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Figure 2 Effects on infarct size of intracoronary infusion of the Na⁺/H⁺ exchanger (NHE) inhibitor cariporide during various periods, in pig hearts subjected to 60 min of regional low-flow ischemia and 24 h of reperfusion. Infarct size was measured at the end of 24 h of reperfusion by both histochemical and histologic methods. The top panel illustrates the experimental protocol, with the vertically hatched bars indicating the periods of cariporide infusion and the arrows showing the coronary sinus cariporide concentrations (in µmol/l) after 30 min of ischemia, immediately before reperfusion and immediately after reperfusion, in the various study groups. Note that a minimum concentration of approximately 1 µmol/l cariporide is required for effective inhibition of sarcolemmal NHE activity in cardiac ventricular myocytes (24). As shown, infarct size was significantly limited by the intracoronary infusion of cariporide during the first 30 min of ischemia or throughout the entire 60 min of ischemia plus the first 10 min of reperfusion. In contrast, infusion of cariporide during the last 15 min of ischemia plus the first 10 min of reperfusion provided no benefit, even though the coronary sinus cariporide concentrations at the end of ischemia and the beginning of reperfusion were sufficient to inhibit NHE activity. Thus, NHE activity during early ischemia, rather than that during late ischemia and early reperfusion, appears to be the principal determinant of the extent of myocardial infarction. I = ischemia; R = reperfusion, * = p < 0.05 versus control. The figure is based on data from Klein et al. (23).