MYOCARDIAL BIOENERGETICS DURING ACUTE HIBERNATION

During moderate reductions of blood flow, the myocardium downregulates contractile function and ATP utilization to result in reduced but sta ble ATP levels, recovery or stability of (reduced) creatine phosphate (CP), and preservation of myocyte viability. The intent of this study was to determine the influence of the level of ischemic blood flow and the major determinants of myocardial O-2 consumption (M(V) over dot o (2)) (heart rate and systolic blood pressure) on recovery of CP during prolonged moderate myocardial hypoperfusion. P-31-nuclear magnetic re sonance spectroscopy was used to measure CP, ATP, and P-i in the subep icardium (Epi) and subendocardium (Endo) of 13 open-chest dogs. Wall t hickening was measured with sonomicrometry. A coronary stenosis reduce d mean myocardial blood flow (microspheres) from 1.10 +/- 0.07 to 0.71 +/- 0.06 ml.g(-1).min(-1) (P < 0.01) and the Endo-to-Epi blood flow r atio from 1.12 +/- 0.07 to 0.59 +/- 0.06 (P < 0.01), and dyskinesis de veloped. Coronary blood flow and systolic wall thickening did not chan ge significantly during 4 h of hypoperfusion. Epi CP and ATP fell to 8 0 +/- 4% (P < 0.05) and 93 +/- 3% of control, respectively, at 30 min. Epi CP then recovered to 87 +/- 5% while ATP decreased further to 83 +/- 5% of baseline by the end of the 240-min ischemic period. Endo CP and ATP fell to 53 +/- 4 and 77 +/- 5% of control, respectively, at 30 min; then Endo CP recovered to 85 +/- 6% while ATP decreased further to 68 +/- 6% of baseline at 240 min of hypoperfusion. ADP levels were significantly increased at 30 min but recovered to baseline by 240 min of hypoperfusion. Delta P-i/CP increased significantly (Endo > Epi) a t the onset of ischemia and then progressively decreased. At 30 min, m ild myocardial acidosis was observed in some hearts with variable pH r ecovery during continuing hypoperfusion. The data demonstrate that var iations in blood flow cannot account for the magnitude of the initial fall in CP or for the final extent of recovery. However, the rate at w hich CP recovered was significantly correlated with the level of blood flow. Variations in the determinants of M(V) over dot o(2) did not ac count for differences in CP recovery.