Left ventricular function in experimental mitral regurgitation with intact chordae tendineae

Left ventricular function in mitral regurgitation has typically been studied in models that either sever the chordae tendineae or create a ventriculoatrial shunt. These methods may have adverse effects on left ventricular function independent of the regurgitant lesion. An animal model of chronic mitral regurgitation was therefore developed that both preserves annuloventricular continuity and avoids the use of external shunts. A circular 0.16 to 0.24 mm/kg defect was created in the anterior mitral valve leaflet of weanling sheep under direct vision with the aid of cardiopulmonary bypass. Six animals were studied preoperatively and immediately postoperatively (acute regurgitation group), and 20 animals were studied 8.1 ± 0.2 (mean ± one standard deviation) months postoperatively (chronic regurgitation group). Animals with chronic mitral regurgitation were compared with an age- and weight-matched control group that was not operated on (n = 7). Volumetric data and ejection fraction were derived from digitalized cineangiographic images. Maximal elastance was calculated from pressure-volume loops obtained from the simultaneous recording of left ventricular pressure by micromanometer-tipped left ventricular catheters, and volumes were obtained from digitalized images of epicardial echocardiographic recordings. Mitral valve perforation resulted in 3+ to 4+ mitral regurgitation and a calculated regurgitant fraction of 37% ± 7% (mean ± one standard deviation). Acute mitral regurgitation was associated with an increase in left ventricular end-diastolic volume from 110 ± 17 to 121 ± 23 ml (p ≤ 0.05) and no change in end-systolic volume. These changes were associated with an increase in fractional shortening, from 29% ±11% to 40% ±10% (p ≤ 0.05), and an increase in velocity of circumferential shortening, from 1.5 ± 0.7 to 2.9 ± 0.7 circ/sec (p ≤ 0.05). However, there was no change in maximal elastance, a load-independent index of left ventricular function. Conversely, animals with chronic mitral regurgitation exhibited an elevated end-diastolic volume (202 ± 32 versus 145 ± 34, p ≤ 0.05), an elevated end-systolic volume (104 ± 17 versus 63 ± 20 ml, p ≤ 0.05), and a reduced ejection fraction (48% ±6% versus 57% ± 9%, p ≤ 0.05) compared with controls. These changes were associated with a reduction in fractional shortening from 26% ±3% to 41% ± 9% (p ≤ 0.05), velocity of circumferential shortening from 1.2 ± 0.1 to 1.7 ± 0.5 circ/sec (p ≤ 0.05), and maximal elastance from