Thorac Cardiovasc Surg 2013; 61 - OP257
DOI: 10.1055/s-0032-1332496

Volume- loading in experimental heterotopic heart transplantation

D Biermann 1, M Didié 2, K Wittköpper 2, P Christalla 2, H Reichenspurner 1, A El-Armouche 2, WH Zimmermann 2
  • 1Universitäres Herzzentrum Hamburg, Herz- und Gefäßchirurgie, Hamburg, Germany
  • 2Zentrum Pharmakologie und Toxikologie, Universitätsmedizin Göttingen, Göttingen, Germany

Objectives: Hemodynamically non-loaded heterotopic heart transplants (NL) in rodent models are widely used to model the effects of unloading the human heart with left ventricular assist devices (LVAD). However, whether NL represents the clinical condition of unloading remains controversial. Here we hypothesize that volume loaded heterotopic heart transplants (VL) in experimental heterotopic heart transplantation (hHTx) are superior to NL.

Methods: Hearts of adult rats were perfused with cardioplegic solution and explanted. 14 and 27 hearts were transplanted abdominally under as NL or VL, respectively. Echocardiography was performed prior to transplantation, at day 1 and 1, 2 as well as 4 weeks after transplantation. LV-pressure and volume were assessed by conductance catheter 4 weeks after transplantation. Fibrosis was quantified histologically by sirius-red staining. Furthermore, positron emission tomography (PET) analyses with F-18-fluorodeoxyglucose (FDG) were performed. Genetic expression patterns were investigated by quantitive real time polymerase chain reaction (qPCR).

Results: After 4 weeks echocardiography showed higher anterior wall thickness (1.9 ± 0.1 vs. 1.2 ± 0.1 mm; p < 0.05) and higher left ventricular weight (349 ± 26 vs. 196 ± 26 mg; p < 0.05) in VL vs. NL. Contractile function measured by anterior wall thickening fraction (22 ± 3 vs. 8 ± 4%; p < 0.05) and fractional area shortening (33 ± 5 vs. 18 ± 4%; p < 0.05) were better in VL compared to NL. Maximal left ventricular pressure in VL was comparable to orthotopic hearts (87 ± 8 vs. 97 ± 4 mmHg; n.s.), whereas it was markedly lower in NL (61 ± 6 vs. 93 ± 6 mmHg; p < 0.05). VL showed enhanced systolic function (dp/dt max: 2986 ± 252 vs. 2032 ± 193 mmHg/s; p < 0.05) and maximal stroke volume (135 ± 20 vs. 53 ± 9 µl; p < 0.05). Both VL and NL showed a similar level of fibrotic remodeling. PET suggested higher glucose metabolisms in VL (not significant). qPCR showed that some markers like collagen 1, structural proteins and showed a difference between heterotopic VL and NL; interestingly, GLUT1 and GLUT4 expression did not differ in VL and NL.

Conclusion: Loading the heart appears to be adequate to maintain contractile properties and morphology but does not prevent myocardial fibrosis. The metabolic activity in terms of regional glucose uptake was not significantly different in NL and VL. Collectively, our data provides strong evidence for a superior utility of VL vs. NL in studies of therapeutic left ventricular unloading.