STUDY ON THE ROLE OF Na_+-H_+ EXCHANGE ON ISCHEMIA-REPERFUSION INjURY

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The inhibition of Na<@D1+@>D1-H<@D1+@>D1 exchange (NHE) with amiloride analogues in vitro has been shown to prevent reperfusion arrythmias and additional cell necrosis. Inhibition of intracellular Ca<@D12+@>D1 overload via NHE inhibition has been suggested as a mechanism of these protective effects. The aim of this study was to examine whether treatment with amiloride analogues reduces the incidence of reperfusion arrythmias and limits infarct size in vivo. Open-chest swine were exposed to a 30 min left anterior descending artery occlusion and 180 min reperfusion during atrial pacing at 150 ppm. In protocol 1, intravenous 5-(N,N-dimethyl)-amiloride (AML) 5mug/kg/min was administered 10 min before coronary occlusion in the treatment group (n=7) and intravenous saline in the control group (n=7). In protocol 2, an intravenous bolus injection of AML 1mg/kg was performed 5 min before reperfusion and followed by 5mug/kg/min intravenous injection in the treatment group (n=7) and saline in the … More control group (n=8). There was no significant difference in the size of the area at risk and hemodynamic parameters between the treatment ans control groups both in the protocols. However, the infarcted area was 0.4(]SY.+-。[)1.0% of the area at risk in the treatment group of the protocol 1, whereas it was 62(]SY.+-。[)29% in the control group (p<0.05). The infarcted area in the treatment group of the protocol 2 was also significantly smaller than that in the control group (10.3(]SY.+-。[)7.1% vs.42.3(]SY.+-。[)18.8%, p<0.05). Pathological examination revealed that all of the infarcted area consisted of contraction band necrosis. There was no significant difference in the incidence of ventricular arrhythmias after reperfusion between the groups in the protocols. Inhibition of NHE with AML prevented reperfusion related cell necrosis in the in vivo swine model. This effect was augmented if the drug was administered before ischemia. However, even if the drug was administered after ischemia (before reperfusion), there was significant reduction of the infarcted area. In this experimental model, there was no effect on reperfusion arrhythmia in the both protocols. Less