Volume overload hypertrophy in a closed-chest model of mitral regurgitation

Abstract

Chronic volume overload hypertrophy as seen in mitral regurgitation in humans eventually may cause left ventricular dysfunction. Longitudinal study of the mechanisms leading to such dysfunction is difficult in humans and more easily performed in an animal model. In this study, we describe a canine model of volume overload hypertrophy produced by mitral regurgitation. An arterially placed grasping forceps was used to disrupt mitral chordae or leaflets; thus mitral regurgitation was produced without the need for thoracotomy. Eleven of 22 dogs had severe mitral regurgitation (regurgitant fraction greater than 0.50) and survived for greater than or equal to 3 mo (average 9.2 +/- 6 mo) after the production of mitral regurgitation. At 3 mo, end-diastolic volume increased from 48 +/- 9 to 85 +/- 19 ml, P less than 0.01. Left ventricular mass increased from 71 +/- 13 to 90 +/- 10 g, P less than 0.01. Left ventricular end-diastolic pressure increased from 9 +/- 3 to 19 +/- 6 mmHg, P less than 0.01. Cardiac output decreased from 2.3 +/- 0.61 to 1.80 +/- 0.64 l/min, P less than 0.05. The mass-to-volume ratio decreased from 1.44 +/- 0.17 to 1.09 +/- 0.13, P less than 0.01. We conclude that this closed-chest model of chronic mitral regurgitation produces significant eccentric cardiac hypertrophy. Despite a doubling of end-diastolic volume, there was a fall in cardiac output and a rise in left ventricular end-diastolic pressure, suggesting cardiac decompensation.