Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bretylium tosylate and bethanidine sulfate were studied in two models of experimental myocardial ischemia. In anesthetized dogs, left anterior descending coronary artery occlusion during rapid atrial pacing (180-200 min-1) produced ventricular tachycardia and fibrillation within 5 min in 9 of 11 dogs studied. In all cases, arrhythmias were preceded by and appeared to be temporally related to progressive fractionation and delay of electrograms recorded from the ischemic zone. In four dogs, bretylium (10 mg/kg) did not alter the time course of electrogram changes nor the time to onset of arrhythmia. However, in five dogs bethanidine (10 mg/kg) markedly exacerbated conduction changes in the ischemic zone and decreased the time to onset of ventricular arrhythmias (173 +/- 35 vs. 262 +/- 34 s control, mean +/- SEM, p less than 0.05). Bethanidine administration also facilitated ischemia-induced ventricular tachycardia and fibrillation in two dogs that did not exhibit ischemia-induced arrhythmias before receiving the drug. In isolated perfused rabbit hearts, global ischemia produced conduction slowing, depolarization of resting membrane potential, and decreases in amplitude and Vmax that were reproducible in serial 10 min ischemic episodes. Bretylium (10 mg/L) did not affect these parameters under either perfused or ischemic conditions. Although bethanidine (10 mg/L) also did not affect these parameters during perfusion, conduction slowing and depression of Vmax during ischemia were accelerated without affecting the time course of change in resting membrane potential. Both bretylium and bethanidine prolonged action potential duration under perfused conditions, but after 10 min of ischemia this effect was no longer evident. The results demonstrate that differences in the electrophysiologic effects of bretylium and bethanidine are markedly accentuated in the setting of acute ischemia. Although both these agents have been demonstrated to have antifibrillatory effects in other experimental settings, under the conditions of this study, bretylium failed to protect against ischemia-induced arrhythmias and acute bethanidine administration produced a proarrhythmic effect in association with an exacerbation of ischemia-induced conduction changes.
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PMID:Ischemia-induced conduction delay and ventricular arrhythmias: comparative electropharmacology of bethanidine sulfate and bretylium tosylate. 247 95

Experimental and clinical studies demonstrate the antifibrillatory effectiveness of bretylium tosylate: Experimental ventricular fibrillation induced either by electrical stimulation or by ischemia is prevented by bretylium. In 2,000 acute myocardial infarction patients who received bretylium prophylactically primary ventricular fibrillation occurred in less than 1% of cases. In a randomized hemodynamic study in acute myocardial infarction patients bretylium induced a significant decrease in heart rate, systolic and mean left ventricular pressures, and in systolic and mean aortic pressures. In addition, a parallel and significant decrease in total pulmonary and systemic resistances was seen, accompanied by decreases in tension time and left ventricular (delta P/delta V) indexes. Bretylium tosylate induces stabilization of electrical systole duration (QTc) in acute myocardial infarction patients. The conclusions of the present review strongly support those of the United States Food and Drug Administration, approving bretylium for prophylaxis and treatment of ventricular fibrillation.
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PMID:Experimental and clinical pharmacology of bretylium tosylate in acute myocardial infarction: a 15-year journey. 379 68

Five patients with recurrent, life-threatening ventricular arrhythmias were given bretylium tosylate intravenously for a minimum of 4 days. Arrhythmias were not related to acute ischemia in any patient. Four patients had inducible ventricular tachycardia, and one patient had inducible ventricular fibrillation requiring cardioversion while taking no medications. Programmed electrical stimulation was then repeated to assess the ability of bretylium to suppress inducible ventricular tachycardia. Bretylium tosylate, at a mean dose of 2.3 mg intravenously per minute, did not suppress inducible ventricular arrhythmias in any patient. Rapid ventricular tachycardia was induced in all patients, and ventricular fibrillation was induced in one patient. Two patients required external cardioversion to terminate their arrhythmias. Bretylium tosylate, given in relatively large doses chronically, did not suppress inducible ventricular arrhythmias in these five otherwise drug-refractory patients with chronic recurrent ventricular tachycardia. This failure to suppress inducible ventricular arrhythmias cannot be attributed to the initial catecholamine release which occurs in the first hour or two after the drug is administered.
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PMID:Failure of bretylium to suppress inducible ventricular tachycardia. 684 14