title: Protective effect of monoclonal antibodies against LFA-1 and ICAM-1 on myocardial reperfusion injury following global ischemia in rat hearts.
abstract: The effects of anti-LFA-1 and anti-ICAM-1 monoclonal antibodies (MAbs) on the reperfusion injury of rat cardiac tissues after global ischemia were studied. Studies were performed using an isolated blood perfused heart preparation in which hearts were subjected to 30 min of global ischemia followed by 40 min of reperfusion. Isolated rat hearts were perfused with blood from an anesthetized support rat with or without anti-LFA-1 or anti-ICAM-1 monoclonal antibody administration (n = 10 in each group). Ventricular function, myocardial tissue water content and myocardial energy status were evaluated in this model. In the control group, ischemia and reperfusion of isolated hearts resulted in a 63.6 +/- 2.7% recovery of left ventricular developed pressure (LVDP) and a 44 +/- 7% increase in coronary vascular resistance compared with pre-ischemic baseline values. Treatment with anti-LFA-1 MAb or anti-ICAM-1 MAb resulted in a 77.2 +/- 1.5% and a 80.4 +/- 3.0% recovery of LVDP, respectively. In addition, increase in coronary vascular resistance was only 23 +/- 7% and 13 +/- 6% in anti-LFA-1 and anti-ICAM-1-treated groups, respectively. Values are significantly different between the control group and MAb-treated groups. Ischemia and reperfusion resulted in a 16% increase of myocardial tissue water content (3.71 +/- 0.03 in pre-ischemic baseline versus 4.29 +/- 0.08 ml/g dry weight) in the control group, whereas that resulted in only 3.0 and 5.7% increase in anti-LFA and anti-ICAM-1-treated groups, respectively. The difference between the control group and MAb-treated groups was significant. Cardiac energy status as assessed by adenosine triphosphate (ATP) concentration was markedly reduced in the control group at 40 min of reperfusion compared with pre-ischemic baseline values (5.70 +/- 0.27 vs. 14.92 +/- 0.48 mumol/g dry weight). In contrast, the reduction of myocardial ATP concentration at 40 min of reperfusion was significantly inhibited by anti-LFA-1 and anti-ICAM-1 monoclonal antibody treatment (5.70 +/- 0.27 vs. 8.96 +/- 0.52 and 8.10 +/- 0.47 mumol/g dry weight, respectively). These results suggest that a LFA-1/ICAM-1 pathway plays a critical role in the pathogenesis of postischemic myocardial injury during early reperfusion period.
authors.affiliation: 2nd Department of Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tamiya
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Uede
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology* / Q000633:toxicity; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology* / Q000633:toxicity; D008297:Male; D051379:Mice; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D009711:Nucleotides; D018799:Intercellular Adhesion Molecule-1