Total mechanical unloading of the heart in classical models of heterotopic heart transplantation leads to cardiac atrophy and functional deterioration. In contrast, partial unloading of failing human hearts with left ventricular (LV) assist devices (LVADs) can in some patients ameliorate heart failure symptoms. Here we tested in heterotopic rat heart transplant models whether partial volume-loading (VL; anastomoses: aorta of donor to aorta of recipient, pulmonary artery of donor to left atrium of donor, superior vena cava of donor to inferior vena cava of recipient; n = 27) is superior to the classical model of myocardial unloading (UL; anastomoses: aorta of donor to aorta of recipient, pulmonary artery of donor to inferior vena cava of recipient; n = 14) with respect to preservation of ventricular morphology and function. Echocardiography, magnetic resonance imaging, and LV-pressure-volume catheter revealed attenuated myocardial atrophy with ~30% higher LV weight and better systolic contractile function in VL compared with UL (fractional area shortening, 34% vs. 18%; maximal change in pressure over time, 2,986 ± 252 vs. 2,032 ± 193 mmHg/s). Interestingly, no differences in fibrosis (Picrosirus red staining) or glucose metabolism (2-[18F]-fluoro-2-deoxy-D-glucose-PET) between VL and UL were observed. We conclude that the rat model of partial VL attenuates atrophic remodelling and shows superior morphological as well as functional preservation, and thus should be considered more widely as a research model.
Keywords: cardiac atrophy; heterotopic heart transplantation; left ventricular assist devices; left ventricular function; rat.