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The acute effects of guanethidine and bretylium on myocardial contractile force, heart rate, mean arterial pressure, and cardiac out put were studied in normal dogs and cardiac denervated, myocardial catecholamine-depleted dogs. Right ventricular contractile force was measured by means of a Walton-Brodie strain-gauge arch. Cardiac output was measured by the dye-dilution technique. In normal dogs, guanethidine produced marked increases of myocardial contractile force, heart rate, cardiac output, and arterial pressure. In the cardiac-denervated dogs. guanethidine produced a small decrease in myocardial contractile force and a small increase in heart rate; the cardiac output and pressor responses were also markedly reduced. Thus, it appears that sudden release of myocardial eateeholamines is largely responsible for the acute circulatory effects of guanethidine. In normal dogs, bretylium increased myoeardial contractile force, heart rate, cardiac output, and arterial pressure. In cardiac denervated dogs, the increase in contractile force produced by bretylium was essentially unchanged from the normal, but the heart rate was decreased, and the cardiac output response appeared slightly reduced. These data suggest that myocard ial catecholamine release plays a limited but definite role in the acute circulatory effects of bretylium. The negative inotropic effect of guanethidine and the negative chronotropic effect of bretylium in the denervated. amine-depleted heart suggest that these responses are direct effects of these drugs which are manifest only in the amine-depleted heart.

Analysis of the Acute Circulatory Effects of Guanethidine and Bretylium