Effects of Inhaled Iloprost on Lung Mechanics and Myocardial Function During One-Lung Ventilation in Chronic Obstructive Pulmonary Disease Patients Combined With Poor Lung Oxygenation.

BACKGROUND: The ventilation/perfusion mismatch in chronic obstructive pulmonary disease (COPD) patients can exacerbate cardiac function as well as pulmonary oxygenation. We hypothesized that inhaled iloprost can ameliorate pulmonary oxygenation with lung mechanics and myocardial function during one-lung ventilation (OLV) in COPD patients combined with poor lung oxygenation. METHODS: A total of 40 patients with moderate to severe COPD, who exhibited the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FIO2) <150 mm Hg 30 minutes after initiating OLV, were enrolled in this study. Patients were randomly allocated into either ILO group (n = 20) or Control group (n = 20), in which iloprost (20 µg) and saline were inhaled, respectively. The PaO2/FIO2 ratio, dead space, dynamic compliance, and tissue Doppler imaging with myocardial performance index (MPI) were assessed 30 minutes after initiating OLV (pre-Tx) and 30 minutes after completion of drug inhalation (post-Tx). Repeated variables were analyzed using a linear mixed-model between the groups. RESULTS: At pre-Tx, no differences were observed in measured parameters between the groups. At post-Tx, PaO2/FIO2 ratio (P < .001) and dynamic compliance (P = .023) were significantly higher and dead space ventilation was significantly lower (P = .001) in iloprost group (ILO group) compared to Control group. Left (P = .003) and right ventricular MPIs (P < .001) significantly decreased in ILO group compared to Control group. CONCLUSIONS: Inhaled iloprost improved pulmonary oxygenation, lung mechanics, and cardiac function simultaneously during OLV in COPD patients with poor lung oxygenation.

GD3 accumulation in cell surface lipid rafts prior to mitochondrial targeting contributes to amyloid-ß-induced apoptosis.

Neuronal apoptosis induced by amyloid ß-peptide (Aß) plays an important role in the pathophysiology of Alzheimer's disease (AD). However, the molecular mechanism underlying Aß-induced apoptosis remains undetermined. The disialoganglioside GD3 involves ceramide-, Fas- and TNF-α-mediated apoptosis in lymphoid cells and hepatocytes. Although the implication of GD3 has been suggested, the precise role of GD3 in Aß-induced apoptosis is still unclear. Here, we investigated the changes of GD3 metabolism and characterized the distribution and trafficking of GD3 during Aß-induced apoptosis using human brain-derived TE671 cells. Extracellular Aß-induced apoptosis in a mitochondrial-dependent manner. GD3 level was negligible in the basal condition. However, in response to extracellular Aß, both the expression of GD3 synthase mRNA and the intracellular GD3 level were dramatically increased. Neosynthesized GD3 rapidly accumulated in cell surface lipid microdomains, and was then translocated to mitochondria to execute the apoptosis. Disruption of membrane lipid microdomains with methyl-ß-cyclodextrin significantly prevented both GD3 accumulation in cell surface and Aß-induced apoptosis. Our data suggest that rapidly accumulated GD3 in plasma membrane lipid microdomains prior to mitochondrial translocation is one of the key events in Aß-induced apoptosis.