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Cardiac function of transplanted rat hearts using a working heart model assessed by magnetic resonance imaging
S Yoshida1, S J Dodd, P J del Nido
1Department of Biological Sciences, Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pennsylvania 15213-2683, USA.
Background:
A direct correlation between graft rejection and cardiac contractile function in small-animal models has been difficult to establish because (i) the conventional non-working heart model is greatly different from the orthotopic heart in terms of left ventricular work and (ii) it is difficult to obtain hemodynamic data in situ. We have used magnetic resonance imaging (MRI) techniques to obtain noninvasive, in-situ quantitation of ventricular volume after heterotopic cardiac transplantation.
Methods:
Infra-renal heterotopic cardiac transplantation was performed on rats using syngeneic and allogeneic untreated donors in both working and non-working left heart models. An occluding balloon catheter in the inferior vena cava was used to vary the pre-load to the graft. An arteriovenous fistula was created to raise inferior caval oxygen saturation. Magnetic resonance imaging measurements were carried out at day 3, 4, and 5 post-transplantation. Left ventricle end-diastolic and end-systolic volumes were calculated using a biplanar ellipsoid model.
Results:
Stroke volume was significantly increased in the working heart model as compared to the non-working model. At day 4 post-transplant, the diastolic pressure-volume relationship in the allograft group was significantly shifted, indicative of decreased myocardial distensibility, whereas the indices of systolic function were preserved.
Conclusions:
We have developed a heterotopic transplant working rat heart model and have used it to assess in-situ cardiac function by MRI. Sensitive indices of diastolic contractile function can be obtained in this rodent transplant model that correlate well with histologic evidence of early rejection.