Cytokines contribute to early hepatic parenchymal injury and microvascular dysfunction after bilateral hindlimb ischemia D.Kirk Lawlor, MD, Robert W.

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Presentation transcript:

Cytokines contribute to early hepatic parenchymal injury and microvascular dysfunction after bilateral hindlimb ischemia D.Kirk Lawlor, MD, Robert W. Brock, MSc, Kenneth A. Harris, MD, Richard F. Potter, PhD Journal of Vascular Surgery Volume 30, Issue 3, Pages 533-541 (September 1999) DOI: 10.1016/S0741-5214(99)70081-9 Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 1 Schematic of the method used for determining liver sinusoidal perfusion. Sinusoidal perfusion was determined by using a point-counting grid. The total number and distance between points was predetermined by using the size of the largest object of interest (ie, sinusoidal area). For a magnification of 600×, the grid would consist of a 6 × 6 array of points. Circled points represent those that fall within the dimensions of a sinusoid. These selected points are then evaluated for specific perfusion criteria and expressed as a proportion of the total number of sinusoids touched by a point. Journal of Vascular Surgery 1999 30, 533-541DOI: (10.1016/S0741-5214(99)70081-9) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 2 Serum cytokine levels. A significant peak in systemic TNF-α occurred at 30 minutes of reperfusion and returned to baseline by 60 minutes. No significant changes in TNF-α levels were measured during the ischemic period or during the remaining 6 hours of reperfusion. No significant changes in IL-1 were detected during the I/R period or at any other point during the 6-hour reperfusion period. Data represent means ± SEM. Asterisk, Significantly greater than any other time (P < .05). Journal of Vascular Surgery 1999 30, 533-541DOI: (10.1016/S0741-5214(99)70081-9) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 3 Serum ALT. Four hours of ischemia followed by 3 hours of reperfusion resulted in a significantly elevated ALT level when compared with the control group. The TNF-α PAb did not provide any benefits to such injury at 3 hours of reperfusion. Data represent means ± SEM. Asterisk, Significantly greater than preischemia prereperfusion levels (P < .05); hatched mark, significantly greater than control levels (P < .05). Journal of Vascular Surgery 1999 30, 533-541DOI: (10.1016/S0741-5214(99)70081-9) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 4 Lethal hepatocyte injury (ie, cell death). I/R group animals demonstrated a significant increase in PI-labeled hepatocytes in both periportal and pericentral regions of the hepatic acinus at 3 hours of reperfusion. The TNF-α PAb significantly diminished the number of dead hepatocytes. No appreciable differences were noted between regions of the acinus in any of the groups. Data represent means ± SEM. Asterisk, Significantly greater than the control and I/R + TNF-α PAb groups (P < .05). Journal of Vascular Surgery 1999 30, 533-541DOI: (10.1016/S0741-5214(99)70081-9) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions

Fig. 5 Sinusoidal perfusion. No apparent differences in total sinusoidal perfusion were observed during the reperfusion period; however, significant flow heterogeneity was demonstrated within the individual regions of the acinus. CPS declined significantly in the I/R group in the periportal region (A) , whereas the magnitude of intermittently perfused sinusoids increased. A similar trend was noted in the pericentral region (B) ; however, the decline in CPS was significantly less. The administration of TNF-α PAb appeared to improve perfusion heterogeneity in both regions of the acinus. Data represent means ± SEM. Asterisk, Significantly different than the control and I/R + TNF-α PAb groups (P < .05); hatched mark, significantly different from the periportal region. Journal of Vascular Surgery 1999 30, 533-541DOI: (10.1016/S0741-5214(99)70081-9) Copyright © 1999 Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter Terms and Conditions