Beneficial effects of verapamil during metabolic acidosis in isolated perfused rat hearts.

Metabolic acidosis was produced in two groups of isolated, glucose-perfused beating rat hearts. The first group (control) was untreated whereas the second group was pretreated for 48 h by the addition of verapamil (1.2 g/L) to the drinking water. Untreated hearts all developed asystole during a 30 min perfusion with an acidotic substrate (pH = 6.8) or during subsequent reequilibration with physiologic substrate (pH = 7.4). Prior to asystole, all untreated hearts showed evidence of severe mechanical and biochemical deterioration evaluated by 31 P NMR spectroscopy. In contrast, hearts of treated rats showed less mechanical and metabolic deterioration, and all recovered during reequilibration. The mechanism of protection of verapamil against the effects of metabolic acidosis is unclear but appears to be related to preserved mitochondrial function by the drug and not to a reduced demand for energy.