INTRACORONARY AMILORIDE PREVENTS CONTRACTILE DYSFUNCTION OF POSTISCHEMIC STUNNED MYOCARDIUM - ROLE OF HEMODYNAMIC-ALTERATIONS AND INHIBITION OF NA+ H+ EXCHANGE AND L-TYPE CA2+ CHANNELS/

Objectives. This study sought to establish the effect of amiloride on stunned myocardium and to determine the role of hemodynamic alteration s and inhibition of sodium/proton (Na+/H+) exchange and L-type cytosol ic calcium (Ca2+) channels. Background. Amiloride is a nonspecific age nt that may reduce reperfusion injury, but its effect on reversible dy sfunction or stunned myocardium is unclear. Methods. Ninety-seven open chest dogs undergoing 15 min of left anterior descending coronary art ery occlusion and 3 h of reperfusion with monitoring of hemodynamic va riables, systolic shortening and myocardial blood flow were randomized to seven intracoronary infusions: control dogs (5% dextrose, n = 16); low dose amiloride (1 mg/min, n = 14); high dose amiloride (5 mg/min) with (n = 12) and without (n = 16) atrial pacing; sodium nitroprussid e (20 mu g/min, n = 16); hexamethylene amiloride (a specific inhibitor of Na+/H+ exchange, 60 mu g/min, n = 14); and nifedipine (a specific inhibitor of L-type Ca2+ channels, 5 mu g/min, n = 9). Drug infusions were started 40 min before occlusion and stopped at 30 min after reper fusion. Results. Forty-three dogs were excluded because of ventricular fibrillation or high collateral how The incidence of ventricular fibr illation was similar in all groups to that in control dogs. Systolic s hortening completely recovered (p = NS vs. baseline; p < 0.01 vs. cont rol group) by 2 h after reperfusion in the low dose amiloride group an d 30 min in the high dose group (p < 0.01 vs. low dose). High dose ami loride increased myocardial blood dow and had positive inotropic and n egative chronotropic effects (p < 0.05 vs. control group). Atrial paci ng did not attenuate recovery. The only effect of low dose amiloride w as increased myocardial blood how after reperfusion. Systolic shorteni ng did not deteriorate after washout of drug effects. Sodium nitroprus side and nifedipine similarly increased myocardial blood pow, but syst olic shortening never recovered. Hexamethylene amiloride had no hemody namic effects, and systolic shortening never recovered. Conclusions. A miloride prevented the contractile dysfunction of myocardial stunning but did not prevent arrhythmias Hemodynamic alterations, increased myo cardial blood flow and inhibition of Na+/H+ exchange or L-type Ca2+ ch annels alone did not account for the improved function. Inhibition of Na+/Ca2+ exchange may be the mechanism of improved postischemic functi on.