COMPARISON OF THE EFFECTS OF ENOXIMONE AND ISOPROTERENOL ON PROTAMINECARDIOTOXICITY IN ANESTHETIZED DOGS

In this study we investigated the effects of isoproterenol and enoximo ne on protamine cardiotoxicity because administration of protamine for heparin reversal during open heart surgery depresses left ventricular function. Eighteen mongrel dogs were entered into this study. After i nduction of general anesthesia and a stabilization period, a thermodil ution catheter was inserted via the jugular vein. Another 2 catheters were inserted into the left ventricle and femoral artery. Heparin and protamine were used in all animals. Heparin dosage was 300 U/kg, and p rotamine dosage was 4.5 mg/kg. The animals were divided into 3 groups. Six animals received enoximone (5 mu g/kg per min), 6 animals receive d isoproterenol (0.05 mu g/kg per min), and 6 animals received no inot ropic agent. Measurements were performed before treatment, 5 min after protamine administration, and at 15-min intervals for 1 h. Cardiac ou tput (CO), mean arterial pressure, pulmonary capillary wedge pressure, first derivative of left ventricular pressure (1+/-) left ventricular systolic pressure, and heart rate were measured. CO was 1582+/-34 ml/ min in the isoproterenol group (I+P), 1684+/-61 ml/min in the enoximon e group (E+P), and 1471+/-37 ml/min in the protamine group (P) (p<0.05 E+P vs I+P and P) 60 min after protamine administration. The first de rivative of left ventricular pressure (dP/dt) was 1995+/-61 mmHg/sec i n the I+P group, 2320+/-85 mmHg/sec in the E+P group, and 1816+/-48 mm Hg/sec in the P group (p<0.05 E+P vs I+P and P). In our experimental s tudy, the isoproterenol and protamine combination did not increase hem odynamic activity. However, isoproterenol alone significantly increase d hemodynamic activity as determined by dP/dt values. Protamine admini stration impairs the effects of beta agonists on the myocardium. In th e protamine group, CO and pressure-dependent values were significantly reduced. Isoproterenol administration did not reverse this deteriorat ion because of the loss of the beta-receptor activity. Inotropic agent s acting through the beta-adrenergic system have partial effects on my ocardium. Enoximone, a phosphodiesterase inhibitor, reverses deteriora tion of cardiac function after protamine administration because it inc reases myocardial function via the phosphodiesterase system.