New method for detection of heart allograft rejection - Validation of sensitivity and reliability in a rat heterotopic allograft model

Background-Patients with inflammatory heart muscle diseases would benefit f rom a safe, convenient, rapidly performed diagnostic technique with real-ti me results not involving tissue removal. We have performed a detailed evalu ation of detection of heart allograft rejection by autofluorescence in a he terotopic abdominal rat heart allograft model ex vivo. Methods and Results-Recipient rats with allograft (Lewis to Fisher 344; n=7 1) and isograft (Lewis to Lewis; n=33) hearts, treated with cyclosporine or untreated, were killed at days 2, 4, 7, 14, 21, 28, and 56 after transplan t. Nontransplant controls with (n=24) or without (n=24) immunosuppressive t herapy were also studied. When the rats were killed, autofluorescence spect ra were acquired under blue-light excitation from midtransverse ventricular sections of native and transplanted hearts. Corresponding sections were th en evaluated pathologically by a modified International Society for Heart a nd Lung Transplantation (ISHLT) grading schema. The spectral differences be tween rejecting and nonrejecting hearts were quantified by linear discrimin ant functions, producing scores that decreased progressively with increasin g severity of tissue rejection. Mean+/-SD discriminant function scores were 2.9+/-1.6, 1.8+/-2.2, -0.1+/-2.8, -1.2+/-2.3, and -2.3+/-3.0 for isografts and allograft ISHLT grades 0, I, II, and III respectively Spearman rank-or der correlation -0.6; P<0.001, test for trend). Cyclosporine had no detecta ble effect on the spectra. Conclusions The correlation between changes in autofluorescence spectra and ISHLT rejection grade strongly supports the possibility of catheter-based, fluorescence-guided surveillance of rejection.