Biochemical and myofilament responses of the right ventricle to severe pulmonary hypertension

Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H832-40. doi: 10.1152/ajpheart.00249.2011. Epub 2011 May 27.


Right ventricular (RV) failure is one of the strongest predictors of mortality both in the presence of left ventricular decompensation and in the context of pulmonary vascular disease. Despite this, there is a limited understanding of the biochemical and mechanical characteristics of the pressure-overloaded RV at the level of the cardiac myocyte. To better understand this, we studied ventricular muscle obtained from neonatal calves that were subjected to hypobaric atmospheric conditions, which result in profound pulmonary hypertension. We found that RV pressure overload resulted in significant changes in the phosphorylation of key contractile proteins. Total phosphorylation of troponin I was decreased with pressure overload, predominantly reflecting changes at the putative PKA site at Ser(22/23). Similarly, both troponin T and myosin light chain 2 showed a significant decline in phosphorylation. Desmin was unchanged, and myosin-binding protein C (MyBP-C) phosphorylation was apparently increased. However, the apparent increase in MyBP-C phosphorylation was not due to phosphorylation but rather to an increase in MyBP-C total protein. Importantly, these findings were seen in all regions of the RV and were paralleled by reduced Ca(2+) sensitivity with preserved maximal Ca(2+) saturated developed force normalized to cross-sectional area in isolated skinned right ventricular myocyte fragments. No changes in total force or cooperativity were seen. Taken together, these results suggest that RV failure is mechanistically unique from left ventricular failure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Animals
  • Animals, Newborn
  • Cattle
  • Disease Models, Animal
  • Excitation Contraction Coupling
  • Heart Ventricles / metabolism
  • Hemodynamics
  • Hyperbaric Oxygenation
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / metabolism*
  • Hypertension, Pulmonary / physiopathology
  • Muscle Proteins / metabolism*
  • Myocardial Contraction
  • Myocardium / metabolism*
  • Phosphorylation
  • Severity of Illness Index
  • Ventricular Dysfunction, Right / etiology
  • Ventricular Dysfunction, Right / metabolism*
  • Ventricular Dysfunction, Right / physiopathology
  • Ventricular Function, Right*
  • Ventricular Pressure


  • Muscle Proteins