INTRAGRAFT EVENTS AFTER HEART-TRANSPLANTATION - AN EXPERIMENTAL-STUDYCOMPARING CYTOLOGY IN CORONARY SINUS BLOOD, PERIPHERAL-BLOOD, AND DAILY HISTOLOGY

Acute rejection is a frequent consequence after heart transplantation. To expand our knowledge of the rejection process and to investigate s ome intragraft events during acute rejection, the following experiment al transplantation model was designed. Right cervical heart transplant ation was performed in 12 mongrel dogs. Two experimental groups of six animals each received different immunosuppressive regimens. All anima ls were treated with daily triple drug therapy. In contrast to group 1 , the animals in group 2 received high-dose steroids during rejection. The condition of the hearts was examined by daily transmural biopsies , graded according to the, Billingham classification. To detect and qu antify alterations in the mononuclear cell subsets of the myocardial v enous return, blood samples from the coronary sinus blood (CS) and fro m peripheral blood (PB) were taken simultaneously with the biopsy. The total number of lymphoblasts and activated lymphocytes was determined and an activation index (AI) was calculated. The data referred to was established from 337 transmural biopsies. The AI of PB (n = 287) corr elated well with the different stages of acute rejection (grade B0: AI = 2.2+/-2.1; grade B1 + 2: AI = 6.3+/-1.7; grade B3: AI = 10.0+/-4.7; P < 0.001). The rejection kinetics of both groups, including the reje ction-free interval following high-dose steroid administration in grou p 2, could be expressed accurately by the AI. The time course of the t otal number of lymphoblasts in CS versus PB demonstrated that the lymp hoproliferative response started 4 days prior to the first intramyocar dial signs of rejection ((x) over bar= .8+/-0.7; n = 12). The maximum number of lymphoblasts was seen on the day of rejection in 1 group 1 a nd 1 day after the onset of histologically proven rejection in group 2 (group 1: n = 6: CS (x) over bar=40.1+/-7.5; PB (x) over bar=12.2+/-4 .1; P < 0.001; group 2: n = 6: CS (x) over bar=39.4+/-8.8; PB (x) over bar=12.9+/-3.7; P < 0.001). Under rejection therapy in group 2 these cells decreased immediately, followed by a short rejection-free interv al. In group 1 the total number of lymphoblasts diminished continuousl y, almost reaching the number in PB at the time of final rejection. In contrast, activated lymphocytes did not render adequate results. Comp arison of daily histology and the data of PB proved there is a good co rrelation between the AI and the different histologic stages of acute rejection. The total number of lymphoblasts in CS during rejection is significantly higher than in PB. Acute rejection seems to be detectabl e almost 4 days before histology and PB cytology by cytologic evaluati on of the CS. There fore, we speculate that the differentation and pro liferation of lymphoblasts during the initial phase of acute rejection takes place within the graft itself.