PENTOXIFYLLINE PREVENTS ENDOTHELIAL DAMAGE DUE TO ISCHEMIA AND REPERFUSION INJURY

Background. Endothelial injury after ischemia and reperfusion is chara cterized by an increase in permeability, cellular edema, and loss of a cetylcholine-mediated vasorelaxation. Three hours of ischemia followed by 2 hr of reperfusion in the New Zealand white rabbit hindlimb has b een shown to result in loss of acetylcholine-induced superficial femor al artery vasorelaxation. The purpose of this study was to evaluate th e effect of intraarterial pentoxyfylline (PTX) on this endothelial inj ury. Methods. New Zealand white rabbits underwent 3 hr of complete hin dlimb ischemia followed by 2 hr of reperfusion. Twenty milliliters of either 100 mu M PTX or normal saline was infused over 20 min via the c ircumflex iliac artery at initiation of reperfusion. Superficial femor al artery rings were then evaluated in vitro for endothelial cell-medi ated relaxation. Rings were exposed to standardized incremental doses of acetylcholine after norepinephrine-induced contraction and percenta ge relaxation was measured. Sections of arteries were also sent for he matoxylin and eosin staining. Results. Similar contraction responses f ollowing NE stimulation were observed between control and PTX-treated rings. Control rings relaxed a mean of 14.97 +/- 3.64, 23.17 +/- 5.61, and 31.84 +/- 8.43% in response to acetylcholine doses of 6 X 10(-8), 1 X 10(-7), and 1.5 X 10(-7) M, respectively. In contrast, PTX-treate d segments relaxed a mean of 47.52 +/- 8.88, 62.32 +/- 6.83, and 76.73 +/- 4.91% to the same doses of acetylcholine. Differences in relaxati on between control and PTX-treated vessels were significantly differen t at each dose (P < 0.05, Student's t test). Histologic examination of the PTX-treated and control arteries revealed an intact endothelium w ithout morphologic differences between the two groups. Conclusion. In this model of rabbit hindlimb ischemia, endothelial cell-mediated vaso relaxation was preserved with the administration of intraarterial PTX during reperfusion compared to controls. The different relaxation resp onses could not be attributed to altered arterial contractility in res ponse to norepinephrine, or explained by histologic changes in the art erial wall. These studies demonstrate a potential modality for therape utic intervention to reduce reperfusion injury after acute limb ischem ia. (C) 1997 Academic Press.