Protective Effects of Monoclonal Antibody to Intercellular Adhesion Molecule-1 in Venous Ischemia-Reperfusion Injury: Experimental Study in Rats

Abstract

Flaps with venous occlusion have a decreased survival rate compared with arterial occlusion. It seems that several factors are involved in the etiology of total venous occlusion, including free radicals, edema, thrombosis, and reperfusion injury. In the present study, the authors evaluated the blockage of polymorphonuclear leukocyte endothelial adhesion by using a monoclonal antibody to the intercellular adhesion molecule 1 (ICAM-1) ligand to prevent venous ischemia-reperfusion injury in rat epigastric island flaps. A skin flap (3 x 4 cm) supplied by the superficial epigastric artery and vein was harvested unilaterally in 40 male Wistar rats. Total venous occlusion of the skin flap was achieved. Arterial inflow was left intact. Rats were randomly divided into four groups (n = 10). In Group 1; rats were intravenously pretreated with 0.5 ml of 0.9 percent normal saline 15 min before applying a venous clamp, and the flaps were subjected to 6 hr of venous ischemia. In Group 2; rats were intravenously pretreated with 0.05 mg of monoclonal antibody to the intercellular adhesion molecule 1 (0.20 mg/kg) in 0.5 ml of 0.9 percent normal saline 15 min before applying the venous clamp, and the flaps were subjected to venous ischemia as in Group 1. In Group 3; rats were pretreated as in Group 1, and the flaps were subjected to 8 hr of venous ischemia. In Group 4; rats were pretreated as in Group 2, and the flaps were subjected to 8 hr of venous ischemia. The flaps were assessed histologically and by measuring viable and non-viable areas on postoperative day 7. Flap measurements revealed that blocking the action of ICAM-1 IN VIVO by administering monoclonal antibody significantly attenuated ischemic injury after 6 or 8 hr of venous occlusion.

Improved skin flap survival in venous ischemia‐reperfusion injury with the use of adipose‐derived stem cells

“…Bilgin‐Karabulut et al also demonstrated that the antioxidants vitamins E and A decrease tissue injury in the venous ischemia‐reperfusion model in the skin flap of the rat . In addition, Demiseren et al have shown that the intercellular adhesion molecule‐1 antibody prevents adhesion of the inflammatory neutrophils by interfering with the endothelium and can reduce venous ischemic tissue injury …”

Blockade of KATP Channels Reduces Endothelial Hyperpolarization and Leukocyte Recruitment upon Reperfusion After Hypoxia

“…In addition, HUVEC are isolated from large veins, while the endothelial inflammatory response associated with ischemia/reperfusion injury is most pronounced in the venular microvasculature (10). (4,(45)(46)(47) or adhesion molecule deficient animals (48,49). Inhibition of selectin function has reduced inflammation and fibrosis in a large animal model of warm and cold ischemia (46 (50,51), however, multicenter randomized trials did not confirm this effect (52); success being limited perhaps by the redundancy of adhesion molecule/leukocyte interactions in vivo (53,54 …”

“…One approach has been the use of T-cell depleting therapies, such as antilymphocyte globulin (41)(42)(43)(44), which, by affecting T-cell number and function, works late in the inflammation/immune activation cascade. Leukocyte recruitment has previously been inhibited in animal models of ischemia/reperfusion and transplantation using antiadhesion molecule therapy (4,(45)(46)(47) or adhesion molecule deficient animals (48,49). Inhibition of selectin function has reduced inflammation and fibrosis in a large animal model of warm and cold ischemia (46).…”

Targeting Adhesion Molecules in Cardiovascular Disorders

“…Rats were followed for 7 days after which the flaps were histologically assessed. In the case of eight hours of ischemia, ICAM-1 antibody treatment had a clear beneficial effect significantly increasing the viable area [45]. Different approaches, e.g.…”