Many studies suggest myocardial ischemia-reperfusion (I/R) injury results largely from cytosolic proton (Hi)-stimulated increases in cytosolic Na (Nai), which cause Na/Ca exchange-mediated increases in cytosolic Ca concentration ([Ca]i). Because cold, crystalloid cardioplegia (CCC) limits [H]i, we tested the hypothesis that in newborn hearts, CCC diminishes Hi, Nai, and Cai accumulation during I/R to limit injury. NMR measured intracellular pH (pHi), Nai, [Ca]i, and ATP in isolated Langendorff-perfused newborn rabbit hearts. The control ischemia protocol was 30 min for baseline perfusion, 40 min for global ischemia, and 40 min for reperfusion, all at 37°C. CCC protocols were the same, except that ice-cold CCC was infused for 5 min before ischemia and heart temperature was lowered to 12°C during ischemia. Normal potassium CCC solution (NKCCC) was identical to the control perfusate, except for temperature; the high potassium (HKCCC) was identical to NKCCC, except that an additional 11 mmol/l KCl was substituted isosmotically for NaCl. NKCCC and HKCCC were not significantly different for any measurement. The following were different (P < 0.05). End-ischemia pHi was higher in the CCC than in the control group. Similarly, CCC limited increases in Nai during I/R. End-ischemia Nai values (in meq/kg dry wt) were 115 ± 16 in the control group, 49 ± 13 in the NKCCC group, and 37 ± 12 in the HKCCC group. CCC also improved [Ca]i recovery during reperfusion. After 40 min of reperfusion, [Ca]i values (in nmol/l) were 302 ± 50 in the control group, 145 ± 13 in the NKCCC group, and 182 ± 19 in the HKCCC group. CCC limited ATP depletion during ischemia and improved recovery of ATP and left ventricular developed pressure and decreased creatine kinase release during reperfusion. Surprisingly, CCC did not significantly limit [Ca]i during ischemia. The latter is explained as the result of Ca release from intracellular buffers on cooling.
|Original language||English (US)|
|Journal||American Journal of Physiology - Heart and Circulatory Physiology|
|State||Published - Mar 2006|
- Na/Ca exchanger
- Na/H exchanger
- Nuclear magnetic resonance
ASJC Scopus subject areas