Response of high-energy phosphates and lactate release during prolonged regional ischemia in vivo

Saul Schaefer, Gregory G. Schwartz, Judith A. Wisneski, Steven D. Trocha, Ian Christoph, Sean K. Steinman, Jorge Garcia, Barry M. Massie, Michael W. Weiner

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Background. The functional impairment of persistently ischemic, or "hibernating," myocardium may serve to maintain myocardial cell viability through a reduction of energy requirements. Although previous studies have, in a variety of experimental models, independently shown variable responses in lactate metabolism and intracellular phosphates during prolonged ischemia, the responses of these metabolites under identical flow conditions have not been adequately described. Methods and Results. To examine the responses of high-energy phosphates and lactate metabolism to prolonged ischemia induced by partial coronary artery stenosis, 12 open-chest pigs were studied using 31P nuclear magnetic resonance spectroscopy. Concurrent measurements of blood flow, segment shortening, high-energy phosphates, and lactate release (in nine animals) were made during 2 hours of regional ischemia. Subendocardial blood flow and segment shortening were persistently depressed during ischemia, with parallel reductions in ATP, phosphocreatine (PCr), and the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). Pi was persistently elevated during the ischemic period. In contrast, lactate release increased significantly from 0.23 ±0.04 to 1.34±0.28 μmol/ml after 15 minutes of ischemia (p<0.05) but then decreased to 0.73±0.17 μmol/ml at 2 hours (p<0.05 versus 15 minutes, p=NS versus control). Similarly, pH increased significantly from a nadir of 6.82±0.07 at 30 minutes of ischemia to 6.98±0.05 at 2 hours. Conclusions. Changes in high-energy phosphates parallel changes in blood flow and function during prolonged ischemia, whereas there is a partial amelioration in lactate production and acidosis. These data support the concept that reduction of myocardial energy requirements during prolonged flow reduction results in signs of reduced ischemia.

Original languageEnglish (US)
Pages (from-to)342-349
Number of pages8
JournalCirculation
Volume85
Issue number1
StatePublished - Jan 1992

Keywords

  • High-energy phosphates
  • Ischemia nuclear
  • Magnetic resonance

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Schaefer, S., Schwartz, G. G., Wisneski, J. A., Trocha, S. D., Christoph, I., Steinman, S. K., Garcia, J., Massie, B. M., & Weiner, M. W. (1992). Response of high-energy phosphates and lactate release during prolonged regional ischemia in vivo. Circulation, 85(1), 342-349.