Prevention of ischemia-reperfusion injury in a rat skin flap model: the role of mast cells, cromolyn sodium, and histamine receptor blockade.
The objective of this study was to examine the role of mast cells and their principal product, histamine, in ischemia/reperfusion injury. Cromolyn sodium, diphenhydramine, and cimetidine were administered to ischemic flaps just before reperfusion and evaluated for flap survival, mast cell count, neutrophil count, and myeloperoxidase levels. Epigastric island skin flaps were elevated in 49 rats; they were rendered ischemic by clamping the artery for 10 hours. Thirty minutes before reperfusion, the rats were treated with intraperitoneal saline (n = 11), cimetidine (n = 11), diphenhydramine (n = 11), or cromolyn sodium (n = 10). Flap survival was evaluated at 7 days. Neutrophil counts, mast cell counts, and myeloperoxidase levels were evaluated 12 hours after reperfusion. Flap necrosis in the sham group of animals (n = 6) was 0.0 percent, as expected, whereas the control group (saline-treated animals) had 47.3+/-33.4 percent necrosis. Animals treated with diphenhydramine and cimetidine demonstrated a significant decrease in flap necrosis to 17.7+/-8.8 percent and 19.4+/-14.7 percent, respectively. This protective effect was not seen with cromolyn sodium (44.3+/-35.6 percent). Both neutrophil and mast cell counts were significantly decreased in flaps from antihistamine-treated and sham animals versus both saline- and cromolyn sodium-treated groups. The administration of diphenhydramine and cimetidine before reperfusion can significantly reduce the extent of flap necrosis and the neutrophil and mast cell counts caused by ischemia/reperfusion. This protective effect is not seen with cromolyn sodium. The protective effect of antihistamines on flap necrosis might be related to the decrease in neutrophils and, possibly, mast cells within the flap.
Cordeiro
P G
PG
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. cordeirp@mskcc.org
Lee
J J
JJ
Mastorakos
D
D
Hu
Q Y
QY
Pinto
J T
JT
Santamaria
E
E
D000818:Animals; D002452:Cell Count; D002927:Cimetidine / Q000494:pharmacology; D004205:Cromolyn Sodium; D004155:Diphenhydramine / Q000494:pharmacology; D005260:Female; D006633:Histamine Antagonists / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology*; D009504:Neutrophils; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013524:Surgical Flaps / Q000098:blood supply*
D006633:Histamine Antagonists; D002927:Cimetidine; D004155:Diphenhydramine; D004205:Cromolyn Sodium