In vivo visualization of the effect of polyclonal antithymocyte globulins on the microcirculation after ischemia/reperfusion in a primate model.
BACKGROUND
Ischemia-reperfusion injury (IRI) leads to increased leukocyte adherence enhancing acute cellular rejection and microvascular dysfunction. Polyclonal antithymocyte globulins (ATGs) induce T-cell depletion and functional impairment of nondepleted lymphocytes in peripheral blood. ATGs represent an important option in the treatment of acute cellular rejection but little is known about their effects on the microcirculation in IRI.


METHODS
In a perfusion system, 19 cynomolgus monkeys were used to evaluate the influence of three different ATGs on the leukocyte-endothelium interaction after cold ischemia. ATGs were administered to human blood 30 min prior to reperfusion of primate extremities. Using intravital fluorescence microscopy the postreperfusion microcirculation of skeletal muscle was visualized.


RESULTS
Significant differences were found between ATG-treated and ATG-free groups concerning blood flow velocity, leukocyte count, and leukocyte-endothelium interaction. ATGs reduced microvascular leukocyte adhesion, count, and blood flow impairment.


CONCLUSIONS
ATGs have a favorable impact on early mechanisms of IRI. Due to reduced leukocyte adherence to the antigen-presenting endothelial cells, recognition events cannot take place in the posttransplant period of reperfusion. In addition to inhibiting acute transplant rejection, increase of posttransplant blood flow supports the use of ATGs as pretransplant induction therapy.
Chappell
Daniel
D
Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Beiras-Fernandez
Andres
A
Hammer
Claus
C
Thein
Eckart
E
D000818:Animals; D000961:Antilymphocyte Serum / Q000494:pharmacology*; D004195:Disease Models, Animal; D007511:Ischemia / Q000503:physiopathology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008252:Macaca fascicularis; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology*
D000961:Antilymphocyte Serum