Attenuation of the effects of rat hemorrhagic shock with a reperfusion injury-inhibiting agent specific to mice.
Death after hemorrhagic shock (HS) may be caused by a generalized reperfusion injury, particularly noticeable in the gut. A period of tissue ischemia followed by reinstitution of perfusion produces severe inflammation that can be blocked in mice by preventing the binding of a pathogenic natural immunoglobulin M (IgM) of defined specificity to antigens in reperfused tissue by using a soluble peptide analogue of the IgM tissue target. We hypothesize that this agent can improve end points of rat HS: death, intestinal injury, and lung injury. Male Sprague-Dawley rats were anesthetized; 50% of calculated blood volume was removed for 120 min, shed blood, then returned; and animals were sacrificed at 72 h. One group of rats received i.v. analogue ([N2] 300 microg) with the return of shed blood. Small intestine and lung were evaluated by histological examination and immunohistochemistry. Lung edema was assessed by Evans blue extravasation and histological examination. I.v. N2 decreased experimental mortality from 62% to 12% (P < 0.05). Associated with this was diminution of gut injury score from 57.8% +/- 5.5% to 19.5% +/- 2.5% (P < 0.05), lung injury from 21.4 +/- 1.5 to 14.8 +/- 1.3 polymorphonuclear leucocytes per high-power field x400 (P < 0.05), and Evans blue extravasation index from 0.61 +/- 0.14 to 0.18 +/- 0.06 (P < 0.05). As well, the deposition of IgM and C3 that is seen in intestinal villi from HS was not present in N2-treated rats. The N2 peptide agent that blocks reperfusion injury in mice prevents death from rat HS, as well as attenuates gut reperfusion injury and its remote target injuries. These data suggest that death from HS is caused by reperfusion injury, and that an agent derived from mice is effective in rats when given in real therapeutic time.
Ahmadi-Yazdi
Cyrus
C
Department of Surgery, Brigham and Women Hospital, Boston, Massachusetts 02115, USA.
Williams
Brian
B
Oakes
Sean
S
Moore
Francis D
FD
D000818:Animals; D007075:Immunoglobulin M / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects*; D055370:Lung Injury / Q000188:drug therapy; D008297:Male; D051379:Mice; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000473:pathology
D007075:Immunoglobulin M; D010455:Peptides