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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/17950

Title: Tirilazad mesylate (U-74006F) inhibits effects of endotoxin in dogs
Authors: Zhang, H
Spapen, H
Manikis, P
Rogiers, P
Metz, G
Buurman, WA
Vincent, JL
Department: St. Michael's Hospital
Keywords: oxygen delivery
oxygen extraction
cardiac function
regional blood flow
tumor necrosis factor
nitric oxide
Issue Date: May-1995
Publisher: American Physiological Society
Citation: Zhang H et al. Tirilazad mesylate (U-74006F) inhibits effects of endotoxin in dogs. Am J Physiol. 1995;268(5 Pt 2):H1847-55.
Abstract: The present study explored the effects of a potent antioxidant, the 21-aminosteroid U-74006F, on the systemic and regional hemodynamics and the oxygen extraction capabilities during endotoxic shock. Twenty-four anesthetized dogs were randomized into three groups. Group 1 (n = 8) served as control. Group 2 (n = 8) and group 3 (n = 8) received 2 mg/kg iv of Escherichia coli endotoxin, followed 30 min later by saline infusion. Group 3 was given U-74006F as an intravenous bolus of 80 micrograms/kg followed by an infusion of 10 micrograms.kg-1.min-1, and group 2 received an equivalent volume of vehicle. Tamponade was induced 30 min later to study the oxygen extraction capabilities of the animals. Compared with the endotoxin-alone group, the U-74006F-treated dogs maintained higher mean arterial pressure, cardiac index, stroke volume index, and left ventricular stroke work index and lower pulmonary vascular resistance. They also showed a higher fractional blood flow to mesenteric and renal beds. Endotoxin administration increased whole body critical oxygen delivery (DO2crit) from 7.7 +/- 2.4 to 12.0 +/- 1.9 ml.kg-1.min-1 (P < 0.05), but U-74006F decreased DO2crit to 7.8 +/- 2.0 ml.kg-1.min-1 (P < 0.05 vs. endotoxin alone). Endotoxin decreased critical oxygen extraction ratio (O2ERcrit) from 75.0 +/- 12.7 to 44.3 +/- 8.7% (P < 0.05), but U-74006F increased O2ERcrit to 64.1 +/- 11.2% (P < 0.05 vs. endotoxin alone). U-74006F also decreased endotoxin-induced elevation of mesenteric and renal DO2crit and markedly increased regional O2ERcrit. Systemic and regional blood lactate concentrations were lower in the U-74006F-treated animals.
URI: http://hdl.handle.net/1807/17950
ISSN: 0002-9513
Appears in Collections:Faculty Publications

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