Amrinone and verapamil-propranolol induced cardiac depression during isoflurane anesthesia in dogs

Abstract

This study was designed to investigate the possibility of whether verapamil diminishes the effects of amrinone, whether amrinone can reverse verapamil-propranolol depression, and also to evaluate whether the order of administering the drugs would have any effect during 1.7-1.8% end-tidal isoflurane anesthesia in dogs. At 3-4-week intervals, each of six conditioned mongrel dogs (23 ± 1 kg) received amrinone (A) (4 mg/kg plus 100 μg·kg-1·min-1), verapamil (V) (200 μg/kg plus 7.5 μg·kg-1·min-1) and propranolol (P) (150 μg/kg plus 0.8 μg·kg-1·min-1) in four different orders of administration: VAP, AVP, VPA, and PVA. Plasma levels achieved were 15 ± 1 to 24 ± 2 μg/ml for amrinone, 24 ± 2 to 59 ± 10 ng/ml for propranolol, and 81 ± 10 to 163 ± 17 ng/ml for verapamil, equivalent to high therapeutic (amrinone) and therapeutic (propranolol, verapamil) levels in humans. The results of this study show that amrinone is able to reverse many of the effects of verapamil-propranolol (group VAP) and also many of the effects of verapamil-propranolol or propranolol-verapamil (groups VPA, PVA) combinations. Amrinone improved cardiac index, left ventricular dP/dt(max), pulmonary capillary wedge pressure, and central venous pressure without increasing catecholamines. However, mean arterial pressure remained decreased with decreased systemic vascular resistance, which necessitates careful consideration depending upon patient circumstances. The results also show that verapamil-propranolol can reverse the positive inotropic effects of amrinone (group AVP). The authors conclude that amrinone is of therapeutic value for the reversal of untoward effects of potent cardiodepressant drugs, such as verapamil and propranolol, even in the presence of inhalation anesthetics.