Human platelets modulate edema formation in isolated rabbit lungs.

Abstract

The role of platelet glucose-6-phosphate dehydrogenase (G-6-PD) in mediating the effects of human platelets on oxidant-induced edema in the isolated perfused rabbit lung was investigated using dehydroepiandrosterone, a specific steroidal inhibitor of G-6-PD. Xanthine oxidase (0.003 and 0.012 U/ml) caused lung edema that was attenuated by coinfusion of washed human platelets. Platelets that were incubated with DEA to inhibit G-6-PD activity augmented xanthine oxidase-induced lung edema and pulmonary hypertension at both doses of xanthine oxidase. Infusion of papavarine to maintain stable pulmonary artery (PA) pressures, incubation of G-6-PD-inhibited platelets with acetylsalicylate, or infusion of a thromboxane-prostaglandin endoperoxide receptor site antagonist, SQ 29548, into the lung perfusate prevented augmentation of lung edema and the PA pressor response by G-6-PD-inhibited platelets. It was concluded that antioxidant-intact platelets attenuate oxidant-induced lung edema by preventing increased membrane permeability, and that G-6-PD-inhibited platelets augment lung edema through hydrostatic mechanisms mediated by release of platelet cyclooxygenase products.

Role of eicosanoids in PAF‐induced increases of the vascular permeability in rat airways

“…However, it is possible that in the presence of PAF-induced cell disjunction, vasoconstrictors may raise hydrostatic pressure by postcapillary vasoconstriction and consequently, potentiate plasma leakage. Our data, as well as those presented by Heffner et al (1989), strongly support this hypothesis. It appears that vascular permeability is only modulated by changes in blood pressure.…”

Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model

“…These results indicate that considerably severe ALI was induced during the 90-min observation period. Our oxidant-induced ALI model has been well established in many studies [9,12,13]. We also tried to carry out a histological examination.…”

“…Piso is the pulmonary capillary pressure at which the lung neither gains nor loses weight, where the Starling forces are balanced [11][12][13]. Piso was determined by discontinuing perfusion and opening a shunt between the two cannulae, so that the Ppa and Pla were equal.…”

“…To establish oxidant-induced ALI, 0.5 mM purine (Sigma Chemical, St Louis, MO, USA) was added to the perfusate. About 5 min later, XO (2 mU·ml -1 ; XO grade IV from milk; Sigma Chemical) was added to the perfusate of the specimens of the study groups [9,12,13]. The lung preparations were perfused for 90 min after the addition of XO to the perfusate.…”

Platelet-neutrophil interactions in sepsis - platelet guilt by association?

“…In the sheep lung fistula model, animals rendered thrombocytopenic for 3 days with antiplatelet serum develop increased pulmonary vascular permeability to protein [13]. In endothelial cell cultures and ex vivo lung models, our own investigations have demonstrated that platelets attenuate tissue injury related to chemical oxidant systems and ischemia reperfusion [14][15][16][17]. The mechanisms for these protective effects are unknown, but may relate to the delivery of platelet antioxidants to regions of oxidant stress [16,17], the release of adenosine leading to increased endothelial cell stores of cAMP [18,19] or the provision of serotonin to cell membranes [20].…”