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Relevance for LVAD–Recovery
a Heart Science Centre, Imperial College London, National Heart and Lung Institute, Harefield Hospital, Harefield UB9 6JH, United Kingdom
Key Words: heart failure • Na/Ca exchanger • mechanical devices • calcium • remodeling
Address for correspondence: Dr. Cesare M.N. Terracciano, Laboratory of Cell Electrophysiology, Imperial College London, Heart Science Centre, Harefield Hospital, Harefield, Middlesex UB9 6JH, UK. Voice: +44-1895-453-874; fax: +44-1895-828-900. c.terracciano{at}imperial.ac.uk
Different strategies can, at least in certain conditions, prevent or reverse myocardial remodeling due to heart failure and induce myocardial functional improvement. Na+/Ca2+ exchanger (NCX) is considered a major player in the pathophysiology of heart failure but its role in reverse remodeling is unknown. A combination of mechanical unloading by left ventricular assist devices (LVADs) and pharmacological therapy has been shown to induce clinical recovery in a limited number of patients with end-stage heart failure. In myocytes isolated from these patients we found that, after LVAD treatment, NCX1/SERCA2a mRNA was 38% higher than at device implant. We studied the ability of NCX to extrude Ca2+ during caffeine-induced SR Ca2+ release in isolated ventricular myocytes from these patients. The time constant of decline was slower in heart failure. In myocytes from patients with clinical recovery following mechanical and pharmacological treatment, NCX1-mediated Ca2+ extrusion was faster compared with myocytes from patient who, despite identical treatment, did not recover. We propose that increased NCX function may be associated with reverse remodeling in patients and that factors that regulate NCX function (i.e., phosphorylation or intracellular [Na+]) other than NCX expression levels alone, may have detrimental consequences on cardiac function.
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