Citations

Cardiac output (CO) assessment as a basic hemodynamic parameter has been of interest in exercise physiology, cardiology, and anesthesiology. Noninvasive techniques available are technically challenging, and thus difficult to use outside of a clinical or laboratory setting. We propose a novel method of noninvasive CO assessment using a single, upper-arm cuff. The method uses the arterial pressure pulse wave signal acquired from the brachial artery during 20-s intervals of suprasystolic occlusion. This method was evaluated in a cohort of 12 healthy individuals (age, 27.7 ± 5.4 yr, 50% men) and compared with an established method for noninvasive CO assessment, the open-circuit acetylene method (OpCirc) at rest, and during low- to moderate-intensity exercise. CO increased from rest to exercise (rest, 7.4 ± 0.8 vs. 7.2 ± 0.8; low, 9.8 ± 1.8 vs. 9.9 ± 2.0; moderate, 14.1 ± 2.8 vs. 14.8 ± 3.2 l/min) as assessed by the cuff-occlusion and OpCirc techniques, respectively. The average error of experimental technique compared with OpCirc was −0.25 ± 1.02 l/min, Pearson’s correlation coefficient of 0.96 (rest + exercise), and 0.21 ± 0.42 l/min with Pearson’s correlation coefficient of 0.87 (rest only). Bland-Altman analysis demonstrated good agreement between methods (within 95% boundaries); the reproducibility coefficient (RPC) = 0.84 l/min with R2= 0.75 at rest and RPC = 2 l/min with R2= 0.92 at rest and during exercise, respectively. In comparison with an established method to quantify CO, the cuff-occlusion method provides similar measures at rest and with light to moderate exercise. Thus, we believe this method has the potential to be used as a new, noninvasive method for assessing CO during exercise.

The molecular mechanisms for lung cell repair are largely unknown. Previous studies identified tripartite motif protein 72 (TRIM72) from striated muscle and linked its function to tissue repair. In this study, we characterized TRIM72 expression in lung tissues and investigated the role of TRIM72 in repair of alveolar epithelial cells. In vivo injury of lung cells was introduced by high tidal volume ventilation, and repair-defective cells were labeled with postinjury administration of propidium iodide. Primary alveolar epithelial cells were isolated and membrane wounding and repair were labeled separately. Our results show that absence of TRIM72 increases susceptibility to deformation-induced lung injury whereas TRIM72 overexpression is protective. In vitro cell wounding assay revealed that TRIM72 protects alveolar epithelial cells through promoting repair rather than increasing resistance to injury. The repair function of TRIM72 in lung cells is further linked to caveolin 1. These data suggest an essential role for TRIM72 in repair of alveolar epithelial cells under plasma membrane stress failure.

Abstract MUC1 (MUC1 in human and Muc1 in nonhumans) is a membrane-tethered mucin that interacts with Pseudomonas aeruginosa (PA) through flagellin. In this study, we compared PA pulmonary clearance and proinflammatory responses by Muc1−/− mice with Muc1+/+ littermates following intranasal instillation of PA or flagellin. Compared with Muc1+/+ mice, Muc1−/− mice showed increased PA clearance, greater airway recruitment of neutrophils, higher levels of TNF-α and KC in bronchoalveolar lavage fluid, higher levels of TNF-α in media of flagellin-stimulated alveolar macrophages, and higher levels of KC in media of tracheal epithelial cells. Knockdown of MUC1 enhanced flagellin-induced IL-8 production by primary human bronchial epithelial cells. Expression of MUC1 in HEK293T cells attenuated TLR5-dependent IL-8 release in response to flagellin, which was completely ablated when its cytoplasmic tail was deleted. We conclude that MUC1/Muc1 suppresses pulmonary innate immunity and speculate its anti-inflammatory activity may play an important modulatory role during microbial infection.

We determined whether a non-invasive gas exchange based estimate of pulmonary vascular (PV) capacitance [PV CAP = stroke volume (SV) x pulmonary arterial pressure (Ppa)] (GX CAP ) tracked the PV response to exercise in heart-failure (HF) patients. Pulmonary wedge pressure (Ppw), Ppa, PV resistance (PVR), and gas exchange were measured simultaneously during cycle exercise in 42 HF patients undergoing right-heart catheterization. During exercise, P ET CO 2 and V E /VCO 2 were related to each other ( r= -0.93, P < 0.01) and similarly related to mean Ppa (mPpa) ( r = -0.39 and 0.36; P < 0.05); P ET CO 2 was subsequently used as a metric of mPpa. Oxygen pulse (O 2 pulse) tracked the SV response to exercise (r = 0.91, P < 0.01). Thus, GX CAP was calculated as O 2 pulse x P ET CO 2 . During exercise, invasively determined PV CAP and non-invasive GX CAP were related (r = 0.86, P < 0.01), and GX CAP correlated with mPpa and PVR (r = -0.46 and -0.54; P < 0.01). In conclusion, noninvasive gas exchange measures may represent a simple way to track the PV response to exercise in HF.

Abstract A previous lectin binding study demonstrated the presence of high molecular-mass mucin-like glycoproteins (HMGP) on the surface of hamster tracheal surface epithelial (HTSE) secretory cells (Proc. Natl. Acad. Sci. USA 1987;84:9304). In the present study, we intended to isolate and characterize these HMGP from the plasma membrane of the primary HTSE cells and then to determine whether or not these membrane HMGP are Muc-1 mucins, a type of mucins originally discovered on the surface of some carcinomas. A subcellular fraction enriched with the plasma membrane was obtained using a sucrose density gradient centrifugation. This fraction contained high molecular-mass glycoconjugates which were excluded from Sepharose CL-4B gel. Biochemical characterization of these glycoconjugates revealed the following characteristics: (1) susceptibility to both pronase and mild alkaline treatments, but totally resistant to proteoglycan-digesting enzymes; (2) partitioning in the detergent phase of Triton X-114 and resistance to digestion by phosphatidylinositol phospholipase C or D; (3) a buoyant density of 1.5 g/ml based on CsCl density gradient centrifugation; (4) polydispersity in terms of both size and charge density; and (5) lack of immunoreactivity with an anti-Muc-1 mucin antibody. We conclude that the plasma membrane of HTSE cells at confluence contains HMGP, which seem to be the integral membrane proteins but different from Muc-1 mucins, and that these membrane HMGP appear to share some similarities with secreted mucins in terms of size and charge.

Patients with pulmonary arterial hypertension (PAH) and heart failure (HF) display many abnormalities in respiratory gas exchange. These abnormalities are accentuated with exercise and track with disease severity. However, use of gas exchange measures in day-to-day clinical practice is limited by several issues, including the large number of variables available and difficulty in data interpretation. Moreover, maximal exercise testing has limitations in clinical populations due to their complexity, patient anxiety and variability in protocols and cost. Therefore, a multivariable gas exchange index (MVI) that integrates key gas exchange variables obtained during submaximal exercise into a severity score that ranges from normal to severe-very-severe is proposed. To demonstrate the usefulness of this index, we applied this to 2 groups (PAH,n=42and HF,n=47) as well as to age matched healthy controls (n=25). We demonstrate that this score tracks WHO classification and right ventricular systolic pressure in PAH (r=0.53and 0.73,P≤0.01) and NYHA and cardiac index in HF (r=0.49and 0.74,P≤0.01). This index demonstrates a stronger relationship than any single gas exchange variable alone. In conclusion, MVI obtained from light, submaximal exercise gas exchange is a useful approach to simplify data interpretation in PAH and HF populations.

Abstract MUC1 (MUC1 in humans and Muc1 in nonhuman species) is a transmembrane mucin-like glycoprotein expressed in epithelial cells lining various mucosal surfaces as well as hematopoietic cells. Recently, we showed that Muc1−/− mice exhibited greater inflammatory responses to Pseudomonas aeruginosa or its flagellin compared with their wild-type littermates, and our studies with cultured cells revealed that MUC1/Muc1 suppressed the Toll-like receptor (TLR) 5 signaling pathway, suggesting its anti-inflammatory role. Here we demonstrate that other TLR signaling (TLR2, 3, 4, 7, and 9) is also suppressed by MUC1/Muc1. The results from this study suggest that MUC1/Muc1 may play a crucial role during airway infection and inflammation by various pathogenic bacteria and viruses.