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 (pHi) 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 (Nai) 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], Nai, and [Ca]iduring ischemia/reperfusion. NMR was used to measure pHi, Nai, [Ca]i, ATP, and PCr in isolated newborn (4–7 days) rabbit hearts Langendorff-perfused with Krebs–Henseleit solution equilibrated with 95% O2/5% CO2at 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, pHiwas higher in PC than control hearts (6.31±0.03v5.83±0.05;P<0.05). Similarly, PC diminished Nai-accumulation during ischemia and reperfusion (P<0.05). Control Nairose 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]irecovery during reperfusion (P<0.05). Control [Ca]irose from 418±43 to 1100±78 (n /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±1.5v56.1±4.1 mmHg at end of reperfusion). Finally, PC improved recovery of left-ventricular developed pressure (LVDP—43.8±12.0v17.2±3.0% of control;P<0.05) and diminished CK release (607±245v2432±639 IU/g dry weight;P<0.05) during reperfusion. The results are consistent with the hypothesis.