Left ventricular assist device support normalizes left and right ventricular beta-adrenergic pathway properties. Academic Article uri icon

Overview

abstract

  • OBJECTIVES: We hypothesized that some aspects of left ventricular assist device (LVAD) reverse remodeling could be independent of hemodynamic factors and would primarily depend upon normalization of neurohormonal milieu. BACKGROUND: The relative contributions of LVAD-induced hemodynamic unloading (provided to the left ventricle [LV]) and normalized neurohormonal milieu (provided to LV and right ventricle [RV]) to reverse remodeling are not understood. METHODS: Structural and functional characteristics were measured from hearts of 65 medically managed transplant patients (MED), 30 patients supported with an LVAD, and 5 nonfailing donor hearts not suitable for transplantation. RESULTS: Compared with MED patients, diastolic pulmonary pressures trended lower (p < 0.01) and cardiac output higher (p < 0.001) in LVAD patients; V(30) (ex vivo ventricular volume yielding 30 mm Hg, an index of ventricular size) in LVAD patients was decreased in the LV (p < 0.05) but did not change significantly in RV. The LVAD support improved force generation in response to beta-adrenergic stimulation in isolated LV (increase in developed force from 6.3 +/- 0.6 to 18.5 +/- 4.4 mN/m(2), p < 0.01) and RV (increase in developed force, from 10.9 +/- 2.0 to 20.5 +/- 3.1 mN/m(2), p < 0.05) trabeculae. The LVAD patients had higher myocardial beta-adrenergic receptor density in LV (p < 0.01) and RV (p < 0.01). Protein kinase A (PKA) hyperphosphorylation of the ryanodine receptor 2 (RyR2)/calcium release channel was significantly reduced by LVAD in both RV and LV (p < 0.01). CONCLUSIONS: Improved beta-adrenergic responsiveness, normalization of the RyR2 PKA phosphorylation, and increased beta-adrenergic receptor density in LV and RV after LVAD support suggest a primary role of neurohormonal environment in determining reverse remodeling of the beta-adrenergic pathway.

publication date

  • March 1, 2005

Research

keywords

  • Heart-Assist Devices
  • Receptors, Adrenergic, beta
  • Ventricular Dysfunction, Left
  • Ventricular Dysfunction, Right

Identity

Scopus Document Identifier

  • 14044258352

Digital Object Identifier (DOI)

  • 10.1016/j.jacc.2004.11.042

PubMed ID

  • 15734609

Additional Document Info

volume

  • 45

issue

  • 5