Metabolic aspects of compensatory mechanisms in cardiac failure

Summary

Three metabolic adaptive or compensatory mechanisms of heart failure were discussed:

• 1. Adaptation of energy production and 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 CPK reaction, so that pronounced changes in the CP/C ratio, related to myocardial oxygen consumption, are accompanied by only small changes in ATP/ADP and hence in free energy of the adeninenucicotide system.

• 2. Adjustment of the oxygen availability by adaptation of the hemoglobin dissociation curve due to an increase in the erythrocyte content of 2,3-DPG. 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-DPG-synthesis is augmented due to respiratory alcalosis and increased concentrations of deoxygenated hemoglobin.

• 3. 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-tiydroxylase the transformation of dopamine to norepinephrine seems to be the rate limiting step for catecholamine synthesis in heart failure.

The studies have been supported by a grant from the Deutsche Forschungsgemeinschaft within the SFB 90 — kardiovaskuläres System — University of Heidelberg/Germany