Aortic regurgitation in the heterotopic rat heart transplant: effect on ventricular remodeling and diastolic function

Use of the heterotopic rat cardiac isograft model is limited by ventricular atrophy attributable to the left ventricle's non-working state. Previous studies indicate that increased left ventricular pressure-volume work minimizes atrophy. We used a simpler approach to increase ventricular work, imposing aortic regurgitation on the transplant. We hypothesized that this would prevent atrophy and preserve left ventricular compliance.

We analyzed heterotopic transplants with aortic valvotomy and without aortic valvotomy (controls). Recipient native hearts served as separate controls. After 15 to 25 days, we measured cardiac wet weight, dry weight, and water content of all groups and measured echocardiographic left ventricular wall thickness and end-diastolic and end-systolic diameters in both transplant groups. Left ventricular volume infusions yielded pressure-volume data that we analyzed using regression methods.

Aortic regurgitant transplants weighed more than control transplants (dry weight, 0.109 +/- 0.013 g vs 0.097 +/- 0.016 g; p = 0.020, 2-way analysis of variance), but all transplants weighed less than native hearts weighed (p = 0.001). Control transplants were less compliant than regurgitant transplants (p = 0.002), but the latter were similar to their own native hearts (p = 0.34). Wall thickness decreased in regurgitant vs control transplants (p = 0.020, Student's t-test), but end-diastolic and end-systolic diameters increased (p < or = 0.001).

Aortic regurgitation in heterotopic transplants improves left ventricular compliance through chamber dilatation without preventing atrophy. Moderate acute aortic regurgitation affects ventricular remodeling more than it stimulates myocardial hypertrophy. Smaller end-diastolic diameter, greater wall thickness, and myocardial edema may explain decreased compliance in non-working transplants.