In vivo microscopic assessment of microcirculatory changes in a concordant xenogeneic primate experimental set up

Organ transplantation is always connected with ischemia and thus reperfusion injury of the graft. One of the characteristics in this process is the temporary and permanent adherence of leukocytes to the endothelium of the graft. This cell-to-cell interaction allows the immunocompetent cells to interact in the sense of antigen recognition with mainly defect endothelial cells. It was the aim to study whether induction therapy with poly-clonal ATG's would reduce or even prohibit these early interactions.

The distal extremities of cynomolgus monkeys were flushed via the femoral vessels and reperfused with ABO-compatible human heparinised blood of a hct of 30%. Microcirculation was observed applying intra-vital microscopy. The images taken by a CCD-camera are recorded on video tapes for later off line evaluation. pATG 1 is directed against jurkat cells, pATG 2 against human thymocytes. In controls the blood vessels were perfused with untreated blood. In groups 2 and 3 the blood was treated with the amount of the ATG's used in clinical therapy 15 min. prior to perfusion. The total ischemia time was 1 hour.

Five minutes after perfusion rolling was seen in the untreated animal, this increased to change into sticking after 30 min. The blood flow (RBC) in larger venoles remained almost normal. Both polyclonal ATG's inhibited the adhesion to a large extend.

Ischemia reperfusion results in increasing adherence of leukocytes in the described model. pATG's suppress this phenomenon completely. This suggests that pATG's contain a number of antibodies directed against various types of cell surface molecules which are involved in reperfusion injury and that pATG's have a favourable influence on the early I/R-mechanisms after organ transplantation and a protective action when used as pre-operative induction therapy.