Protective effects of the new lazaroid "U-83836E" in splanchnic artery occlusion (SAO) shock.
We studied the effects of the new antioxidant drug U-83836E during splanchnic artery occlusion (SAO) shock in the rat. Serum tumor necrosis factor (TNF-alpha), white blood cell (WBC) count, mean arterial blood pressure (MAP), survival rate and the responsiveness to acetylcholine of aortic rings were investigated. SAO shock produced a marked increase in serum TNF-alpha (241.4 +/- 18.2 U/ml vs Not Detectable in basal), reduced MAP (51.4 +/- 4 mmHg vs 85.1 +/- 5 mmHg), survival time (80 +/- 10 min vs > 240 min), WBC count (2.8 +/- 0.4 x 10(3)/mm3 cells vs 11.7 +/- 0.9 x 10(3)/mm3 cells) and blunted the responsiveness to ACh of aortic rings (60 +/- 3% tension vs 23 +/- 4% tension). The analogue of vitamin E, U-84836E, administered at onset of reperfusion, lowered serum TNF-alpha (38.4 +/- 6.5 U/ml; p < 0.001), improved MAP (67.5 +/- 3.8 mmHg; p < 0.001), WBC count (8.9 +/- 0.6 x 10(3)/mm3; p < 0.001), and survival time (235 +/- 15 min; p < 0.001), and restored the responsiveness to ACh of aortic rings (32 +/- 3.7% tension; p < 0.001). These preliminary data suggest that this new compound could be a promising drug in shock therapy.
Institute of Pharmacology, School of Medicine, University of Messina, Italy.
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001157:Arterial Occlusive Diseases / Q000150:complications / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D007511:Ischemia / Q000517:prevention & control; D007958:Leukocyte Count / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012769:Shock / Q000209:etiology / Q000517:prevention & control*; D013152:Splanchnic Circulation / Q000187:drug effects*; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D002839:Chromans; D010879:Piperazines; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; C066382:U 78517F; D000109:Acetylcholine