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

Abstract

The relations between ATP depletion, increased cytosolic free calcium concentration [( Cai]), contracture development, and lethal myocardial ischemic injury, as evaluated by enzyme release, were examined using 19F nuclear magnetic resonance to measure [Cai] 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 degrees C was induced in beating hearts, potassium-arrested hearts, magnesium-arrested hearts, and hearts pretreated with 0.9 microM diltiazem to reduce but not abolish contractility. In the beating hearts, time-averaged [Cai], which is intermediate between the systolic and the basal [Cai], was 544 +/- 74 nM. In contrast, in the potassium- and 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 [Cai] 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 [Cai] during and following contracture development. Reperfusion with oxygenated perfusate shortly after peak contracture development resulted in a return of [Cai] 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 [Cai] precedes lethal myocardial ischemic injury. This rise in [Cai] may accelerate the depletion of cellular ATP and may directly contribute to the development of lethal ischemic cell injury.

The mitochondrial permeability transition pore and its role in cell death

“…This is accompanied by only a small temporary rise in ADP as the adenine nucleotides are degraded to nucleosides and bases [115][116][117]. There is therefore a net loss of adenine nucleotides.…”

Beneficial effects of N‐acetylcysteine and cysteine in stunned myocardium in perfused rat heart

“…Bolli and his colleagues (1988) using electron paramagnetic resonance spectroscopy detected a burst of free radical formation within the coronary venous effluent in dogs subjected to 15min of coronary occlusion and reperfusion; other studies found that production of free radicals increased markedly in isolated hearts of rabbit or rat undergoing global ischaemia and reperfusion (Zweier et al, 1987;Garlick et al, 1987; Kramer et al, 1987) and pretreatment with the oxygen radical-scavenging agents superoxide dismutase and catalase reduced the degree of left ventricular dysfunction in canine models of stunned myocardium (Gross et al, 1986;Ambrosio et al, 1987;. Nevertheless, recent studies also indicate that other factors independent of free radicals are involved in the pathogenesis of myocardial stunning such as: calcium overload (Kusuoka et al, 1987; Lee et al, 1987;Steenbergen et al, 1990;Sun & Lin, 1990), heterogeneous impairment of myocardial perfusion (Stahl et al, 1986) and neutrophil accumulation in the postischaemic myocardium (Westlin & Mullane, 1989) and so on.…”

Influence of ischemic preconditioning in myocardial protection in patients undergoing myocardial revascularization with intermittent crossclamping of the aorta. Analysis of ions and blood gases

“…The decrease in the levels of tissular ATP was followed by a significant increase in intracellular Ca +2 levels 24 . Several authors 19,25,26 suggest that the increase in the intracellular calcium is one of the major determinants of the ischemic lesion, through a calcium-dependent mechanism that activates the catabolic enzymes, leading to irreversible damage of the plasmatic membrane, and determining cellular death.…”