Right ventricular contractile protein function in rats with left ventricular myocardial infarction

Area of Science:

• Cardiovascular Physiology
• Cardiac Muscle Mechanics
• Heart Failure Pathophysiology

Background:

• Experimental heart failure (HF) models are crucial for understanding disease mechanisms.
• Right ventricular (RV) function is often compromised in advanced heart failure.
• Contractile filament dysfunction may contribute to impaired cardiac contractility.

Purpose of the Study:

• To investigate contractile function in rat right ventricular trabeculae from a post-myocardial infarction heart failure model.
• To assess the impact of heart failure on force-sarcomere length and force-calcium relationships.
• To determine the contribution of contractile filament function to reduced force development in heart failure.

Main Methods:

• Isolated rat right ventricular trabeculae were studied from sham-operated and myocardial infarction (MI)-induced heart failure groups.
• Sarcomere length (SL) was measured using laser diffraction and force (F) using silicon strain gauges.
• Force-sarcomere length, force-[Ca2+]o, and force-intracellular [Ca2+] relationships were assessed in intact and chemically permeabilized (skinned) fibers.

Main Results:

• Heart failure was associated with left ventricular dilation and pulmonary congestion.
• RV trabeculae from HF rats showed depressed force development at a fixed sarcomere length and reduced responsiveness to extracellular calcium.
• Skinned RV trabeculae from HF rats exhibited impaired force-intracellular calcium relationships, indicating depressed contractile filament function.

Conclusions:

• Reduced force development in this experimental heart failure model is partly due to impaired function of the cardiac contractile filaments.
• These findings highlight the role of intrinsic myocyte dysfunction in the pathophysiology of right ventricular failure.
• Understanding these mechanisms can inform therapeutic strategies for heart failure.