Abstract
Summary
The two beta-adrenergic receptor blocking drugs, propranolol and sotalol (MJ-1999), were studied for their effects on myocardial oxygen consumption (MVO2) and hemodynamic functions in anesthetized, open chest dogs. Propranolol (0.5 and 1.0 mg/kg) and sotalol (5.0 mg/kg) iv produced a significant decrease in MVO2, although the effect of the latter drug was greater in magnitude and persisted longer. No significant effects on arterial or left ventricular blood pressure were produced by either drug.
The decreases in MVO2 were associated with a negative chronotropic and inotropic effect, the former change being more pronounced with sotalol. Coronary sinus blood flow (CSBF) also was decreased by both drugs, with sotalol having a greater effect than either of the doses of propranolol. The lowering of MVO2 by sotalol can be attributed largely to its negative chronotropic effect. This is supported by studies with the (+) -isomer (relatively weaker as a beta-blocker) showing significantly less change in MVO2 compared to the recemic drug. In addition, racemic sotalol failed to significantly lower MVO2 in heart rate-controlled experiments. The decrease in CSBF could be explained by the lowering of the oxygen demands of the heart accompanying heart rate and contractility changes, although a direct coronary vasoconstriction mechanism may also contribute to the observed decrease in CSBF. These results are discussed in terms of the possible application of these drugs to the treatment of ischemic heart disease.
Data and statistical computations were provided by the Research Data Facility, Pacific Medical Center (Dir., R. Abbott). Sotatol was donated by the Mead Johnson Research Center, Evansville, Ind.
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