A CD18 antibody prevents lung injury but not hypotension after intestinal ischemia-reperfusion.
Antibodies to the neutrophil CD18 integrin have been shown to ameliorate the local effects of intestinal ischemia and reperfusion (I/R). In addition to local mucosal injury, intestinal I/R results in systemic hypotension and injury to the lungs with lung leukosequestration. This study tests the effect of a CD18 monoclonal antibody on the hypotension and lung injury after intestinal I/R. In anesthetized rabbits, the superior mesenteric artery was clamped for 60 min followed by 3 h of reperfusion. Animals were treated with saline, an anti-CD18 monoclonal antibody (R15.7 MAb), or nonspecific immunoglobulin G. Another non-ischemic group were sham controls. Neutrophil sequestration was assessed by measure of lung myeloperoxidase (MPO) and permeability by lung-to-blood concentration ratio of 125I-labeled bovine serum albumin and wet-to-dry weight ratio. Immediately after reperfusion, mean arterial pressure fell to 49 +/- 2.1 mmHg and remained at this level. The hypotension was unaffected by treatment with R15.7 MAb. Thirty minutes after reperfusion, the circulating white blood cell count fell to 2.91 +/- 0.53 x 10(3)/mm3 vs. sham 6.40 +/- 0.66 x 10(3)/mm3 (P < 0.05). Treatment with R15.7 MAb prevented this fall in white blood cell count (5.75 +/- 1.59 x 10(3)/mm3). At 3 h of reperfusion in saline-treated animals there was increased MPO, 74.8 +/- 4.9 U/g vs. 42.0 +/- 4.8 U/g in sham animals (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Hill
J
J
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02215.
Lindsay
T
T
Valeri
C R
CR
Shepro
D
D
Hechtman
H B
HB
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D001794:Blood Pressure; D018821:CD18 Antigens; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000502:physiology; D007022:Hypotension / Q000503:physiopathology / Q000517:prevention & control*; D007422:Intestines / Q000098:blood supply / Q000502:physiology*; D007511:Ischemia / Q000503:physiopathology*; D008168:Lung / Q000276:immunology / Q000503:physiopathology*; D009504:Neutrophils / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology*; D012711:Serum Albumin, Radio-Iodinated
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D012711:Serum Albumin, Radio-Iodinated; D009195:Peroxidase