A specific inhibitor of apoptosis decreases tissue injury after intestinal ischemia- reperfusion in mice Alik Farber, MD, John P. Connors, MD, Robert.

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A specific inhibitor of apoptosis decreases tissue injury after intestinal ischemia- reperfusion in mice Alik Farber, MD, John P. Connors, MD, Robert M. Friedlander, MD, Robert J. Wagner, BS, Richard J. Powell, MD, Jack L. Cronenwett, MD Journal of Vascular Surgery Volume 30, Issue 4, Pages 752-760 (October 1999) DOI: 10.1016/S0741-5214(99)70115-1 Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 1 Time course of experiment demonstrating inhibitor (ZVAD), placebo (ZFA), or carrier dosing schedule, operative intervention, and physiologic insult (ischemia, reperfusion). sc, Subcutaneously; ip, intraperitoneally. Journal of Vascular Surgery 1999 30, 752-760DOI: (10.1016/S0741-5214(99)70115-1) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 2 Representative hematoxylin-eosin stained sections of small bowel showing histologic intestinal injury grading.23 (Original magnification ×40, Nikon microscope). Grade 1 , Normal mucosal villi; grade 2 , development of mucosal sloughing; grade 3 , epithelial layer lifting up in sheets, presence of a few denuded villous tips, and mild capillary congestion; grade 4 , exposed lamina propria, dilated capillaries, and evidence of hemorrhage; grade 5 , digestion and disintegration of the lamina propria. Journal of Vascular Surgery 1999 30, 752-760DOI: (10.1016/S0741-5214(99)70115-1) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 3 Correlation between duration of ischemic interval and magnitude of histologic injury (n = 4 animals/time point; 6 hours of reperfusion; r = 0.69; mean ± standard error of the mean). Journal of Vascular Surgery 1999 30, 752-760DOI: (10.1016/S0741-5214(99)70115-1) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 4 Relationship between apoptotic index (apoptotic cells/10 high-power fields) and duration of ischemic interval (n = 4/time point; mean ± standard error of the mean; *P ≤ .05 compared with sham controls, Student t test). Journal of Vascular Surgery 1999 30, 752-760DOI: (10.1016/S0741-5214(99)70115-1) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 5 Determination of mature IL-1β in ischemic and normal small bowel specimens. Mature IL-1β was determined from mechanically and enzymatically digested bowel using a specific ELISA assay (n = 6/group; mean concentration ± standard error of the mean; P < .05, Student t test). Journal of Vascular Surgery 1999 30, 752-760DOI: (10.1016/S0741-5214(99)70115-1) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 6 Effect of apoptosis inhibitor (ZVAD) and placebo (ZFA) on histologic injury grade after 50 minutes of ischemia and 6 hours of reperfusion. Apoptosis inhibition (ZVAD) markedly reduced injury compared with placebo (ZFA) to the extent that it was statistically similar to sham injury (P = .7; n = 11, ZVAD; n = 9, ZFA; n = 6, sham controls; mean ± standard error of the mean; Kruskall-Wallis, Mann-Whitney, ANOVA with Fisher ad hoc tests). Journal of Vascular Surgery 1999 30, 752-760DOI: (10.1016/S0741-5214(99)70115-1) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions