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Updated: Sep 7, 2025
Induction of Right Ventricular Failure by Pulmonary Artery Constriction and Evaluation of Right Ventricular Function in Mice
Published on: May 13, 2019
[Role of inflammation and apoptosis in right ventricular dysfunction induced by injurious mechanical ventilation in
Jun Liu1,2, Dong Han1, Tingting Wang2
1Department of Emergency Intensive Care Unit, Affiliated Hospital of Jiangnan University, Wuxi 214122, Jiangsu, China.
Objective:
To investigate whether myocardial inflammation and apoptosis are involved in right ventricular dysfunction (RVD) induced by injurious mechanical ventilation with high tidal volume (VT) in rats.
Methods:
Total 30 adult male SD rats were randomly divided into the control group (CON group), the low VT ventilation group (LVT group) and the injurious mechanical ventilation group (HVT group), with 10 rats in each group. The CON group was maintained spontaneous breathing, the LVT group and HVT group were ventilated with different VT 6 mL/kg and 20 mL/kg for 4 hours, respectively. The right jugular vein and the left carotid artery were catheterized and connected with the PowerLab biological signal acquisition and analysis system to record heart rate (HR), mean arterial pressure (MAP), right ventricular systolic pressure (RVSP), the maximum rate of rising of right ventricular pressure (+dp/dt max). Echocardiography was performed to measure left ventricular end-diastolic diameter (LVEDd), right ventricular end-diastolic diameter (RVEDd), tricuspid annulus plane systolic migration (TAPSE) and myocardial performance index (MPI). The rats were sacrified by cervical dislocation. Specimens of right ventricle tissues were taken for hematoxylin-eosin (HE) staining, and morphological changes of right ventricle tissues were observed under light microscope. Real time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), caspase-3, apoptosis-related proteins Bax and Bcl-2.
Results:
HR, MAP, +dp/dt max gradually decreased, while RVSP gradually increased in different group with the increase of VT ventilation. There was no significant difference between the CON group and LVT group. However, there was a statistically significant difference with respect to these index in HVT group as compared to CON group and LVT group [HR (bpm): 397.6±5.7 vs. 433.0±4.8, 441.6±7.8; MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 102.0±2.4 vs. 108.5±2.2, 110.6±2.1; +dp/dt max (mmHg/s): 2 357.65±62.80 vs. 2 661.27±55.62, 2 679.43±75.13; RVSP (mmHg): 28.8±1.0 vs. 22.6±10.8, 21.9±0.4; all P < 0.05]. Echocardiography findings showed that RVEDd/LVEDd and MPI gradually increased, TAPSE gradually decreased in different group with the increase of VT ventilation. There was no significant difference between the LVT group and CON group. However, there was a statistically significant difference with respect to these indexes in HVT group as compared to the CON group and LVT group [RVEDd/LVEDd: 0.36±0.02 vs. 0.26±0.01, 0.23±0.02; MPI: 1.23±0.03 vs. 0.84±0.04, 0.86±0.03; TAPSE (mm): 1.65±0.03 vs. 1.88±0.02, 1.91±0.04; all P < 0.05]. Histopathological observation of the right ventricle tissue showed that myocardial cells of the rats in the CON group were orderly arranged and uniformed in size. In the LVT group, there was a small amount of inflammatory cell infiltration in the myocardial interstitium, while in the HVT group, the myocardial cell arrangement was obviously disordered, the structure was obviously damaged, and more inflammatory cell infiltration was found. RT-PCR and Western blotting analysis showed that the mRNA and protein expressions of IL-6, TNF-α, caspase-3 and Bax in HVT group were significantly higher than those in the LVT group and CON group [mRNA expression (2-ΔΔCt): IL-6 were 1.97±0.07 vs. 1.09±0.02, 1.02±0.03, TNF-α were 1.69±0.10 vs. 1.10±0.03, 1.05±0.04, caspase-3 were 1.82±0.09 vs. 1.08±0.02, 1.06±0.03, Bax were 2.19±0.14 vs. 1.07±0.03, 1.04±0.03; protein expression (gray value): IL-6 were 0.64±0.02 vs. 0.38±0.03, 0.31±0.04, TNF-α were 0.50±0.04 vs. 0.16±0.01, 0.15±0.01, caspase-3 were 0.58±0.02 vs. 0.29±0.01, 0.25±0.02, Bax were 0.50±0.03 vs. 0.21±0.01, 0.26±0.02; all P < 0.05], and the mRNA and protein expressions of Bcl-2 in the HVT group were lower than those in the LVT group and CON group [mRNA expression (2-ΔΔCt): 1.23±0.05 vs. 1.43±0.05, 1.50±0.08; protein expression (gray value): 0.42±0.02 vs. 0.62±0.03, 0.65±0.03, all P < 0.05].
Conclusion:
Myocardial inflammation and apoptosis may be involved in RVD induced by injurious mechanical ventilation.
Insights
High tidal volume mechanical ventilation in rats induced right ventricular dysfunction by causing myocardial inflammation and apoptosis. These findings suggest a link between injurious ventilation and heart damage.
Area of Science:
- Cardiology and Respiratory Physiology
- Molecular Biology and Pathology
Background:
- Mechanical ventilation is crucial for respiratory support but can induce lung injury.
- High tidal volume (VT) ventilation is associated with ventilator-induced lung injury (VILI).
- The impact of injurious mechanical ventilation on right ventricular function is not fully understood.
Purpose of the Study:
- To investigate the role of myocardial inflammation and apoptosis in right ventricular dysfunction (RVD).
- To determine if injurious mechanical ventilation with high VT in rats induces RVD.
- To examine the molecular mechanisms, including inflammatory and apoptotic markers, in the right ventricle.
Main Methods:
- Adult male Sprague-Dawley rats were divided into control, low VT (6 mL/kg), and high VT (20 mL/kg) groups.
- Hemodynamic parameters (HR, MAP, RVSP, +dp/dt max) and echocardiographic indices (RVEDd/LVEDd, TAPSE, MPI) were measured.
- Right ventricular tissues were analyzed for histopathology, and mRNA/protein expression of IL-6, TNF-α, caspase-3, Bax, and Bcl-2 were quantified using RT-PCR and Western blotting.
Main Results:
- High VT ventilation significantly impaired right ventricular systolic pressure and contractility, evidenced by increased RVSP and decreased +dp/dt max.
- Echocardiography revealed impaired right ventricular dimensions and function in the high VT group, with increased RVEDd/LVEDd and MPI, and decreased TAPSE.
- Histology showed myocardial inflammation and disorganization in the high VT group. Molecular analysis indicated significantly upregulated IL-6, TNF-α, caspase-3, and Bax, with downregulated Bcl-2 expression in the high VT group compared to controls.
Conclusions:
- Injurious mechanical ventilation with high tidal volume induces right ventricular dysfunction in rats.
- Myocardial inflammation and apoptosis, indicated by elevated pro-inflammatory cytokines and altered apoptosis-related protein expression, are involved in this process.
- These findings highlight the potential cardiotoxic effects of high VT mechanical ventilation.
