Haemodynamic effects of hypotension induced by KRN2391 and nicardipine in isoflurane anaesthetized dogs.

PURPOSE

The investigational agent, KRN2391, is a potassium channel opener with a nitrate moiety which possesses potent vasodilatory action. We compared the haemodynamic effect of KRN2391. Induced hypotension with those of nicardipine.

METHODS

Sixteen dogs were anaesthetized with isoflurane 1.3% in oxygen (1 MAC). After the baseline period. mean arterial pressure (MAP) was decreased to 60 mmHg for 60 min with an infusion nicardipine (n = 8).

RESULTS

The KRN2391- and nicardipine-induced hypotension resulted in maximal decreased systemic vascular resistance of 35% and 25%, increases in cardiac index of 145% and 197%, and stroke volume index of 150% and 212%, respectively, (P < 0.01). There was no change in heart rate. Nicardipine was associated with increases (P < 0.01) in both right atrial and mean pulmonary artery pressures, whereas these variables remained unchanged with KRN2391. Pulmonary capillary wedge pressure decreased with KRN2391 (P < 0.01), but not with nicardipine.

CONCLUSION

While both drugs were equally able of inducing hypotension, our results show that the haemodynamic profile of KRN2391- and nicardipine-induced hypotension was a hyperdynamic state expressed by the marked increase in cardiac index with varying changes in right and left ventricular filling pressures, and suggest that KRN2391 may be a useful vasodilator for induced hypotension.