Mitochondrial integrity in a neonatal bovine model of right ventricular dysfunction

Am J Physiol Lung Cell Mol Physiol. 2015 Jan 15;308(2):L158-67. doi: 10.1152/ajplung.00270.2014. Epub 2014 Nov 21.


Right ventricular (RV) function is a key determinant of survival in patients with both RV and left ventricular (LV) failure, yet the mechanisms of RV failure are poorly understood. Recent studies suggest cardiac metabolism is altered in RV failure in pulmonary hypertension (PH). Accordingly, we assessed mitochondrial content, dynamics, and function in hearts from neonatal calves exposed to hypobaric hypoxia (HH). This model develops severe PH with concomitant RV hypertrophy, dilation, and dysfunction. After 2 wk of HH, pieces of RV and LV were obtained along with samples from age-matched controls. Comparison with control assesses the effect of hypoxia, whereas comparison between the LV and RV in HH assesses the additional impact of RV overload. Mitochondrial DNA was unchanged in HH, as was mitochondrial content as assessed by electron microscopy. Immunoblotting for electron transport chain subunits revealed a small increase in mitochondrial content in HH in both ventricles. Mitochondrial dynamics were largely unchanged. Activity of individual respiratory chain complexes was reduced (complex I) or unchanged (complex V) in HH. Key enzymes in the glycolysis pathway were upregulated in both HH ventricles, alongside upregulation of hypoxia-inducible factor-1α protein. Importantly, none of the changes in expression or activity were different between ventricles, suggesting the changes are in response to HH and not RV overload. Upregulation of glycolytic modulators without chamber-specific mitochondrial dysfunction suggests that mitochondrial capacity and activity are maintained at the onset of PH, and the early RV dysfunction in this model results from mechanisms independent of the mitochondria.

Keywords: cardiac; mitochondria; pulmonary hypertension; right ventricle.

Publication types

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

MeSH terms

  • Animals
  • Cattle*
  • DNA Copy Number Variations
  • Disease Models, Animal*
  • Electron Transport Complex I / metabolism
  • Glucose Transporter Type 4 / biosynthesis
  • Heart Failure / pathology
  • Heart Ventricles / physiopathology*
  • Hypertension, Pulmonary / pathology*
  • Hypertrophy, Right Ventricular / physiopathology*
  • Hypoxia-Inducible Factor 1, alpha Subunit / biosynthesis
  • Male
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Phosphofructokinase-1 / biosynthesis
  • Protein Kinase C / biosynthesis
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Ventricular Dysfunction, Right / pathology*
  • Ventricular Function, Right


  • Glucose Transporter Type 4
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Vascular Endothelial Growth Factor A
  • Phosphofructokinase-1
  • Protein Kinase C
  • Electron Transport Complex I