Comparison of the protective effects of ischemic preconditioning and the Na⁺/H⁺ exchanger blockade

The protective effects of ischemic preconditioning (IP) and Na⁺/H⁺ exchanger blockade (NHE(b)) by two blockers [ethylisopropylamiloride (EIPA) and HOE 642] were compared in the isovolumic perfused rat heart. The impairment in systolic and diastolic function detected in control ischemic hearts (C) exposed to 20 min of ischemia and 30 min of reperfusion was diminished in similar extent by IP and by NHE(b) with EIPA and HOE 642. At the end of the reperfusion period +dP/dt(max) values were 57 ± 9% in C hearts and 94 ± 6%, 82 ± 6% and 104 ± 6% after IP and NHE(b) with EIPA and HOE 642, respectively. A depletion of ATP levels detected in C hearts after reperfusion (from 20.2 ± 0.8 μmol/g dry weight before ischemia to 6.9 ± 0.7 μmol/g dry weight) was partially prevented by both IP and NHE(b) with EIPA (9.2 ± 0.7 μmol/g dry weight and 11.1 ± 0.5 μmol/g dry weight, respectively). The ischemic contracture (IC), assessed by the left ventricular end diastolic pressure (LVEDP), observed in C hearts (35 ± 4 mmHg) was not decreased by IP (40 ± 4 mmHg) but it was prevented by NHE(b) (18 ± 4 mmHg and 10 ± 3 mmHg with EIPA and HOE 642, respectively). The ATP levels at the end of the ischemic period were similar in C and IP hearts (4.1 ± 0.2 μmol/g dry wt vs. 3.3 ± 0.4 μmol/g dry wt) but they were significantly higher after NHE(b) with HOE 642 (7.0 ± 1.0 μmol/g dry wt). PKC inhibition by chelerythrine abolished the protection induced by IP after reperfusion although not the improvement induced by NHE(b) with EIPA. According to the present results, we can conclude that despite the fact that IP and NHE(b) are protecting the postischemic function in a similar magnitude, both interventions are different in terms of modifying IC that develops during the ischemic period. IC was prevented by NHE(b) whereas it was not by IP. Furthermore, IP protection and not that obtained by NHE(b) is abolished by PKC.