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)

Using anaesthetised rats we have assessed (1) whether the density of alpha 1 adrenergic receptors increases during coronary artery occlusion, (2) whether any change in density can be associated with the onset of reperfusion induced ventricular fibrillation, and (3) whether alpha 1 blockade with prazosin modifies the incidence of reperfusion induced ventricular fibrillation. The incidence of fibrillation upon reperfusion after 3, 5, 10, 20 and 30 min occlusion was 20, 75, 50, 16 and 10% (n = 10-12 in each group) respectively. alpha 1 Receptor density was measured using [3H]-prazosin in non-ischaemic and ischaemic tissue obtained after 0, 5 and 30 min ischaemia. Receptor density was not significantly altered at the time of maximum incidence of reperfusion induced ventricular fibrillation (5 min occlusion) but did significantly increase in both non-ischaemic and ischaemic tissue after 30 min occlusion, when the incidence of fibrillation upon reperfusion was very low (8%). At this time the values were 17.0(SEM 2.3) and 18.4(0.6)fmol.mg-1 protein in non-ischaemic and ischaemic zones as compared to 10.7(0.6) and 12.8(1.0)fmol.mg-1 protein in sham operated control animals (p less than 0.05 in both cases). Prazosin (0.1 or 1.0 mg.kg-1 body wt intravenously, 5 min prior to coronary occlusion) did not alter the incidence of ventricular fibrillation, ventricular tachycardia or total number of premature ventricular complexes upon reperfusion. We conclude that ischaemia induced changes in alpha 1 receptor density do not parallel changes in vulnerability to reperfusion induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dissociation between reperfusion induced arrhythmias and increases in ventricular alpha 1 receptor density in the anaesthetised rat. 255 4

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

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