In a circulation completely dependent on ECMO support, maximum achievable flow directly depended on the vascular factors governing venous return - i.e. closing conditions, stressed vascular volume and the elastance and resistive properties of the vasculature. Both treatments increased maximum achievable ECMO flow at stable DO2, via increases in stressed volume by different mechanisms. Vascular resistance and pump afterload decreased with Volume Expansion.

BackgroundCisplatin plus pemetrexed combination therapy is considered the standard treatment for patients with advanced, non-squamous, non-small-cell lung cancer (NSCLC). However, advanced NSCLC has a 5-year survival rate of below 10%, which is mainly due to therapy resistance. We previously showed that the NSCLC cell line A549 harbors different subpopulations including a mesenchymal-like subpopulation characterized by increased chemo- and radiotherapy resistance. Recently, therapy resistance in hematological and solid tumors has been associated with increased mitochondrial activity. Thus, the aim of this study was to investigate the role of the mitochondrial activity in NSCLC chemotherapy resistance.MethodsBased on MitoTracker staining, subpopulations characterized by the highest 10% (Mito-High) or lowest 10% (Mito-Low) mitochondrial mass content were sorted by FACS (Fluorescence-Activated Cell Sorting) from paraclonal cultures of the NSCLC A549 cell line . Mitochondrial DNA copy numbers were quantified by real-time PCR whereas basal cellular respiration was measured by high-resolution respirometry. Cisplatin and pemetrexed response were quantified by proliferation and colony formation assay.ResultsPemetrexed treatment of parental A549 cells increased mitochondrial mass over time. FACS-sorted paraclonal Mito-High cells featured increased mitochondrial mass and mitochondrial DNA copy number compared to the Mito-Low cells. Paraclonal Mito-High cells featured an increased proliferation rate and were significantly more resistant to cisplatin treatment than Mito-Low cells. Interestingly, cisplatin-resistant, paraclonal Mito-High cells were significantly more sensitive to pemetrexed treatment than Mito-Low cells. We provide a working model explaining the molecular mechanism underlying the increased cisplatin- and decreased pemetrexed resistance of a distinct subpopulation characterized by high mitochondrial mass.ConclusionsThis study revealed that cisplatin resistant A549 lung cancer cells can be identified by their increased levels of mitochondrial mass. However, Mito-High cells feature an increased sensitivity to pemetrexed treatment. Thus, pemetrexed and cisplatin target reciprocal lung cancer subpopulations, which could explain the increased efficacy of the combination therapy in the clinical setting.

Building on recent work by Chandar et al., we construct X-ray luminosity functions (XLFs) for different classes of X-ray binary (XRB) donors in the nearby star-forming galaxy M83 through a novel methodology. Rather than classifying low- versus high-mass XRBs based on the scaling of the number of X-ray sources with stellar mass and star formation rate, respectively, we utilize multiband Hubble Space Telescope imaging data to classify each Chandra-detected compact X-ray source as a low-mass (i.e., donor mass ≲3 M ⊙), high-mass (donor mass ≳8M ⊙), or intermediate-mass XRB based on either the location of its candidate counterpart on optical color–magnitude diagrams or the age of its host star cluster. In addition to the standard (single and/or truncated) power-law functional shape, we approximate the resulting XLFs with a Schechter function. We identify a marginally significant (at the 1σ-to-2σ level) exponential downturn for the high-mass XRB XLF, at ℓ ≃ 38.48 − 0.33 + 0.52 (in log CGS units). In contrast, the low- and intermediate-mass XRB XLFs, as well as the total XLF of M83, are formally consistent with sampling statistics from a single power law. Our method suggests a non-negligible contribution from low- and possibly intermediate-mass XRBs to the total XRB XLF of M83, i.e., between 20% and 50%, in broad agreement with X-ray-based XLFs. More generally, we caution against considerable contamination from X-ray emitting supernova remnants to the published, X-ray-based XLFs of M83, and possibly all actively star-forming galaxies.