Short-term mechanical unloading with left ventricular assist devices after acute myocardial infarction conserves calcium cycling and improves heart function

Xufeng Wei, Tieluo Li, Brian Hagen, Pei Zhang, Pablo G. Sanchez, Katrina Williams, Shuying Li, Giacomo Bianchi, Ho Sung Son, Changfu Wu, Christopher Defilippi, Kai Xu, William J. Lederer, Zhongjun J. Wu, Bartley P. Griffith

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 Ca 2+-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.

Original languageEnglish
Pages (from-to)406-415
Number of pages10
JournalJACC: Cardiovascular Interventions
Volume6
Issue number4
DOIs
Publication statusPublished - 2013 Apr 1

Fingerprint

Heart-Assist Devices
Myocardial Infarction
Calcium
Equipment and Supplies
Sheep
Calcium-Transporting ATPases
Patch-Clamp Techniques
Cardiac Myocytes
Endoplasmic Reticulum
Adenosine Triphosphatases
Dilatation
Electron Microscopy
Proteins
Heart Failure
Morbidity
Mortality

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Short-term mechanical unloading with left ventricular assist devices after acute myocardial infarction conserves calcium cycling and improves heart function. / Wei, Xufeng; Li, Tieluo; Hagen, Brian; Zhang, Pei; Sanchez, Pablo G.; Williams, Katrina; Li, Shuying; Bianchi, Giacomo; Son, Ho Sung; Wu, Changfu; Defilippi, Christopher; Xu, Kai; Lederer, William J.; Wu, Zhongjun J.; Griffith, Bartley P.

In: JACC: Cardiovascular Interventions, Vol. 6, No. 4, 01.04.2013, p. 406-415.

Research output: Contribution to journalArticle

Wei, X, Li, T, Hagen, B, Zhang, P, Sanchez, PG, Williams, K, Li, S, Bianchi, G, Son, HS, Wu, C, Defilippi, C, Xu, K, Lederer, WJ, Wu, ZJ & Griffith, BP 2013, 'Short-term mechanical unloading with left ventricular assist devices after acute myocardial infarction conserves calcium cycling and improves heart function', JACC: Cardiovascular Interventions, vol. 6, no. 4, pp. 406-415. https://doi.org/10.1016/j.jcin.2012.12.122
Wei, Xufeng ; Li, Tieluo ; Hagen, Brian ; Zhang, Pei ; Sanchez, Pablo G. ; Williams, Katrina ; Li, Shuying ; Bianchi, Giacomo ; Son, Ho Sung ; Wu, Changfu ; Defilippi, Christopher ; Xu, Kai ; Lederer, William J. ; Wu, Zhongjun J. ; Griffith, Bartley P. / Short-term mechanical unloading with left ventricular assist devices after acute myocardial infarction conserves calcium cycling and improves heart function. In: JACC: Cardiovascular Interventions. 2013 ; Vol. 6, No. 4. pp. 406-415.
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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 Ca 2+-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.",
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T1 - Short-term mechanical unloading with left ventricular assist devices after acute myocardial infarction conserves calcium cycling and improves heart function

AU - Wei, Xufeng

AU - Li, Tieluo

AU - Hagen, Brian

AU - Zhang, Pei

AU - Sanchez, Pablo G.

AU - Williams, Katrina

AU - Li, Shuying

AU - Bianchi, Giacomo

AU - Son, Ho Sung

AU - Wu, Changfu

AU - Defilippi, Christopher

AU - Xu, Kai

AU - Lederer, William J.

AU - Wu, Zhongjun J.

AU - Griffith, Bartley P.

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N2 - 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 Ca 2+-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.

AB - 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 Ca 2+-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.

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KW - cardiac remodeling

KW - heart failure

KW - left ventricular assist devices

KW - myocardial infarction

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