Profile of eicosanoids in breath condensate in asthma and COPD.

The collection of exhaled breath condensates (EBC) is a noninvasive method for obtaining samples from the lungs. Eicosanoids are lipid mediators implicated in the asthmatic inflammatory response. The objective of our study was to investigate whether the profile of eicosanoid lipid mediators in EBC can characterize the inflammation in asthma and chronic obstructive pulmonary disease (COPD). EBC samples were collected from 22 healthy controls (C), 25 mild intermittent asthmatics (MIA), 20 with moderate to severe asthma (MSA) and 20 with moderate to severe COPD. EBC samples were analyzed by unique tandem mass spectrometry that allows the quantification of up to 25 eicosanoid mediators simultaneously. No differences were found between MIA and C. Subjects with MSA and COPD had higher levels of 6-keto, PGE2, LTB4, 11-12 EET and AA, while lower levels of LXA4, 11DHyTxB2, 11HETE and 8,9EET, when compared to MSA and C (p < 0.05). Our study shows that the analysis of EBC through mass spectrometry is mixed and has a similar response in MSA and COPD when compared to MIA and controls.

Tetrahydrobiopterin is present in high quantity in human milk and has a vasorelaxing effect on newborn rat mesenteric arteries.

Breast milk reduces the incidence of necrotizing enterocolitis (NEC). BH4 is a cofactor for endothelial NOS (eNOS). Reduced BH4 levels, or its oxidation to dihydrobiopterin (BH2), uncouple eNOS resulting in formation of reactive oxygen species (ROS) that have been implicated in the pathogenesis of NEC. We evaluated colostrum and mature breast milk, as well as infant formula, BH4 and BH2 content. In addition, we tested the BH4 effect on the newborn rat mesenteric arterial vascular tone. BH4 and BH2 content increased 3-fold in mature breast milk, when compared with colostrum (p < 0.01), without a change in their ratio. Infant formula had a negligible BH4 content and lower biopterins ratio, when compared with breast milk. eNOS is the predominant synthase isoform in newborn rat mesenteric arteries. In the presence of BH4, mesenteric arteries contracted less to thromboxane A2 analog U46619 (p < 0.01) and this effect was abolished following eNOS inhibition. BH4 (10⁻6 M) vasorelaxed the newborn rat mesenteric arteries. We conclude that when compared with infant formula, breast milk has a high BH4 content that increases as breastfeeding continues. Given its mesenteric arterial vasorelaxing effect, BH4 may play an important role in the reduced NEC incidence among breast fed infants.

Avaliaçäo hemodinâmica e de trocas gasosas pós-preservaçäo em um novo modelo paracorpóreo de reperfusäo pulmonar isolada / Gas exchange and hemodynamic evaluation post preservation in a new paracorporeal model in single pulmonary reperfusion

A compreensäo do significado fisiológico dos eventos bioquímicos após a preservaçäo pulmonar em ratos, tem sido dificultada pela falta de um modelo adequado para assessar a fisiologia envolvida. Nós desenvolvemos um modelo de perfusäo "ex vivo" paracorpóreo de pulmäo de rato, o qual permite a avaliaçäo de trocas gasosas e da hemodinâmica da funçäo pulmonar. Após anestesia e heparinizaçäo o bloco coraçäo/pulmäo era removido e o pulmäo esquerdo reperfundido durante uma hora num fluxo constante de 4 ml/min com sangue venoso homólogo drenado da veia cava inferior do rato paracorpóreo (hospedador). O pulmäo efluente era retornado no mesmo fluxo para a aorta distal do hospedeiro. O modelo foi validado pela verificaçäo da funçäo pulmonar após isquemia a temperatura ambiente. Os animais foram divididos em 3 grupos (N=6), de acordo com o intervalo de isquemia (grupo 1:20min; grupo 2:3 horas; grupo 3:4horas). Nos grupos 1 e 2 PO2' PCO2' pressäo média da via aérea (Paw) e pressäo da artéria pulmonar (Ppa) estavam dentro dos limites da normalidade e estável durante o experimento. Em contraste, os pulmöes no grupo 3 demonstraram alta Ppa e baixa PO2 no sangue efluente (PeffO2), quando comparado aqueles encontrados em grupo 1 ou 2. Ocorreu um ganho significante de peso durante a reperfusäo no grupo 3 (4.23 + ou - 0.9g; p menor do que 0.002). Para cada pulmäo, o PeffO2 final correlacionava com o ganho de peso (R2=0.81; p menor do que 0.0001). Nossos resultados indicam que este modelo pode ser de forma confiável usado para detectar a disfunçäo pulmonar após lesäo isquemica