Effects of unloading on the failing myocardium

Studies on cardiac myocytes from patients treated with LVADs: Left ventricular assist devices (LVADs) are an effective treatment for end-stage heart failure. In a limited number of patients, when associated with pharmacological therapy (“combination therapy”), this treatment leads to substantial clinical improvement (Yacoub, European Heart Journal, 2001) . Cardiomyocytes isolated from biopsies taken after LVAD treatment showed reductions in cell volume and cell surface area compared with cardiomyocytes from tissue taken at implantation of the device. L-type Ca current and sarcoplasmic reticulum (SR) Ca content were increased in myocytes from treated hearts (Terracciano et al. , European Heart Journal 2003) . To correlate the cellular electrophysiological properties with the clinical outcome we compared measurements in cardiomyocytes obtained from tissue taken at LVAD explantation in patients with clinical recovery with those obtained from hearts of patients who, despite identical treatment, did not show clinical recovery and their ejection fraction off-pump remained low after treatment, thus requiring transplantation. We found that alterations in excitation-contraction coupling, and sarcoplasmic reticulum (SR) Ca handling in particular, are a key functional determinant for clinical recovery. In contrast, regression of cellular hypertrophy did not appear to be a determining factor (Terracciano et al., Circulation 2004).

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