Is force production in the myocardium directly dependent upon the free energy change of ATP hydrolysis?

We believe that the weight of present evidence suggests that acute contractile failure in hypoxic or ischaemic cardiac muscle is accompanied by a fall in A but this fall is not the direct cause of the reduced force production. The main established causes of acute contractile failure are the effects of intracellular pH and of Pi accumulation on the contractile proteins and, at a later stage, failure of calcium release. It is worth stressing the role of Pi accumulation both because the effects of Pi have only been recognised relatively recently and because it has a large depressant effect. Pi accumulation is the best candidate to explain the rapid fall of force which occurs during hypoxia and ischaemia when ATP levels are unchanged and before pH changes are substantial.