Antibody against neutrophil adhesion improves reperfusion and limits alveolar infiltrate following unilateral pulmonary artery occlusion.
Relief of unilateral pulmonary arterial occlusion results in bilateral lung injury and results in only partial restoration of pulmonary blood flow distal to the site of occlusion. We hypothesized that the "no reflow" phenomenon was in part due to neutrophil adherence and aggregation in the pulmonary vasculature. The study was carried out in two phases. First, we studied the effect of neutrophil depletion on left lung blood flow following 24 hr of left pulmonary artery occlusion. Hydroxyurea was used to deplete circulating neutrophils to 77 +/- 18/mm3 (means +/- sem) (n = 6) as compared to 708 +/- 165/mm3 in control rabbits (n = 8). In both groups left lung blood flow immediately following reperfusion was markedly reduced at 6.4 +/- 2.2% of cardiac output in control rabbits and 7.3 +/- 2.3 in treated rabbits. However, at 4 hr, neutrophil-depleted animals had significantly greater flow (18.7 +/- 3.6 vs 8.4 +/- 2.3% for control rabbits, P less than 0.05). In both groups, flow remained substantially below the normal rabbit left lung blood flow of 39.8 +/- 2.2%. To test whether the improved reflow was due to decreased numbers of neutrophils limiting aggregation, or whether active neutrophil adherence played a role, we tested the effect of a monoclonal antibody that interferes with neutrophil adhesiveness (MoAb 60.3) on reflow and on neutrophil emigration into the alveoli. We found that MoAb 60.3 did not affect initial reflow.(ABSTRACT TRUNCATED AT 250 WORDS)
Bishop
M J
MJ
Department of Anesthesiology, University of Washington, Seattle 98195.
Kowalski
T F
TF
Guidotti
S M
SM
Harlan
J M
JM
D000818:Animals; D000911:Antibodies, Monoclonal; D001157:Arterial Occlusive Diseases / Q000503:physiopathology*; D002448:Cell Adhesion / Q000502:physiology; D003250:Constriction; D009504:Neutrophils / Q000502:physiology*; D010208:Papaverine / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000473:pathology; D011651:Pulmonary Artery / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000502:physiology; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology*
D000911:Antibodies, Monoclonal; D010208:Papaverine