Anaerobic glycolysis and the development of ischaemic contracture in isolated rat heart

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Abstract
The relationship between myocardial ATP content and the increase in left ventricular resting tension during ischaemia (ischaemic contracture) was studied in isolated rat hearts perfused for 15 min either with aerobic buffer (pO2>500 mmHg) containing non-glycolytic substrate, acetate (5 mmol·litre−1), or with hypoxic buffer (pO2< 10 mmHg) with glucose (10 mmol·litre−1) before making them totally ischaemic for 10 min. ATP was determined spectrophotometrically from extracts of frozen whole hearts. Left ventricular tension was recorded by intraventricular balloon catheter. Myocardial ATP content was 15.4±1.0 μmol·g−1 dry weight μmol·g−1) after 10 min stabilising period, 14.1±0.9 μmol·g−1 after 15 min aerobic perfusion (plus acetate) and 9.0±1.3 μmol·g−1 after 15 min hypoxic perfusion (plus glucose). During 10 min of ischaemia ATP decreased in aerobic hearts to 5.4 ± 1.1 μmol·g−1 and to 7.9 ± 1.0 μmol·g−1 in hypoxic hearts. The left ventricular resting tension increased during ischaemia in hypoxic hearts to 9±5% of control systolic pressure (0=diastolic pressure, 100=systolic pressure during stabilising period), whereas in aerobic hearts the tension began to increase immediately and was 84±22% of systolic pressure at the end of the ischaemic period. In parallel control experiments, hearts were also perfused either with glucose-containing aerobic buffer or acetate-containing hypoxic buffer. ATP was well preserved during aerobic perfusion (plus glucose) but decreased markedly during hypoxic perfusion (plus acetate). There was no increase in resting tension in the aerobic hearts (plus glucose) whereas the resting tension increased considerably during hypoxic perfusion (plus acetate). The results indicate that the initiation of ischaemic contracture occurs at much higher myocardial ATP level when ATP comes from mitochondrial sources than when ATP is generated by anaerobic glycolysis. The difference may be due to intracellular compartmentalisation of ATP providing different amounts of ATP available for contractile proteins or for cellular membranes to maintain calcium homeostasis.