The importance of capillary density-stroke work mismatch for right ventricular adaptation to chronic pressure overload

J Thorac Cardiovasc Surg. 2017 Dec;154(6):2070-2079. doi: 10.1016/j.jtcvs.2017.05.102. Epub 2017 Jun 15.

Abstract

Objective: Mechanisms of right ventricular (RV) adaptation to chronic pressure overload are not well understood. We hypothesized that a lower capillary density (CD) to stroke work ratio would be associated with more fibrosis and RV maladaptive remodeling.

Methods: We induced RV chronic pressure overload over a 20-week period in 2 piglet models of pulmonary hypertension; that is, a shunt model (n = 5) and a chronic thromboembolic pulmonary hypertension model (n = 5). We assessed hemodynamic parameters and RV remodeling as well as RV CD, fibrosis, and angiogenic factors expression.

Results: Although RV was similarly hypertrophied in both models, maladapted RV remodeling with impaired systolic function was only seen in chronic thromboembolic pulmonary hypertension group members who had lower CD (484 ± 99 vs 1213 ± 74 cap/mm2; P < .01), lower CD to stroke work ratio (0.29 ± 0.07 vs 0.82 ± 0.16; P = .02), higher myocardial fibrosis (15.4% ± 3.8% vs 8.0% ± 2.5%; P < .01), as well as a higher angiogenic and fibrosis factors expression.

Conclusions: The RV adaptive response to chronic pressure overload differs between 2 different piglet models of PH. Mismatch between angiogenesis and workload (CD to stroke work ratio) was associated with greater degree of myocardial fibrosis and RV dysfunction and could be a promising index of RV maladaptation. Further studies are needed to understand the underlying mechanisms.

Keywords: adaptive remodeling; angiogenesis; fibrosis; pulmonary hypertension; right ventricle.

Publication types

  • Comparative Study
  • Video-Audio Media

MeSH terms

  • Adaptation, Physiological
  • Angiogenic Proteins / metabolism
  • Animals
  • Animals, Newborn
  • Capillaries / metabolism
  • Capillaries / pathology
  • Capillaries / physiopathology*
  • Chronic Disease
  • Disease Models, Animal
  • Fibrosis
  • Heart Ventricles / metabolism
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology*
  • Hemodynamics*
  • Hypertension, Pulmonary / complications*
  • Hypertension, Pulmonary / physiopathology
  • Hypertrophy, Right Ventricular / etiology*
  • Hypertrophy, Right Ventricular / metabolism
  • Hypertrophy, Right Ventricular / pathology
  • Hypertrophy, Right Ventricular / physiopathology
  • Male
  • Neovascularization, Pathologic*
  • Sus scrofa
  • Time Factors
  • Ventricular Dysfunction, Right / etiology*
  • Ventricular Dysfunction, Right / metabolism
  • Ventricular Dysfunction, Right / pathology
  • Ventricular Dysfunction, Right / physiopathology
  • Ventricular Function, Right*
  • Ventricular Remodeling*

Substances

  • Angiogenic Proteins