Nucleotide degradation and functional impairment during cardioplegia: amelioration by inosine
DeWitt, D.F.; Jochim, K.E.; Behrendt, D.M.
Circulation 67(1): 171-178
1983
ISSN/ISBN: 0009-7322 PMID: 6847795 DOI: 10.1161/01.cir.67.1.171
Accession: 006004936
The degradation of adenine nucleotide levels and impairment of functional recovery associated with exposure to hypothermic (20.degree. C) cardioplegia was studied in 84 isolated working rat hearts. After a 1-h control period, hearts were exposed to 1 h of cardioplegia that consisted of increasingly longer periods of cardioplegic solution (CPS) infusion (30 s and 10, 30 and 60 min), followed by increasingly shorter periods of global ischemia (59.5 min and 50, 30 and 0 min). Hearts were then reperfused for 1 h with control perfusate, during which recovery of cardiac output was monitored. Additional hearts were freeze-clamped at various points in the protocols to determine adenine nucleotide levels (ATP, ADP, AMP and their sum TAN [total adenine nucleotides]). Exposure to increasingly longer periods of CPS perfusion resulted in proportionally greater degradation of nucleotides and poorer recovery of cardiac output. Inclusion of inosine in the CPS reduced the degradation of ATP and TAN and improved functional recovery. Addition of inosine to the recovery perfusate as well as the CPS further improved nucleotide levels and recovery of cardiac output. Apparently, washout of nucleotide degradation products in the CPS or reperfusion prevents their salvage for nucleotide resynthesis and impairs functional recovery from cardioplegia.