Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs.

Abstract

The effects of aminophylline, 1 mg/kg/min infused intravenously for 10 minutes, were examined on left ventricular (LV) diameter, pressure, an indexes of myocardial contractility, as well as systemic, coronary and regional hemodynamics in conscious dogs. Aminophylline increased mean arterial pressure 12 +/- 2%, LV systolic pressure 8 +/- 1%, LV dP/dt 20 +/- 2%, velocity of myocardial fiber shortening 13 +/- 2% and heart rate 5 +/- 2%, and reduced LV end-diastolic diameter 2 +/- 0.5%. Vascular resistance rose in the systemic bed 13 +/- 5%, the coronary bed 26 +/- 3%, the mesenteric bed 26 +/- 5% and the iliac bed 36 +/- 4%, but did not rise in the renal bed. Both beta-adrenergic receptor blockade with propranolol and chronic treatment with reserpine attentuated but did not abolish the positive inotropic response induced by aminophylline. Alpha-adrenergic receptor blockade with phentolamine prevented aminophylline-induced vasoconstriction in the systemic, coronary, mesenteric and iliac beds. In contrast to the vasoconstriction with i.v. aminophylline, when the drug was infused directly into the iliac artery, it elicited marked iliac vasodilation. Thus, in the intact conscious dog, i.v. aminophylline, in a dose that had little effect on heart rate, increased LV contractility and reduced preload. The increase in contractility was dependent in part on intact beta-adrenergic nervous activity and endogenous catecholamine stores. The increase in systemic, coronary, iliac and mesenteric resistances involved alpha-adrenergic mechanisms. These actions appear to involve autonomic mechanisms, because the only direct effect of aminophylline on the iliac artery was marked vasodilation.