The involvement of lactate and calcium as mediators of the electrical and mechanical responses of the myocardium to conditions of simulated ischaemia

Rat isolated and superfused atria were exposed to a lactate-containing solution simulating the composition of extracellular fluid during myocardial ischaemia (SI). 2. Atria subjected to SI showed a decreased adenosine 5'-triphosphate (ATP) content, a rise in diastolic tension, a diminished conduction velocity of action potentials and shortened refractory periods. All these changes were less pronounced during lactate-free SI. 3. Atria preloaded with calcium displayed exaggerated responses measured electrically and mechanically during exposure to SI, whereas atria previously depleted of calcium displayed diminished electrical and mechanical responses to SI. Neither calcium loading nor calcium depletion modified the SI-induced depletion of the atrial stores of ATP. 4. Sulphinpyrazone protected atria against all aspects of the response to SI, but failed to protect the muscle under conditions of lactate-free SI. It is concluded that during SI, sulphinpyrazone protects against a lactate-mediated inhibition of the glycolytic synthesis of ATP. 5. Flufenamate exaggerated all responses of the atria to SI. These deleterious actions were still observed during lactate-free SI. It is concluded that flufenamate inhibits the synthesis of ATP in the mitochondria.