Increased Ca2+ sensitivity of myofibrillar tension in ischaemic vs dilated cardiomyopathy

Abstract

1. There is evidence that different aetiologies of heart failure, especially ischaemic vs dilated cardiomyopathy (ICM and DCM, respectively), may influence the prognosis of patients with this disease. Patients with ICM have a worse prognosis than those with DCM; the mechanisms underlying this difference have not yet been clarified. The aim of the present study was to investigate whether there are changes in myofibrillar function depending on the aetiology of human heart failure. 2. Ca(2+) -dependent tension (DT) and actomyosin ATPase activity (MYO) in Triton X-skinned fibre preparations of the left ventricular myocardium from patients with heart failure due to ICM (n=5) and DCM (n=5) were measured. Tension-dependent ATP consumption was calculated by the ratio of DT and MYO ('tension cost'). Non-failing myocardium (NF) from donor hearts, which could not be transplanted because of technical reasons, was evaluated as a control. 3. Although DT was reduced, the myofibrillar Ca(2+) sensitivity of DT and MYO, as well as tension cost, were increased in preparations from ICM and DCM myocardium compared with NF. The Ca(2+) sensitivity of DT and MYO was significantly increased in ICM compared with DCM preparations, resulting in more economic cross-bridge cycling in ICM than in DCM. 4. In conclusion, ICM is associated with an increased Ca(2+) sensitivity of myofibrillar tension and ATPase activity accompanied by decreased tension cost compared with DCM. Thus, the worse prognosis associated with ICM does not seem to be due to differences in myofibrillar function.