title: Hepatic integrity dependent on matrix metalloproteinase inhibition, not tumor necrosis factor alpha or different bleeding rates.
abstract: Discrepancies in the levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) following hemorrhagic shock (HS) may be due to the inconsistent rates of bleeding. The purpose of this study was to investigate the effects of rapid versus slow bleeding rates on TNF-alpha levels and if inhibition of TNF-alpha convertase by a matrix metalloproteinase inhibitor (MMPI) affects hepatic integrity in animals exposed to 35% HS. Sprague-Dawley male rats (n = 24, 300-350 g) were divided into four groups: HS 15 (produced over 15 min), HS 30 (produced over 30 min), and HS with MMPI (2.5 mg/kg British Biotech 1101: HS15 + MMPI, HS30 + MMPI). Mean arterial blood pressure (MAP), serum TNF-alpha,levels, and hepatic resting membrane potentials (E(m)) were obtained. A Student t test was performed. TNF-alpha levels for HS 15, HS15 + MMPI, HS 30, and HS 30 + MMPI were 474, 40, 32, and 50 pg/ml, respectively. The hepatic resting membrane potentials for HS 15, HS15 + MMPI, HS 30, and HS 30 + MMPI were -26, -30, -23, and -31 mV, respectively. In conclusion, circulating TNF-alpha levels are affected by the rate of bleeding in hemorrhagic shock. However, despite the differences in the magnitude of TNF-alpha in untreated animals, hepatic integrity was compromised. Interestingly, MMPI, an inhibitor of TNF-alpha convertase, stabilizes the membrane potential in both types of hemorrhagic shock.
authors.affiliation: Department of Surgery, University of Nevada School of Medicine, 2040 West Charleston Boulevard, Suite 501, Las Vegas, Nevada 89102, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Santibanez-Gallerani
authors.forename: A E
authors.initials: AE
authors.lastname: Barber
authors.forename: S J
authors.initials: SJ
authors.lastname: Williams
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: G T
authors.initials: GT
authors.lastname: Shires
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D001794:Blood Pressure; D002339:Carotid Arteries; D005109:Extracellular Matrix / Q000201:enzymology; D008099:Liver / Q000098:blood supply / Q000201:enzymology* / Q000276:immunology; D008102:Liver Circulation; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008564:Membrane Potentials; D008666:Metalloendopeptidases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein