CLINICAL STUDY: CORONARY ARTERY DISEASE
Energy stores and metabolites in chronic reversibly and irreversibly dysfunctional myocardium in humans
Henrik Wiggers, MD*,
Morten Noreng, MD ,
Peter K. Paulsen, MD, DMSc ,
Morten Bøttcher, MD*  ,
Henrik Egeblad, MD, DMSc*,
Torsten T. Nielsen, MD, DMSc* and
Hans Erik Bøtker, MD, PhD*
* Department of Cardiology, Skejby Hospital, Aarhus University Hospitals, Aarhus, Denmark
Department of Anaesthesiology, Skejby Hospital, Aarhus University Hospitals, Aarhus, Denmark
Department of Thoracic Surgery, Skejby Hospital, Aarhus University Hospitals, Aarhus, Denmark
Positron Emission Tomography Center, Aarhus General Hospital, Aarhus University Hospitals, Aarhus, Denmark
Manuscript received January 27, 2000;
revised manuscript received July 12, 2000,
accepted September 11, 2000.
Reprint requests and correspondence: Dr. Henrik Wiggers, Department of Cardiology, Skejby Hospital, Aarhus University Hospitals, Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark
henrikwiggers{at}dadlnet.dk
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/µg NCP) and lactate levels (59 ± 27 and 52 ± 29 nmol/µg 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/µg NCP) and increased lactate levels (114 ± 52 vs. 89 ± 24 nmol/µg 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.
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Abbreviations and Acronyms
| | CABG | = coronary artery bypass grafting | | FDG | = 18F-fluoro-2-deoxyglucose | | MBF | = myocardial blood flow | | NCP | = noncollagen protein | | PAS | = periodic acid Schiff | | PET | = positron emission tomography | | WMSI | = wall motion score index |
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