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Myocardial protection with carvedilol
G Z Feuerstein1, S A Hamburger, E F Smith
1Department of Pharmacology, SmithKline Beecham Pharmaceuticals p.l.c., King of Prussia, Pennsylvania 19406.
Insights
Carvedilol, a beta-blocker and vasodilator, reduced heart attack size more effectively than propranolol in animal models. This suggests carvedilol offers superior cardioprotection against myocardial infarction.
Area of Science:
- Cardiovascular Pharmacology
- Experimental Cardiology
Background:
- Carvedilol is a cardiovascular drug with both beta-adrenoceptor antagonist and vasodilator properties.
- Beta-blockers reduce myocardial workload and are cardioprotective.
- Carvedilol's dual action may enhance cardioprotection beyond pure beta-blockers.
Purpose of the Study:
- To investigate the efficacy of carvedilol versus propranolol in reducing infarct size in experimental models of acute myocardial infarction.
- To compare the cardioprotective effects of carvedilol's combined beta-blockade and vasodilation with propranolol's beta-blockade alone.
Main Methods:
- Acute myocardial infarction was induced in rats, pigs, and dogs by coronary artery occlusion and reperfusion.
- Animals received intravenous vehicle, carvedilol, or propranolol before or after ischemia.
- Infarct size was quantified using image analysis of stained tissue sections.
Main Results:
- Carvedilol demonstrated a greater reduction in infarct size compared to propranolol in rat, pig, and dog models.
- The study design included varying occlusion and reperfusion times across species.
- Drug administration timing varied, including pre-ischemia and post-ischemia protocols.
Conclusions:
- Carvedilol provides superior cardioprotection in experimental myocardial infarction compared to propranolol.
- The vasodilating property of carvedilol contributes to enhanced salvage of ischemic myocardium.
- These findings support carvedilol's potential as a therapeutic agent for acute myocardial infarction.
Abstract:
Carvedilol is a multiple-action cardiovascular agent that is both a beta-adrenoceptor antagonist and a vasodilator and has recently been made available for the treatment of mild-to-moderate hypertension. Clinical trials are ongoing to establish the efficacy of carvedilol in angina and congestive heart failure. beta-Adrenoceptor antagonists are known to reduce myocardial work secondary to reductions in heart rate and contractility; accordingly, they have been shown to be cardioprotective in animals and in humans. Because carvedilol has beta-adrenoceptor antagonist activity, it also should provide significant cardioprotection. The additional vasodilating activity of carvedilol, which will further reduce myocardial work by decreasing afterload and myocardial wall tension, should provide more salvage of ischemic myocardium than that afforded by a pure beta-adrenoceptor antagonist, such as propranolol. We investigated the ability of carvedilol and propranolol to reduce infarct size in experimental models of acute myocardial infarction in the rat, pig, and dog. The left anterior descending coronary artery was occluded for 30 (rat) or 45 min (pig) and then reperfused for 24 h (rat) or 4 h (pig). In the dog, the left circumflex coronary artery was occluded for 60 min and reperfused for 24 h. Vehicle, carvedilol, or propranolol was administered intravenously 15 min before ischemia (and, in the rat only, repeated 4 h after ischemia). An additional group of dogs was subjected to permanent left anterior descending coronary artery occlusion for 6 h, and carvedilol or propranolol was given 15 min after occlusion. Infarct size was examined on stained tissue sections using quantitative image analysis.(ABSTRACT TRUNCATED AT 250 WORDS)