Myocardial bioenergetics during acute hibernation

Jianyi Zhang, Yutaka Ishibashi, Yi Zhang, Marcel H J Eijgelshoven, Dirk J. Duncker, Hellmut Merkle, Robert J. Bache, Kamil Ugurbil, Arthur H L From

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Abstract

During moderate reductions of blood flow, the myocardium downregulates contractile function and ATP utilization to result in reduced but stable 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 O2 consumption (MV(O2)) (heart rate and systolic blood pressure) on recovery of CP during prolonged moderate myocardial hypoperfusion. 31P-nuclear magnetic resonance spectroscopy was used to measure CP, ATP, and P(i) in the subepicardium (Epi) and subendocardium (Endo) of 13 open-chest dogs. Wall thickening was measured with sonomicrometry. A coronary stenosis reduced 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 ratio from 1.12 ± 0.07 to 0.59 ± 0.06 (P < 0.01), and dyskinesis developed. Coronary blood flow and systolic wall thickening did not change significantly during 4 h of hypoperfusion. Epi CP and ATP fell to 80 ± 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. ΔP(i)/CP increased significantly (Endo > Epi) at the onset of ischemia and then progressively decreased. At 30 min, mild myocardial acidosis was observed in some hearts with variable pH recovery during continuing hypoperfusion. The data demonstrate that variations 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 which CP recovered was significantly correlated with the level of blood flow. Variations in the determinants of MV(O2) did not account for differences in CP recovery.

Original languageEnglish (US)
Pages (from-to)H1452-H1463
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume273
Issue number3
StatePublished - 1997

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Keywords

  • Blood flow
  • Coronary stenosis
  • Creatine phosphate
  • Myocardial ischemia
  • Phosphorus-31 nuclear magnetic resonance spectroscopy

Cite this

Zhang, J., Ishibashi, Y., Zhang, Y., Eijgelshoven, M. H. J., Duncker, D. J., Merkle, H., Bache, R. J., Ugurbil, K., & From, A. H. L. (1997). Myocardial bioenergetics during acute hibernation. American Journal of Physiology - Heart and Circulatory Physiology, 273(3), H1452-H1463.