Time- and dose-related regional fluxes of tissue-type plasminogen activator in anesthetized endotoxemic pigs

Nyberg, A; Jakob, S M; Seeman-Lodding, H; Porta, F; Bracht, H; Bischofberger, H; Jern, C; Takala, J; Aneman, A (2008). Time- and dose-related regional fluxes of tissue-type plasminogen activator in anesthetized endotoxemic pigs. Acta anaesthesiologica Scandinavica, 52(1), pp. 57-64. Oxford: Wiley-Blackwell 10.1111/j.1399-6576.2007.01481.x

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BACKGROUND: Acute endotoxinemia elicits an early fibrinolytic response. This study analyzes the effects of the dose and duration of endotoxin infusion on arterial levels of tissue-type plasminogen activator (tPA) and pulmonary, mesenteric and hepatic plasma tPA fluxes. METHODS: Pigs were randomized to receive an acute, high-dose (for 6 h, n=13, high ETX) or a prolonged, low-dose (for 18 h, n=18, low ETX) infusion of endotoxin or saline vehicle alone (for 18 h, n=14, control). All animals were fluid resuscitated to maintain a normodynamic circulation. Systemic and regional blood flows were measured and arterial, pulmonary arterial, portal and hepatic venous blood samples were analyzed to calculate regional net fluxes of tPA. Plasma tumor necrosis factor (TNF-alpha) levels were analyzed. RESULTS: Mesenteric tPA release and hepatic uptake increased maximally at 1.5 h in ETX groups related to dose. Maximal mesenteric tPA release [high ETX 612 (138-1185) microg/min/kg, low ETX 72 (32-94) microg/min/kg, median+/-interquartile range] and hepatic tPA uptake [high ETX -1549 (-1134 to -2194) microg/min/kg, low ETX -153 (-105 to -307) microg/min/kg] correlated to TNF-alpha levels. Regional tPA fluxes returned to baseline levels at 6 h in both ETX groups and also remained low during sustained low ETX. No changes were observed in control animals. CONCLUSIONS: Endotoxemia induces an early increase in mesenteric tPA release and hepatic tPA uptake related to the severity of endotoxemia. The time patterns of changes in mesenteric and hepatic tPA fluxes are similar in acute high-dose endotoxemia and sustained low-dose endotoxemia.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
UniBE Contributor:	Jakob, Stephan, Porta, Francesca Margherita, Bracht, Hendrik, Bischofberger, Heidi, Takala, Jukka
ISSN:	0001-5172
ISBN:	17999715
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:55
Last Modified:	05 Dec 2022 14:17
Publisher DOI:	10.1111/j.1399-6576.2007.01481.x
PubMed ID:	17999715
Web of Science ID:	000251763800009
URI:	https://boris.unibe.ch/id/eprint/23282 (FactScience: 40818)