BAHNSON, HT

BERNSTEIN, RL

GRIFFITH, BP

HARDESTY, RL

STARZL, TE

English

PubMed

Griffith, BP

Hardesty, RL

Bahnson, HT

Bernstein, RH

Starzl, TE

Name not available

Cardiac transplants with cyclosporin A and low dose prednisone: Histologic graduation of rejection

D-Scholarship@Pitt

1 l I Cardiac Transplants With Cyclosporin-A and Low-Dose Prednisone: Histologic Graduation of Rejection S. P. Griffith, R. L. Hardesty, H. T. Bahnson, R. L. Serns(ein, and T. E. Starzl CARDIAC histology has been reviewed in 16 patients between April 1980 and March 1981 to evaluate the effect of cyclospo-rin-A (CyA) and low-dose prednisone in a new trial of orthotopic cardiac transplanta-tion. The usual maintenance dose of CyA has been 5-10 mg/kg/day, and prednisone 15-20 mg/ day.1 HydrOC()rtisone, 1 g intravenously, has been used to combat rejection. usually without alteration of the prednisone dose. Ninety-two endomyocardial biopsies have been performed and a minimum of three specimens from each evaluated by light microscopy. Each specimen is fixed in 10% buffered formalin and stained with hematoxy-lin and eosin. Masson's trichrome. and methyl-green pyronine. No mortality but some morbidity has resulted from the percuta-neous endomyocardial biopsy; pericardial tamponade occurred once 6 hr following a procedure, and a second patient formed a superior mediastinal hematoma. Morphological features and grading of rejection by endomyocardial biopsy is based on those described by Billingham for patients receiving conventional immunosuppression with azathioprine. antithymocyte globulin. and prednisone." In this series. miid rejection has included varied degrees of lymphocytic endocardial infiltration, focal interstitial infil-tration, and endocardial plus interstitial edema (Fig. 1). Moderate rejection occurs with increased monocytic infiltration and moderate myocyte necrosis. The latter feature distinguishes this group of eyA-treated patients from those treated with conventional immunosuppression in whom myocyte necro-sis is rare and focal. Severe rejection has occurred with widespread necrosis and inflammation (Fig. 2). Increased active fibro-sis and scar formation have been prominent following myocyte necrosis, and mild to mod-Transplantation Proceedings. Vol. XV. No. 1 (Marchi. 1983 erate round cell infiltration has persisted for more than a month after moderate to severe rejection episodes (Fig. 3). The previously described pattern of fine interstitial fibrosis attributed to CyA has been common in this series.J During acute rejection episodes, round cells stain positively with methyl-green pyro-mne. Eleven of 15 biopsies at 1 wee'k showed no (3) or mild (8) rejection; whereas, for the subsequent 5 weeks, mild and moderate rejec-tion approached an equal distribution (Fig. 4). Moderate rejection in 8, noted within the first 6 weeks, has improved to mild in every instance. Two of 16 patients showed severe rejection within the first 6 weeks. CyA had been withdrawn for 3 days prior to clinical rejection (2 weeks) in one instance because of renal toxicity. Hypotension and low cardiac output antedated severe histologic changes. Clinical and histologic rejection improved at 5 weeks, and at 18 weeks, mild morphological rejection correlated with a cardiac index (Cl) of 2.2 liter/min/sq m and pulmonary capil-lary wedge pressure (PCW) of 9 mm Hg. One year posttransplantation, the biopsy showed marked interstitial fibrosis. Cardiac catheteri-zation recorded a normal ejection fraction of 59%, but a low Cl of 1.9 liter/min/sq m and widened arteriovenous oxygen difference of 6 vol %. Clinically, the patient was in controlled congestive failure but died suddenly in a dis-From the Departmenls of Surgery and Pathology. UniverSity of Pittsburgh. School of Medicine. Pills-burgh. Pa. Reprint requests should be addressed to Dr. B. P. Griffith. Departmenl of Surgery. University of PittS-burgh. School of Medicine. 1084 Scaife Hall. Pittsburgh. Pa.15261. © 1983 by Grune & Strallon. Inc. 0041-1345/83/1501-0299$01.00/0 1241 1242 I. :." ~ ~ ..... ~~ ~K:~- .-KK~D -"'.-'" :. . ;: ....... ~ . '·.1 .. .... Fig. 1. Endomyocardial biopsy showing mild acute rejection with round cell infiltration and edema of endocardium and interstitium (hematoxylin and eosinl. tant city 13 months postoperatively with a low output syndrome. Autopsy studies are pend-ing. Severe rejection in the second patient (4 weeks) improved to moderate. which per-sisted. Clinical rejection occurred at 23 weeks with moderate histologic changes. Improve-ment to mild rejection correlated with a CI of 2.3 and PCW of IS. Moderate fibrosis and mild rejection was noted 44 weeks postopera-tively; and although this patient had devel-oped mild congestive heart failure, his hemo-dynamics had not changed. Precipitous heart failure occurred at 47 weeks and resulted in death. Autopsy demonstrated diffuse intersti-tial fibrosis, mild acute rejection, and a left Fig. 2. Endomyocardial biopsy showing severe acute rejection with mixed inflammatory infiltration and myocyte nacrosia (hemotoxylin and eosinl. GRIFFITH ET AL. Fig. 3. Endomyocardial biopsy showing marked interstitial fibrosis (Masson's trichrome I. ventricular infarction. The distal left coronary arteries were focally narrowed by severe subintimal round cell infiltration. Cy A with low-dose prednisone (IS mg/ day) is effective immunosuppression for use in cardiac transplantation based on minimal clinical and generally mild to moderate histo-logic rejection with the first 6 weeks. The resolution of moderate (4-6 weeks) to mild (10-30 weeks) changes of rejection suggests its effectiveness. Histologic changes are gen-erally similar to those described in a patient treated with azathioprine, antithymocyte globulin, and prednisone; however, the pattern 10 9 8 7 HISTOLOGIC REJECTION-CAROIAC TRANSPLANTATION CyA+ PREDNISONE HISTOLOGIC CHANGE o NONE m 1It0000ATE OlD MI LD IllJ SEVERE , I ( 3 Z /' / ... WEEKS Fig. 4. Histologic gradetion of endomyocardial biopsy specimens obtained from 1 to 6 weaks post-transplantation. ,;81 st-1 t f i-f ! ,. I l ". I \ i· ! . 1 CARDIAC TRANSPLANTS WITH CyA AND PREDNISONE of resolution may differ. The two patients who developed severe histologic rejection in this series continued with moderate rejection after 1243 some initial resolution. The common result 1 year followirg transplantation included a scarred and compromised graft. REFERENCES l. Griffith BP, Hardesty RL. Deeb GM. et al: Ann Surg 196:92. 1982 2. Billingham ME: Hum PathoIIO:367, 1979 3. Billingham ME: Heart Transplant 1:25. 1981 

CARDIAC TRANSPLANTS WITH CYCLOSPORIN-A AND LOW-DOSE PREDNISONE - HISTOLOGIC GRADUATION OF REJECTION

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CARDIAC TRANSPLANTS WITH CYCLOSPORIN-A AND LOW-DOSE PREDNISONE - HISTOLOGIC GRADUATION OF REJECTION

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