Possible evaluation of hemodynamic effects of the potassium channel opener KRN2391 on induced hypotension in dogs.

KRN2391 is potassium channel opener with a nitrate moiety which possesses potent vasodilatory action. The hemodynamic profiles of KRN2391-induced hypotension are still not well understood. The aim of this study was to investigate the potential use of KRN2391 for induced hypotension. Eight dogs were anesthetized with 0.87% halothane in oxygen (1 MAC). After the baseline period, mean arterial pressure (MAP) was reduced to 60 mmHg for 60 min by the infusion of KRN2391. MAP was reduced approximately 50% and was associated with a 80% maximum reduction (P<0.01) in systemic vascular resistance but was not accompanied by a significant change in heart rate. Hypotension induced by KRN2391 was associated with a 224% maximum increase (P<0.01) in cardiac index (CI) and a 136% maximum increase (P<0.01) in stroke volume index (SVI) during induced hypotension. Both CI and SVI remained significantly increased after the termination of drug infusion. Left ventricular maximum dP/dt increased significantly during and after induced hypotension. Right atrial and mean pulmonary artery pressures increased significantly, whereas pulmonary capillary wedge pressure remained unchanged. The results of the present study show that KRN2391 is effective in reducing afterload during induced hypotension, and suggest that the hemodynamic profiles of KRN2391-induced hypotension are a hyperdynamic state as expressed by twofold increases in CI concomitant with the increase in right ventricular filling pressures.