Left ventricular function in experimental volume overload hypertrophy

Left ventricular function in volume overload hypertrophy is controversial. In humans, chronic severe volume overload eventually results in left ventricular dysfunction; paradoxically, experimental volume overload hypertrophy has nearly always been associated with normal left ventricular function. However, in most cases, experimental volume overload hypertrophy has either been mild or only present for a short duration. To help resolve the issue of contractile function in volume overload hypertrophy, we examined ventricular function in a recently described model of severe chronic experimental mitral regurgitation. Left ventricular function was measured before and 3 mo after the creation of severe mitral regurgitation (averaged regurgitant fraction 0.64 +/- 0.04). At 3 mo end-diastolic volume had increased from 78 +/- 5 to 114 +/- 7 ml (P less than 0.01). Significant left ventricular hypertrophy had occurred with an increase in the left ventricular weight-to-body weight ratio from 3.84 +/- 0.2 to 5.22 +/- 0.2 (P less than 0.01). All indicators of left ventricular function (ejection fraction, the end ejection stress-volume relationship, this relationship corrected for eccentric hypertrophy, and mean velocity of circumferential fiber shortening at a common stress) were reduced at 3 mo. Our study produced 64% volume overload which was maintained for 3 mo at which time there was a 36% increase in left ventricular mass. This amount of volume overload of this duration produced significant left ventricular dysfunction.