Cardiohemodynamic effects of cromakalim and pinacidil, potassium-channel openers, in the dog, special reference to venous return.

The cardiohemodynamic effects of the potassium-channel openers, cromakalim and pinacidil, were studied by the use of the closed-loop method (for both drugs) and the cardiopulmonary bypass technique (for cromakalim only) in anesthetized, open-chest dogs. In closed-loop preparations, both drugs (cromakalim, 3 to 100 micrograms/kg; pinacidil, 10 to 300 micrograms/kg) administered intravenously decreased systemic blood pressure and increased venous return (sum of the flow through the inferior and the superior vena cava) and cardiac output (CO). With the highest doses of both drugs, venous return and CO decreased in some preparations in which right atrial pressure rose, and the maximum rate of rise of left ventricular pressure (LV dP/dt max) diminished. Except such preparations, right atrial pressure, heart rate, and atrioventricular conduction time remained virtually unchanged. The fall in systemic blood pressure produced by intermediate doses of pinacidil was greater in the preparations in which baroceptor reflexes were eliminated (denervated preparations) than in those with the reflexes left intact (nerve-intact preparations). The increases in venous return and CO, however, were not different when comparing the nerve-intact and the denervated preparations. In cardiopulmonary-bypass preparations, higher doses of cromakalim increased venous return while producing a fall in systemic blood pressure, suggesting that the decreased venous return and CO seen with higher doses of the potassium-channel openers in the closed-loop preparations were secondary to the decreased cardiac contractility. The potassium-channel openers should be characterized as vasodilators, which preferentially reduce afterload and increase venous return.