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)

To assess the ability of N-acetylcysteine to reduce the vulnerability of the heart to arrhythmias and improve its mechanical function during ischemia and reperfusion, groups of Langendorff-perfused rat hearts (15 per group) were subjected to 20 minutes of aerobic perfusion, 10 minutes of regional ischemia and 10 minutes of reperfusion. The hearts were perfused with N-acetylcysteine throughout the study. The incidences of ventricular premature beats and ventricular tachycardia induced by ischemia fell from 93% and 67%, in the N-acetylcysteine-free control group, to 40% and 27% with 8 microM N-acetylcysteine, to 33% and 27% with 80 microM N-acetylcysteine, and to 40% and 13% with 2000 microM N-acetylcysteine. The incidence of ventricular fibrillation induced by reperfusion was reduced from 93% to 60%, 67% and 47%, respectively. N-acetylcysteine had no significant effect upon the coronary flow and heart rate. When the ischemic period was prolonged to 30 minutes, N-acetylcysteine (8 microM) was shown to delay the time of onset of arrhythmias during ischemia and reperfusion. Thus, the incidences of ventricular premature beats and ventricular tachycardia were greatest after 15 minutes of ischemia in controls but were maximal after 18 minutes in hearts treated with N-acetylcysteine. N-acetylcysteine (8 microM) also improved the recovery of mechanical function after ischemia both in Langendorff preparations and in working preparations. In the working heart the post-ischemic recovery of aortic flow, coronary flow, cardiac output and aortic developed pressure after ischemia was improved from their control values of 30 +/- 5%, 82 +/- 2%, 43 +/- 2% and 63 +/- 4% to 59 +/- 7%, 98 +/- 5%, 71 +/- 3% and 80 +/- 6% respectively. Our results support the concept that agents which can alter redox state may exert protective effects against myocardial injury during both ischemia and reperfusion.
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PMID:The influence of N-acetylcysteine on cardiac function and rhythm disorders during ischemia and reperfusion. 171 1

We examined the effects of tedisamil on ventricular fibrillation (VF) elicited by regional ischemia and by reperfusion in isolated rat hearts (n = 12/group). During 30 min of ischemia, 0.1, 0.55, and 3 microM tedisamil had no influence on the incidence of VF (an index of VF initiation). However, sustained VF (SVF, defined as that lasting greater than 120 s, an index of VF maintenance) was reduced in a concentration-dependent manner from 73 to 54, 17 (p less than 0.05), and 0% (p less than 0.05), respectively. Tedisamil caused sinus bradycardia but this was not the basis for tedisamil's antiarrhythmic activity since SVF was also inhibited in separate groups of hearts that were paced throughout the study. Tedisamil had no effect on reperfusion-induced VF initiation. However, VF maintenance was, again, inhibited, with SVF incidence reduced from 75% to 40, 20, and 0% (p less than 0.05), respectively, by increasing concentrations of tedisamil. A similar effect was, again, observed in paced hearts. The average cycle length of the electrogram during VF correlated with preceding width of the ventricular complex; both of these variables were concentration-dependently increased by tedisamil and mean values of each correlated inversely with the incidence of SVF. The ratio of SVF cycle length to ventricular tachycardia cycle length was 1:3, and this ratio was conserved in the presence and absence of drug. The data are consistent with a drug-induced increase in the probability of spontaneous termination of multiple wave-front re-entry.
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PMID:Influence of tedisamil on the initiation and maintenance of ventricular fibrillation: chemical defibrillation by Ito blockade? 172 Aug 45

The completeness of brain ischemia with a multi-arterial clamping method in dogs was examined using EEG, evoked potentials (EPs) and vessel staining with Evans blue. EEG was monitored by bipolar parietal lead. EPs stimulating electrodes were inserted into the first thoracic (T1) epidural space and recording electrodes into the C2 epidural space, brain stem and cerebral cortex. EPs were measured at 30 s intervals with 50 measurements each time using 3.0 mA current of 100 microseconds duration. In dogs in which brain ischemia was brought about by ventricular fibrillation (VF group, n = 5) EEG disappeared within 40 s in all dogs and the amplitudes of EPs at the C2 spinal cord, brain stem and cerebral cortex after 10 min ischemia were 57%, 0% and 0%, respectively. In the dogs in which a multi-arterial clamping method (clamping internal thoracic arteries, brachiocephalic trunk and left subclavian artery while lowering systolic arterial pressure (AP) below 50 Torr) was used (AC group, n = 5) EEG was still recognizable at 5 min in 2 dogs and the amplitudes of EPs at the C2, brain stem and cerebral cortex at 10 min ischemia were 103%, 53% and 0%, respectively. Stainings with Evans blue were observed in all soft tissue at and below thoracic level, entire intervertebral venous plexus, venous sinuses of cranial dura mater and spinal cord below the lower part of cervical region. Bright red fluorescence by Evans blue was observed microscopically in the vessels of the spinal cord, brain stem and cerebrum (1 dog only). In conclusion a multi-arterial clamping method with arterial hypotension brings about only incomplete brain ischemia.
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PMID:A multi-arterial clamping method with arterial hypotension does not bring about complete brain ischemia in dogs. 172

The protective effect of hypothyroidism against lethal ventricular tachyarrhythmias (VT) in the subacute phase of experimental myocardial infarction (MI) was investigated in 10 thyroidectomized dogs using a conscious model of sudden coronary death. Four weeks after surgical ablation of the thyroid, and having established biochemical hypothyroidism, anterior MI was produced by 120 min of occlusion-reperfusion of the left anterior descending coronary artery. In the subacute phase of MI, the inducibility of VT was investigated using programmed ventricular stimulation (PVS), and the effects on spontaneous development of ventricular fibrillation (VF) were studied by production of posterolateral ischemia at a site remote from the area of the previous infarction. Ischemia was produced by the passage of anodal direct current through a silver wire electrode implanted in the left circumflex coronary (LCX) artery. The results were compared to those from a cohort of 20 existing euthyroid controls that had undergone an identical experimental protocol. No differences were found in heart rate and other electrocardiographic parameters such as the PR, QRS, and QT (paced at 2.5 Hz) and the QTc interval between the hypo- and euthyroid groups. During PVS in the subacute phase of anterior MI, the measured threshold voltage and ventricular refractory periods were similar in both groups. The incidence of inducibility of VT was 100% in the euthyroid animals compared to 60% in the hypothyroid dogs, suggesting an antiarrhythmic effect of hypothyroidism. The incidence of sustained vs. nonsustained VT was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothyroidism renders protection against lethal ventricular arrhythmias in a conscious canine model of sudden death. 172 67

Calcium-channel antagonists are widely used in the treatment of supraventricular tachyarrhythmias. The potential benefits of these agents in the management of ventricular arrhythmias, however, are not widely appreciated. Ventricular arrhythmias result from abnormalities of impulse generation and/or impulse conduction. The calcium ion has been implicated in both mechanisms. Myocardial cytosolic calcium increases during ischemia and sympathetic nervous system activation. Elevations in cytosolic calcium provoke oscillatory depolarizations of the cardiac membrane, triggering sustained action potential generation and extrasystoles. Myocardial ischemia also results in a dispersion of refractory period, producing random re-entrant circuits and ventricular fibrillation. Alterations in action potential duration that produce this dispersion of refractory period are associated with spatial and temporal nonuniformities of intracellular calcium transients. Calcium-channel antagonists have been shown to prevent afterdepolarizations and to reduce the endocardial to epicardial dispersion of the refractory period during myocardial ischemia, and therefore could prevent malignant arrhythmias. A slow inward calcium current may, in fact, be required for the initiation and maintenance of ventricular fibrillation. Calcium antagonists reduce, whereas calcium agonists enhance, the susceptibility to ventricular fibrillation induced by the combination of exercise and acute myocardial ischemia. The cardioprotection occurs independently of actions on vascular smooth muscle. Thus, calcium antagonists that exert direct myocardial actions may prove to be particularly effective in the prevention of sudden cardiac death in patients. The challenge remains to develop calcium antagonists that selectively modulate myocardial calcium entry without compromising cardiac mechanical function.
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PMID:The antiarrhythmic and antifibrillatory effects of calcium antagonists. 172 98

Intracellular overloading by calcium ions may play an important role in the development of ischemic ventricular fibrillation, as shown by experimental data. Mechanisms are those that develop secondary to the rise in cytosolic calcium thought to occur in ischemia. After-depolarizations are stressed as a possible cause of automaticity and triggered arrhythmias in ventricular tissue. The ideal calcium antagonist should be able to inhibit such afterdepolarizations in ischemic tissue without having a negative inotropic effect on nonischemic tissue. Hence, it might be possible to extend the beneficial results of verapamil found in a recent postinfarct trial to show even better postinfarct protection by a calcium antagonist with these specific properties. On the other hand, a highly vascular-selective calcium antagonist, by avoiding any effect on the myocardium, could also be desirable in postinfarct patients with heart failure. Future trials should compare these two types of calcium antagonists. If the adverse effect of calcium antagonists on heart failure could be avoided, then the calcium antagonists would stand along-side the beta-blockers as agents able to prevent postinfarct sudden death. Furthermore, the combination of calcium antagonists and beta-blockade could then become attractive as potentially powerful postinfarct protection.
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PMID:Calcium antagonists, ventricular arrhythmias, and sudden cardiac death: a major challenge for the future. 172 11

The initiating cause of the first ectopic beat and its precipitation of sustained lethal arrhythmia in acute myocardial ischemia is not clear. Comparable uncertainties surround sudden death in myocardial failure. Progress in control of ventricular fibrillation has been slow, perhaps because diagnosis and treatment have been based on the premise that ischemic biochemical changes solely cause the alterations in electrophysiological behavior. Alternative approaches need exploration. Evidence that mechanical changes can initiate electrophysiological changes by a process sometimes referred to as "mechanoelectric feedback" is accumulating. It operates when any primary mechanical change in ventricular muscle, e.g., contraction produces a change in its electrical properties. Mechanical changes are prevalent in ischemia and cardiac failure. If mechanoelectric feedback operates here, it is not surprising that arrhythmias in some of these pathologies parallel the degree of mechanical myocardial dysfunction rather than electrophysiological changes, independent of etiology. This mechanoelectric feedback system may exist as an intrinsic property of normal myocardium, providing a feedback control of activation processes at both the cellular and gross levels. Its disruption during pathological events produces instability in the system and thus ventricular arrhythmia. This concept provides a new potential avenue for arrhythmia therapy.
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PMID:Myocardial mechanics and arrhythmia. 172 49

Extensive atherosclerotic coronary artery disease is by far the most common pathological finding in patients with sudden cardiac death, and acute myocardial ischemia is often a contributing factor. Clinical trials using beta-blockers in postinfarction patients and bypass coronary artery surgery in patients with stable coronary artery disease have demonstrated a reduction in both sudden and total cardiac mortality after intervention. Information concerning the presence and extent of coronary artery disease, global and regional ventricular function, the presence or absence of ventricular aneurysms, and whether or not ischemia is inducible influences therapeutic management. Myocardial revascularization should be considered a primary therapy in patients with critical coronary artery stenosis, significant regions of myocardium at risk, and no inducible ventricular arrhythmias at electrophysiological testing. In patients with inducible polymorphic ventricular tachycardia or ventricular fibrillation, postoperative testing is essential, since only 50% will be suppressed by coronary artery surgery alone. In patients with inducible sustained monomorphic ventricular tachycardia and scars due to prior myocardial infarction, surgical revascularization alone will usually not be sufficient to prevent postoperative induction of the same arrhythmia. There are no data to support percutaneous transluminal coronary angioplasty as the sole therapy for post-sudden death patients who have inducible ventricular tachycardia or ventricular fibrillation on electrophysiological testing.
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PMID:Role of myocardial revascularization in sudden cardiac death. 172 93

The analysis of the autonomic control of the heart, by means of indirect markers, may represent a new approach for identifying patients at higher risk for sudden cardiac death after a myocardial infarction. This possibility is based on the evidence that autonomic responses during acute myocardial ischemia are a major determinant of the outcome (i.e., occurrence of ventricular fibrillation or survival). Specifically, sympathetic activation can trigger malignant arrhythmias, whereas vagal activity may exert a protective effect. Several experimental observations have provided new insights on the relation between sympatho-vagal interactions and the likelihood for the occurrence of ventricular fibrillation. In an established experimental model for sudden death involving conscious dogs with a healed myocardial infarction, either depressed reflex chronotropic responses during a blood pressure rise or reduced variability of heart rate (respectively, markers of reflex and tonic cardiac vagal activity) identify dogs at greater risk to develop malignant arrhythmias during a new ischemic episode. In anesthetized cats, direct neural recording of vagal activity to the heart confirmed that vigorous reflex vagal activation during acute myocardial ischemia is associated with protection from ventricular fibrillation. Furthermore, in these experiments the reflex neural response to acute myocardial ischemia was predicted by the analysis of baroreflex sensitivity. The antifibrillatory effect of vagal activation is confirmed by the prevention of ventricular fibrillation during acute ischemia in dogs susceptible to sudden cardiac death by direct electrical stimulation of the right vagus. The clinical counterpart of these experimental data lies in three separate prospective studies showing a higher cardiac mortality in patients who after a myocardial infarction have a depressed baroreflex sensitivity or a decreased heart rate variability. A definitive answer on the role that the analysis of markers of cardiac vagal activity may play in risk stratification of patients with coronary artery disease should be provided by Autonomic Tone and Reflexes After Myocardial Infarction (ATRAMI), an ongoing prospective study. In ATRAMI, baroreflex sensitivity and heart rate variability will be assessed within 20 days after a myocardial infarction in 1,200 patients enrolled in Europe, U.S.A., and Japan with a minimum follow up of one year.
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PMID:Autonomic nervous system and sudden cardiac death. Experimental basis and clinical observations for post-myocardial infarction risk stratification. 172 9

Cardiac arrest causes a rapid loss of cerebral adenosine triphosphate [corrected] (ATP) and a decrease in cerebral intracellular pH (pHi). Depending on the efficacy of cardiopulmonary resuscitation (CPR), cerebral blood flow levels (CBF) ranging from near zero to near normal have been reported experimentally. Using 31P magnetic resonance spectroscopy, the authors tested whether experimental CPR with normal levels of cerebral blood flow can rapidly restore cerebral ATP and pHi despite the progressive systemic acidemia associated with CPR. After 6 min of ventricular fibrillation in six dogs anesthetized with fentanyl and pentobarbital, ATP was reduced to undetectable concentrations and pHi decreased from 7.11 +/- 0.02 to 6.28 +/- 0.09 (+/- SE) as measured by 31P magnetic resonance spectroscopy. Application of cyclic chest compression by an inflatable vest placed around the thorax and infusion of epinephrine (40 micrograms/kg bolus plus 8 micrograms/kg/min, intravenously) maintained cerebral perfusion pressure greater than 70 mmHg for 50 min with the dog remaining in the magnet. Prearrest cerebral blood flows were generated. Cerebral pHi recovered to 7.03 +/- 0.03 by 35 min of CPR, whereas arterial pH decreased from 7.41 +/- 0.4 to 7.08 +/- 0.04 and cerebral venous pH decreased from 7.29 +/- 0.03 to 7.01 +/- 0.04. Cerebral ATP levels recovered to 86 +/- 7% (+/- SE) of prearrest concentration by 6 min of CPR. There was no further recovery of ATP, which remained significantly less than control. Therefore, in contrast to hyperemic reperfusion with spontaneous circulation and full ATP recovery, experimental CPR may not be able to restore ATP completely after 6 min of global ischemia despite restoration of CBF and brain pHi to prearrest levels.
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PMID:Brain bioenergetics during cardiopulmonary resuscitation in dogs. 172 40


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