© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
Inorganic phosphate content and free energy change of ATP hydrolysis in regional short-term hibernating myocardium
Abteilung für Pathophysiologie, Zentrum für Innere Medizin des Universitätsklinikums, Essen, 45122 Essen, Federal Republic of Germany
* Corresponding author. Tel.: +49 (201) 723 4480; Fax: +49 (201) 723 4481; E-mail: gerd.heusch@uni-essen.de
Objective: Short-term myocardial hibernation is characterized by an adaptation of contractile function to the reduced blood flow, the recovery of creatine phosphate content and lactate balance back towards normal, whereas ATP content remains reduced at a constant level. We examined the hypothesis that, despite the absence of ATP recovery, the short-term hibernating myocardium regains an energetic balance. Methods: An enzymatic method was modified for the measurement of inorganic phosphate (Pi) in transmural myocardial drill biopsies (about 5 mg). In 12 anaesthetized swine, moderate ischemia was induced by reduction of coronary inflow into the cannulated left anterior descending coronary artery to decrease regional myocardial function (sonomicrometry) by 50%. Results: The development of short-term hibernation was verified by the recovery of creatine phosphate content, the persistence of inotropic reserve in response to dobutamine and the absence of necrosis (triphenyl tetrazolium chloride). At 5-min ischemia, Pi was increased from 3.6±0.3 (SD) to 8.1±1.1 µmol/gwet wt (p<0.05). The free energy of ATP hydrolysis (
GATP) was decreased from –57.8±0.8 to –52.2±1.4 kJ/mol (p<0.05). The relationships between function and Pi (r=–0.81) and GATP (r=–0.83), respectively, during control and at 5-min ischemia became invalid at 90-min ischemia, as myocardial blood flow and function remained reduced at a constant level, but Pi decreased back to 4.9±0.9 µmol/g (p<0.05 vs. control and 5-min ischemia), and GATP fully recovered back to –57.2±1.3 kJ/mol (p<0.05 vs. 5-min ischemia). Conclusions: In short-term hibernating myocardium, myocardial inorganic phosphate content recovers partially and the free energy change of ATP hydrolysis returns to control values. Contractile function remains reduced by mechanisms other than an energetic deficit.
KEYWORDS Short-term hibernation; Swine; Inorganic phosphate; Free energy of ATP hydrolysis
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