Hemodynamic effects of the intravenous administration of cyclorirobuxine D in anesthetized pigs

The present study was undertaken in anesthetized pigs to determine the primary effects of cyclorirobuxine D given intravenously on hemodynamic variables. In eight pigs, the administration of 1.5 mg/kg of cyclorirobuxine D caused a small increase in aortic blood pressure. When this response was prevented, a decrease in heart rate was obtained in each of the eight pigs. When this response was also prevented, an increase in the maximum rate of change of left ventricular systolic pressure (left ventricular dP/dt(max)) was observed. In four pigs, the decrease in heart rate and the increase in left ventricular dP/dt(max) were progressively augmented by graded increases in the dose of cyclorirobuxine D. In six pigs, the responses of hemodynamic variables to cyclorirobuxine D were not affected by blockade of cholinergic and adrenergic receptors. In a further six pigs, blockade of nitric oxide synthase with N(ω)-nitro-L-arginine methyl ester did not affect the decrease in heart rate caused by the drug, but abolished the increases in left ventricular dP/dt(max) and aortic blood pressure. The present study showed that intravenous administration of cyclorirobuxine D primarily caused a decrease in heart rate and an increase in left ventricular inotropic state, which secondarily determined an increase in aortic blood pressure, and suggested that the response of heart rate involved a direct effect of the drug on the heart, while the response of left ventricular contractility was related to mechanisms dependent on the release of nitric oxide.