Thromboxane and pulmonary hypertension following E. coli endotoxin infusion in sheep: Effect of an imidazole derivative

Watkins, W. D.; Hüttemeier, Peter C.; Kong, Derek Kai; Peterson, Myron B.

doi:10.1016/0090-6980(82)90073-9

Cited by 72 publications

(24 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibition of TxA2 synthesis by dazoxiben essentially prevented increased Ppa, Pw, and PVR after endotoxin infusion, even though the vasoconstrictor PGF2a concentration was elevated. Similar results following endotoxin infusion had been observed in sheep given a different thromboxane synthesis inhibitor (9).…”

Section: Discussionsupporting

confidence: 73%

“…Infusion of endotoxin or live bacteria into awake animals has been shown to increase pulmonary artery pressure and pulmonary vascular permeability (3,4), and in sufficient quantities, results in increased lung water (5). Endotoxin caused large elevations of aortic plasma thromboxane A2(TxA2),' prostacyclin (PGI2) (6)(7)(8)(9), and prostaglandin F2a(PGF2a,), but prostaglandin E2(PGE2) either did not increase (6-8, 10, 11) or it increased transiently (12,13). Acute hemodynamnic and permeability changes also accompanied endotoxemia.…”

Section: Introductionmentioning

confidence: 99%

“…Watkins et al (9) used an imidazole derivative (RO-22-3581, Hoffman-La Roche Inc., Nutley, NJ) that is a selective thromboxane synthetase inhibitor to demonstrate that TxA2 mediates most of the pulmonary hypertension after endotoxin infusion. The role of TxA2 on other hemodynamic and permeability changes, however, remains undefined.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Thromboxane A2 mediates lung vasoconstriction but not permeability after endotoxin.

Winn¹,

Harlan²,

Nadir³

et al. 1983

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T The effect of dazoxiben, a selective thromboxane (Tx) synthetase inhibitor, on systemic and pulmonary hemodynamics, eicosanoids, and lung permeability was assessed in awake goats with lung lymph fistulae following infusion of Escherichia coli endotoxin (1 Mg/kg). Animals received endotoxin either with no treatment or pretreatment with a bolus (25 mg/kg) followed by a maintenance infusion (10 mg/kg per h) of dazoxiben. In untreated animals, the peak rise of 26.8 cm H20 in pulmonary artery (Ppa) and of 13.5 cm H20 in wedge (Pw) pressures occurred at the same time as the peak elevations in plasma thromboxane B2 (TxB2). Maximum reduction in cardiac output (Qt) also occurred at the same time. Lung lymph flow (QL) increased during this period and remained elevated for at least 6 h after endotoxin. TxB2 levels had returned from a peak of 13.1 to 0.7 ng/ml by 2 h. In dazoxiben-treated animals, plasma concentrations of TxB2 were never significantly elevated. Increases in Ppa and Pw were markedly reduced and decreased Qt was transient. QL in treated animals began to increase by 30 min after endotoxin and reached a peak by 2 h. Increased QL in treated animals was not as great as in the untreated animals. Moreover, lymphplasma protein ratios increased significantly in treated animals. Plasma prostaglandin (PG)F2a and 6-keto-PGF1, concentrations were elevated in both groups after endotoxin with values significantly greater in treated animals. We conclude that selective inhibition of Tx ameliorates many adverse hemodynamic consequences of endotoxemia but does not prevent lung permeability changes.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thromboxane A2 mediates lung vasoconstriction but not permeability after endotoxin.

Winn¹,

Harlan²,

Nadir³

et al. 1983

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…An increase in pulmonary arterial pressure and pulmonary vascular resistance has been observed by a number of investigators after experimental sepsis (26) or after the administration of endotoxin (27,28). Although the mechanism of the pulmonary vasoconstriction is not perfectly clear, recent data provide evidence that thromboxane A2 plays a major role (29,30).…”

Section: Discussionmentioning

confidence: 92%

Fever in Young Lambs: Carotid Denervation Alters the Febrile Response to a Small Dose of Bacterial Pyrogen

1992

Pediatr Res

View full text Add to dashboard Cite

ABSTRACT. Experiments were done on 13 young lambs vasopressin, which may function as a physiologically important to determine if carotid denervation influences the cardio-antipyretic substance in the brain (6), plays a role (7). vascular and metabolic responses to i.v. administration ofWe have recently shown that carotid-intact lambs develop a bacterial pyrogen [Salmonella abortus equi (SAE) 0.3 pg]. fever of approximately 0.7"C in response to a small dose of Each lamb was anesthetized with halothane and prepared bacterial pyrogen (i.e. 0.3 pg SAE lipopolysaccharide) by the 3rd for measurements of cardiac output, arterial and mixed wk of postnatal life (8). Previous experiments on adult rats have venous oxygen saturations, and body core temperature. No provided evidence that discrete bilateral lesions of the NTS, sooner than 3 d after surgery, measurements were made which disrupts afferent neural activity from the arterial baroreduring a control period and at 10-min intervals for 120 min ceptors, alter the cardiovascular and metabolic responses to after i.v. administration of SAE in seven carotid-intact thermogenic stimuli (i.e. a change in ambient temperature) (9). lambs and six carotid-denervated lambs. Administration of With this in mind, the present experiments have been done to SAE produced a short-lived fever of about 1°C in the determine whether carotid denenation alters the temperature carotid-intact lambs, whereas no change in body core tem-and the cardiorespiratory or metabolic responses to bacterial perature was observed in the carotid-denervated lambs. In pyrogen in young lambs. carotid-intact lambs, the rise in body core temperature began approximately 40 min after administration of SAE MATERIALS AND METHODSand continued for approximately 50 min. This rise in body core temperature was preceded by the onset of shivering Thirteen lambs ranging in age from 14 to 28 d were studied. and an increase in total body oxygen consumption. Carotid Each lamb was separated from its ewe 3 to 7 d after birth and denervation produced changes in some of the cardiovascu-was housed in our laboratory in a Plexiglas cage with continuous lar variables during the control period (i.e. arterial oxygen access to milk (Lamb Milk Replacer; Land O'Lakes, Inc., Fort content, cardiac index, heart rate, and pulmonary blood Dodge, IA). The lambs were among other lambs, fed and slept pressure); however, there were no additional significant a d libitum, and soon became accustomed to their surroundings changes in any of the metabolic or cardiovascular variables and the laboratory personnel. after administration of SAE. The mechanism of these Surgical preparation. Each lamb underwent one operation unexpected findings remains to be determined. (Pediatr before study. For surgery, each lamb was given atropine sulfate Res 31: 107-111,1992) (0.2 mg/kg s.c.) and anesthesia was induced by having the lamb breathe 3 to 4% halothane in oxygen via a mask. The trachea Abbreviations was then intubated with a cuffed endotracheal tube, and anesthesia w...

show abstract

“…Receptor antagonist and/or synthetase inhibitor analysis have been carried out in patients with ARDS. Thromboxane synthesis inhibitors and/or antagonists improved the acute cardiopulmonary effects of bolus endotoxin [13][14][15] and increased patient survival [16][17][18]. The thromboxane A 2 synthesis inhibitor ketoconazole was found to significantly reduce the rate of ARDS development in sepsis patients and decrease their mortality rate [19].…”

Section: Discussionmentioning

confidence: 99%

Eicosanoids as Risk and Prognostic Factors for Acute Respiratory Distress Syndrome in Sepsis Patients

Takahashi¹,

Shibata²,

Endo³

2017

J Pulm Respir Med

View full text Add to dashboard Cite

Thromboxane and pulmonary hypertension following E. coli endotoxin infusion in sheep: Effect of an imidazole derivative

Cited by 72 publications

References 9 publications

Thromboxane A2 mediates lung vasoconstriction but not permeability after endotoxin.

Thromboxane A2 mediates lung vasoconstriction but not permeability after endotoxin.

Fever in Young Lambs: Carotid Denervation Alters the Febrile Response to a Small Dose of Bacterial Pyrogen

Eicosanoids as Risk and Prognostic Factors for Acute Respiratory Distress Syndrome in Sepsis Patients

Contact Info

Product

Resources

About