Optimal hypothermic preservation of arrested myocardium in isolated perfused rabbit hearts: A ³¹P NMR study

The purpose of this study was to (1) relate myocardial high-energy phosphate stores to functional recovery after ischemia and reperfusion, (2) assess the bioenergetics and functional influence of clinically relevant myocardial hypothermia, and (3) examine tissue pH as an independent indicator of postischemic recovery of function. Rabbit hearts were perfused via a modified Langendorff technique, monitored for developed pressure (DP) and left ventricular end-diastolic pressure (LVEDP) via an isovolumic left ventricular balloon catheter, and placed in a Brucker NMR magnet (4.7 tesla) to measure phosphocreatine (PCr), adenosine triphosphate (ATP), and pH. Hearts underwent 1 hour of global ischemia at 7 °, 17 °, 27 ° and 37 °C initiated by one dose of K⁺ cardioplegia followed by 30 minutes of reperfusion. After reperfusion, DP (expressed as a percentage of preischemic control) and LVEDP (mm Hg) in 7 ° and 17 °C hearts were no different (96 + 5% vs 97 ± 3%; 5 ± 2 mm Hg vs 6 ± 2 mm Hg; p = NS), but were better (p < 0.01) than 27 ° hearts (72 ± 6%, 17 ± 6 mm Hg) and 37 ° hearts (31 ± 7%, 60 ± 6 mm Hg). PCr was severely depleted in all groups. ATP was 90 ± 7% and 87 ± 5% of preischemic control in the 7 ° and 17 ° hearts, which was significantly better than the 68 ± 3% and 21 ± 3% in the 27 ° and 37 ° groups (p < 0.01). The pH at end ischemia was 6.83, 6.89, 6.54, and 5.86 for the 7 °, 17 °, 27 °, and 37 ° hearts, respectively (7 ° vs 27 ° or 37 °, p < 0.01; 17 ° vs 27 ° or 37 °, p < 0.01). Linear regression of DP on end-ischemic ATP (EIATP) and end-ischemic pH revealed: DP = 0.96 (EIATP) + 20 (r = 0.92) and DP = 60 (pH) -317 (r = 0.86). We conclude that (1) end-ischemic ATP predicts recovery of ventricular function, and, furthermore, there appears a threshold ATP concentration (80% of control) below which full recovery of function will not occur; (2) end-ischemic pH predicts recovery of ventricular function; (3) 7 °C hypothermic ischemia does not cause a clinically significant cold injury; and (4) in a single-dose crystalloid cardioplegia model, end-ischemic pH is linearly related to recovery of function (r = 0.86).