Role of Prostaglandins and Related Compounds in the Pathophysiology of Endotoxic and Septic Shock

Fink, Mitchell P.

doi:10.1055/s-2007-1012593

Cited by 9 publications

(4 citation statements)

References 46 publications

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“…generally considered to be important mediators of the pulmonary vascular reaction (Parratt 8i Sturgess 1977, Cook et al 1980, Ball et al 1983, Fink 1985. This study was performed to investigate whether arachidonic acid metabolites of the cyclo-oxygenase pathway were involved in the intestinal vasoconstriction following E. coli infusion.…”

Section: Intravenous Infusion Of Live E Coli In Cats Causesmentioning

confidence: 99%

The role of prostanoids in the feline intestinal vascular and central haemodynamic responses to i.v. infusion of live E. coli

Schützer

Haglund

Falk

1987

Acta Physiologica Scandinavica

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Bacterial infusion in the cat, causing experimental septic shock, induces an early vascular response mainly characterized by pulmonary hypertension and intestinal vasoconstriction. Prostanoids are held to be important mediators of the pulmonary vascular reaction. This study was performed to explore the involvement of prostanoids in the central haemodynamics and the small intestinal vascular reactions in experimental septic shock. Aortic blood pressure was continuously monitored, as were aortic blood flow, the pressure in a. pulmonalis and the small intestinal venous outflow. All cats (n = 24) were given live E. coli (10(10) ml-1) as a continuous intravenous infusion. One series was pretreated with indomethacin, another with UK-38,485, a specific thromboxane A2 synthetase inhibitor, and a third series served as untreated control. The pulmonary hypertensive response was clearly attenuated in the two pretreated series, in fact abolished in the one given UK-38,485. The early intestinal vasoconstriction was eliminated in the two pretreated series. Later during bacteraemia, when untreated and indomethacin-pretreated cats showed intestinal vasoconstriction, UK-38-485-pretreated animals kept intestinal blood flow within the preseptic range. These data suggest that in the cat, thromboxane A2 is the prostanoid mediating the vascular reactions, not only in the lung but also in the small intestine.

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Section: Intravenous Infusion Of Live E Coli In Cats Causesmentioning

confidence: 99%

The role of prostanoids in the feline intestinal vascular and central haemodynamic responses to i.v. infusion of live E. coli

Schützer

Haglund

Falk

1987

Acta Physiologica Scandinavica

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“…Among the variety of endogenous substances stimulated by LPS, the arachidonic acid metabolites have been implicated as significant pathogenic mediators (3,4). Administration of LPS in several species of laboratory animals has been shown to enhance synthesis of the fatty acid cyclooxygenase products thromboxane A2 (TxA2) and prostacyclin (PG12) (5)(6)(7)(8).…”

mentioning

confidence: 99%

“…Administration of LPS in several species of laboratory animals has been shown to enhance synthesis of the fatty acid cyclooxygenase products thromboxane A2 (TxA2) and prostacyclin (PG12) (5)(6)(7)(8). TxA2, a potent vasoconstrictor, bronchoconstrictor, and platelet aggregator, has been implicated as a possible mediator of certain pathogenic sequelae of endotoxic shock (3,4). Several specific thromboxane synthetase inhibitors including imidazole (9), 7-IHA ( lo), Dazoxiben ( 1 1 ), pyridine derivatives ( 12), and OKY-158 1 ( 13) have been tested in experimental endotoxic shock in the rat.…”

mentioning

confidence: 99%

“…Picotamide has been shown to be well tolerated during prolonged oral administration in patients and to have effects on coagulation, fibrinolysis, and platelet aggregation ( 17,18). Peritoneal macrophages have been shown to synthesize TxA2 and PGI2 in response to endotoxin stimulation in vitro and to provide a useful approach to test the pharmacologic selectivity of putative drugs that alter arachidonic acid metabolism (3,19). These observations prompted us to assess the potential thromboxane synthetase inhibitory action of picotamide.…”

mentioning

confidence: 99%

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Selective Thromboxane Synthetase Inhibition by Picotamide and Effects on Endotoxin-Induced Lethality

Matera

Chisari

Altavilla

et al. 1988

Experimental Biology and Medicine

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The efficacy of N,N'-bis-(3-picolyl)-methoxyisophthalamide (picotamide) as an in vitro thromboxane synthetase inhibitor and its effect on endotoxin (LPS)-induced lethality in rats were assessed. Picotamide at 0.5 and 1.0 mM concentrations significantly ( P < 0.05) inhibited basal and LPS-stimulated synthesis of TxA2 measured by its stable immunoreactive (i) metabolite TxB2 in rat peritoneal macrophages. This compound did not inhibit synthesis of i6-keto-PGFI,, the stable metabolite of PG12, and produced significant shunting to i6-keto-PGF,,. For lethality studies rats were pretreated, by gavage with picotamide, at either 75, 150, 300, or 600 mg/kg 2 hr prior to iv S. enteritidis (LPS, 20 mg/kg). Both 150 and 300 mg/kg doses of picotamide significantly ( P < 0.05) improved survival in endotoxin shock at 48 hr. These studies demonstrate that picotamide is a selective thromboxane synthetase inhibitor, and that it may be useful during disease states characterized by increased TxA2 synthesis. o 1988 society for Experimental Biology and Medicine.

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Altered Guanine Nucleotide Protein Function: Potential Role in Endotoxin Tolerance

Coffee

Halushka

Wise

et al. 1993

Host Defense Dysfunction in Trauma, Shock and Sepsis

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Role of Prostaglandins and Related Compounds in the Pathophysiology of Endotoxic and Septic Shock

Cited by 9 publications

References 46 publications

The role of prostanoids in the feline intestinal vascular and central haemodynamic responses to i.v. infusion of live E. coli

The role of prostanoids in the feline intestinal vascular and central haemodynamic responses to i.v. infusion of live E. coli

Selective Thromboxane Synthetase Inhibition by Picotamide and Effects on Endotoxin-Induced Lethality

Altered Guanine Nucleotide Protein Function: Potential Role in Endotoxin Tolerance

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