Energy stores and metabolites in chronic reversibly and irreversibly dysfunctional myocardium in humans

OBJECTIVES Our goal was to study metabolic energy stores and lactate content in chronic reversibly and irreversibly dysfunctional myocardium. BACKGROUND It is unknown whether metabolism is deranged in chronic reversibly and irreversibly dysfunctional myocardium in humans. Semiquantitative histological examinations have shown altered mitochondrial morphology and glycogen accumulation in dysfunctional regions. METHODS We studied 25 patients with a mean ejection fraction of 38 +/- 9% scheduled for coronary artery bypass surgery. Regional perfusion and metabolism were assessed by positron emission tomography, and regional function was assessed by echocardiography. Perioperative myocardial biopsies were obtained from a control region and from a dysfunctional region. We analyzed biopsies for contents of noncollagen protein (NCP), ATP, ADP, AMP, glycogen and lactate. Six months after surgery we assessed wall motion by echocardiography to group patients in those with (n = 11) and without (n = 14) functional improvement. RESULTS Reversibly dysfunctional myocardium had reduced perfusion (0.59 +/- 0.16 vs. 0.69 +/- 0.20 ml/g/min, p < 0.05), similar glucose-tracer uptake (92 +/- 12 and 95 +/- 14%), ATP/ADP ratio (2.4 +/- 1.1 and 2.4 +/- 0.7), glycogen content (631 +/- 174 and 632 +/- 148 nmol/<mu>g NCP) and lactate levels (59 +/- 27 and 52 +/- 29 nmol/mug NCP) compared with control regions. Irreversibly dysfunctional regions (n = 14) had severely reduced perfusion (0.48 +/- 0.15 vs. 0.72 +/- 0.12 ml/g/min, p < 0.001) and glucose-tracer uptake (52 +/- 16 vs. 94 +/- 15%, p < 0.001), reduced ATP/ADP ratio (1.5 +/- 0.9 vs. 2.3 +/- 0.9, p < 0.05), similar glycogen content (579 +/- 265 vs. 593 +/- 127 nmol/<mu>g NCP) and increased lactate levels (114 +/- 52 vs. 89 +/- 24 nmol/mug NCP, p < 0.01) compared with control regions. CONCLUSIONS Contents of metabolic energy stores and lactate in chronic reversibly dysfunctional myocardium were preserved. In contrast, energy stores were depleted in myocardium without functional recovery after revascularization. (J Am Cell Cardiol 2001;37:100-8) (C) 2001 by the American College of Cardiology.