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Titolo:
Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection
Autore:
Collins, BJ; Blum, MG; Parker, RE; Chang, AC; Blair, KSA; Zorn, GL; Christman, BW; Pierson, RN;
Indirizzi:
Vanderbilt Univ, Sch Med, Dept Cardiothorac Surg, Nashville, TN USA Vanderbilt Univ Nashville TN USA pt Cardiothorac Surg, Nashville, TN USA Vanderbilt Univ, Sch Med, Dept Allergy Pulm & Crit Care Med, Nashville, TNUSA Vanderbilt Univ Nashville TN USA Pulm & Crit Care Med, Nashville, TNUSA Nashville Vet Affairs Med Ctr, Nashville, TN 37232 USA Nashville Vet Affairs Med Ctr Nashville TN USA 37232 hville, TN 37232 USA
Titolo Testata:
JOURNAL OF APPLIED PHYSIOLOGY
fascicolo: 6, volume: 90, anno: 2001,
pagine: 2257 - 2268
SICI:
8750-7587(200106)90:6<2257:TMPHAL>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
DECAY-ACCELERATING FACTOR; ENDOTHELIAL-CELLS; NATURAL ANTIBODIES; VASCULAR TONE; COMPLEMENT; PIG; XENOGRAFTS; MODEL; BLOOD; XENOTRANSPLANTATION;
Keywords:
xenotransplantation; microvascular permeability; macrophage; platelet; neutrophil; eicosanoid;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Pierson, RN Dept Cardiac & Thorac Surg, 2986 Vanderbilt Clin, Nashville, TN 37232 USA Dept Cardiac & Thorac Surg 2986 Vanderbilt Clin Nashville TN USA 37232
Citazione:
B.J. Collins et al., "Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection", J APP PHYSL, 90(6), 2001, pp. 2257-2268

Abstract

The role of thromboxane (Tx) in hyperacute rejection of pig lung by human blood was studied in an ex vivo model, wherein lungs from juvenile piglets were perfused with fresh heparinized human blood. In this model, hyperacutelung rejection was characterized by an abrupt rise in pulmonary vascular resistance (PVR; >1 cmH(2)O . ml(-1). min) and prolific Tx elaboration (>15 ng/ml) within 5 min and loss of function within 10 min. Although papaverinesignificantly blunted the rise in PVR (<0.2 cmH(2)O<bullet>ml(-1). min), Tx production was not inhibited (>20 ng/ml), and florid tracheal edema was usually evident within 20 min. In contrast, both inhibition of Tx synthesis (Tx < 3 ng/ml) with OKY-046 and blockade of the Tx receptor with SQ-30741 (Tx. 20 ng/ml) were not only associated with significantly lower peak PVRs (<0.2 cmH(2)O . ml(-1). min) but also with attenuated increase in lung wet-to-dry ratio and airway edema. In concert, elaboration of histamine and tumor necrosis factor was blunted, and median survival increased >10-fold to 2 h (SQ-30741) and >4 h (OKY-046). Depletion of the pig lung macrophages withdichloromethyl bisphosphonate in liposomes, but not Pall filtration of thehuman blood or liposomes alone, significantly inhibited Tx elaboration (<0.2 vs. >8 ng/ml for Pall filtration or liposomes) and blunted PVR elevation(< 0.3 cmH(2)O<bullet>ml(-1). min) during initial perfusion. C3a and histamine elaboration were inhibited, and median survival was significantly prolonged (>4 h). These findings implicate Tx in the inflammation associated with hyperacute lung rejection and demonstrate that pulmonary intravascular macrophages are critical to its elaboration.

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Documento generato il 18/01/21 alle ore 16:07:04