CLINICAL STUDY: HEART FAILURE
Severe energy deprivation of human hibernating myocardium as possible common pathomechanism of contractile dysfunction, structural degeneration and cell death
Albrecht Elsässer, MD* ,*,
Klaus-Detlev Müller, MD ,
Woitek Skwara, MD,
Christoph Bode, MD*,
Wolfgang Kübler, MD, FRCP and
Achim M. Vogt, MD
* Department of Cardiology, University of Freiburg, Freiburg, Germany
Department of Experimental Cardiology, Max-Planck-Institute for Physiological and Clinical Research (W. G. Kerckhoff-Institute), Bad Nauheim, Germany
Kerckhoff-Clinic, Bad Nauheim, Germany
Department of Cardiology, University of Heidelberg, Heidelberg, Germany
Manuscript received September 27, 2001;
revised manuscript received January 2, 2002,
accepted January 11, 2002.
* Reprint requests and correspondence: Dr. Albrecht Elsässer, Department of Cardiology, University of Freiburg, Hugstetterstr. 3, D-79106 Freiburg, Germany.
elsaesser{at}med1.ukl.uni-freiburg.de
OBJECTIVES: We tested the hypothesis that severe alterations in myocardial energy metabolism play an important role in the pathophysiology of human hibernating myocardium (HHM).
BACKGROUND: It is well established that a disturbed myocardial energy metabolism results in impairments of contractile performance, structure and viability. All of these are important characteristics of HHM.
METHODS: In 16 patients with documented coronary artery disease and impaired left ventricular function, HHM was preoperatively detected by thallium-201 scintigraphy, radionuclide ventriculography and low-dose dobutamine echocardiography. These regions were validated as HHM by their recovery of contractile function three months following revascularization. During open-heart surgery, transmural biopsies were removed from the hibernating areas and analyzed both biochemically and morphologically. These findings were compared to normal human myocardium. All metabolite contents given were normalized for the degree of fibrosis (control: 9.8 ± 0.5%; HHM: 28.1 ± 3.0%; p < 0.05), providing myocellular contents.
RESULTS: In HHM, decreased contents (µmol/g wet weight) in adenosine triphosphate (ATP) (control: 4.17 ± 0.26; HHM: 1.72 ± 0.25; p < 0.001), creatine phosphate (5.67 ± 0.70 vs. 0.84 ± 0.13; p < 0.001) and creatine (27.6 ± 3.19 vs. 11.2 ± 1.56; p < 0.0001) were found, but contents in lactate (2.22 ± 0.26 vs. 25.38 ± 3.53; p < 0.001), purine bases (0.58 ± 0.09 vs. 1.26 ± 0.13; p < 0.001) and protons (pH units: 7.199 ± 0.01 vs. 6.59 ± 0.07; p < 0.001) were increased. Levels in adenosine diphosphate, adenosine monophosphate and inorganic phosphate remained unchanged. Energy depletion in HHM was reflected by decreases in the free energy of ATP hydrolysis and in energy charge.
CONCLUSIONS: These data confirm our hypothesis that HHM is energy-depleted myocardium, exhibiting signs of chronic reduction in resting blood flow and a downregulation of energy turnover. The alterations in energy metabolism observed may become operative in triggering and maintaining contractile dysfunction, continuous tissue degeneration and cardiomyocyte loss.
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Abbreviations and Acronyms
| | ADP | | adenosine diphosphate | | AMP | | adenosine monophosphate | | ANOVA | | analysis of variance | | ATP | | adenosine triphosphate | | CABG | | coronary artery bypass grafting | | CMF | | cellular myocardial fraction | | CP | | creatine phosphate | | Cr | | creatine | | EC | | energy charge | | HEP | | high-energy phosphate | | HHM | | human hibernating myocardium | | HPLC | | high performance liquid chromatography. |
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