Tamiya Y, Yamamoto N, Uede T
2nd Department of Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Japan.
Immunopharmacology. 1995 Feb;29(1):53-63. doi: 10.1016/0162-3109(95)00044-t.
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.
研究了抗淋巴细胞功能相关抗原-1（LFA-1）和抗细胞间黏附分子-1（ICAM-1）单克隆抗体（MAb）对大鼠全心缺血后心脏组织再灌注损伤的影响。研究采用离体血液灌注心脏标本，使心脏经历30分钟全心缺血，随后再灌注40分钟。将离体大鼠心脏用来自麻醉的供体大鼠的血液进行灌注，灌注时给予或不给予抗LFA-1或抗ICAM-1单克隆抗体（每组n = 10）。在该模型中评估心室功能、心肌组织含水量和心肌能量状态。在对照组中，离体心脏的缺血和再灌注导致左心室舒张末压（LVDP）恢复至缺血前基线值的63.6±2.7%，冠状动脉血管阻力增加44±7%。用抗LFA-1单克隆抗体或抗ICAM-1单克隆抗体治疗后，LVDP的恢复率分别为77.2±1.5%和80.4±3.0%。此外，抗LFA-1和抗ICAM-1治疗组的冠状动脉血管阻力增加分别仅为23±7%和13±6%。对照组与单克隆抗体治疗组的值有显著差异。缺血和再灌注导致对照组心肌组织含水量增加16%（缺血前基线时为3.71±0.03，再灌注后为4.29±0.08 ml/g干重），而在抗LFA-1和抗ICAM-1治疗组中分别仅增加3.0%和5.7%。对照组与单克隆抗体治疗组之间的差异显著。与缺血前基线值相比，在再灌注40分钟时，通过三磷酸腺苷（ATP）浓度评估的心脏能量状态在对照组中明显降低（5.70±0.27对14.92±0.48 μmol/g干重）。相反，抗LFA-1和抗ICAM-1单克隆抗体治疗显著抑制了再灌注40分钟时心肌ATP浓度的降低（分别为5.70±0.27对8.96±0.52和8.10±0.47 μmol/g干重）。这些结果表明，LFA-1/ICAM-1通路在再灌注早期缺血后心肌损伤的发病机制中起关键作用。
