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 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.
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 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.
Authors: Konstantinos G Malliaras; John V Terrovitis; Stavros G Drakos; John N Nanas Journal: J Cardiovasc Transl Res Date: 2008-09-30 Impact factor: 4.132
Authors: E R Pfeiffer; A T Wright; A G Edwards; J C Stowe; K McNall; J Tan; I Niesman; H H Patel; D M Roth; J H Omens; A D McCulloch Journal: J Mol Cell Cardiol Date: 2014-09-26 Impact factor: 5.000
Authors: Stavros G Drakos; Abdallah G Kfoury; Craig H Selzman; Divya Ratan Verma; John N Nanas; Dean Y Li; Josef Stehlik Journal: Curr Opin Cardiol Date: 2011-05 Impact factor: 2.161