Hemodynamic Effects of Nicardipine and Phentolamine in Combination with Norepinephrine in a Canine Low-output-state Model.

Norepinephrine (NE) is one of the most potent positive inotropic drugs available for the treatment of low-output state following open-heart surgery. However, its inotropic effect is often masked by a significant increase of peripheral vascular resistance due to marked vasoconstriction. The purpose of the present study was to investigate whether the use of nicardipine (Nc) and phentolamine (Ph) in combination with NE could ameliorate the adverse vaso-constrictive action of NE. A low-output-state (LOS) model was produced by global myocardial ischemia due to electrically induced intermittent ventricular fibrillations in open-chest dogs. Twenty-eight dogs were divided into 6 groups according to the drugs infused after producing LOS. In the control group, hemodynamic changes similar to the clinical low-output state were observed, e.g., a decrease in cardiac output (CO) and left ventricular dp/dt, and an increase in the systemic vascular resistance (SVR). The use of NE alone produced marked increases in the systemic arterial pressure (SAP), heart rate, and SVR, with a slight increase in CO. The infusion of Nc alone produced decreases in SVR and SAP with a slight increase in CO. The concomitant infusion of NE and Nc produced increases in SV and CO, and decreases in SAP and SVR. The infusion of Ph alone produced no significant hemodynamic changes. The combined use of NE and Ph produced increases in CO, SAP and heart rate, but not to a significant extent. These results suggest that there are major advantages in the concomitant use of NE and Nc for the control of LOS.