Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog

R. B. Jennings, H. K. Hawkins, J. E. Lowe, M. L. Hill, S. Klotman, K. A. Reimer

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Abstract

The relationship between progressive depletion of high energy phosphate and the onset of lethal cell injury in ischemic myocardium following coronary occlusion has been evaluated. Myocardial ischemia was induced by proximal occlusion of the circumflex coronary artery for 15, 30, 40, or 60 minutes. Cell injury in the severely ischemic posterior papillary muscle (PP) was evaluated by electron microscopy and by measuring the capacity of slices of the injured PP to maintain electrolytes, resynthesize high energy phosphate, and exclude inulin during in vitro incubation. ATP content in the ischemic myocardium decreased to 35%, 9%, 7%, and 5% of control values after 15, 30, 40, and 60 minutes of ischemia, respectively, and was associated with a corresponding depletion of total adenine nucleotides. The loss of 65% of the ATP after 15 minutes of ischemia (reversible injury) was associated with only minimal ultrastructural changes and no significant defects of electrolytes in incubated slices. However, the depletion of over 90% of the ATP after 40 minutes of ischemia (irreversible injury) was associated with significant fine structural changes and markedly altered cell volume regulation. The results suggest a close relationship between the marked depletion of high energy phosphates and the development of lethal injury in acutely ischemic myocardium.

Original languageEnglish (US)
Pages (from-to)187-214
Number of pages28
JournalAmerican Journal of Pathology
Volume92
Issue number1
StatePublished - Dec 1 1978

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Jennings, R. B., Hawkins, H. K., Lowe, J. E., Hill, M. L., Klotman, S., & Reimer, K. A. (1978). Relation between high energy phosphate and lethal injury in myocardial ischemia in the dog. American Journal of Pathology, 92(1), 187-214.