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

https://doi.org/10.1016/j.jcin.2012.12.122Get rights and content
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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.

Key Words

calcium cycling
cardiac remodeling
heart failure
left ventricular assist devices
myocardial infarction

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
CaT
Ca2+ transient
CHP
calcium handling protein
EF
ejection fraction
ICa
inward Ca2+ current
LV
left ventricle/ventricular
LVAD
left ventricular assist device
LVEDV
left ventricular end-diastolic volume
LVESV
left ventricular end-systolic volume
MI
myocardial infarction
NCX-1
Na+-Ca2+ exchanger-1
PLB
phospholamban
SERCA-2α
sarco-/endoplasmic reticulum calcium ATPase-2α
SR
sarcoplasmic reticulum

Cited by (0)

The project was funded by the National Institutes of Health/National Heart, Lung, and Blood Institute (grant R01HL 081106 to Dr. Griffith) and by the William G. McGowan Charitable Fund. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.