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.
OBJECTIVE
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).


RESULTS
We studied cell size and Ca regulation in enzymatically dissociated 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.
Terracciano
Cesare M N
CM
Imperial College London, National Heart & Lung Institute, Heart Science Centre, Harefield, UK. c.terracciano@imperial.ac.uk
Harding
Sian E
SE
Adamson
Dawn
D
Koban
Maren
M
Tansley
Patrick
P
Birks
Emma J
EJ
Barton
Paul J R
PJ
Yacoub
Magdi H
MH
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D048429:Cell Size; D003131:Combined Modality Therapy; D004594:Electrophysiology; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy; D006353:Heart-Assist Devices; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*
D015220:Calcium Channels; D002118:Calcium