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. 2020 Jun 30;18(1):262.
doi: 10.1186/s12967-020-02440-7.

Changes in heart morphometric parameters over the course of a monocrotaline-induced pulmonary arterial hypertension rat model

Mateusz K Hołda  1   2   3 , Elżbieta Szczepanek  4 , Joanna Bielawska  5 , Natalia Palka  6 , Dorota Wojtysiak  7 , Paulina Frączek  8 , Michał Nowakowski  9 , Natalia Sowińska  9 , Zbigniew Arent  9 , Piotr Podolec  6 , Grzegorz Kopeć  6
Affiliations

Changes in heart morphometric parameters over the course of a monocrotaline-induced pulmonary arterial hypertension rat model

Mateusz K Hołda et al. J Transl Med. .

Abstract

Background: Aim of this study was to assess changes in cardiac morphometric parameters at different stages of pulmonary arterial hypertension (PAH) using a monocrotaline-induced rat model.

Methods: Four groups were distinguished: I-control, non-PAH (n = 18); II-early PAH (n = 12); III-end-stage PAH (n = 23); and IV-end-stage PAH with myocarditis (n = 7).

Results: Performed over the course of PAH in vivo echocardiography showed significant thickening of the right ventricle free wall (end-diastolic dimension), tricuspid annular plane systolic excursion reduction and decrease in pulmonary artery acceleration time normalized to cycle length. No differences in end-diastolic left ventricle free wall thickness measured in echocardiography was observed between groups. Significant increase of right ventricle and decrease of left ventricle systolic pressure was observed over the development of PAH. Thickening and weight increase (241.2% increase) of the right ventricle free wall and significant dilatation of the right ventricle was observed over the course of PAH (p < 0.001). Reduction in the left ventricle free wall thickness was also observed in end-stage PAH (p < 0.001). Significant trend in the left ventricle free wall weight decrease was observed over the course of PAH (p < 0.001, 24.3% reduction). Calculated right/left ventricle free wall weight ratio gradually increased over PAH stages (p < 0.001). The reduction of left ventricle diameter was observed in rats with end-stage PAH both with and without myocarditis (p < 0.001).

Conclusions: PAH leads to multidimensional changes in morphometric cardiac parameters. Right ventricle morphological and functional failure develop gradually from early stage of PAH, while left ventricle changes develop at the end stages of PAH.

Keywords: Cardiac remodelling; Left ventricle mass loss; Monocrotaline-induced PAH; Pulmonary hypertension; Right ventricular failure.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart demonstrating experiment’s structure. MCT: monocrotaline, PAH: pulmonary arterial hypertension, RVFWTd - end-diastolic right ventricular free wall thickness
Fig. 2
Fig. 2
Histological cross-sections of left ventricle myocardium (hematoxylin and eosin) showing different stages of inflammatory cells infiltration to myocardium. a Lack of inflammation, b moderate inflammation, c severe inflammation
Fig. 3
Fig. 3
Body weight change over the time of the study (box whisker plots)
Fig. 4
Fig. 4
Transthoracic echocardiogram images in the apical 4-chamber end-diastolic projection showing a normal heart of the rat from the control group and b failing heart with end-stage monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rat. LV: left ventricle, RV: right ventricle
Fig. 5
Fig. 5
a Between groups hemodynamic parameters differences. b Measured weights of the heart structures with between-group comparisons (box whisker plots). c Measured thicknesses of the heart structures with between-group comparisons (box whisker plots). d Measured diameters of the heart structures with between-group comparisons (box whisker plots). IVS: interventricular septum, LV: left ventricle, RV: right ventricle
See this image and copyright information in PMC

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