Metabolic aspects of programmed cell survival and cell death in the heart

Normal cardiac function requires a tight interaction between metabolism, co ntractile function and gene expression. The main perturbation challenging t his equilibrium in vivo is ischemia, which alters energy flux through the c ontrol of key enzymes. The review highlights metabolic imprints and energet ic aspects of programmed cell survival, programmed cell death, and of necro sis. When sustained and severe, ischemia leads to a total collapse of energ y transfer, to the accumulation of metabolic endproducts, and to the develo pment of myocardial necrosis. When moderate; ischemia results in a coordina ted cellular response including enhanced anaerobic glucose metabolism, a mo dification of cardiac gene expression and the development of specific mecha nisms for programmed cell survival (preconditioning, stunning, hibernation) . Repetitive stress results in a decrease of contractile function, a downre gulation of gene expression and an impairment of energy transfer, which eve ntually cause the heart to fail. When the failing heart becomes energy-depl eted, the programs of cell survival are no longer operational and programme d cell death ensues. To define the point of departure from programmed cell survival to cell death remains a major challenge. (C) 2000 Elsevier Science B.V. All rights reserved.