Submitted on August 2, 2004
Accepted on October 6, 2005
Effects of cold cardioplegia on pH, Na, and Ca in newborn rabbit hearts
Steven E Anderson1*, Hong Liu1, Andrea Beyschau1, and Peter M Cala1
1 Physiology and Membrane Biology, University of California, Davis, CA, USA
* To whom correspondence should be addressed. E-mail: seanderson{at}ucdavis.edu.
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] ([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 pHi, Nai, [Ca]i, and ATP in isolated Langendorff-perfused newborn rabbit hearts. Control was 30 min baseline perfusion, 40 min global ischemia, and 40 min reperfusion, all at 37°C. CCC protocols were the same except iced CCC was infused for 5 min prior to ischemia and heart temperature was lowered to 12°C during ischemia. NKCCC was identical to control except for temperature; HKCCC was identical to NKCCC except 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 CCC than control. Similarly, CCC limited increases in Nai during I/R. End ischemia Nai (mEq/kg dry weight) were 115±16 in control, 49±13 in NKCCC, and 37±12 in HKCCC. CCC also improved [Ca]i recovery during reperfusion. After 40 min reperfusion [Ca]i (nmol/L) was 302±50 in control, 145±13 in NKCCC, and 182±19 in HKCCC. CCC limited ATP depletion during ischemia and improved recovery of ATP and left-ventricular developed pressure and decreased CK release during reperfusion. Surprisingly, CCC did not significantly limit [Ca]i during ischemia. The latter is explained as the result of calcium release from intracellular buffers upon cooling.
