POLYMORPHONUCLEAR LEUKOCYTE BEHAVIOR IN A NONHUMAN PRIMATE FOCAL ISCHEMIA MODEL

There is increasing interest in the role of poly morphonuclear (PMN) l eukocytes in the evolution of focal cerebral infarction. Surgical prep aration of focal cerebral ischemia models may alter leukocyte reactivi ty and thereby make interpretation of leukocyte function following isc hemia/reperfusion difficult. The effects of surgical preparation and o f experimental ischemia/reperfusion on granulocyte function have been examined prospectively in a baboon model. Twenty-six adolescent male b aboons underwent surgical preparation, of which 21 underwent middle ce rebral artery occlusion/reperfusion. Four additional animals served as nonsurgical controls. Peripheral venous blood specimens were taken fo r performing assays of leukocyte function at defined intervals before and after both the surgical preparation (i.e., the overall procedure f or implantation of the middle cerebral artery occlusion device) and oc clusion/reperfusion. A stress related elevation in total leukocyte num ber was attributed mainly to an increase in the number of circulating PMN leukocytes. Values rose from 13.9 +/- 4.9 x 10(3) to 27.8 +/- 5.8 x 10(3)/mu 1, (+/-SD; n = 21) for total leukocyte number, with p < 0.0 01, and from 4.3 +/- 2.1 x 10(3) to 15.9 +/- 4.7 x 10(3)/mu 1 (n = 21) for PMN leukocytes, with p < 0.001. Surgical preparation had no effec t (p greater than or equal to 0.4) on the ability of PMN leukocytes, i solated 24 h after the implantation procedure, to display polarization , 0(2)(.-) production, or p-glucuronidase release when stimulated with human C5a. A moderate decrease in the chemotactic response to C5a res olved within the 7-day postsurgery (preocclusion) period. Three-hour m iddle cerebral artery occlusion and l-h reperfusion resulted in a sign ificant reduction in C5a-induced polarization. The preocclusion value of 82 +/- 9.7 (n = 7) was compared with the occlusion/reperfusion valu e at 58.8 +/- 13.7 (n = 6; p < 0.05). A moderate decrease was observed in C5a-induced 0(2)(.-) and P-glucuronidase release, as well as a dec rease in the chemotactic response. In the nonhuman primate model, the reversible alterations (i.e., chemotaxis) in granulocyte function that were noted following surgical preparation resolved within 7 days. In contrast, middle cerebral artery occlusion/reperfusion was associated with a more dramatic and significant reduction in multiple granulocyte functions elicited by the endogenous mediator C5a as observed 1 h pos treperfusion.