Thromboxane contributes to pulmonary hypertension in ischemia-reperfusion lung injury.

Abstract

Exposure of isolated perfused rabbit lungs (IPL) to ischemia-reperfusion causes a transient increase in pulmonary arterial (PA) pressure at the onset of reperfusion. Because thromboxane A2 (TxA2) is a potent vasoconstrictor, we hypothesized that it may contribute to the ischemia-reperfusion-induced pressor response. To evaluate this hypothesis, we exposed IPL perfused with a cell-free solution to 40 min of warm ischemia followed by reperfusion and measured perfusate immunoreactive thromboxane B2 (iTxB2) and 6-ketoprostaglandin F1 alpha (i6-keto-PGF1 alpha). We observed that ischemia-reperfusion IPL compared with controls had an increase in PA pressure (40.2 +/- 4.8 vs. 9.3 +/- 0.3 mmHg, P < 0.05), lung edema (29.3 +/- 6.3 vs. -0.2 +/- 0.2 g, P < 0.05), iTxB2 perfusate levels (155 +/- 22 vs. < 50 pg/ml, P < 0.05), and i6-keto-PGF1 alpha (436 +/- 33 vs. 61 +/- 16 pg/ml, P < 0.05). In ischemia-reperfusion IPL, infusion of SQ 29548 (10(-6) M), a specific TxA2/prostaglandin H2 receptor antagonist, attenuated the PA pressor response and the degree of edema. We conclude that pulmonary hypertension associated with ischemia-reperfusion results in part from pulmonary release of TxA2. Furthermore, TxA2 directly through membrane effects or indirectly through hydrostatic mechanisms increases the severity of ischemia-reperfusion-induced lung edema.

• Authors: C A Zamora, D A Baron, J E Heffner
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 74 Issue 1 Pg. 224-9 (Jan 1993) ISSN: 8750-7587 [Print] United States
• PMID: 8444695 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• Fatty Acids, Unsaturated
• Hydrazines
• Receptors, Thromboxane
• Thromboxanes
• Thromboxane B2
• Thromboxane A2
• 6-Ketoprostaglandin F1 alpha
• SQ 29548

Topics

• 6-Ketoprostaglandin F1 alpha (immunology, metabolism)
• Animals
• Blood Pressure (physiology)
• Bridged Bicyclo Compounds, Heterocyclic
• Fatty Acids, Unsaturated
• Hydrazines (pharmacology)
• Hypertension, Pulmonary (etiology, pathology, physiopathology)
• In Vitro Techniques
• Ischemia (physiopathology)
• Lung (pathology)
• Organ Size (physiology)
• Pulmonary Circulation (physiology)
• Pulmonary Edema (physiopathology)
• Rabbits
• Radioimmunoassay
• Receptors, Thromboxane (antagonists & inhibitors)
• Reperfusion Injury (complications, pathology, physiopathology)
• Thromboxane A2 (immunology, metabolism, physiology)
• Thromboxane B2 (immunology, metabolism)
• Thromboxanes (immunology, metabolism, physiology)
• Vasoconstriction (physiology)