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The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
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Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats

Ralph T Schermuly1, Klaus P Kreisselmeier, Hossein A Ghofrani

  • 1Department of Internal Medicine, Justus-Liebig-University Giessen, Giessen, Germany. ralph.schermuly@innere.med.uni-giessen.de

American Journal of Respiratory and Critical Care Medicine
|September 6, 2003
PubMed

Insights

Sildenafil treatment significantly reduced pulmonary hypertension and right heart enlargement in rats. This phosphodiesterase 5 inhibitor also decreased mortality, offering potential for treating pulmonary hypertension.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Pulmonary Medicine

Background:

  • Pulmonary hypertension (PH) is a severe condition characterized by high blood pressure in the pulmonary arteries.
  • Monocrotaline (MCT) injection in rats is a widely used model to induce PH and right heart failure (cor pulmonale).
  • Sildenafil, a phosphodiesterase 5 (PDE5) inhibitor, is being explored for PH therapy.

Purpose of the Study:

  • To investigate the chronic effects of sildenafil on established monocrotaline-induced pulmonary hypertension in rats.
  • To evaluate sildenafil's impact on hemodynamic parameters, cardiac structure, and survival rates in this PH model.

Main Methods:

  • Rats were injected with monocrotaline (MCT) to induce pulmonary hypertension.
  • Sildenafil was administered chronically during different phases of PH development (Days 14-28 and Days 28-42 post-MCT).
  • Hemodynamic measurements (pulmonary artery pressure, vascular resistance, oxygen saturation), right heart hypertrophy assessment, and survival rates were evaluated.

Main Results:

  • MCT injection led to significantly elevated pulmonary artery pressure, vascular resistance, and right heart hypertrophy, alongside decreased oxygenation.
  • Chronic sildenafil administration (Days 14-28 and 28-42) attenuated the development of pulmonary hypertension and right heart hypertrophy.
  • Sildenafil treatment preserved gas exchange, maintained systemic arterial pressure, increased plasma cyclic guanosine monophosphate, and significantly reduced mortality.

Conclusions:

  • Sildenafil effectively attenuates monocrotaline-induced pulmonary hypertension and associated right heart hypertrophy (cor pulmonale) in rats.
  • The PDE5 inhibitor demonstrates protective effects on hemodynamics, cardiac structure, and survival in a rat model of PH.
  • These findings support the potential therapeutic role of sildenafil in managing pulmonary hypertension.

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