Copyright © 2003 by the European Society of Cardiology.
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Changes in sarcolemmal Ca entry and sarcoplasmic reticulum Ca content in ventricular myocytes from patients with end-stage heart failure following myocardial recovery after combined pharmacological and ventricular assist device therapy
a Imperial College London, National Heart & Lung Institute, Heart Science Centre, Harefield, UK
b Imperial College London, National Heart & Lung Institute, Cardiac Medicine, London, UK
* Correspondence to: Dr Cesare M.N. Terracciano, Imperial College London, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK. Tel: +44 (0)1895 823 737 ext 5254; fax: +44 (0)1895 828 900
E-mail address: c.terracciano{at}imperial.ac.uk
Received 15 October 2002; revised 15 April 2003; accepted 30 April 2003
Aims Support with left ventricular assist devices (LVAD) improves cardiac performance in patients with end-stage heart failure. In some cases this strategy, combined with pharmacological treatment, has led to a clinical improvement which remained after LVAD explant. This study defines changes in Ca handling at the cellular level in failing left ventricular tissue taken at LVAD implant (LVAD core) and LVAD removal (post-LVAD).
Methods and results We studied cell size and Ca regulation in enzymaticallydissociated cardiac myocytes. We used confocal microscopy and electrophysiological techniques to investigate the SR Ca content and major Ca movements across the sarcolemma during the action potential. We firstly recorded a significant reduction in cell capacitance and cell volume consistent with regression of cellular hypertrophy in post-LVAD myocytes compared with LVAD core myocytes. Ca entry via sarcolemmal Ca channels during the action potential using action potential voltage-clamping was significantly increased in post-LVAD myocytes compared with LVAD cores myocytes. Finally, SR Ca content (assessed by integrating the caffeine-induced Na/Ca exchanger transient inward current) in post-LVAD myocytes was also significantly increased compared with LVAD cores myocytes.
Conclusions These results show that in myocytes from patients after LVAD support there is more Ca entry to trigger Ca release and more SR Ca content, leading to improved contractile function.
Key Words: Heart-assist device Heart failure Calcium Sarcoplasmic reticulum Myocytes
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