Correlation between cytosolic free calcium, contracture, ATP, and irreversible ischemic injury in perfused rat heart

C. Steenbergen, E. Murphy, J. A. Watts, R. E. London

Research output: Contribution to journalArticle

Abstract

The relations between ATP depletion, increased cytosolic free calcium concentration ([Ca(i)]), contracture development, and lethal myocardial ischemic injury, as evaluated by enzyme release, were examined using 19F nuclear magnetic resonance to measure [Ca(i)] in 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA)-loaded perfused rat hearts. Total ischemia at 37°C was induced in beating hearts, potassium-arrested hearts, magnesium-arrested hearts, and hearts pretreated with 0.9 μM diltiazem to reduce but not abolish contractility. In the beating hearts, time-averaged [Ca(i)], which is intermediate between the systolic and the basal [Ca(i)], was 544 ± 74 nM. In contrast, in the potassium- and magnesium-arrested hearts, the time-averaged values are lower than in the beating hearts (352 ± 88 nM for potassium arrest, 143 ± 22 nM for magnesium arrest). During ischemia, ATP depletion, contracture, and a rise in [Ca(i)] are delayed by cardiac arrest, but all occur more rapidly in the potassium-arrested hearts than in the magnesium-arrested hearts. The diltiazem-treated hearts were generally similar to the magnesium-arrested hearts in their response to ischemia. Under all conditions, contracture development was initiated after tissue ATP had fallen to less than 50% of control; invariably, there was a progressive rise in [Ca(i)] during and following contracture development. Reperfusion with oxygenated perfusate shortly after peak contracture development resulted in a return of [Ca(i)] to its preischemic level, resynthesis of creatine phosphate, no significant enzyme release, and no substantial loss of 5F-BAPTA from the heart. The data demonstrate that an increase in [Ca(i)] precedes lethal myocardial ischemic injury. This rise in [Ca(i)] may accelerate the depletion of cellular ATP and may directly contribute to the development of lethal ischemic cell injury.

Original languageEnglish (US)
Pages (from-to)135-146
Number of pages12
JournalCirculation research
Volume66
Issue number1
DOIs
StatePublished - Jan 1 1990

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Keywords

  • 5F-BAPTA
  • F NMR
  • cytosolic free calcium
  • myocardial ischemia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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