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% O₂/5% CO₂ at 36 ± 1°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, 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 flow 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.