Effect of anti-CD18 antibody on myocardial neutrophil accumulation and infarct size after ischemia and reperfusion in dogs.
BACKGROUND
Polymorphonuclear neutrophils (PMNs) accumulate in postischemic myocardium and may cause injury to myocardium or to vessels by production of oxygen free radicals or by release of proteases and lipases. PMN accumulation is dependent on adherence to endothelium, which is mediated by a family of glycoproteins on the PMN surface, each of which has a common beta-subunit (CD18). The purpose of this study was to determine whether an antibody (IB4) against the CD18 protein could attenuate PMN accumulation and limit myocardial infarct size.


RESULTS
F(ab')2 fragments of a mouse monoclonal antibody to human adherence-promoting leukocyte glycoprotein (CD18) were used. Infarct size after 90 minutes of ischemia and 3 hours of reperfusion was compared in dogs with (n = 8) and without (n = 8) the anti-CD18 treatment. Myocardial PMN accumulation was assessed with 111In-labeled autologous PMNs. Anti-CD18 treatment significantly reduced the number of PMNs in the ischemic region (19,123 +/- 5,352/mg versus 5,204 +/- 927/mg in the control and treated groups, respectively; p < 0.05). In addition, the ratio of myocardial blood flow (ischemic/nonischemic wall) at 45 minutes into reperfusion was higher in the treated than in the control group (1.18 +/- 0.18 versus 0.69 +/- 0.09; p < 0.05). Nevertheless, infarct size was similar between the control and treated groups (40.5 +/- 7.4% versus 48.5 +/- 4.4% of the area at risk; p = NS). Transmural mean collateral blood flow to the ischemic myocardium was similar between the two groups, and the inverse relation between infarct size and collateral blood flow was not shifted by anti-CD18 therapy.


CONCLUSIONS
Although PMN accumulation contributed to reduced postischemic microvascular perfusion, it caused insufficient additional myocardial cell death to measurably affect infarct size in this model.
Tanaka
M
M
Department of Pathology, Duke University Medical Center, Durham, N.C. 27710.
Brooks
S E
SE
Richard
V J
VJ
FitzHarris
G P
GP
Stoler
R C
RC
Jennings
R B
RB
Arfors
K E
KE
Reimer
K A
KA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D018821:CD18 Antigens; D002453:Cell Cycle; D003326:Coronary Circulation; D004285:Dogs; D005260:Female; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology / Q000628:therapy; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology*; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D012709:Serum Albumin / Q000378:metabolism; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D016028:Receptors, Leukocyte-Adhesion; D012709:Serum Albumin