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Updated: Feb 19, 2026
Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension
Published on: April 11, 2016
Altered Right Ventricular Mechanical Properties Are Afterload Dependent in a Rodent Model of Bronchopulmonary
Jitandrakumar R Patel1, Gregory P Barton2, Rudolf K Braun2
1Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, United States.
Insights
Neonatal hyperoxia exposure in rats causes pulmonary hypertension and right ventricular dysfunction. These effects are reversible, highlighting the importance of reducing afterload for RV recovery in bronchopulmonary dysplasia.
Area of Science:
- Cardiovascular Physiology
- Neonatal Physiology
- Pulmonary Hypertension Research
Background:
- Infants with bronchopulmonary dysplasia (BPD) face high risks of pulmonary hypertension (PH) and right ventricular (RV) dysfunction.
- The impact of BPD-related alveolar simplification and abnormal pulmonary microvascular development on RV contractile function remains unclear.
Purpose of the Study:
- To investigate the effects of hyperoxia-induced PH on RV contractile properties in a rat model of BPD.
- To explore the molecular mechanisms underlying these functional changes.
Main Methods:
- Utilized a rat model of BPD induced by 14 days of hyperoxia (85% oxygen) post-birth.
- Measured in vivo RV pressure and isolated RV skinned trabeculae to assess passive force, maximal Ca2+ activated force, calcium sensitivity (pCa50), and rate of force redevelopment (k-tr).
- Analyzed myofibrillar protein expression, including myosin heavy chain (MHC) and troponin isoforms.
Main Results:
- Hyperoxia-exposed rats showed elevated RV systolic and diastolic pressures at 21 days, which normalized by 35 days.
- At 21 days, RV trabeculae exhibited increased passive force, maximal Ca2+ activated force, and calcium sensitivity, with depressed cross-bridge cycling kinetics.
- Protein analysis revealed increased beta-myosin heavy chain (β-MHC), atrial myosin light chain 1 (aMLC1), and slow skeletal troponin I (ssTnI) in 21-day old hyperoxic trabeculae, with normalization by 35 days.
Conclusions:
- Neonatal hyperoxia increases RV afterload, altering RV steady-state and dynamic contractile properties through changes in β-MHC, aMLC1, and ssTnI expression.
- These hyperoxia-induced functional deficits are reversible and coincide with PH resolution, emphasizing the critical role of reducing RV afterload for functional recovery.
Abstract:
Infants born premature are at increased risk for development of bronchopulmonary dysplasia (BPD), pulmonary hypertension (PH), and ultimately right ventricular (RV) dysfunction, which together carry a high risk of neonatal mortality. However, the role alveolar simplification and abnormal pulmonary microvascular development in BPD affects RV contractile properties is unknown. We used a rat model of BPD to examine the effect of hyperoxia-induced PH on RV contractile properties. We measured in vivo RV pressure as well as passive force, maximum Ca2+ activated force, calcium sensitivity of force (pCa50) and rate of force redevelopment (ktr) in RV skinned trabeculae isolated from hearts of 21-and 35-day old rats pre-exposed to 21% oxygen (normoxia) or 85% oxygen (hyperoxia) for 14 days after birth. Systolic and diastolic RV pressure were significantly higher at day 21 in hyperoxia exposed rats compared to normoxia control rats, but normalized by 35 days of age. Passive force, maximum Ca2+ activated force, and calcium sensitivity of force were elevated and cross-bridge cycling kinetics depressed in 21-day old hyperoxic trabeculae, whereas no differences between normoxic and hyperoxic trabeculae were seen at 35 days. Myofibrillar protein analysis revealed that 21-day old hyperoxic trabeculae had increased levels of beta-myosin heavy chain (β-MHC), atrial myosin light chain 1 (aMLC1; often referred to as essential light chain), and slow skeletal troponin I (ssTnI) compared to age matched normoxic trabeculae. On the other hand, 35-day old normoxic and hyperoxic trabeculae expressed similar level of α- and β-MHC, ventricular MLC1 and predominantly cTnI. These results suggest that neonatal exposure to hyperoxia increases RV afterload and affect both the steady state and dynamic contractile properties of the RV, likely as a result of hyperoxia-induced expression of β-MHC, delayed transition of slow skeletal TnI to cardiac TnI, and expression of atrial MLC1. These hyperoxia-induced changes in contractile properties are reversible and accompany the resolution of PH with further developmental age, underscoring the importance of reducing RV afterload to allow for normalization of RV function in both animal models and humans with BPD.
