3.5 +/- 0.5 (P less than 0.01 vs control). The alpha 1-antagonist prazosin 10(-8) M prevented the methoxamine-induced fall in ventricular fibrillation threshold. The alpha 2-agonist BHT 933 (azepexole) in the presence of atenolol 10(-6) M produced no alteration in the ventricular fibrillation threshold. Methoxamine 10(-6) M to 10(-5) M had a positive inotropic effect with increased left ventricular pressure development, myocardial oxygen consumption and QT-interval; however, tissue levels of cyclic AMP remained unchanged. Methoxamine 10(-6) M did not alter heart rate, coronary flow rate or deplete tissue levels of adenosine triphosphate, phosphocreatine or glycogen. The enhanced vulnerability to ventricular fibrillation induced by methoxamine could be demonstrated only at supraphysiological extracellular calcium concentrations (2.5 mM) but not at physiological calcium concentrations (1.25 mM). The arrhythmogenic and inotropic effect of methoxamine 10(-6) M was prevented by inhibition of transsarcolemmal Ca2+ ion influx by nisoldipine 10(-8) M or by inhibition of release of Ca2+ from sarcoplasmic reticulum by ryanodine 10(-9) M to 10(-8) M. Thus in isolated normoxic rat heart preparations, activity of the alpha 1-receptor appears to mediate ventricular arrhythmogenesis but only in the setting of myocardial calcium overload. The arrhythmogenic effect of alpha 1-stimulation may be due to increased transsarcolemmal calcium influx and enhanced release of calcium from the sarcoplasmic reticulum; increased myocardial oxygen consumption secondary to greater left ventricular pressure development may contribute in part.
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PMID:Arrhythmogenic action of alpha 1-adrenoceptor stimulation in normoxic rat ventricular myocardium: influence of nisoldipine, reduced extracellular Ca2+ and ryanodine. 289 42

Absence of a Major Arrhythmogenic Role for Cyclic AMP. Journal of Molecular and Cellular Cardiology (1986) 18, 375-387. We examined the mechanism whereby beta-adrenoceptor antagonism exerts an antiarrhythmic effect in early myocardial ischaemia. Ligation of the anterior descending coronary artery in the anaesthetized open-chest pig resulted in severe transmural anteroseptal ischaemia. Blood flow in the mid-ischaemic zone 20 min after ligation was decreased to 5.7 +/- 0.7% of the preligation control value. Epicardial ST-segment deflections of 6.7 +/- 0.4 mV were recorded over this zone. A distinct phase of ventricular arrhythmias was evident about 10 to 30 min after ligation. A high incidence of ventricular fibrillation (14/16 pigs) was associated with a circumstantial increase in levels of cyclic AMP in ischaemic tissue. Twenty minute values were: 1.10 +/- 0.06, P less than 0.05 v. the non-ischaemic tissue level of 0.86 +/- 0.05 nmol/g. Propranolol 3 mg/kg IV, metoprolol 20 mg/kg IV or sotalol 10 mg/kg IV were given between 30 min prior to and 10 min after ligation. Adequate beta-adrenoceptor antagonism by each agent could be proven. Metoprolol decreased the incidence of ventricular fibrillation (2/13, P less than 0.0005 v. control group), while propranolol or sotalol did not. All three beta-antagonists decreased tissue levels of cyclic AMP prior to ligation. However, the temporary increase in ischaemic tissue after ligation could not be prevented. Furthermore, cyclic AMP in ischaemic tissue 20 min after ligation was higher in the metoprolol group than in the propranolol or sotalol group (0.94 +/- 0.04 v. 0.81 +/- 0.02 P less than 0.05, and 0.79 +/- 0.03 nmol/g P less than 0.01, respectively). Blood flow in the mid-ischaemic zone of the metoprolol group was increased to 8.6 +/- 0.6% of preligation control value (P less than 0.0001 v. control group). In contrast, blood flow in the mid-ischaemic zone of the propranolol or sotalol group was decreased. Metoprolol also reduced epicardial ST-segment deflections over the mid-ischaemic zone to 3.5 +/- 0.2 mV (P less than 0.0001 v. control group). ST-segment deflections in the propranolol group were increased. The mechanism whereby metoprolol prevented ventricular fibrillation may be explained by a decrease in the severity of ischaemia but not in terms of changes of tissue levels of cyclic AMP.
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PMID:Prevention of ventricular fibrillation by metoprolol in a pig model of acute myocardial ischaemia: absence of a major arrhythmogenic role for cyclic AMP. 301 99

The isolated perfused rat heart was used to assess the influence of extracellular potassium ([K+]0) on vulnerability of the heart to ventricular fibrillation (VF). The VF threshold is reduced when [K+]0 is lowered from 5.9 to 2.0 and 3.0 mmol/l. The vulnerable period is not only widened but VF can be obtained by stimuli on the R wave. The opposite effects are encountered when [K+]0 is increased to 9.0 mmol/l. These alterations in vulnerability to VF are accompanied by an increased incidence of tachyarrhythmias and spontaneous VF during coronary artery ligation and following reperfusion on reduction of [K+]0, with elimination of these arrhythmias on increasing [K+]0 to 9.0 mmol/l. The cellular biochemical responses that accompanied the altered electrical behaviour on alterations of [K+]0 involved the tissue levels of cyclic AMP in both non-ischaemic and ischaemic myocardium and tissue levels of Ca2+ whereas tissue levels of high energy phosphates, adenosine, inosine, hypoxanthine, lactate, Na+, K+ and Mg2+ did not discriminate between hearts vulnerable and hearts resistant to VF. In this model the extracellular K+ level is a determinant of vulnerability to ventricular fibrillation while ischaemic tissue levels of Ca2+ provide the best correlation with alterations in vulnerability.
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PMID:Permissive action of potassium on arrhythmogenesis in the rat heart. 302 46

OPC-8212, a positive inotropic agent that increases intracellular cyclic AMP and stimulates the Ca current, was compared with amrinone and AR-L 115 in their effects on canine ventricular arrhythmias. OPC-8212, up to 3 mg kg-1, did not worsen 24 h coronary ligation arrhythmias, while it aggravated ventricular arrhythmias seen 48 h after coronary ligation. However, OPC-8212 did not at any time induce ventricular fibrillation in dogs subjected to coronary ligation. OPC-8212, up to 3 mg kg-1, had no arrhythmogenic or antiarrhythmic effect on digitalis-induced arrhythmias, while amrinone and AR-L 115 showed antiarrhythmic effects. With adrenaline-induced arrhythmias, the three drugs aggravated ventricular tachycardia to produce ventricular fibrillation. The absence of a worsening effect of the new positive inotropic agents on digitalis arrhythmia may be helpful in clinical setting of combined therapy of these new drugs with digitalis.
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PMID:Effects of OPC-8212, a new positive inotropic agent, on canine ventricular arrhythmias. 374 63

Early experiments with the calcium antagonist verapamil showed that it could inhibit the transsarcolemmal influx of calcium ions induced by isoproterenol in ventricular myocardium without inhibiting the effect of beta stimulation to increase tissue cyclic AMP. Current views of the effects of the beta-receptor-adenylate cyclase-cyclic AMP system of the calcium channel suggest that both calcium antagonists and beta-adrenoceptor antagonists should inhibit transsarcolemmal calcium influx if calcium is the third messenger of beta-agonist catecholamines. When high concentrations of circulating catecholamines are added to normal isolated hearts, two of the effects include increased vulnerability to ventricular fibrillation and high rates of enzyme release. These effects are antagonized by beta-adrenoceptor inhibitors and by calcium antagonists, which suggests a classical second (cyclic AMP) and third (calcium) messenger effect. In the presence of coronary artery ligation, the ventricular fibrillation threshold falls and enzyme release is enhanced. Both effects are associated with an increased tissue cyclic AMP level in the ischemic zone and are susceptible to calcium antagonist procedures. Neither effect can be fully stopped by beta-adrenoceptor antagonism. Therefore the evidence from this model with coronary artery ligation favors the views that 1) cyclic AMP accumulates in ischemic tissue by a process not fully susceptible to inhibition by beta-adrenoceptor antagonists; and 2) calcium ions are associated with the development of ventricular fibrillation and enzyme release by a process susceptible to inhibition by calcium antagonist agents such as verapamil, nifedipine, and diltiazem.
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PMID:Calcium antagonists, ventricular fibrillation, and enzyme release in ischemic rat hearts. 613 39

To clarify the relationship between the concentrations of norepinephrine (NE) and cyclic AMP (c-AMP) in the myocardium and the incidence of ventricular fibrillation (VF), we studied 48 dogs in which VF was induced by the ligation of the left anterior descending coronary artery. The animals were divided into two groups of equal size: The first received no drugs, the second received d,l-propranolol (0.5 mg/kg) 15 min before coronary ligation. Myocardial samples were taken at regular intervals from normal and ischemic areas to determine NE and c-AMP concentrations. In the untreated group, no significant change in the concentrations of NE and c-AMP was observed in 12 dogs that did not develop VF. In the other 12 dogs that developed VF, there was a significant increase in c-AMP in the ischemic area immediately after the onset of the dysrhythmia. A significant increase in NE concentration both in normal and ischemic myocardium was observed in only 8 of these latter 12 dogs. Premedication with propranolol significantly reduced the incidence of VF, but it still occurred in 5 out of 24 dogs. Increase in c-AMP without an increase in NE in ischemic area was observed in these five dogs. These results suggest that c-AMP may play a role in the development of VF during acute ischemia.
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PMID:Myocardial concentration of norepinephrine and cyclic AMP in ventricular fibrillation during acute myocardial ischemia. 618 66

The cause of death in patients who die suddenly or after an acute myocardial infarction is, in most cases, ventricular fibrillation. Most of these patients suffer from ischemic heart disease and atherosclerotic narrowing of the coronary arteries. Ischemic changes include hypoxia, accumulation of metabolites, depletion of energy-yielding substrates, ionic shifts and structural changes. There is an increased sympathetic activity and often a higher vagal tone. Recent observations support the idea that there is an elevated regional adrenergic activity in the ischemic area with increased tissue levels of cyclic AMP. This seems to be one of several important factors contributing to the occurrence of ventricular fibrillation. Increased sympathetic activity might mediate reentry mechanisms as well as enhanced automaticity.
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PMID:Myocardial metabolic changes related to ventricular fibrillation. 624 18

The isolated rat heart with ligation of the left coronary artery was used to assess the role of the beta 1- adrenergic receptor-cyclic AMP mechanism in the genesis of vulnerability to ventricular fibrillation in early myocardial ischaemia. Coronary artery ligation was followed after 3 min by a reduction in ventricular fibrillation threshold which reached a minimum at 15 min. This was accompanied by reduction of ATP and phosphocreatine while cyclic AMP was significantly increased in ischaemic myocardium. The dl-, l- and d-isomers of propranolol attenuated the decrease in ventricular fibrillation threshold and the increase in ischaemic myocardial cyclic AMP, without altering the tissue depletion of ATP. Specific beta 1-adrenergic receptor antagonism with atenolol did not prevent either the increase of tissue cyclic AMP or the reduction in ventricular fibrillation threshold and high energy phosphates. These findings suggest that the mechanism whereby vulnerability to fibrillation is increased in very early myocardial ischaemia is linked to changes in cyclic AMP content of ischaemic myocardium and appears independent of depletion of myocardial high energy phosphates.
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PMID:Influence of propranolol isomers and atenolol on myocardial cyclic AMP, high energy phosphates and vulnerability to fibrillation after coronary artery ligation in the isolated rat heart. 627 92

The effect of exercise training on cardiovascular mortality is controversial. The purpose of this study was to determine the effect of a period of treadmill training on the ventricular fibrillation threshold of the isolated rat heart. Trained hearts had higher threshold values during standard, control perfusion conditions, and when exposed to hypoxia, hypoxia plus isoproterenol infusion, or when subjected to coronary artery ligation. Myocardial metabolic studies failed to define the mechanism for the effect of running training. However, in coronary ligated hearts, the content of the arrhythmogenic substance 3',5' cyclic adenosine monophosphate (cyclic AMP) was reduced in the ischemic zone of hearts from trained rats. Cyclic AMP levels were also lower in trained hearts during control perfusions. We conclude that running training increases the resistance of the heart to ventricular fibrillation by mechanisms that are largely unknown, although they may involve cyclic AMP.
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PMID:Physical training increases ventricular fibrillation thresholds of isolated rat hearts during normoxia, hypoxia and regional ischemia. 629 6

In the isolated rat heart, changes in the ventricular fibrillation threshold (VFT) relate to the myocardial cyclic AMP content rather than to the high-energy phosphate content. After coronary ligation the reduction in VFT correlates with the increase in ischemic tissue cyclic AMP. Agents that reduce the myocardial cyclic AMP (propranolol, 16 microM in perfusate, or amiodarone, 42 microM/kg pretreatment) prevent the postligation fall of the VFT without altering high-energy phosphate depletion. Conversely, theophylline (500 microM), which increases cyclic AMP in ischemic myocardium, causes a greater reduction of VFT without increasing high-energy phosphate depletion. Spontaneous ventricular tachycardia and fibrillation are uncommon in coronary ligated hearts in the first 15 min after ligation (10-20%); these arrhythmias are greatly increased either by reducing the perfusate potassium from 5.9 to 3.0 mM or by pretreating hearts with 1-methyl-3-isobutyl xanthine (10 microM), a cyclic-AMP phosphodiesterase inhibitor. Adenosine (100 microM) antagonizes the increased arrhythmogenesis in both low perfusate potassium and cyclic-AMP phosphodiesterase-inhibited hearts, in the latter without reducing the ischemic tissue cyclic AMP levels. The antiarrhythmic action of adenosine in these hearts is independent of reducing tissue cyclic AMP. Adenosine generated in ischemic myocardium may serve as an endogenous antagonist to the arrhythmogenic action of cyclic AMP.
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PMID:Modulation of myocardial cyclic AMP and vulnerability to fibrillation in the rat heart. 630 87


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