Incomplete recovery of myocyte contractile function despite improvement of myocardial architecture with left ventricular assist device support

Amrut V. Ambardekar, John S. Walker, Lori A. Walker, Joseph C. Cleveland, Brian D. Lowes, Peter M. Buttrick

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background-Unloading a failing heart with a left ventricular assist device (LVAD) can improve ejection fraction (EF) and LV size; however, recovery with LVAD explantation is rare. We hypothesized that evaluation of myocyte contractility and biochemistry at the sarcomere level before and after LVAD may explain organ-level changes. Methods and Results-Paired LV tissue samples were frozen from 8 patients with nonischemic cardiomyopathy at LVAD implantation (before LVAD) and before cardiac transplantation (after LVAD). These were compared with 8 nonfailing hearts. Isolated skinned myocytes were purified and attached to a force transducer, and dimensions, maximum calcium-saturated force, calcium sensitivity, and myofilament cooperativity were assessed. Relative isoform abundance and phosphorylation levels of sarcomeric contractile proteins were measured. With LVAD support, the unloaded EF improved (10.0±1.0% to 25.6±11.0%, P=0.007), LV size decreased (LV internal dimension at end diastole, 7.6±1.2 to 4.9±1.4 cm; P<0.001), and myocyte dimensions decreased (cross-sectional area, 1247±346 to 638±254 μm2; P=0.001). Maximum calcium-saturated force improved after LVAD (3.6±0.9 to 7.3±1.8 mN/mm2, P<0.001) implantation but was still lower than in nonfailing hearts (7.3±1.8 versus 17.6±1.8 mN/mm2, P<0.001). An increase in troponin I (TnI) phosphorylation after LVAD implantation was noted, but protein kinase C phosphorylation of TnI decreased. Biochemical changes of other sarcomeric proteins were not observed after LVAD. Conclusions-There is significant improvement in LV and myocyte size with LVAD, but there is only partial recovery of EF and myocyte contractility. LVAD support was associated only with biochemical changes in TnI, suggesting that alternate mechanisms might contribute to contractile changes after LVAD and that additional interventions may be needed to alter biochemical remodeling of the sarcomere to further enhance myofilament and organ-level recovery. (Circ Heart Fail. 2011;4:425-432.).

Original languageEnglish (US)
Pages (from-to)425-432
Number of pages8
JournalCirculation: Heart Failure
Volume4
Issue number4
DOIs
StatePublished - Jul 1 2011

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Heart-Assist Devices
Muscle Cells
Troponin I
Sarcomeres
Myofibrils
Phosphorylation
Calcium
Contractile Proteins
Diastole
Heart Transplantation
Transducers
Cardiomyopathies
Biochemistry
Protein Kinase C
Protein Isoforms

Keywords

  • Heart failure
  • Ventricle-assist device
  • Ventricular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Incomplete recovery of myocyte contractile function despite improvement of myocardial architecture with left ventricular assist device support. / Ambardekar, Amrut V.; Walker, John S.; Walker, Lori A.; Cleveland, Joseph C.; Lowes, Brian D.; Buttrick, Peter M.

In: Circulation: Heart Failure, Vol. 4, No. 4, 01.07.2011, p. 425-432.

Research output: Contribution to journalArticle

Ambardekar, Amrut V. ; Walker, John S. ; Walker, Lori A. ; Cleveland, Joseph C. ; Lowes, Brian D. ; Buttrick, Peter M. / Incomplete recovery of myocyte contractile function despite improvement of myocardial architecture with left ventricular assist device support. In: Circulation: Heart Failure. 2011 ; Vol. 4, No. 4. pp. 425-432.
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abstract = "Background-Unloading a failing heart with a left ventricular assist device (LVAD) can improve ejection fraction (EF) and LV size; however, recovery with LVAD explantation is rare. We hypothesized that evaluation of myocyte contractility and biochemistry at the sarcomere level before and after LVAD may explain organ-level changes. Methods and Results-Paired LV tissue samples were frozen from 8 patients with nonischemic cardiomyopathy at LVAD implantation (before LVAD) and before cardiac transplantation (after LVAD). These were compared with 8 nonfailing hearts. Isolated skinned myocytes were purified and attached to a force transducer, and dimensions, maximum calcium-saturated force, calcium sensitivity, and myofilament cooperativity were assessed. Relative isoform abundance and phosphorylation levels of sarcomeric contractile proteins were measured. With LVAD support, the unloaded EF improved (10.0±1.0{\%} to 25.6±11.0{\%}, P=0.007), LV size decreased (LV internal dimension at end diastole, 7.6±1.2 to 4.9±1.4 cm; P<0.001), and myocyte dimensions decreased (cross-sectional area, 1247±346 to 638±254 μm2; P=0.001). Maximum calcium-saturated force improved after LVAD (3.6±0.9 to 7.3±1.8 mN/mm2, P<0.001) implantation but was still lower than in nonfailing hearts (7.3±1.8 versus 17.6±1.8 mN/mm2, P<0.001). An increase in troponin I (TnI) phosphorylation after LVAD implantation was noted, but protein kinase C phosphorylation of TnI decreased. Biochemical changes of other sarcomeric proteins were not observed after LVAD. Conclusions-There is significant improvement in LV and myocyte size with LVAD, but there is only partial recovery of EF and myocyte contractility. LVAD support was associated only with biochemical changes in TnI, suggesting that alternate mechanisms might contribute to contractile changes after LVAD and that additional interventions may be needed to alter biochemical remodeling of the sarcomere to further enhance myofilament and organ-level recovery. (Circ Heart Fail. 2011;4:425-432.).",
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AU - Lowes, Brian D.

AU - Buttrick, Peter M.

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N2 - Background-Unloading a failing heart with a left ventricular assist device (LVAD) can improve ejection fraction (EF) and LV size; however, recovery with LVAD explantation is rare. We hypothesized that evaluation of myocyte contractility and biochemistry at the sarcomere level before and after LVAD may explain organ-level changes. Methods and Results-Paired LV tissue samples were frozen from 8 patients with nonischemic cardiomyopathy at LVAD implantation (before LVAD) and before cardiac transplantation (after LVAD). These were compared with 8 nonfailing hearts. Isolated skinned myocytes were purified and attached to a force transducer, and dimensions, maximum calcium-saturated force, calcium sensitivity, and myofilament cooperativity were assessed. Relative isoform abundance and phosphorylation levels of sarcomeric contractile proteins were measured. With LVAD support, the unloaded EF improved (10.0±1.0% to 25.6±11.0%, P=0.007), LV size decreased (LV internal dimension at end diastole, 7.6±1.2 to 4.9±1.4 cm; P<0.001), and myocyte dimensions decreased (cross-sectional area, 1247±346 to 638±254 μm2; P=0.001). Maximum calcium-saturated force improved after LVAD (3.6±0.9 to 7.3±1.8 mN/mm2, P<0.001) implantation but was still lower than in nonfailing hearts (7.3±1.8 versus 17.6±1.8 mN/mm2, P<0.001). An increase in troponin I (TnI) phosphorylation after LVAD implantation was noted, but protein kinase C phosphorylation of TnI decreased. Biochemical changes of other sarcomeric proteins were not observed after LVAD. Conclusions-There is significant improvement in LV and myocyte size with LVAD, but there is only partial recovery of EF and myocyte contractility. LVAD support was associated only with biochemical changes in TnI, suggesting that alternate mechanisms might contribute to contractile changes after LVAD and that additional interventions may be needed to alter biochemical remodeling of the sarcomere to further enhance myofilament and organ-level recovery. (Circ Heart Fail. 2011;4:425-432.).

AB - Background-Unloading a failing heart with a left ventricular assist device (LVAD) can improve ejection fraction (EF) and LV size; however, recovery with LVAD explantation is rare. We hypothesized that evaluation of myocyte contractility and biochemistry at the sarcomere level before and after LVAD may explain organ-level changes. Methods and Results-Paired LV tissue samples were frozen from 8 patients with nonischemic cardiomyopathy at LVAD implantation (before LVAD) and before cardiac transplantation (after LVAD). These were compared with 8 nonfailing hearts. Isolated skinned myocytes were purified and attached to a force transducer, and dimensions, maximum calcium-saturated force, calcium sensitivity, and myofilament cooperativity were assessed. Relative isoform abundance and phosphorylation levels of sarcomeric contractile proteins were measured. With LVAD support, the unloaded EF improved (10.0±1.0% to 25.6±11.0%, P=0.007), LV size decreased (LV internal dimension at end diastole, 7.6±1.2 to 4.9±1.4 cm; P<0.001), and myocyte dimensions decreased (cross-sectional area, 1247±346 to 638±254 μm2; P=0.001). Maximum calcium-saturated force improved after LVAD (3.6±0.9 to 7.3±1.8 mN/mm2, P<0.001) implantation but was still lower than in nonfailing hearts (7.3±1.8 versus 17.6±1.8 mN/mm2, P<0.001). An increase in troponin I (TnI) phosphorylation after LVAD implantation was noted, but protein kinase C phosphorylation of TnI decreased. Biochemical changes of other sarcomeric proteins were not observed after LVAD. Conclusions-There is significant improvement in LV and myocyte size with LVAD, but there is only partial recovery of EF and myocyte contractility. LVAD support was associated only with biochemical changes in TnI, suggesting that alternate mechanisms might contribute to contractile changes after LVAD and that additional interventions may be needed to alter biochemical remodeling of the sarcomere to further enhance myofilament and organ-level recovery. (Circ Heart Fail. 2011;4:425-432.).

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