Metabolic aspects of compensatory mechanisms in cardiac failure.
Three metabolic adaptive or compensatory mechanisms of heart failure were discussed: Adaptation of energy production and of energy availability in the myocardial cell. With increased myocardial oxygen demands this is achieved by a progressive displacement of the mass action ratio of the creatine phosphokinase reaction, so that pronounced changes in the creatine phosphate-ratio, related to myocardial oxygen consumption, are accompanied by only small changes in adenosine-5'-triphosphate adenosine-5'-diphosphate and hence in free energy of the adenine-nucleotide system. Adjustment of the oxygen availability by adaptation of the hemoglobin dissociation curve due to an increase in the erythrocyte content of 2, 3-diphosphoglycerate. This is accompanied by a swelling of erythrocytes as a consequence of an increase in the Gibbs-Donnan potential. In patients with congestive heart failure 2,3-diphosphoglycerate-synthesis is augmented due to respiratory alkalosis and increased concentrations of deoxygenated hemoglobin. Increase in the sympathetic drive of the heart due to increased net discharge of the neurotransmitter caused by reduced neuronal reuptake of norepinephrine. The diminished myocardial norepinephrine content in heart failure is due to the diminished neuronal uptake and to insufficient de novo catecholamine synthesis in the heart. Rather than tyrosine-hydroxylase the transformation of dopamine to norepinephrine seems to be the rate limiting step for catecholamine synthesis in heart failure.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D004163:Diphosphoglyceric Acids / Q000378:metabolism; D004734:Energy Metabolism; D004912:Erythrocytes / Q000378:metabolism; D006333:Heart Failure / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000378:metabolism; D013318:Stroke Volume; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*
D004163:Diphosphoglyceric Acids; D006454:Hemoglobins; D010725:Phosphocreatine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009638:Norepinephrine