Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation.

Area of Science:

• Cardiovascular Physiology
• Cardiac Cell Biology
• Pathophysiology of Heart Failure

Background:

• Mitral regurgitation (MR) leads to left ventricular volume overload.
• The underlying mechanisms of associated cardiac dysfunction remain incompletely understood.

Purpose of the Study:

• To determine if left ventricular contractile dysfunction in MR stems from primary cardiac muscle cell defects.
• To elucidate the basis of observed changes in cellular contractile function.

Main Methods:

• Induction of chronic MR in dogs via mitral chordae tendineae transection.
• Assessment of left ventricular function using end-ejection stress-volume relation (EESVR).
• Characterization of cardiac muscle cell (cardiocyte) contractile performance and morphometric analysis.

Main Results:

• MR induced significant contractile abnormalities at both ventricular and cellular levels.
• Ventricular and cellular dysfunction strongly correlated with decreased cardiocyte myofibril volume fraction.
• No significant change in left ventricular interstitial volume was observed.

Conclusions:

• Chronic MR causes intrinsic cardiocyte contractile defects, evidenced by myofibrillar loss.
• The contractile dysfunction is not due to interstitial changes.
• Failure of compensatory hypertrophy contributes to progressive functional decline in MR.