Dataset Information

Whole body periodic acceleration improves survival and microvascular leak in a murine endotoxin model.

ABSTRACT: Sepsis is a life threatening condition which produces multi-organ dysfunction with profound circulatory and cellular derangements. Administration of E.Coli endotoxin (LPS) produces systemic inflammatory effects of sepsis including disruption of endothelial barrier, and if severe enough death. Whole body periodic acceleration (pGz) is the headward-footward motion of the body. pGz has been shown to induce pulsatile shear stress to the endothelium, thereby releasing vascular and cardio protective mediators. The purpose of this study was to determine whether or not pGz performed as a pre-treatment or post-treatment strategy improves survival in a lethal murine endotoxin model.This study was designed as a prospective randomized controlled study in mice. pGz was performed in mice as pre-treatment (pGz-LPS, 3 days prior to LPS), post-treatment (LPS- pGz, 30 min after LPS) strategies or Control (LPS-CONT), in a lethal murine model of endotoxemia. Endotoxemia was induced with intraperitoneal injection of E.Coli LPS (40mg/kg). In a separate group of mice, a nonspecific nitric oxide synthase inhibitor (L-NAME) was provided in their drinking water and pGz-LPS and LPS-pGz performed to determine the effect of nitric oxide (NO) inhibition on survival. In another subset of mice, micro vascular leakage was determined. Behavioral scoring around the clock was performed in all mice at 30 min intervals after LPS administration, until 48 hrs. survival or death. LPS induced 100% mortality in LPS-CONT animals by 30 hrs. In contrast, survival to 48 hrs. occurred in 60% of pGz-LPS and 80% of LPS-pGz. L-NAME abolished the survival effects of pGz. Microvascular leakage was markedly reduced in both pre and post pGz treated animals and was associated with increased tyrosine kinase endothelial-enriched tunica interna endothelial cell kinase 2 (TIE2) receptor and its phosphorylation (p-TIE2). In a murine model of lethal endotoxemia, pGz performed as a pre or post treatment strategy significantly improved survival, and markedly reduced microvascular leakage. The effect was modulated, in part, by NO since a non-selective inhibitor of NO abolished the pGz survival effect.

SUBMITTER: Adams JA

PROVIDER: S-EPMC6347233 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Whole body periodic acceleration improves survival and microvascular leak in a murine endotoxin model.

Adams Jose A JA Uryash Arkady A Lopez Jose R JR Sackner Marvin A MA

PloS one 20190125 1

Sepsis is a life threatening condition which produces multi-organ dysfunction with profound circulatory and cellular derangements. Administration of E.Coli endotoxin (LPS) produces systemic inflammatory effects of sepsis including disruption of endothelial barrier, and if severe enough death. Whole body periodic acceleration (pGz) is the headward-footward motion of the body. pGz has been shown to induce pulsatile shear stress to the endothelium, thereby releasing vascular and cardio protective m ...[more]

PMID: 30682019

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Project description:Myocardial infarction (MI) may produce significant inflammatory changes and adverse ventricular remodeling leading to heart failure and premature death. Pharmacologic, stem cell transplantation, and exercise have not halted the inexorable rise in the prevalence and great economic costs of heart failure despite extensive investigations of such treatments. New therapeutic modalities are needed. Whole Body Periodic Acceleration (pGz) is a non-invasive technology that increases pulsatile shear stress to the endothelium thereby producing several beneficial cardiovascular effects as demonstrated in animal models, normal humans and patients with heart disease. pGz upregulates endothelial derived nitric oxide synthase (eNOS) and its phosphorylation (p-eNOS) to improve myocardial function in models of myocardial stunning and preconditioning. Here we test whether pGz applied chronically after focal myocardial infarction in rats improves functional outcomes from MI. Focal MI was produced by left coronary artery ligation. One day after ligation animals were randomized to receive daily treatments of pGz for four weeks (MI-pGz) or serve as controls (MI-CONT), with an additional group as non-infarction controls (Sham). Echocardiograms and invasive pressure volume loop analysis were carried out. Infarct transmurality, myocardial fibrosis, and markers of inflammatory and anti-inflammatory cytokines were determined along with protein analysis of eNOS, p-eNOS and inducible nitric oxide synthase (iNOS).At four weeks, survival was 80% in MI-pGz vs 50% in MI-CONT (p< 0.01). Ejection fraction and fractional shortening and invasive pressure volume relation indices of afterload and contractility were significantly better in MI-pGz. The latter where associated with decreased infarct transmurality and decreased fibrosis along with increased eNOS, p-eNOS. Additionally, MI-pGz had significantly lower levels of iNOS, inflammatory cytokines (IL-6, TNF-α), and higher level of anti-inflammatory cytokine (IL-10). pGz improved survival and contractile performance, associated with improved myocardial remodeling. pGz may serve as a simple, safe, non-invasive therapeutic modality to improve myocardial function after MI.

Project description:BackgroundStress fractures are injuries caused by repetitive loading during activities such as running. The application of advanced analytical methods such as machine learning to data from multiple wearable sensors has allowed for predictions of biomechanical variables associated with running-related injuries like stress fractures. However, it is unclear if data from a single wearable sensor can accurately estimate variables that characterize external loading during running such as peak vertical ground reaction force (vGRF), vertical impulse, and ground contact time. Predicting these biomechanical variables with a single wearable sensor could allow researchers, clinicians, and coaches to longitudinally monitor biomechanical running-related injury risk factors without expensive force-measuring equipment.PurposeWe quantified the accuracy of applying quantile regression forest (QRF) and linear regression (LR) models to sacral-mounted accelerometer data to predict peak vGRF, vertical impulse, and ground contact time across a range of running speeds.MethodsThirty-seven collegiate cross country runners (24 females, 13 males) ran on a force-measuring treadmill at 3.8-5.4 m/s while wearing an accelerometer clipped posteriorly to the waistband of their running shorts. We cross-validated QRF and LR models by training them on acceleration data, running speed, step frequency, and body mass as predictor variables. Trained models were then used to predict peak vGRF, vertical impulse, and contact time. We compared predicted values to those calculated from a force-measuring treadmill on a subset of data (n = 9) withheld during model training. We quantified prediction accuracy by calculating the root mean square error (RMSE) and mean absolute percentage error (MAPE).ResultsThe QRF model predicted peak vGRF with a RMSE of 0.150 body weights (BW) and MAPE of 4.27 ± 2.85%, predicted vertical impulse with a RMSE of 0.004 BW*s and MAPE of 0.80 ± 0.91%, and predicted contact time with a RMSE of 0.011 s and MAPE of 4.68 ± 3.00%. The LR model predicted peak vGRF with a RMSE of 0.139 BW and MAPE of 4.04 ± 2.57%, predicted vertical impulse with a RMSE of 0.002 BW*s and MAPE of 0.50 ± 0.42%, and predicted contact time with a RMSE of 0.008 s and MAPE of 3.50 ± 2.27%. There were no statistically significant differences between QRF and LR model prediction MAPE for peak vGRF (p = 0.549) or vertical impulse (p = 0.073), but the LR model's MAPE for contact time was significantly lower than the QRF model's MAPE (p = 0.0497).ConclusionsOur findings indicate that the QRF and LR models can accurately predict peak vGRF, vertical impulse, and contact time (MAPE < 5%) from a single sacral-mounted accelerometer across a range of running speeds. These findings may be beneficial for researchers, clinicians, or coaches seeking to monitor running-related injury risk factors without force-measuring equipment.

Dataset Information

Whole body periodic acceleration improves survival and microvascular leak in a murine endotoxin model.

Publications

Whole body periodic acceleration improves survival and microvascular leak in a murine endotoxin model.

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