Prevention of cardiac reperfusion injury following global ischemia by a monoclonal antibody, R2-1A6.
The effect of R2-1A6 monoclonal antibody on the reperfusion injury of heterotopically transplanted rat cardiac tissues after global ischemia was studied. Histological, functional as well as myocardial energy status were evaluated in control and R2-1A6-treated rats. The strong binding of neutrophils to cardiac endothelial cell surface and strong tissue edema were present at 10 min after the initiation of reperfusion and subsequently interstitial hemorrhage and myocardial degeneration were present in the control group. The mean survival date of grafted hearts was about 7.7 days in the control group. In contrast, the significantly less severe binding of neutrophils to endothelial cells, tissue edema, interstitial hemorrhage, and myocardial degeneration were present in R2-1A6-treated rats. All grafted hearts survived up to 14 days in R2-1A6-treated group. Myocardial ATP content decreased from preischemic value of about 4 mumol/g to post-ischemic value of 0.57 mumol/g. After reperfusion of ischemic hearts, myocardial ATP values remained to be a range of 1.27-1.03 mumol/g in control group. However, myocardial ATP values recovered up to 2.28 mumol/g in R2-1A6-treated group. Thus, these experiments indicated that neutrophil adherence to endothelial cells is a critical early event in the process leading to post-ischemic reperfusion injury in global ischemia and the R2-1A6 treatment resulted in significant protection against cardiac reperfusion injury following global ischemia.
Yamamoto
N
N
2nd Department of Surgery, Sapporo Medical University School of Medicine, Chuo-ku, Japan.
Tamiya
Y
Y
Uede
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001834:Body Water / Q000378:metabolism; D002452:Cell Count; D006085:Graft Survival; D008264:Macrophages / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009504:Neutrophils / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism; D051381:Rats; D016378:Tissue Transplantation
D000911:Antibodies, Monoclonal; D009711:Nucleotides; D000255:Adenosine Triphosphate