EFFECTS OF A NEW NA+ H+ ANTIPORTER INHIBITOR ON POSTISCHEMIC REPERFUSION IN PIG-HEART/

We investigated the effects of a new compound (3-methylsulfonyl-4-pipe ridinobenzoyl) guanidine hydrochloride (HOE 694) known to inhibit the Na+/H+ exchanger in a porcine model of ischemia/reperfusion. Ischemia was induced by coronary occlusion (twice for 10 min, with a 30-min rep erfusion interval) followed by a 4-h reperfusion period. Treated anima ls (n=8) received HOE 694 as a bolus (7 mg/kg) 20 min before ischemia and subsequently as a continuous infusion (0.07 mg/kg) throughout the experiment. Control pigs (n=11) received vehicle. Regional wall functi on (percentage of segment shortening, % SS) of the treated animals was significantly improved as compared with that of controls after the 4- h reperfusion period (74.1+/-2.5 vs. 50.9+/-5.4, p<0.005). Ventricular fibrillation (VF) could be prevented completely in treated pigs but o ccurred in 9 of 11 control animals (p<0.001). Ultrastructural changes after ischemia and reperfusion were moderate and slightly abnormal in controls but much milder and completely recovered in the treated group , respectively. The tissue content of high-energy phosphates did not s how a significant difference between groups. Inhibition of the sarcole mmal Na+/H+ antiporter with HOE 694 is antiarrhythmic and diminishes m yocardial ischemic cell injury by preventing Na+ overload.