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RESULTS: Binomial analysis showed that channels greater than 2cm part (sampling deeper tissue) were more highly correlated with MAP alues than channels less than 2cm during event periods (p 0.0182). ruskal-Wallis tests yield significant differences in correlations across 4 ites in the frontal region for control and event time periods (p 0.02 2/24 controls, p 0.02 12/13 events). Sensitivity analysis based on ndividual channel amplitudes showed it is necessary to lower the alert hreshold by 90%, relative to the largest observed oxygen saturation hange, in order for 50% of the channels to report the event.

METHODS: Human neutrophils were incubated in 10uM HS or saline and labeled with antibodies to PSGL-1, LFA-1, Mac1alpha, L-selectin and beta-2 integrin CBRM1/5 epitope prior to flow cytometry analysis. Additional neutrophils were activated with IL-8, fMLP, or TNFalpha, or treated with 30uM TAPI-0 (an inhibitor of the enzyme responsible for L-selectin cleavage) prior to HS/saline treatment, labeling, and flow cytometry. Nine C57BL/6 mice were administered an intravenous dose of 20uM HS or saline. Mice then underwent 3h of unilateral tourniquetinduced hindlimb ischemia, followed by 3h of reperfusion. The bilateral gastrocnemius muscles were harvested and stained with H&E. Neutrophil infiltration was quantified.

RESULTS: Histologic analysis showed greater preservation of cellular architecture at 4h, 3.3h, and 0.3h. Quantitatively, AI of non-HS-treated ischemic tissue was 17.2/5.0%. A significant reduction in AI was seen at 4h (4.7/1.4%, p0.001), 3.3h (2.6/1.0%, p0.015) and 0.3h (1.8/0.7%, p0.022). No protection was seen at 5h (14.2/1.2%), 3h (10.6/ 3.1%), 1h (11.4/1.9%), 0h (15.0/2.8%), or 1h (11.2/1.2%). CONCLUSIONS: These data establish the boundaries of the bimodal protection afforded by pharmacologic pre- and postconditioning with HS, and reveal that the pre-ischemic window is slightly wider than the post-ischemic window. Defining the “protective intervals” of HS delivery is a crucial step towards clinical use of HS for the purpose of protection from IRI.