Cardiac metabolism in myocardial ischemia.
Myocardial ischemia occurs for a mismatch between blood flow and metabolic requirements, when the rate of oxygen and metabolic substrates delivery to the myocardium is insufficient to meet the myocardial energy requirements for a given myocardial workload. During ischemia, substantial changes occur in cardiac energy metabolism, as a consequence of the reduced oxygen availability. Some of these metabolic changes are beneficial and may help the heart adapt to the ischemic condition. However, most of the changes are maladaptive and contribute to the severity of the ischemic injury leading stunned or hibernating myocardium, cell death and ultimately to contractile disfunction. Dramatic changes in cardiac metabolism and contractile function, also occur during myocardial reperfusion as a consequence of the generation of oxygen free radicals, loss of cation homeostasis, depletion of energy stores, and changes in subcellular activities. The reperfusion injury may cause in the death of cardiac myocytes that were still viable immediately before myocardial reperfusion. This form of myocardial injury, by itself can induce cardiomyocyte death and increase infarct size. During acute ischemia the relative substrate concentration is the prime factor defining preference and utilization rate. Allosteric enzyme regulation and protein phosphorylation cascades, partially controlled by hormones such as insulin, modulate the concentration effect; together they provide short-term adjustments of cardiac energy metabolism. The expression of metabolic genes is also dynamically regulated in response to developmental and (patho)physiological conditions, leading to long-term adjustments. Specific nuclear receptor transcription factors and co-activators regulate the expression of these genes. Understanding the functional role of these changes is critical for developing the concept of metabolic intervention for heart disease. The paper will review the alterations in energy metabolism that occur during acute and chronic ischemia.
Rosano
Giuseppe M C
GM
IRCCS San Raffaele, Centre for Clinical and Basic Research, Department of Medical Sciences, Via Della Pisana 235, 00166, Rome, Italy. giuseppe.rosano@sanraffaele.it
Fini
Massimo
M
Caminiti
Giuseppe
G
Barbaro
Giuseppe
G
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*