Energetic myocardial metabolism and oxidative stress: let's make them our friends in the fight against heart failure.
Heart failure (HF) is a syndrome causing a huge burden in morbidity and mortality worldwide. Current medical therapies for HF are aimed at suppressing the neurohormonal activation. However, novel therapies are needed for HF, independent of the neurohormonal axis, that can improve cardiac performance and prevent the progression of heart dysfunction. The modulation of cardiac metabolism may represent a new approach to the treatment of HF. The healthy heart converts chemical energy stored in fatty acids (FA) and glucose. Utilization of FA costs more oxygen per unit of ATP generated than glucose, and the heart gets 60-90% of its energy for oxidative phosphorylation from FA oxidation. The failing heart has been demonstrated to be metabolically abnormal, in both animal models and in patients, showing a shift toward an increased glucose uptake and utilization. The manipulation of myocardial substrate oxidation toward greater carbohydrate oxidation and less FA oxidation may improve ventricular performance and slow the progression of heart dysfunction. Impaired mitochondrial function and oxidative phosphorylation can reduce cardiac function by providing an insufficient supply of ATP to cardiomyocytes and by increasing myocardial oxidative stress. Although there are no effective stimulators of oxidative phosphorylation, several classes of drugs have been shown to open mitochondrial K(ATP) channels and, indirectly, to improve cardiac protection against oxidative stress. This article focuses on the energetic myocardial metabolism and oxidative status in the normal and failing heart, and briefly, it overviews the therapeutic potential strategies to improve cardiac energy and oxidative status in HF patients.
Scolletta
Sabino
S
Department of Surgery and Bioengineering, Unit of Cardiothoracic Anaesthesia and Intensive Care, University of Siena, Viale Bracci 1, Siena, Italy. scolletta@unisi.it
Biagioli
Bonizella
B
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D052281:Creatine Kinase, Mitochondrial Form / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006333:Heart Failure / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010101:Oxygen Consumption; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D013379:Substrate Specificity
D002317:Cardiovascular Agents; D005227:Fatty Acids; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D052281:Creatine Kinase, Mitochondrial Form; D005947:Glucose