NEUTROPHIL ACCUMULATION IN ISCHEMIC CANINE MYOCARDIUM - INSIGHTS INTO TIME COURSE, DISTRIBUTION, AND MECHANISM OF LOCALIZATION DURING EARLY REPERFUSION

被引:270
作者
DREYER, WJ
MICHAEL, LH
WEST, MS
SMITH, CW
ROTHLEIN, R
ROSSEN, RD
ANDERSON, DC
ENTMAN, ML
机构
[1] METHODIST HOSP,CARDIOVASC SCI SECT,HOUSTON,TX 77030
[2] BAYLOR UNIV,DEPT PEDIAT,SPEROS P MARTEL SECT LEUKOCYTE BIOL & INFLAMMAT RES,HOUSTON,TX 77030
[3] BAYLOR UNIV,DEBAKEY HEART CTR,DEPT MED,HOUSTON,TX 77030
[4] BAYLOR UNIV,DEPT PEDIAT,LILLIE FRANK ABERCROMBIE SECT CARDIOL,HOUSTON,TX 77030
[5] BAYLOR UNIV,VET AFFAIRS MED CTR,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030
[6] BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT
关键词
REPERFUSION INJURY; CHEMOTAXIS; NEUTROPHILS; MONOCLONAL ANTIBODIES;
D O I
10.1161/01.CIR.84.1.400
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background. We have previously demonstrated that chemotactic factors released from the ischemic canine myocardium peak early during reperfusion and that they elicit neutrophil adherence reactions in vitro that are dependent on the CD18 glycoprotein family. In this study we investigated the hypothesis that neutrophil localization in ischemic canine myocardium in vivo occurs over a similar time course during early reperfusion and involves a CD18-dependent mechanism. Methods and Results. We occluded the circumflex coronary artery for 1 hour in acute, open-chest dogs, followed by reperfusion for 1, 2, 3, or 4 hours. Regional myocardial blood flow was determined using radiolabeled microspheres, and localization was traced using technetium-99m-labeled autologous neutrophils. In the first hour of reperfusion, neutrophil localization occurred preferentially within the subendocardial region and was inversely related to flow. Neutrophil localization diminished across the ischemic myocardium from endocardium to epicardium but remained negatively related to flow in the midmyocardial region. Regardless of flow, little neutrophil localization occurred in the subepicardial region. Neutrophil localization was greatest in the first hour of reperfusion and diminished thereafter. By 4 hours of reperfusion, the rate of localization was markedly attenuated relative to 1 hour. Dogs given anti-CD18 monoclonal antibody R15.7 (1 mg/kg i.v.) before occlusion underwent 1 hour of occlusion followed by 1 hour of reperfusion. When compared with 1-hour reperfusion controls, the R15.7-treated dogs demonstrated significant attenuation of neutrophil localization in the subendocardial region. Conclusions. These data support the concepts that rapid neutrophil localization during reperfusion occurs within regions of previous myocardial ischemia and that neutrophils preferentially localize within the subendocardial region. The rate of neutrophil localization is greatest within the first hour after the initiation of reperfusion, and localization is, at least in part, CD18 dependent. Therapies directed against neutrophil-mediated reperfusion injury should be initiated with these considerations in mind.
引用
收藏
页码:400 / 411
页数:12
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