Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In previous studies, we showed that dibenzepin HCl (D) and other tricyclic antidepressants (TCAD), given either before or during occlusion of the left anterior descending artery (LAD), decreased the incidence of ventricular fibrillation (VF) following occlusion and reperfusion. Moreover, once VF develops in treated animals, it changes into a transient type, reverting spontaneously to a sinus rhythm. In the treated cats, retrograde perfusion of the occluded coronary artery was observed, most likely as a result of increased collateral blood flow. This latter effect is the subject of the present study. The LAD was occluded at its origin in 43 cats, 28 of which were treated either with D or with 5-iminodibenzyl HCl; the remaining 15 were untreated controls. Two hours after the occlusion, methylene blue was injected into the left atrium to determine color demarcation between the perfused and unperfused myocardium, and the cat was then killed. After fixing for 2 or 3 days in 4% formaldehyde, the hearts were sectioned transversely. The results showed that in the 15 control cats, the blood-supplied (blue) area ranged between 16% and 56% of the left ventricular muscle (mean 39%), while in the 28 treated cats the blue area was between 44% and 83% (mean 66%). These results clearly indicate the beneficial effect of TCAD on the blood supply of the occluded area and can explain, in part, the ability of these drugs to prevent VF even if infused after the coronary occlusion, and their protective effect against VF following reperfusion. No other antiarrhythmic drugs have been shown to possess this latter action.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of tricyclic antidepressants on ventricular fibrillation and collateral blood supply following acute coronary occlusion. 287 24

Cocaine is a potent sympathomimetic drug that can provoke lethal cardiac events. Cocaine-induced alterations in autonomic balance, particularly during myocardial ischemia, could contribute significantly to these adverse reactions. To test this hypothesis, we produced a 2-min left circumflex coronary artery (LCX) occlusion in unanesthetized mongrel dogs (n = 7) instrumented to measure left ventricular pressure (LVP), ventricular electrogram, and coronary blood flow (CBF) with and without various doses of cocaine (0.0, 0.5, 1, 2, and 4 mg/kg). At least 24 h elapsed between cocaine doses, which were given in random order. Time series analysis of heart rate (HR) variability was used as an index of cardiac vagal tone (0.24-1.04 Hz). Cocaine elicited dose-dependent increases in HR that were accompanied by corresponding decreases in cardiac vagal tone. The peak response was achieved approximately 1 min after cocaine was given and returned to precocaine values 15 (0.5 and 1 mg/kg), 30 (2 mg/kg), or 60 (4 mg/kg) min later. Myocardial ischemia elicited significant increases in HR and reductions in cardiac vagal tone that were accentuated by cocaine (1, 2, and 4 mg/kg); e.g., cocaine (2 mg/kg) elicited a greater HR (control 119.3 +/- 5.9, occlusion 149.7 +/- 9.6; cocaine 144 +/- 11.9, occlusion 178.3 +/- 10.4 beats/min) and vagal tone (control 5.6 +/- 0.7, occlusion 2.6 +/- 0.3; cocaine 5.2 +/- 0.7, occlusion 1.3 +/- 0.5 ln s2) response to 2-min coronary occlusion. beta-Adrenoceptor blockade (propranolol HCl 1 mg/kg) attenuated the HR response but elicited greater reduction (lower values were achieved) in vagal tone during coronary artery occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of cocaine on cardiac vagal tone before and during coronary artery occlusion: cocaine exacerbates the autonomic response to myocardial ischemia. 750 7

alpha-Adrenergic receptor responsiveness has been reported to increase during myocardial ischemia, correlating with onset of malignant arrhythmias. If alpha-adrenoceptor mechanisms play a significant role in induction of life-threatening arrhythmias, inhibition of these receptors with specific alpha-adrenoceptor antagonists should protect against disturbances in cardiac rhythm. To test this hypothesis, we induced ventricular fibrillation (VF) in 21 mongrel dogs with healed myocardial infarctions (MI) by 2-min coronary artery occlusion during exercise. On a subsequent day, the exercise plus ischemia test was repeated after the alpha 1-adrenoceptor antagonist prazosin HCl (0.5 mg/kg intravenously, i.v.; n = 14) or the alpha 1A-adrenergic receptor subtype antagonist WB4101 (2.0 mg/kg i.v., n = 9). Prazosin elicited a significant reduction in left ventricular systolic pressure (LVSP, control 157.0 +/- 6.5 vs. prazosin 118.5 +/- 2.7 mm Hg) and prevented arrhythmias in 13 of 14 animals (chi square p < 0.001). No other hemodynamic parameters, either before or during the coronary occlusion, were altered by prazosin. WB4101 did not alter any hemodynamic parameters either before or during coronary artery occlusion, yet prevented VF in 7 of 9 animals (chi square p < 0.025), delaying onset of malignant arrhythmias in the remaining animals. A second control exercise plus ischemia test reproducibly induced VF in all animals. Together these data demonstrate that alpha-adrenoceptor antagonists can prevent VF independent of hemodynamic changes. In particular, the data suggest that activation of the alpha 1A-adrenergic receptor subtype may contribute importantly to development of malignant arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of alpha 1-adrenergic receptor antagonists on susceptibility to malignant arrhythmias: protection from ventricular fibrillation. 752 95

Cocaine-induced increases in catecholamines and the resulting enhanced activation of myocardial adrenergic receptors could contribute significantly to the formation of ventricular fibrillation (VF). In order to test this hypothesis, a 2-min coronary occlusion was initiated during the last minute of exercise in instrumented mongrel dogs. Forty-one animals were selected in which this test failed to provoke ventricular arrhythmias. The test was repeated after cocaine HCl (1.0 mg/kg). Cocaine significantly (P < .01) increased heart rate, left ventricular systolic pressure and positive left ventricular dP/dt, as well as elicited VF in 34 animals. The cocaine exercise plus ischemia test was repeated in animals after pretreatment with either the beta adrenergic receptor antagonist propranolol HCl (1.0 mg/kg, n = 14) or the alpha adrenergic receptor antagonist prazosin HCl (0.5 mg/kg, n = 15). Both propranolol and prazosin reduced the hemodynamic effects of cocaine and prevented VF in 12 of 14 and 12 of 15 animals, respectively. The studies were then repeated with heart rate matched to the cocaine heart rate by ventricular pacing. Prazosin (n = 5) but not propranolol (n = 4) still prevented VF even with heart rate held constant. Finally, the alpha-1A adrenergic receptor subtype antagonist WB4101 (2.0 mg/kg, n = 10) also prevented cocaine VF in 7 of 10 animals without changing heart rate. In contrast, the alpha-1B adrenergic receptor antagonist chloroethylclonidine (2.0 mg/kg, n = 3) failed to prevent VF. Thus, alpha but not beta adrenergic receptor antagonists can prevent cocaine-induced malignant arrhythmias independently of their action on heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of adrenergic receptor antagonists on cocaine-induced ventricular fibrillation: alpha but not beta adrenergic receptor antagonists prevent malignant arrhythmias independent of heart rate. 790 62

It is increasingly apparent that cocaine can provoke lethal cardiac events, including ventricular fibrillation (VF). Cocaine-induced accumulation of intracellular calcium could contribute significantly to the development of these lethal arrhythmias. In order to test this hypothesis, a 2-min coronary occlusion was initiated during the last minute of exercise in instrumented mongrel dogs. Twenty-eight animals were selected in which this test failed to induce ventricular arrhythmias. The test was repeated after cocaine HCl (1.0 mg/kg). Cocaine significantly (P < .01) increased heart rate, left ventricular pressure and d(left ventricular pressure)/dt maximum, and elicited VF in 21 animals. The cocaine exercise+ischemia test was repeated in the animals that developed VF after the pretreatment with the following calcium channel antagonists: diltiazem (n = 8, 1.0 mg/kg), flunarizine (n = 7, 2.5 mg/kg), magnesium sulfate (n = 7, 100 mg/kg), nifedipine (n = 7 100 micrograms/kg), Ro 40-5967 (n = 7, 1.0 mg/kg) and verapamil (n = 6, 250 micrograms/kg). Diltiazem, flunarizine, nifedipine, Ro 40-5967 and verapamil completely suppressed cocaine-induced VF, whereas magnesium prevented VF in five of seven animals. Many of the calcium channel antagonists attenuated the heart rate and systolic pressure increases provoked by cocaine, as well as the heart rate increase induced by the ischemia. Heart rate was therefore matched to the cocaine values by ventricular pacing (verapamil+pace, n = 5), whereas the pressure increases were prevented by nitroprusside (n = 4). Even with heart rate held constant, verapamil prevented VF, whereas nitroprusside failed to protect any animal. Thus, myocardial calcium entry may play a critical role in cocaine-induced VF, whereas calcium antagonists can prevent these malignant arrhythmias independently of their vascular action.
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PMID:Effect of calcium channel antagonists on cocaine-induced malignant arrhythmias: protection against ventricular fibrillation. 833 69