HOE 694 significantly improved regional wall function (% segment shortening 74.1 vs 50.9, p<0.005) and completely prevented ventricular fibrillation in a porcine model of ischemia/reperfusion.
Does HOE 694 improve regional wall function and prevent ventricular fibrillation in a porcine model of ischemia/reperfusion?
Inhibition of the Na+/H+ antiporter with HOE 694 diminishes myocardial ischemic cell injury and prevents ventricular fibrillation in a porcine model.
Absolute Event Rate: 74.1% vs 50.9%
p-value: p=< 0.005
We investigated the effects of a new compound (3-methylsulfonyl-4-piperidinobenzoyl) 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 reperfusion interval) followed by a 4-h reperfusion period. Treated animals (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 function (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 occurred 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 show a significant difference between groups. Inhibition of the sarcolemmal Na+/H+ antiporter with HOC 694 is antiarrhythmic and diminishes myocardial ischemic cell injury by preventing Na+ overload.
Sack et al. (1994) studied Ischemia/reperfusion (n=19). HOE 694 vs. Vehicle was evaluated on Regional wall function (percentage of segment shortening) (p=< 0.005). HOE 694 significantly improved regional wall function (% segment shortening 74.1 vs 50.9, p<0.005) and completely prevented ventricular fibrillation in a porcine model of ischemia/reperfusion.