Severe hemorrhagic shock and the intestine

Since PolyHb has no blood group antigens and can be stored for a much longer time than donor blood even at room temperature, there is the potential of using this onsite for the treatment of hemorrhagic shock. However, if the ischemia is severe and prolonged before reperfusion, there could be ischemia-reperfusion injuries. In severe sustained hemorrhagic shock, there is severe vasoconstriction of some organs, especially the intestine and kidneys. Furthermore, the intestine is rich in xanthine oxidase that catalyzes the formation of superoxide. Thus, the intestine is very vulnerable to ischemia-reperfusion injury and

Fig. 4.2. Hydroxy! radical production assessed by the measurement of 3,4 dihydroxybenzoate in ischemic intestine perfused with 5 g/d! of PolyHb (■) or 5g/d! of PolyHb-SOD-CAT (•). Intestinal effluent samples are collected during reperfusion at the indicated times. Data are presented as means ± SD. *denotes statistical significance; P < 0.05. (From Razack, D'Agnillo & Chang, 1997.)

Fig. 4.2. Hydroxy! radical production assessed by the measurement of 3,4 dihydroxybenzoate in ischemic intestine perfused with 5 g/d! of PolyHb (■) or 5g/d! of PolyHb-SOD-CAT (•). Intestinal effluent samples are collected during reperfusion at the indicated times. Data are presented as means ± SD. *denotes statistical significance; P < 0.05. (From Razack, D'Agnillo & Chang, 1997.)

therefore it would be a sensitive model for testing ischemia-reperfusion injury. In severe sustained hemorrhagic shock, reperfusion with red blood cells that contain the normal amounts of CAT and SOD may not be adequate to prevent ischemia-reperfusion. Since PolyHb-CAT-SOD can contain more enzymes than red blood cells, we tested this preparation for reperfusion in an ischemia-reperfusion intestine model (Razack, D'Agnillo & Chang 1997). Figure 4.2 shows that the use of PolyHb for reperfusion results in a significant increase in oxygen radicals. The use of PolyHb-CAT-SOD does not give rise to such an increase in oxygen radicals.

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