Establishment of a canine model of pulmonary arterial hypertension induced by dehydromonocrotaline and ultrasonographic study of right ventricular remodeling

Clin Exp Hypertens. 2023 Dec 31;45(1):2190503. doi: 10.1080/10641963.2023.2190503.

Abstract

Objective: Pulmonary arterial hypertension (PAH) means high blood pressure in the lungs. We aimed to observe the right ventricular size, wall thickness and characteristic functional changes and their associations with PAH in an established model of beagle dogs, and to explore convenient, reliable and sensitive ultrasound indicators for assessing right ventricular remodeling.

Methods: Twenty healthy beagle dogs (8-10 kg) were randomly divided into control group (N-dimethylformamide, n = 10) and dehydromonocrotaline (DHMCT) group (DHMCT, n = 10). N-dimethylformamide or DHMCT was injected through a catheter into the right atrium, and then right heart catheterization, routine echocardiography and two-dimensional speckle tracking imaging (2D-STI) were performed before modeling (0 weeks) and 8, 14 weeks after modeling. Hemodynamic parameters and right ventricular function-related ultrasound data were acquired. At the end of the experiment, the animals were killed and the lung tissues were taken for HE staining. Left and right ventricular walls were separated and weighed respectively, and right ventricular hypertrophy index (RVHI) was measured. The associations of the routine ultrasound data and 2D-STI data at each time point with hemodynamic parameters and RVHI were analyzed.

Results: At 0, 8 and 14 weeks, gradual decreases in the right ventricular global longitudinal strain (RVLS) were found in DHMCT group. RVH occurred in DHMCT group, and DHMCT group had a significantly higher RVHI than that of control group (49.83 ± 4.83% vs. 39.80 ± 1.40%, P < .001) and larger pulmonary artery media thickness. RVLS had significant positive correlations with RVSP (r = 0.74, P < .001), mRVP (r = 0.72, P < .001), PASP (r = 0.75, P < .001), mPAP (r = 0.72, P < .001) and PVR (r = 0.68, P < .001). There was a significant positive correlation between RVLS and RVHI (r = 0.74, P < .001).

Conclusion: The right ventricular function in PAH can be effectively assessed by echocardiography, and RVLS measured by 2D-STI sensitively reflects right ventricular remodeling following PAH.

Keywords: Dehydromonocrotaline; echocardiography; pulmonary arterial hypertension; right ventricular remodeling; two-dimensional speckle tracking.

MeSH terms

  • Animals
  • Dimethylformamide
  • Dogs
  • Hypertension, Pulmonary* / diagnostic imaging
  • Hypertension, Pulmonary* / etiology
  • Hypertrophy, Right Ventricular / diagnostic imaging
  • Hypertrophy, Right Ventricular / etiology
  • Pulmonary Arterial Hypertension*
  • Ventricular Dysfunction, Right*
  • Ventricular Function, Right
  • Ventricular Remodeling

Substances

  • monocrotaline pyrrole
  • Dimethylformamide