Thromboxane generation after thrombin. Protective effect of thromboxane synthetase inhibition on lung fluid balance.

Garcia-Szabo, R. R.; Peterson, Myron B.; Watkins, W. D.; Bizios, Rena; Kong, Derek Kai; Malik, Asrar B.

doi:10.1161/01.res.53.2.214

Cited by 46 publications

(13 citation statements)

References 26 publications

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“…Garcia-Szabo et al 20 demonstrated that a selective inhibitor of thromboxane synthesis prevented the thrombin-induced increases in pulmonary lymph flow and the lymph protein clearance in intact sheep, suggesting that TxA 2 contributes to the increase in lung vascular permeability after thrombin infusion. However, while administration of arachidonic acid produced pulmonary venoconstriction associated with TxA 2 production in lungs, the microvascular permeability was not increased.…”

Section: Discussionmentioning

confidence: 99%

Effects of a thromboxane A2 analogue and prostacyclin on lung fluid balance in newborn lambs.

Yoshimura

Tod

Pier

et al. 1989

Circulation Research

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We have previously shown that the pulmonary venoconstriction produced by a stable thromboxane A 2 analogue (STAJ is attenuated by prostacyclin (PGIi), but PGI, increases the STA 2 -induced edema. The present study was designed to determine the effects of STA 2 and PGI 2 on the fluid balance in isolated blood-perfused newborn lamb lungs. Vascular permeability was evaluated by use of the fluid filtration coefficient (Kf) and the osmotic reflection coefficient for total proteins (cr, hematocrit-protein double indicator technique), and pulmonary capillary pressure (Pc) was estimated by the double occlusion technique. All lungs had a period of hydrostatic stress induced by elevation of the left atriai pressure from 5 to 20 mm Hg to promote fluid filtration, and the rate of lung weight gain (AW/AT) during this period was determined. Studies were made in four groups; before the hydrostatic stress, lungs were given 1) STA 2 (50 /*g, n=6), 2) PGI 2 (0.4 /ig/kg/min, n = 6), 3) both PGI 2 and STA 2 (n=6), or 4) vehicles (control, n=5). Measurements of Kf were made at the baseline period and after the hydrostatic stress. T hromboxane A 2 (TxA 2 ) is a potent pulmonary vasoconstrictor that may be involved in the early phase of endotoxin-induced pulmonary hypertension and edema. This pulmonary hypertensive response has been suggested to be the result of TxA 2 -mediated pulmonary venoconstriction since the protein-poor lung lymph flow is increased in this early phase.12 By use of the arterial and venous occlusion technique in isolated newborn lamb lungs, we have recently demonstrated that a stable TxA 2 analogue, 9,11-epithioll,12-methano-TxA 2 (STA 2 ), produced pulmonary hypertension primarily by causing pulmonary Received March 27, 1989; accepted June 16, 1989. venoconstriction. 3 Although exogenous prostacyclin (PGI 2 ) attenuated this response to STA 2 by decreasing the pulmonary venoconstriction, PGI 2 administration significantly increased the STA 2 -induced pulmonary edema.3 These observations were interpreted as being consistent with an increase in microvascular permeability by PGI 2 that potentiated the STA 2 -induced pulmonary edema, despite the attenuation of the elevation of the pulmonary microvascular pressure by PGI 2 . However, the possibility that PGI 2 increased lung vascular surface area rather than permeability was not completely excluded in this study because vascular permeability was not directly evaluated.Pulmonary microvascular membrane permeability may be estimated by changes in filtration coefficient (Kf) in isolated perfused lungs. 4 However, when changes in the number of perfused microvessels occur, as with microvascular embolism, vasodilation, or vasoconstriction, Kf may not be a reliable parameter of changes in permeability because Kf depends on membrane surface area.

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Section: Discussionmentioning

confidence: 99%

Effects of a thromboxane A2 analogue and prostacyclin on lung fluid balance in newborn lambs.

Yoshimura

Tod

Pier

et al. 1989

Circulation Research

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“…However, there is disagreement concerning the effect of TxA 2 on pulmonary microvascular permeability [10, 24,27]. Thromboxane synthetase inhibition prevents an increase in pulmonary vascular permeability in sheep after thrombin infusion [7] or after limb ischemia and reperfusion [8]. These findings suggest that T x A 2 contributes primarily to increased lung vascular permeability.…”

Section: Introductionmentioning

confidence: 99%

Effects of thromboxane A2 analogue on vascular resistance distribution and permeability in isolated blood-perfused dog lungs

Shibamoto

Wang

Yamaguchi

et al. 1995

Lung

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This study was designed to determine the effects of thromboxane A2 (TxA2) on the distribution of vascular resistance, lung weight, and microvascular permeability in isolated dog lungs perfused at a constant pressure with autologous blood. The stable TxA2 analogue (STA2; 30 micrograms, n = 5) caused an increase in pulmonary capillary pressure (Pc) assessed as double-occlusion pressure to 14.0 +/- 0.4 mmHg from the baseline of 7.9 +/- 0.3 mmHg with progressive lung weight gain. Pulmonary vascular resistance increased threefold exclusively due to pulmonary venoconstriction. Pulmonary venoconstriction was confirmed in lungs perfused in a reverse direction from the pulmonary vein to the artery (n = 5), as evidenced by marked precapillary vasoconstriction and a sustained lung weight loss. Furthermore, in lungs perfused at a constant blood flow (n = 5), STA2 also caused selective pulmonary venoconstriction. Vascular permeability measured by the capillary filtration coefficient and the isogravimetric Pc at 30 and 60 min after STA2 infusion did not change significantly from baseline in any lungs studied. Moreover, elevation of Pc by raising the venous reservoir of the intact lobes (n = 5) to the same level as the STA2 lungs caused a greater or similar weight gain compared with the STA2 lungs. Thus, we conclude that TxA2 constricts selectively the pulmonary vein resulting in an increase in Pc and lung weight gain without significant changes in vascular permeability in isolated blood-perfused dog lungs.

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“…The rise in mean pulmonary artery pressure after infusion of thrombin may probably be due to aprofound increase in pulmonary vascular resistance resulting from thrombin-induced release of thromboxane AZ (20,8). It is therefore conceivable that the improvement of the mean pulmonary artery pressure after thrombin infusion in the indomethacin group might be due mainly to inhibition of thromboxane synthesis resulting from cyclooxygenase inhibition, and consequently to a decrease in pulmonary vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

“…Evidence for this assumption is mostly based on studies using various cyclooxygenase inhibitors. Among these arachidonate metabo-lites, thromboxane is known to be associated with sequences of events that follow infusion of thrombin in the rat (20), and with the development of thrombin-induced pulmonary edema in sheep (8,9). lncreased permeability to protein may also result from entrapment of fibrin (6) and leukocytes (2 1,s) in the lung.…”

Section: Introductionmentioning

confidence: 99%

Effect of Indomethacin on Thrombin-Induced Pulmonary Edema in the Rat

Ahn

Sandler²,

Wegener³

et al. 1995

Upsala Journal of Medical Sciences

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The preventive effect of indomethacin on thrombin-induced pulmonary edema was studied in rats.Administration of thrombin caused a significant increase in lung weight, wet weight to dry weight ratio (WWDW), and relative lung water content. During infusion of thrombin, mean pulmonary artery pressure rose and mean systemic artery pressure fell, Pa02 decreased progressively and there was a continuous rise in pH and PaC02.An inhibitor of cyclooxygenase, indomethacin, at a dose of 1 mgkg body weight, induced a significant further increase in lung weight (p<0.05), and a tendency towards an increase in WW/DW and water content compared with animals given thrombin alone. Treatment with indomethacin, however, counteracted the elevated pulmonary artery pressure occurring in the early phase after thrombin infusion, but not that in the late phase. Systemic artery pressure was not affected by indomethacin. The increases in pH and PaCOz after thrombin infusion were attenuated and remained stable almost at baseline level after indomethacin administration. Tndomethacin did not prevent the hypoxemia induced by thrombin infusion.In conclusion, although indomethacin prevented the early increase in pulmonary artery pressure due to thrombin and the decrease in pH and the increase in PaC02, it caused lung vascular permeability to protein to increase more than with thrombin alone.

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Thromboxane generation after thrombin. Protective effect of thromboxane synthetase inhibition on lung fluid balance.

Cited by 46 publications

References 26 publications

Effects of a thromboxane A2 analogue and prostacyclin on lung fluid balance in newborn lambs.

Effects of a thromboxane A2 analogue and prostacyclin on lung fluid balance in newborn lambs.

Effects of thromboxane A2 analogue on vascular resistance distribution and permeability in isolated blood-perfused dog lungs

Effect of Indomethacin on Thrombin-Induced Pulmonary Edema in the Rat

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