(Circulation. 2000;102:3124.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Hibernation in Noncontracting Mammalian Cardiomyocytes
From the Department of Biochemistry, The University of Western Australia, Nedlands, Australia.
Correspondence to Peter Arthur, PhD, Department of Biochemistry, The University of Western Australia, Nedlands 6907, Australia. E-mail: parthur{at}cyllene.uwa.edu.au
Background—The aim of the present study was to establish whether isolated neonatal mammalian cardiomyocytes were capable of downregulating energy-using processes other than contraction while maintaining metabolic stability when oxygen availability was reduced.
Methods and Results—Metabolic response of cardiomyocytes was investigated under moderate (5 to 6 µmol/L) and severe (2 to 3 µmol/L) forms of hypoxia. Cells exposed to oxygen concentrations of 5 to 6 µmol/L exhibited rates of oxygen consumption, which were decreased to 64% of normoxic rates. Rates of cellular energy usage were decreased because this reduced rate of oxygen consumption was not associated with either decreased intracellular ATP and phosphocreatine concentrations or a compensatory switch to glycolysis. When cells were exposed to oxygen concentrations of 2 to 3 µmol/L, rates of oxygen consumption decreased to 9% of normoxic rates. This decreased rate of oxygen consumption was associated with energetic stress, because a significant switch to glycolysis occurred and intracellular phosphocreatine concentrations were decreased by 40%. Rates of cellular energy usage were further decreased as indicated by stable intracellular ATP concentrations.
Conclusions—Our results suggest that isolated cardiomyocytes are capable of downregulating energy-consuming processes other than contraction when oxygen supply is decreased. Regions of myocardial tissue are also capable of downregulating metabolic activity during ischemia by shutting down contractile activity (myocardial hibernation). We suggest that metabolic downregulation associated with myocardial hibernation may not be exclusively due to reduced rates of contractile activity. Other energy-using processes (eg, protein synthesis, mRNA synthesis, ion channel activity, and proton leak) may also be shut down.
Key Words: hibernation • hypoxia • metabolism • myocytes • respiration
This article has been cited by other articles:
 |
|
 |
|
  E. Rissanen, H. K. Tranberg, and M. Nikinmaa Oxygen availability regulates metabolism and gene expression in trout hepatocyte cultures Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1507 - R1515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Radisic, W. Deen, R. Langer, and G. Vunjak-Novakovic Mathematical model of oxygen distribution in engineered cardiac tissue with parallel channel array perfused with culture medium containing oxygen carriers Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1278 - H1289. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Radisic, L. Yang, J. Boublik, R. J. Cohen, R. Langer, L. E. Freed, and G. Vunjak-Novakovic Medium perfusion enables engineering of compact and contractile cardiac tissue Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H507 - H516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Li, X. Wang, F. Du, Y. Ren, G. Drzewiecki, J. K.-J Li, and J. Kedem Effects of partial ischaemia and volume loading on myocardial efficiency and cardiac performance in dogs Cardiovasc Res, July 1, 2002; 55(1): 122 - 130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Casey, J. L. Pakay, M. Guppy, and P. G. Arthur Hypoxia Causes Downregulation of Protein and RNA Synthesis in Noncontracting Mammalian Cardiomyocytes Circ. Res., April 19, 2002; 90(7): 777 - 783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G.C. Hughes Cellular models of hibernating myocardium: implications for future research Cardiovasc Res, August 1, 2001; 51(2): 191 - 193. [Full Text] [PDF]
|
|
|
|
|
|
T. M. Casey, J. L. Pakay, M. Guppy, and P. G. Arthur Hypoxia Causes Downregulation of Protein and RNA Synthesis in Noncontracting Mammalian Cardiomyocytes Circ. Res., April 19, 2002; 90(7): 777 - 783. [Abstract] [Full Text] [PDF]
|
|