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

OBJECTIVES Our goal was to study metabolic energy stores and lactate conten t in chronic reversibly and irreversibly dysfunctional myocardium. BACKGROUND It is unknown whether metabolism is deranged in chronic reversib ly and irreversibly dysfunctional myocardium in humans. Semiquantitative hi stological examinations have shown altered mitochondrial morphology and gly cogen accumulation in dysfunctional regions. METHODS We studied 25 patients with a mean ejection fraction of 38 +/- 9% s cheduled for coronary artery bypass surgery. Regional perfusion and metabol ism were assessed by positron emission tomography, and regional function wa s assessed by echocardiography. Perioperative myocardial biopsies were obta ined from a control region and from a dysfunctional region. We analyzed bio psies for contents of noncollagen protein (NCP), ATP, ADP, AMP, glycogen an d lactate. Six months after surgery we assessed wall motion by echocardiogr aphy to group patients in those with (n = 11) and without (n = 14) function al 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), gl ycogen content (631 +/- 174 and 632 +/- 148 nmol/<mu>g NCP) and lactate lev els (59 +/- 27 and 52 +/- 29 nmol/mug NCP) compared with control regions. I rreversibly 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 upt ake (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. 59 3 +/- 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 reve rsibly dysfunctional myocardium were preserved. In contrast, energy stores were depleted in myocardium without functional recovery after revasculariza tion. (J Am Cell Cardiol 2001;37:100-8) (C) 2001 by the American College of Cardiology.