Injury in Perfused Rat Heart

Abstract

The relations between ATP depletion, increased cytosolic free calcium concentration ([Ca;]), contracture development, and lethal myocardial ischemic injury, as evaluated by enzyme release, were examined using 19F nuclear magnetic resonance to measure [CaiJ in 1,2-bis(2amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA)-loaded perfused rat hearts. Total ischemia at 370 C was induced in beating hearts, potassium-arrested hearts, magnesium-arrested hearts, and hearts pretreated with 0.9 JAM diltiazem to reduce but not abolish contractility. In the beating hearts, time-averaged [Cai], which is intermediate between the systolic and the basal [Cail, was 544±+74 nM. In contrast, in the potassiumand magnesium-arrested hearts, the time-averaged values are lower than in beating hearts (352+88 nM for potassium arrest, 143+±22 nM for magnesium arrest). During ischemia, ATP depletion, contracture, and a rise in [Cal] 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 [Cal] during and following contracture development. Reperfusion with oxygenated perfusate shortly after peak contracture development resulted in a return of [Ca1] 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 [Ca1] precedes lethal myocardial ischemic injury. This rise in [Cal] may accelerate the depletion of cellular ATP and may directly contribute to the development of lethal ischemic cell injury. (Circulation Research 1990;66:135-146)

8 Figures and Tables

Cite this paper

@inproceedings{Steenbergen2005InjuryIP, title={Injury in Perfused Rat Heart}, author={Charles Steenbergen and Elizabeth Jane Murphy and John Albert Watts}, year={2005} }