Right ventricular response to abnormal loading conditions in mice

  • Beatrijs Bartelds, Dept of Pediatric Cardiology, CVC, GUIDE, University Medical Center Groningen, University of Groningen, The Netherlands
  • Annemiek Smit-van Oosten, University Medical Center Groningen, University of Groningen, The Netherlands
  • Janny Takens, Dept of Pediatric Cardiology, CVC, GUIDE, University Medical Center Groningen, University of Groningen, The Netherlands
  • Marcel Nederhoff, Department of Medical Physiology, UMCU, Utrecht, The Netherlands
  • Leon de Windt, Department of Medical Physiology, UMCU, Utrecht, The Netherlands
  • Wiek van Gilst, Dept of Cardiology, CVC, GUIDE, University Medical Center Groningen, University of Groningen, The Netherlands
  • Rolf Berger, Dept of Pediatric Cardiology, CVC, GUIDE, University Medical Center Groningen, University of Groningen, The Netherlands

    • Background:
    Right ventricular (RV) dysfunction is an important determinant of long-term outcome of patients with congenital heart diseases, associated with abnormal ventricular loading conditions (pressure and/or volume load). The pathophysiological mechanisms are yet poorly understood. We aimed to characterize two mice models inducing different types of RV overload, using functional and pathophysiological outcome parameters.
    Methods and Results:
    We developed a mouse model of RV pressure load by banding of the pulmonary artery (Banding) and of volume load by an aorto-caval shunt (Shunt). Exercise capacity, measured by voluntary cage-wheel exercise before and 4 wks after surgery, was reduced in Banding-mice, whereas it was unchanged in Shunt-mice (Control vs. Banding vs. Shunt: -100±64 vs. -374±255* vs. -150±174 min., *=p<0.05 vs. Control).
    Cardiac MRI (9.4T-scanner) 4 wks after surgery revealed increased enddiastolic and -systolic RV volumes with preserved RV-stroke volume, -output and ejection fraction in Banding-mice (Figure). Shunt-mice also showed increased RV-volumes, but in contrast to Banding-mice, increased RV-stroke volume and -output, whereas RV ejection fraction was decreased (Control vs. Banding vs. Shunt: 67.9±4.3 vs. 61.9±5.8 vs. 58.0±8.6*). At autopsy, banding- and shunt-mice showed similar degrees of severe RV-hypertrophy, expressed as RV/BW (Control vs. Banding vs. Shunt: 0.88±0.17 vs. 1.61±0.25* vs. 1.49±0.27*).
    Conclusions:
    Pressure vs. volume overload of the RV in these mice models induced similar degrees of RV-hypertrophy, but marked differences in functional characteristics. These mice models, with rodent-MRI and exercise-testing, allow for further unraveling the pathophysiological and molecular adaptation of the RV to different types of abnormal loading.