Development and modulation of experimental right ventricular hypertrophy in rats

Area of Science:

• Cardiovascular Physiology
• Cardiac Remodeling
• Pharmacology

Background:

• Right ventricular (RV) hypertrophy is a significant pathological condition.
• Understanding the mechanisms and potential treatments for RV hypertrophy is crucial for cardiovascular health.
• Existing models for studying RV hypertrophy have limitations.

Purpose of the Study:

• To create and characterize two distinct rat models of RV hypertrophy: chronic myocardial infarction and pulmonary artery stenosis.
• To investigate the effects of angiotensin-converting enzyme (ACE) inhibition with ramipril on RV hypertrophy in the pulmonary artery stenosis model.

Main Methods:

• Development and characterization of chronic myocardial infarction and pulmonary artery stenosis models in rats.
• Measurement of RV function using a Millar ultraminiature catheter pressure transducer in closed-chest, anesthetized rats.
• Assessment of myocyte size and cross-sectional area.
• Evaluation of the impact of ramipril (1 mg/kg daily) on RV pressure, weight, and myocyte hypertrophy.

Main Results:

• The chronic myocardial infarction model showed depressed left ventricular (LV) function and increased RV systolic pressure (RVSP), RV dp/dtmax, and RV weight/body weight ratio, with enlarged RV myocytes.
• The pulmonary artery stenosis model demonstrated elevated RVSP and RV dp/dtmax, with increased RV weight and myocyte size.
• Ramipril treatment did not affect the increase in RVSP or RV weight in the pulmonary artery stenosis model but significantly reduced the increase in RV myocyte volume and cross-sectional area compared to untreated animals.

Conclusions:

• Both chronic myocardial infarction and pulmonary artery stenosis serve as effective models for inducing RV hypertrophy in rats.
• ACE inhibition with ramipril demonstrates a cellular-level effect on mitigating RV hypertrophy, specifically reducing myocyte enlargement, even without altering overall RV pressure or weight.
• These findings highlight the potential of ACE inhibitors to modulate the cellular mechanisms underlying RV hypertrophic remodeling.