Short-Term Mechanical Unloading With Left Ventricular Assist Devices After Acute Myocardial Infarction Conserves Calcium Cycling and Improves Heart Function

Abstract

Objectives This study sought to demonstrate that short-term cardiac unloading with a left ventricular (LV) assist device (LVAD) after acute myocardial infarction (MI) can conserve calcium cycling and improve heart function. Background Heart failure secondary to MI remains a major source of morbidity and mortality. Alterations in calcium cycling are linked to cardiac dysfunction in the failing heart. Methods Adult Dorsett hybrid sheep underwent acute MI and were mechanically unloaded with an axial-flow LVAD (Impella 5.0) for 2 weeks (n = 6). Six sheep with MI only and 4 sham sheep were used as controls. All animals were followed for 12 weeks post-MI. Regional strains in the LV were measured by sonomicrometry. Major calcium-handling proteins (CHPs), including sarco-/endoplasmic reticulum calcium ATPase-2α (SERCA-2α), Na+-Ca2+ exchanger-1, and phospholamban, and Ca2+-ATPase activity were investigated. The electrophysiological calcium cycling in single isolated cardiomyocytes was measured with the patch-clamp technique. The related ultrastructures were studied with electron microscopy. Results LVAD unloading alleviated LV dilation and improved global cardiac function and regional contractility compared with the MI group. The regional myocardial strain (stretch) was minimized during the unloading period and even attenuated compared with the MI group at 12 weeks. Impaired calcium cycling was evident in the adjacent noninfarcted zone in the MI group, whereas CHP expression was normalized and Ca2+-ATPase activity was preserved in the LVAD unloading group. The electrophysiological calcium cycling was also conserved, and the ultrastructural damage was ameliorated in the unloaded animals. Conclusions Short-term LVAD unloading may conserve calcium cycling and improve heart function during the post-infarct period.

Effects of small platform catheter-based left ventricular assist device support on regional myocardial signal transduction

“…Our previous study (5) focused on the effects of LVAD support on regional LV remodeling. Specifically, partial LV unloading with the Impella 5.0 LVAD for only 2 weeks post-MI was found to reduce diastolic strain (i.e., local cardiomyocyte stretch/preloading) in the MI-adjacent zone at up to 12 weeks following MI.…”

“…These are described in detail in (5). In brief, adult Dorsett hybrid sheep (53.2 ± 0.9 kg) were used.…”

“…However, it is less clear whether LV MCS at or around the time of MI actually attenuates pathologic LV remodeling and reduces the extent/severity of LV dysfunction. To address this question, we previously reported the development of a large animal model of MI, and investigated the effects of short-term MCS via the Abiomed Impella small-platform LV assist device (LVAD) on subsequent regional and global pathologic remodeling and systolic function (5). LVAD support for 2 weeks following MI resulted in reduced peri-infarct zone diastolic strains assessed 12 weeks following MI, with improved (increased) peri-infarct zone systolic strains and LV ejection fraction.…”

Attenuation of the unfolded protein response and endoplasmic reticulum stress after mechanical unloading in dilated cardiomyopathy

“…Heerdt et al (15) found that restored contractile function after LVAD correlated with SERCA2a improvement, which has led to novel therapeutic avenues supplementing SERCA2a to the failing myocardium (40). A recent study in sheep with myocardial infarction confirmed preserved SERCA2a levels, calcium cycling, and cardiac function with short-term mechanical support (37). NCX1 levels, which act to compensate decreased cytoplasmic clearance of Ca 2ϩ by SERCA2a (18), were also restored by LVAD support, consistent with animal and human models of HF (8).…”

Impella™ Left Ventricular Assist Device for Acute Peripartum Cardiomyopathy After Cesarean Delivery

“…9 MCADs exert their beneficial effect through multiple pathways and may yield reverse remodeling, conserve calcium cycling, and short-term mechanical unloading. 10,11 The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analyzed 99 women with PPCM between 2006 and 2012. 4 The ventricular assist devices that were used in the INTERMACS registry included total artificial heart, continuous and pulsatile left ventricular assist devices and biventricular assist devices.…”