Ischemic preconditioning: Effects on pH, Na and Ca in newborn rabbit hearts during ischemia/reperfusion

In adult hearts, ischemic preconditioning (PC) has been shown to decrease ischemia-induced changes in intracellular pH (pH(i)) and [Ca] ([Ca](i)) and decrease associated injury. These results are consistent with the interpretation that PC decreases the stimulus for Na uptake via Na/H exchange, thereby decreasing intracellular Na (Na-i) accumulation, and thus decreasing the change in force driving Na/Ca exchange, which otherwise contributes to ischemia-induced increases in [Ca](i). Given documented age-related differences in myocardial responses to ischemia, we tested the hypothesis that in newborn hearts, PC will diminish intracellular [H], Na-i, and [Ca](i) during ischemia/reperfusion. NMR was used to measure pH(i). Na-i, [Ca](i), ATP, and PCr in isolated newborn (4-7 days rabbit hearts Langendorff-perfused with Krebs-Henseleit solution equilibrated with 95% O-2/5% CO2 at 36 +/- 1 degrees C. Control hearts were perfused 30 min before initiating 40 min global ischemia followed by 40 min reperfusion. PC hearts were treated the same except four 5-min intervals of ischemia each followed by 10 min of perfusion which preceded global ischemia. At end ischemia, pH(i) was higher in PC than control hearts (6.31 +/- 0.03 v 5.83 +/- 0.05; P<0.05). Similarly, PC diminished Na-i-accumulation during ischemia and reperfusion (P<0.05). Control Na-i rose from 16.2 +/- 2.6 to 108.8 +/- 10.3 (mEq/kg dry weight) and recovered to 55.2 +/- 10.1 and the corresponding values for PC hearts were 25.6 +/- 6.2, 70.0 +/- 7.9 and 21.9 +/- 5.2. PC also improved [Ca](i) recovery during reperfusion (P<0.05). Control [Ca](i) rose from 418 +/- 43 to 1100 +/- 78 (nM/l) and recovered to 773 +/- 63, whereas in PC hearts the values were 382 +/- 40, 852 +/- 136 and 371 +/- 45, respectively. In addition, PC decreased coronary resistance during reperfusion (P<0.05) as reflected by lower perfusion pressures under constant now conditions (65.9 +/- 1.5 v 56.1 +/- 4.1 mmHg at end of reperfusion). Finally, PC improved recovery of left-ventricular developed pressure (LVDP-43.8 +/- 12.0 v 17.2 +/- 3.0% of control; P<0.05) and diminished CK release (607 +/- 245 v 2432 +/- 639 IU/ g dry weight; P<0.05) during reperfusion. The results are consistent with the hypothesis. (C) 1998 Academic Press Limited.