Thromboxane contributes to pulmonary hypertension in ischemia-reperfusion lung injury.
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.
Zamora
C A
CA
Division of Pulmonary Disease/Critical Care Medicine, University of Texas Health Science Center, San Antonio 78284.
Baron
D A
DA
Heffner
J E
JE
D015121:6-Ketoprostaglandin F1 alpha / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology*; D008168:Lung / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D011652:Pulmonary Circulation / Q000502:physiology*; D011654:Pulmonary Edema / Q000503:physiopathology; D011817:Rabbits; D011863:Radioimmunoassay; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D015427:Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D013929:Thromboxane B2 / Q000276:immunology / Q000378:metabolism; D013931:Thromboxanes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D017482:Receptors, Thromboxane; D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C045749:SQ 29548