Anti-shock effects of human superoxide dismutase in splanchnic artery occlusion (SAO) shock.
We studied the effects of human superoxide dismutase (h-SOD) in splanchnic artery occlusion (SAO) shock. Pentobarbital anesthetized rats subjected to total occlusion of the superior mesenteric and the celiac arteries for 40 min developed a severe shock state usually resulting in a fatal outcome within 20 min after the release of the occlusion. h-SOD (10 mg/kg) was infused intravenously starting at reperfusion and lasting for 10 min. SAO shock rats treated with h-SOD maintained postreperfusion MABP at significantly higher values compared to rats receiving the vehicle (final MABP 84 +/- 6 vs 46 +/- 1 mm Hg, P less than 0.01, respectively). Treatment with h-SOD attenuated the plasma accumulation of free amino-nitrogen compounds (P less than 0.01 from vehicle) as well as the activity of the lysosomal protease cathepsin D (P less than 0.05 from vehicle). Furthermore, the plasma activity of a myocardial depressant factor was significantly lower in h-SOD-treated rats than in SAO rats receiving only the vehicle (27 +/- 1 vs 64 +/- 3 U/ml, P less than 0.01). SAO shock rats treated with h-SOD also exhibited a significantly higher survival rate than the SAO shock +/- vehicle group (88% vs 11%, P less than 0.01, respectively). These results support the role of oxygen-derived radicals in the pathophysiology of SAO shock, and indicate that h-SOD effectively ameliorates the deleterious effects of oxygen radicals in this severe model of ischemia and reperfusion.
Bitterman
H
H
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Aoki
N
N
Lefer
A M
AM
D000818:Animals; D001794:Blood Pressure; D001810:Blood Volume; D002402:Cathepsin D / Q000097:blood; D006801:Humans; D008297:Male; D008638:Mesenteric Arteries; D008641:Mesenteric Vascular Occlusion / Q000150:complications*; D009201:Myocardial Depressant Factor / Q000097:blood; D009584:Nitrogen / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D012769:Shock / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D009201:Myocardial Depressant Factor; D011994:Recombinant Proteins; D013482:Superoxide Dismutase; D002402:Cathepsin D; D009584:Nitrogen