Patrick Tansley

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

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.

The effect on microvascular function of combined mechanical circulatory support and pharmacological therapy during induction of myocardial recovery

LVAD therapy significantly improved LV ejection fraction (EF%: 21% 3.8% to 37% 11.39%) and cardiac output (CO: 3.49 1.3 to 7.3 0.2 l/m) in all patients with intergroup differences; other parameters were not appreciably altered. After an initial precipitous decline, BNP, ET-1 and NOR serum levels remained significantly lower in all patients. BNP and ET-1 exhibited a striking parallelism. Both manifested a bi-phasic tendency and their trendlines revealed an inverse proportionality to corresponding EF% measurements. In contrast, no discernible pattern could be seen with AT II. Several patients (n 5) exhibited either no attenuation or an increase in BNP plasma levels. All were ICMP patients; most (4/5) suffered from right heart failure postoperatively and showed decreased or unchanged EF%. Conclusions: Plasma BNP and ET-1 levels strongly correlate with the status of LV function. Alterations in these levels during LVAD support may be of potential use as a therapeutic indicator.