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Metabolic Recovery of Isolated Adult Rat Cardiomyocytes after Energy Depletion: Existence of an ATP Threshold?

https://doi.org/10.1006/jmcc.1998.0805Get rights and content

Abstract

The question was investigated whether cardiomyocytes can be resuscitated after extreme energy depletion, i.e. after loss of ATP >70%. Isolated ventricular cardiomyocytes of the adult rat were exposed to metabolic inhibition with dinitrophenol and cyanide (DNP 0.2 mm; KCN 2 mm). After rapid energy depletion, cells were “reoxygenated” by wash-out of DNP and KCN. Intracellular calcium, cell length, ATP and creatine phosphate (CrP) of the cardiomyocytes were monitored. Metabolic inhibition resulted in a depletion of the stores of ATP and CrP by more than 95% of the normoxic values and caused a cytosolic Ca2+overload. Parameters of metabolic recovery were: (i) resynthesis of CrP; (ii) recovery of a normal cytosolic Ca2+control; and (iii) the elicitation of energy-dependent hypercontracture. “Reoxygenation”, i.e. wash-out of metabolic inhibitors, reactivated oxidative phosphorylation. Consecutively, CrP levels recovered to 76.0±7.3%, ATP levels recovered to 10.4±2.3% (means±s.dn=10) of the initial normoxic values, a normoxic intracellular calcium level was re-established and hypercontracture was elicited. Prolongation of metabolic inhibition with KCN (2 mm) or inhibition of the Na+/K+pump with ouabain (0.5 mm) disabled the cardiomyocytes to recover from cytosolic Ca2+overload and prevented hypercontracture. It is concluded that even after extensive energy depletion metabolic resuscitation of the myocardial cell remains possible and a critical range of ATP for recovery, i.e. a “threshold” of a 70% loss of ATP, does not exist.

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Please address all correspondence to: B. Siegmund, Physiologisches Institut, Justus-Liebig-Universität, Aulweg 129, D-35292 Giessen, Germany.

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