Splanchnic artery occlusion shock: vinblastine-induced leukopenia reduces tumour necrosis factor and thromboxane A2 formation, and increases survival rate.
This study was designed to assess the role of leukocytes in rats subjected to splanchnic artery occlusion for 45 min followed by reperfusion (SAO shock). Leukopenia was induced by an intravenous injection of vinblastine (1 mg/kg) 72 h before SAO shock. Survival rate (within 6 h), plasma levels of thromboxane B2 (TxB2), serum levels of tumour necrosis factor (TNF-alpha), and histological alteration of the intestinal tract were investigated. Control rats [white blood cells (WBC) = 10362 +/- 630/mm3] died within 2 h following ischaemia and reperfusion. Leukopenic (WBC = 1263 +/- 311/mm3) animals which underwent SAO shock survived more than 2 h and 50% of them were still alive after 6 h. Plasma TxB2 levels significantly increased in WBC count normal rats subjected to SAO shock (8.4 +/- 2.1 ng/ml), compared to sham animals (0.4 +/- 0.08 ng/ml); however SAO shock raised TxB2 levels significantly less (2.1 +/- 1.1 ng/ml) in leukopenic rats. Serum TNF-alpha, undetectable in sham-shocked rats (either with normal WBC count or without), rose up to 150 +/- 12 U/ml in shocked rate and to 45 +/- 5 U/ml (P < 0.01) in shocked animals with leukopenia. SAO shock induced a massive necrosis of the intestinal tract in rats with normal WBC count. Leukopenia prevented ileum necrosis in SAO shock. These data indicate that leukocytes play an important role in splanchnic artery occlusion and reperfusion.
Canale
P
P
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
Squadrito
F
F
Zingarelli
B
B
Altavilla
D
D
Ioculano
M
M
Campo
G M
GM
Caputi
A P
AP
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000276:immunology; D002452:Cell Count / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D007970:Leukopenia / Q000139:chemically induced / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000276:immunology; D012769:Shock / Q000209:etiology / Q000276:immunology*; D013152:Splanchnic Circulation; D015996:Survival Rate; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014747:Vinblastine / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D013928:Thromboxane A2; D014747:Vinblastine