Pulmonary Vascular Responses To Selective Lung Cooling in Intact Dogs

Pennington, D G; Hyman, Albert L.; Woolverton, William C.

doi:10.3181/00379727-137-35792

Cited by 15 publications

(14 citation statements)

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“…Endotoxic shock is associated with many pathophysiological sequelae including thrombocytopaenia, disseminated intravascular coagulation (Muller-Berghaus, 1978), and pulmonary and mesenteric vasoconstriction (Pennington et al, 1973;Brobmann et al, 1970). Lysosomal labilization (Janoff et al, 1962) and hepatocellular dysfunction (Coalsen et al, 1978) are also associated with en-dotoxaemia.…”

Section: Introductionmentioning

confidence: 99%

Beneficial effects of UK 37248, a thromboxane synthetase inhibitor, in experimental endotoxic shock in the rat.

Halushka¹,

Cook²,

Wise³

1983

Brit J Clinical Pharma

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1 The effects of pretreatment with the thromboxane synthetase inhibitor UK 37248 (dazoxiben) administered 30 min before intravenous endotoxin (S. enteriditis) in the rat was investigated. 2 Plasma prostaglandins and thromboxanes were determined via radioimmunoassay. Endotoxaemia was associated with significant elevations above control values (<200pg/ml) in plasma thromboxane B2 (TXB2), prostaglandin E (PGE) and 6-keto-prostaglandin Fla (6-keto-PGFia). Within 30 min after endotoxin administration plasma immunoreactive (i) iTXB2 was 875±90pg/ml (n=9), iPGE was 1670±271 (n=9) and i6-keto-PGFia was 1191±209 pg/ml (n= 10). By 4 h plasma iTXB2 was 1743±328 pg/ml (n=5), iPGE was 2589±494pg/ml (n=9) and i6-keto-PGFia was 4251±984pg/ml (n=10). UK 37248 pretreatment resulted in a significant (P<0.001) decrease in plasma iTXB2 at 30min and 4h to 193±28pg/ml (n=5) and 421±57pg/ml (n=5), respectively. Unexpectedly UK 37248 also significantly decreased plasma i6-keto PGFia at 30 min and 4 h to 360±75 pg/ml (n= 10) (P<0.005) and 1920±513 pg/ml (n= 10) (P<0.05), respectively. iPGE plasma levels were not significantly changed in the UK 37248-pretreated rats 30 min (2210±370 pg/ml (n=9) or 4 h 3529± 1093 pg/ml (n= 13) after endotoxin compared to the vehicle-treated rats. 3 UK 37248 significantly (P<0.05) reduced the endotoxin mortality rate at 24 h from 69% (n= 13) to 30% (n= 13). UK 37248 also reduced splanchnic infarction from 90% (n = 20) to 6% (n = 16). 4 UK 37248 significantly improved the endotoxin-induced thrombocytopaenia, disseminated intravascular coagulation, hypoglycaemia and lysosomal labilization. 5 We conclude that UK 37248 provides significant beneficial effects in experimental endotoxic shock in the rat.

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Section: Introductionmentioning

confidence: 99%

Beneficial effects of UK 37248, a thromboxane synthetase inhibitor, in experimental endotoxic shock in the rat.

Halushka¹,

Cook²,

Wise³

1983

Brit J Clinical Pharma

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“…INTRODUCTION Polymorphonuclear neutrophils (PMN)' disappear from the peripheral circulation during septicemia, endotoxemia, and anaphylaxis (1,2). Many of these cells are lodged in the microvasculature of lung, liver, or other vital organs (3,4). Investigations in several laboratories suggest how this effect is mediated.…”

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confidence: 99%

“…C5a, a polypeptide generated during complement activation (complement is activated in septicemia/endotoxemia [5]); N-formylmethionyl-leucyl-phenylalanine (FMLP), an analogue of factors released by growing bacteria (6); and platelet activating factor (PAF), a phospholipid released into the blood of animals during anaphylaxis (7), aggregate and degranulate PMN in vitro and, when injected into rabbits, produce neutropenia (7-10). Neutropenia appears closely related to aggregation: both responses develop at comparable doses of stimulus, become maximal within 0.5-3 min, and reverse within [1][2][3][4][5] (10), and is reported as percentage of total cellular enzyme released. Rabbit platelets were isolated from blood and aggregated as described (10) using a Chrono-Log Aggregometer (Chrono-Log Corp., Havertown, PA).…”

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confidence: 99%

Neutropenia induced by systemic infusion of 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid: correlation with its in vitro effects upon neutrophils.

O’Flaherty¹,

Thomas²,

Cousart³

et al. 1982

J. Clin. Invest.

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“…to differences in study design, because in anesthetized lambs, U466 19 did not significantly change cardiac output (36). Thromboxane A2 is an important mediator of the pulmonary hypertension caused by the infusion of endotoxin or live or heatkilled group B streptococci (8)(9)(10)(11)(12)(13)(14). Infusion of Escherichia coli endotoxin into lambs and sheep causes a marked early increase in pulmonary arterial pressure associated with an increase in plasma concentrations of thromboxane B2 (8-10, 12,39).…”

Section: Discussionmentioning

confidence: 99%

“…They may also be important mediators of the hemodynamic changes occumng in the adult respiratory distress syndrome (7), endotoxic shock (8)(9)(10)(11)(12)(13)(14), and the syndrome of persistent pulmonary hypertension of the newborn (15). The most potent pulmonary vasoconstricting metabolites of arachidonic acid are the peptidoleukotrienes (leukotrienes C4 and D4) , formed via the lipooxygenase pathway, and thromboxane A2 (8,10, 1 1, 13,14), formed via the cyclooxygenase pathway.…”

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confidence: 99%

Leukotriene Antagonists Attenuate Thromboxane-Inducible Pulmonary Hypertension

1989

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ABSTRACT. Leukotrienes C4 and Dd and thromboxane A2 are potent vasoconstrictors that may mediate pulmonary vasoconstriction in many clinical situations. There is a complex interaction among leukotrienes and thromboxane A2, because inhibition of thromboxane synthesis prevents some of the hemodynamic effects of exogenous leukotrienes. Similarly, if leukotrienes mediate thromboxane A*-induced pulmonary vasoconstriction, then leukotriene antagonists should attenuate the effects of a thromboxane A2-mimetic such as U46619. First, dose response curves for the hemodynamic effects of U46619 were performed on seven spontaneously breathing newborn lambs. Then a putative leukotriene receptor antagonist, FPL57231,l mg/ kg/min, or a putative leukotriene synthesis antagonist, U60257, 30 mg/kg, was given before infusing U46619 (1 pg/kg/min). U46619 caused significant dose-dependent increases in pulmonary and systemic arterial pressures (p < Metabolites of arachidonic acid may mediate the pulmonary vasoconstriction seen in utero (1,2) and during alveolar hypoxia (3-6). They may also be important mediators of the hemodynamic changes occumng in the adult respiratory distress syndrome (7), endotoxic shock (8-14), and the syndrome of persistent pulmonary hypertension of the newborn (15). The most potent pulmonary vasoconstricting metabolites of arachidonic acid are the peptidoleukotrienes (leukotrienes C4 and D4) (16-IS), formed via the lipooxygenase pathway, and thromboxane A2 (8, 10, 1 1, 13, 14), formed via the cyclooxygenase pathway. There is a complex interaction among these leukotrienes and thromboxane Az. TO date, the evidence suggests that leukotriene C4 and D4 stimulate the production of thromboxane A2 (16, 18-2 1). These studies would imply that thromboxane A2 is involved in leukotriene-induced pulmonary vasoconstriction. The pur- Supported by Grants HL 355 18 and HL 24056 from the National Heart, Lung and Blood Institute and by a Grant-in-Aid from the American Lung Association. 8pose of the present study was to investigate the other possibility: that thromboxane A2 stimulates the production or release of leukotrienes. Because of the instability of thromboxane A2 and the limited potency of its stable measurable metabolite, thromboxane Bz, we used the specific thromboxane Az-mimetic, U46619 (Upjohn Co., Kalamazoo, MI) (22-29). In newborn lambs, after characterizing the pulmonary and systemic hemodynamic effects of U466 19 by performing dose-response studies, we attempted to block or attenuate the hemodynamic response to U466 19 using FPL5723 1, a putative leukotriene receptor antagonist (Fisons plc, Loughborough, England) (2, 5, 16) and U60257, a putative leukotriene synthesis inhibitor (Upjohn) (1, 6, 30-34). MATERIALS AND METHODS Surgical Preparations.Under local anesthesia with 1 % lidocaine hydrochloride, seven newborn lambs at 1 to 3 d of age had polyvinyl catheters placed into a hind leg artery and vein and advanced to the descending aorta and inferior vena cava, respectively. General anesthesia was then induced by ha...

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Pulmonary Vascular Responses To Selective Lung Cooling in Intact Dogs

Cited by 15 publications

References 0 publications

Beneficial effects of UK 37248, a thromboxane synthetase inhibitor, in experimental endotoxic shock in the rat.

Beneficial effects of UK 37248, a thromboxane synthetase inhibitor, in experimental endotoxic shock in the rat.

Neutropenia induced by systemic infusion of 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid: correlation with its in vitro effects upon neutrophils.

Leukotriene Antagonists Attenuate Thromboxane-Inducible Pulmonary Hypertension

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