Kawata H, Aoki M, Hickey P R, Mayer J E
Department of Cardiovascular Surgery, Children's Hospital, Boston, MA 02115.
Circulation. 1992 Nov;86(5 Suppl):II364-70.
Prior studies have shown that leukocytes are important in reperfusion injury after normothermic ischemia, and recently discovered leukocyte adhesion molecules that bind to endothelial ligands may be involved in this process. No studies on the role of leukocyte adhesion molecules in hypothermic ischemia are available.
We assessed the effect of preischemic administration of monoclonal antibody to the leukocyte adhesion molecule CD18 on recovery of isolated blood-perfused neonatal lamb hearts arrested for 2 hours with 15 degrees C K+ cardioplegic solution by comparing nine antibody-treated and nine control hearts. At 30 minutes after reperfusion, antibody-treated hearts compared with control hearts had better percent recovery of maximum left ventricular (LV) developed pressure (83.9 +/- 2.2% versus 73.6 +/- 3.0%, mean +/- SEM), LV dP/dt (78.4 +/- 3.3% versus 67.4 +/- 3.4%), coronary blood flow (159.5 +/- 12.2% versus 84.4 +/- 3.5%), and myocardial oxygen consumption (129.8 +/- 16.5% versus 71.2 +/- 6.2%) (all p < 0.05). In each heart, we also tested coronary vascular resistance (CVR) response to 10(-6) mol/l acetylcholine (ACh) infusion to assess endothelial function. Percent recovery of CVR response to ACh was higher in antibody-treated hearts (38.4 +/- 4.3%) than control hearts (13.4 +/- 12.8%) (p = 0.08).
These results suggest that leukocyte adherence to endothelium mediated by CD18 plays an important role in reperfusion after hypothermic ischemia. Antibody to CD18 may be useful in myocardial and endothelial protection during surgically induced ischemia.
先前的研究表明，白细胞在常温缺血后的再灌注损伤中起重要作用，最近发现的与内皮配体结合的白细胞粘附分子可能参与了这一过程。目前尚无关于白细胞粘附分子在低温缺血中作用的研究。
通过比较9个抗体处理组和9个对照组的新生羔羊离体血液灌注心脏，我们评估了缺血前给予白细胞粘附分子CD18单克隆抗体对用15℃钾离子停搏液停搏2小时后的心脏恢复情况的影响。再灌注30分钟时，与对照组心脏相比，抗体处理组心脏的左心室（LV）最大舒张末压恢复百分比更高（83.9±2.2%对73.6±3.0%，平均值±标准误），LV dP/dt更高（78.4±3.3%对67.4±3.4%），冠状动脉血流量更高（159.5±12.2%对84.4±3.5%），心肌耗氧量更高（129.8±16.5%对71.2±6.2%）（所有p<0.05）。在每颗心脏中，我们还测试了冠状动脉血管阻力（CVR）对10(-6)mol/l乙酰胆碱（ACh）输注的反应，以评估内皮功能。抗体处理组心脏对ACh的CVR反应恢复百分比高于对照组心脏（38.4±4.3%对13.4±12.8%）（p=0.08）。
这些结果表明，由CD18介导的白细胞与内皮的粘附在低温缺血后的再灌注中起重要作用。CD18抗体可能有助于在手术诱导的缺血期间保护心肌和内皮。
