Pulmonary air embolism causes physical obstruction of microvasculature and leads to permeability changes, release of mediators, and injury to lung tissue. In this study we employed an isolated perfused rat lung model to investigate the primary and secondary effects produced by infusion of air into the pulmonary artery. Infusion of various doses of air (0.10-0.25 ml) over a 1-min period produced a dose-dependent increase in pulmonary arterial pressure and lung weight gain. In contrast, when a constant air dose was administered over various periods of time (0.25 ml over 0.5-8.0 min), the pulmonary arterial pressure rose to the same extent regardless of the infusion rate, whereas the lung weight gain increased proportionately with the rate of infusion. Total vascular resistance rose from 1.41 +/- 0.04 to 5.04 +/- 0.09 mmHg.ml-1.min in rats given 0.25 ml air over 1 min (n = 14, P less than 0.001), with greater than or equal to 90% of this increase occurring in the arterial segments. Both thromboxane B2 and endothelin concentrations also increased in the perfusate, suggesting their involvement in this increased resistance. Furthermore the pulmonary filtration coefficient increased from 0.21 +/- 0.05 to 1.28 +/- 0.26 g.min-1.cmH2O-1.100 g (n = 8, P less than 0.001), and the protein concentration in lung lavage fluid also rose, indicating lung injury. Leukocyte counts in the perfusate were unaffected by embolization, but chemiluminescent activity was increased, indicating a possible role for activated leukocytes in lung injury induced by air emboli.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hypoxia and exertion are considered as the two main factors in the development of high-altitude pulmonary oedema (HAPE), however its pathophysiology remains unclear. Therefore, we established a model in which 32 Sprague-Dawley rats were randomly assigned to normoxic rest, hypoxic rest, normoxic exercise and hypoxic exercise.An altitude of 4,700 m was simulated using hypobaric hypoxia, while exercise consisted 48 h walk with 15-20 min breaks every 4 h. Arterial blood gas, bronchoalveolar lavage (BAL), lung wetto-dry weight (W/D) ratio and histological measurements were conducted on each animal.In rats exercising in hypoxia, BAL protein and lung W/D ratio were significantly increased but no changes in BAL leukotriene B 4 and immunoglobulin M were observed. In the same group, lung histology showed typical haemorrhagic lung oedema and disruption of both alveolar epithelium and capillary endothelium while hypoxia or exertion alone only induced slight endothelium and epithelium swelling/disruption.Our study established a direct link between histological and physiological evidence of HAPElike symptoms and we demonstrated that hypoxia and exertion can synergistically induce HAPElike symptoms in Sprague-Dawley rats without inducing lung inflammation. We therefore propose that alveolar epithelium and capillary endothelium stress failure play a major role in the development of HAPE.KEYWORDS: Exercise, high-altitude pulmonary oedema, hypobaric hypoxia, rat model, stress failure H igh-altitude pulmonary oedema (HAPE) is a potentially fatal condition that may affect nonacclimatised individuals who ascend rapidly to altitudes .3,000 m [1, 2]. Approximately 2% of individuals exposed to high altitude are affected severely enough by HAPE to seek treatment [3]. However, the incidence of sub-clinical HAPE may be as high as 75% in individuals travelling at an altitude .4,500 m [4].Hypoxia and exertion have been identified as the two main factors in HAPE development [5]. However, the exact mechanisms that trigger the development of HAPE are not completely understood. Although factors such as inflammation and decreased alveolar fluid clearance are thought to be important in HAPE pathophysiology [6][7][8][9], pulmonary capillary stress failure, which results from an uneven hypoxic pulmonary vascoconstriction [10,11], has been suggested to be the primary inciting mechanism. Indeed, increased pulmonary capillary transmural pressure [12][13][14] causes the rupture of the alveolocapillary membrane [15], allowing the flooding of the alveolar space with a protein rich and haemorrhagic oedema fluid. HOPKINS et al. [16] found evidence of stress failure in exercising humans under hypoxic conditions, and SWENSON et al. [17] showed the presence of red blood cells as well as increased protein concentration in BAL fluid from humans with HAPE, without significant changes in BAL cytokines. However, whether pulmonary capillary stress failure is the primary mechanism in the development of HAPE is not conclusive since direct evidence of capi...

Overproduction of proinflammatory factors is associated with obesity and diabetes. Interleukin (IL)-18 as a member of IL-1 cytokine family is increased in obese, in diabetic, and even in polycystic ovary syndrome (PCOS) patients. In the present study we evaluated the association of serum IL-18 levels with insulin resistance in PCOS women. Forty-two PCOS women and 38 control subjects were enrolled in this study and matched with respect to age and body mass index (BMI). Serum IL-18 levels and hormones were measured for all subjects. Furthermore, euglycemic hyperinsulinemic clamp test was performed in selected 30 PCOS women and 11 control subjects. Serum IL-18 levels were elevated in PCOS women compared with the control (p = 0.033). IL-18 levels were positively correlated with homeostasis model assessment index (HOMA) beta index, which assesses beta cell function (p = 0.035), but were inversely correlated with clamp indices, which best represent insulin resistance status: M, Clamp ISI*100, and MCRg values (p = 0.006, 0.010, and 0.009 respectively). No correlation was found between IL-18 and age, BMI, waist-to-hip ratio (WHR), lipid profile, dehydroepiandrosterone-sulfate (DHEAS), sex hormone- binding globulin (SHBG), or fasting insulin levels. In conclusion, in the present study, serum IL-18 levels were significantly increased in PCOS women and firmly associated with insulin resistance displayed by euglycemic hyperinsulinemic clamp test. It indicates that IL-18 may be a contributing factor linking inflammation and insulin resistance in PCOS women.

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