Myocardial fatty acid metabolism and cardiac performance in heart failure.
It is well established that cardiac metabolism is abnormal in heart failure (HF). Experimental studies suggest that in severe HF, cardiac metabolism reverts to a more fetal-like substrate use characterized by enhanced glucose and downregulated free fatty acid (FFA) metabolism. Correspondingly, in humans, when FFA levels are similar, myocardial glucose metabolism is increased, and FFA metabolism is decreased. However, depression of left ventricular function and insulin resistance induces a shift back to greater FFA uptake and oxidation by increasing circulating FFA availability. Myocardial insulin resistance may further impair myocardial glucose uptake and lead to an energy depletion state. Experimental and preliminary clinical studies suggest that metabolic modulators enhancing myocardial glucose oxidation may improve cardiac function in patients with chronic HF. However, it has been found that acute FFA deprivation is harmful to the cardiac performance. Optimizing myocardial energy metabolism may serve as an additional approach for managing HF, but further studies are warranted.
Tuunanen
Helena
H
Turku PET Centre, Turku University Central Hospital, PO Box 52, FIN-20521 Turku, Finland.
Ukkonen
Heikki
H
Knuuti
Juhani
J
D000255:Adenosine Triphosphate / Q000378:metabolism; D015536:Down-Regulation; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007333:Insulin Resistance; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D010101:Oxygen Consumption; D049268:Positron-Emission Tomography
D005230:Fatty Acids, Nonesterified; D000255:Adenosine Triphosphate; D005947:Glucose