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(Circulation. 1999;100:1236-1241.)
© 1999 American Heart Association, Inc.

Basic Science Reports

New Method for Detection of Heart Allograft Rejection

Validation of Sensitivity and Reliability in a Rat Heterotopic Allograft Model

David C. Morgan, PhD; Janet E. Wilson, BSc, MT(ASCP); Calum E. MacAulay, PhD; Nicholas B. MacKinnon, BSc, AScT; Jennifer A. Kenyon, BSc; Paul S. Gerla, BSc; Chunming Dong, MD, PhD; Haishan Zeng, PhD; Peter D. Whitehead; Christopher R. Thompson, MD, CM; Bruce M. McManus, MD, PhD

From Biomax Technologies, Inc, Vancouver, BC (D.C.M., P.S.G., P.D.W., C.R.T.); Department of Pathology and Laboratory Medicine, St. Paul's Hospital–University of British Columbia, Vancouver, BC (J.E.W., J.A.K., C.D., B.M.M.); Cancer Imaging, BC Cancer Agency, Vancouver, BC (C.E.M., N.B.M., H.Z.); and Division of Cardiology, St. Paul's Hospital, University of British Columbia, Vancouver, BC (C.R.T.).

Correspondence to Bruce M. McManus, MD, PhD, St. Paul's Hospital–University of British Columbia, 1081 Burrard St, Vancouver, BC V6Z 1Y6. E-mail mcmanus{at}interchange.ubc.ca

Background—Patients with inflammatory heart muscle diseases would benefit from a safe, convenient, rapidly performed diagnostic technique with real-time results not involving tissue removal. We have performed a detailed evaluation of detection of heart allograft rejection by autofluorescence in a heterotopic abdominal rat heart allograft model ex vivo.

Methods and Results—Recipient rats with allograft (Lewis to Fisher 344; n=71) 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 transplant. Nontransplant controls with (n=24) or without (n=24) immunosuppressive therapy were also studied. When the rats were killed, autofluorescence spectra were acquired under blue-light excitation from midtransverse ventricular sections of native and transplanted hearts. Corresponding sections were then evaluated pathologically by a modified International Society for Heart and Lung Transplantation (ISHLT) grading schema. The spectral differences between rejecting and nonrejecting hearts were quantified by linear discriminant functions, producing scores that decreased progressively with increasing 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-order correlation -0.6; P<0.001, test for trend). Cyclosporine had no detectable 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.

Key Words: transplantation • rejection • biopsy • spectroscopy

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