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)

Hypoxia in isolated myocytes results in accumulation of long-chain acylcarnitines (LCA) in sarcolemma. Inhibition of carnitine acyltransferase I (CAT-I) with sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) prevents both the accumulation of LCA in the sarcolemma and the initial electrophysiologic derangements associated with hypoxia. Another amphiphilic metabolite, lysophosphatidylcholine (LPC), accumulates in the ischemic heart in vivo, in part because of inhibition of its catabolism by accumulating LCA. It induces electrophysiologic alterations in vitro analogous to early changes induced by ischemia in vivo. The present study was performed to determine whether POCA could prevent accumulation of both LCA and LPC induced by ischemia in vivo and if so, whether attenuation of early arrhythmogenesis would result. LAD coronary artery occlusions were induced for 5 min in chloralose-anesthetized cats. Coronary occlusion in untreated control animals elicited prompt, threefold increases of LCA (73 +/- 8 to 286 +/- 60 pmol/mg protein) and twofold increase of LPC (3.3 +/- 0.4 to 7.5 +/- 0.9 nmol/mg protein) selectively in the ischemic zone, associated with ventricular tachycardia (VT) or ventricular fibrillation (VF) occurring within the 5-min interval before acquisition of myocardial samples in 64% of the animals. POCA prevented the increase of both LCA and LPC. It also prevented the early occurrence of VT or VF (within 5 min of occlusion) in all animals studied. The antiarrhythmic effect of POCA was not attributable to favorable hemodynamic changes or to changes in myocardial perfusion measured with radiolabeled microspheres. Thus, inhibition of CAT-I effectively reduced the incidence of lethal arrhythmias induced early after the onset of ischemia. Accordingly, pharmacologic inhibition of this enzyme provides a promising approach for prophylaxis of sudden cardiac death, that typically occurs very soon after the onset of acute ischemia, in man.
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PMID:Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation. 292 26

Early reports of "reperfusion arrhythmia" after experimental temporary coronary occlusion raised concern that these arrhythmias, particularly ventricular fibrillation and ventricular tachycardia, might occur in association with reperfusion of an occluded coronary vessel during thrombolysis. Such an occurrence could increase the risk of transfer of such patients. To provide a more definitive answer to this question, we reviewed hospital and transfer records for all patients with acute myocardial infarction transferred by our critical care transfer service between January 1, 1985, and November 30, 1987, noting the occurrence of five types of arrhythmia: ventricular fibrillation, ventricular tachycardia, premature ventricular contractions, bradycardia, and atrioventricular block, both before and during transfer. Five hundred patients with acute myocardial infarction less than 48 hours old were transferred during this period. Two hundred twenty-five patients received thrombolytic therapy; 270 did not (five unknown). The type of acute myocardial infarction was known for 471 patients: 192 were anterior, 203 were inferior, and 76 were lateral. There were no deaths during transfer. Overall survival through hospitalization was 91%. The incidence of arrhythmia was 36% before transport and 12% during transport. There was no difference in arrhythmias overall, or with respect to any of the five arrhythmias specified, between patients who received thrombolytic therapy before and during transport and those who did not. Reperfusion arrhythmia does not appear to be a clinically significant entity during the transport of patients who are receiving IV thrombolytic therapy.
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PMID:Reperfusion arrhythmia: myth or reality? 292 30

Ventricular fibrillation threshold was significantly lower in hypertrophied hearts than in normal hearts. Ischemia produced by coronary occlusion reduced fibrillation threshold in both normal and hypertrophied hearts, but the maximum reduction in fibrillation threshold was observed earlier in hypertrophied hearts.
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PMID:Ventricular fibrillation threshold during acute ischemia in hypertrophied rat hearts. 296 28

To determine the relative importance of arachidonic acid pathway products on vulnerability to ventricular fibrillation (VF), we examined the effects of synthesis inhibitors and a receptor blocker acting in the cyclooxygenase (C) and lipoxygenase (L) pathways on VF thresholds in a feline model of coronary occlusion. Thresholds for the induction of VF wer measured before and after a 5-minute coronary occlusion in drug-treated animals and control subjects. Animals were treated with BW755c, a dual L and C inhibitor, CGS-8515, and L inhibitor, FPL-55712, a leukotriene receptor blocker, or sulfinpyrazone, a C inhibitor. BW755c, CGS-8515, and FPL-55712 all prevented an otherwise significant fall in VF threshold during coronary occlusion (p less than 0.01) independent of an effect on effective refractory period, heart rate, or blood pressure. In contrast, sulfinpyrazone, the only compound devoid of an effect on the L pathway, did not protect against an occlusion-related fall in VF threshold. BW755c and CGS-8515 inhibited the synthesis of L and C metabolites coincident with their protection against VF (p less than 0.01). We conclude that agents that antagonize the effects of L products protect against enhanced ventricular vulnerability during acute ischemia, whereas C inhibition alone may not afford this protection.
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PMID:Modulation of arachidonic acid metabolites and vulnerability to ventricular fibrillation during myocardial ischemia in the cat. 314 41

1. Nifedipine and DHM9 (carboxymethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate) were studied for their effects on arrhythmias resulting from regional myocardial ischaemia in conscious rats, and for their effects on left ventricular developed pressure in vitro. 2. Nifedipine possessed antiarrhythmic activity at a high dose of 10 mg kg-1 i.v., but not at 0.5 or 2 mg kg-1. Ventricular fibrillation (VF), tachycardia (VT), and ventricular premature beats (VPB) were all attenuated to a similar degree; nifedipine did not have a selectivity of action for high frequency arrhythmias. 3. Before coronary occlusion, the three doses of nifedipine reduced arterial blood pressure by a similar magnitude, indicating a similar (maximal) degree of systemic vasodilatation. The reductions in blood pressure were accompanied by reflex tachycardia. Heart rate and blood pressure did not correlate with the incidence or severity of arrhythmias. 4. DHM9 had no influence on arrhythmias, haemodynamic variables or the ECG, even at 20 mg kg-1 i.v. 5. Nifedipine concentration-dependently reduced contractility in perfused paced (5 Hz) rat ventricles in vitro. Raising the concentration of K+ in the perfusion fluid from 3 to 10 mequiv.l-1 increased the potency (-log10 EC50) of nifedipine up to four fold, and caused a significant depression in excitability. 6. DHM9 at up to 3 x 10(-5) M had no significant influence on ventricular contractility in vitro. 7. The results provided indirect evidence in support of the hypothesis that calcium antagonists inhibit ischaemia-induced arrhythmias by virtue of inhibition of the slow inward current (Isi) in the ischaemic ventricular myocardium.
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PMID:The mechanism of action of calcium antagonists on arrhythmias in early myocardial ischaemia: studies with nifedipine and DHM9. 320 85

Mongrel dogs with healed myocardial infarctions were given a 2 min coronary occlusion during an exercise test. The exercise plus ischemia test induced ventricular fibrillation in nine animals. One week later, the test was repeated after pretreatment with magnesium sulfate (100 mg/kg i.v.). Magnesium prevented ventricular fibrillation in seven of the nine animals without adverse side effects. Thus, magnesium may be useful in the management of ventricular fibrillation during ischemia.
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PMID:Prevention of ventricular fibrillation with magnesium sulfate. 322 Jan 16

Growing evidence supports the concept that neutrophils accumulating in reperfused ischaemic myocardium play a detrimental role in evolving infarction. Lignocaine, an antiarrhythmic drug commonly used clinically, interferes with neutrophil function in vitro and potentially in vivo. To test the hypothesis that lignocaine may influence infarct size by reducing neutrophil accumulation in reperfused ischaemic myocardium, 31 dogs underwent a 2 h occlusion of the left anterior descending coronary artery, followed by 6 h of reperfusion. One group of dogs received saline (controls) the other a perfusion of lignocaine 0.06 mg.kg-1.min-1 starting 30 min before coronary occlusion and lasting for the duration of the experiment. Blood lignocaine concentrations at the onset of reperfusion were 3.3(0.6) micrograms.ml-1. 111Indium labelled autologous neutrophils were injected at the time of occlusion and their accumulation in the myocardium measured by digital scintigraphy of heart slices. The area at risk and infarct size were evaluated by planimetry of the heart slices (7 mm) after perfusion of Evans blue dye and triphenyltetrazolium staining. Ventricular fibrillation occurred in six controls and in five dogs receiving lignocaine. The phenomenon occurred early during the occlusion period in the lignocaine group (five dogs) and at reperfusion in controls (five dogs; p less than 0.05). In the remaining 20 dogs, 10 in each group, a linear correlation was found between myocardial 111In labelled neutrophil and circulating neutrophil counts at the onset of reperfusion (r = 0.076, p less than 0.05) and with infarct size (r = 0.96 and 0.74, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lignocaine in experimental myocardial infarction: failure to prevent neutrophil accumulation and ventricular fibrillation and to reduce infarct size. 322 56

A previous study by the authors showed that myocardial infarct size in the rabbit, measured after 45 mins of ischemia and 3 h of reperfusion, could be limited by administration of superoxide dismutase (SOD) plus catalase. The present study examined whether this infarct size limitation is sustained for the following three days. Under anesthesia, a coronary branch of the Japanese white rabbit was occluded for 45 mins and then reperfused. Three days after surgery, the heart was excised and the volume of myocardium supplied by the occluded coronary branch (ischemic zone size) was assessed with fluorescent particles and the infarct size was estimated by hematoxylin and eosin and with Mallory's staining. The SOD plus catalase group (n = 14) received 15,000 units/kg of SOD plus 50,000 units/kg of catalase in saline over 90 mins, starting 15 mins before the coronary occlusion. Saline was infused in the control group (n = 15). Three rabbits in the control group and three in the SOD plus catalase group died of ventricular fibrillation during the ischemic period. Three control and two SOD plus catalase rabbits were excluded because the ischemic zone was ambiguous. The percentage of the ischemic zone which was infarcted was 59.4 +/- 6.9% (mean +/- SE) in the control group (n = 9) and 49.4 +/- 5.1% in the SOD plus catalase group (n = 9). These were not statistically different. Ischemic zone size and hemodynamic parameters were similar in the two groups. These findings suggest that SOD plus catalase may serve only to delay rather than prevent myocardial infarction.
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PMID:Effect of superoxide dismutase plus catalase on myocardial infarct size in rabbits. 322 70

A conscious rat system has been developed to investigate the ability of alpha- and beta-adrenoceptor blocking agents to modify the severity of ischemia- and reperfusion-induced arrhythmias. Ischemia-induced arrhythmias were studied during a 30 min period of occlusion of the left anterior descending (LAD) coronary artery, and 100% of control animals (n = 24) exhibited ventricular tachycardia and 63% ventricular fibrillation. Beta-adrenoceptor blockade with atenolol (1 mg/kg body weight) significantly reduced the incidence of ventricular fibrillation to 17% (p less than 0.05). In contrast, alpha-adrenoceptor blockade with prazosin (0.01, 0.1 or 1 mg/kg body weight) failed to reduce the incidence of arrhythmias and actually increased mortality. This higher mortality with prazosin was associated with bradyarrhythmias. Administration of atenolol (1 mg/kg body weight) also reduced the incidence of reperfusion-induced ventricular fibrillation after a 5 min period of ischemia from 100% to 58% (p less than 0.05). Prazosin could not be tested due to the high mortality during coronary occlusion. Autopsy studies of hearts from the control, atenolol and prazosin groups indicated that all groups had similar occluded zone volumes. In conclusion, in conscious rats beta-blockade with atenolol reduced the incidence of both ischemia- and reperfusion-induced arrhythmias, whereas alpha-blockade with prazosin at the 3 doses studied failed to exert a protective effect and actually increased mortality.
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PMID:Ischemia- and reperfusion-induced arrhythmias in conscious rats--studies with prazosin and atenolol. 324 20

1. The effects of the calcium blockers bepridil and verapamil on latency time to ventricular fibrillation (VF) and VF incidence were assessed in 109 anesthetized dogs, submitted to coronary occlusion and reperfusion. 2. In 19 dogs (Group I) submitted to global left ventricular ischemia, both bepridil and verapamil significantly (P less than 0.05) prolonged latency time as compared to 14 untreated controls. However, VF was not prevented by any of these drugs. Both drugs were given 15 min before coronary ligation. 3. In 76 dogs (Group II) submitted to regional myocardial ischemia (left anterior descending coronary artery (LAD) occlusion for 2 hours followed by 30 min reperfusion), VF incidence during occlusion was significantly reduced by verapamil as compared to controls (0/21 vs 10/25; P less than 0.05) but not by bepridil (10/25 vs 12/30; P = ns). During reperfusion, however, neither drug affected fibrillation incidence or latency time. 4. No correlation was observed between anti-arrhythmic drug effects and infarct size as measured by triphenyl tetrazolium chloride. 5. We conclude that both bepridil and verapamil significantly delayed the occurrence of fibrillation in acute ischemia due to coronary ligation. However, only verapamil prevented fibrillation and this effect was restricted to the occlusion phase. In contrast, during reperfusion, neither drug prevented fibrillation. Thus, VF during occlusion and reperfusion is likely to be mediated by different mechanisms.
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PMID:Effects of calcium blockers on ventricular fibrillation during acute myocardial infarction. 326 73


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