Measurement of nonlinear pO 2 decay in mouse lungs using 3 He-MRI

ABSTRACT: Spatial and temporal variations in oxygen partial pressure ( pO 2 ) during breath-hold can be exploited to obtain important regional parameters of lung function. In the course of apnea, the oxygen concentration is known to decay exponentially. Therefore, the initial pO 2 ( p 0 ) can be used to represent local ventilation, and the oxygen depletion time constant can characterize perfusion. The protocol, based on a nonlinear model of pO 2 decay, was validated in six healthy mice. Parametric maps of p 0 and oxygen depletion time constant were obtained for pure He/air mixture, in agreement with physiology

Albiglutide, a Long Lasting Glucagon-Like Peptide-1 Analog, Protects the Rat Heart against Ischemia/Reperfusion Injury: Evidence for Improving Cardiac Metabolic Efficiency

BACKGROUND: The cardioprotective effects of glucagon-like peptide-1 (GLP-1) and analogs have been previously reported. We tested the hypothesis that albiglutide, a novel long half-life analog of GLP-1, may protect the heart against I/R injury by increasing carbohydrate utilization and improving cardiac energetic efficiency. METHODS/PRINCIPAL FINDINGS: Sprague-Dawley rats were treated with albiglutide and subjected to 30 min myocardial ischemia followed by 24 h reperfusion. Left ventricle infarct size, hemodynamics, function and energetics were determined. In addition, cardiac glucose disposal, carbohydrate metabolism and metabolic gene expression were assessed. Albiglutide significantly reduced infarct size and concomitantly improved post-ischemic hemodynamics, cardiac function and energetic parameters. Albiglutide markedly increased both in vivo and ex vivo cardiac glucose uptake while reducing lactate efflux. Analysis of metabolic substrate utilization directly in the heart showed that albiglutide increased the relative carbohydrate versus fat oxidation which in part was due to an increase in both glucose and lactate oxidation. Metabolic gene expression analysis indicated upregulation of key glucose metabolism genes in the non-ischemic myocardium by albiglutide. CONCLUSION/SIGNIFICANCE: Albiglutide reduced myocardial infarct size and improved cardiac function and energetics following myocardial I/R injury. The observed benefits were associated with enhanced myocardial glucose uptake and a shift toward a more energetically favorable substrate metabolism by increasing both glucose and lactate oxidation. These findings suggest that albiglutide may have direct therapeutic potential for improving cardiac energetics and function

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Développements méthodologiques pour l imagerie moléculaire dans le système cardiovasculaire et les noyaux polarisés par Résonance Magnétique Nucléaire

The research in Magnetic Resonance Imaging combining the proton molecular imaging and the hyperpolarized gases (helium-3) imaging is a promising way in the field of the cardiovascular and lung applications. In this context, the subjects of this thesis were to develop the instrumentations and to set up sequences and MR protocols dedicated to the small animal (mice) imaging for non-invasive longitudinal studies of the chronic cardiovascular and lung pathologies. The first chapter is dedicated to the vascular pathologies and the state of art of the knowledge of the MR contrast agents in cardiovascular and lung imaging. The second chapter is dedicated to the molecular imaging of the atherosclerosis plaque to evaluate new contrast agents: 1) non-specific, ex-vivo with a multi-spectral analysis of the atherosclerosis plaque components on human coronary arteries. 2) Specific, to asses the arterial wall inflammation in-vivo in ApoE-/- mice by targeting P-selectin (adhesion molecule expressed in an early stage of the pathology and atherothrombosis). In the third chapter, the real-time cardio-respiratory gating is described which was developed: 1) to study contrast agents of the atherosclerosis plaque in mice at the level of the aortic root and the carotids origin where atherosclerosis predominantly develops. 2) to enable non invasive evaluation of cardiac modifications induced by endurance exercise training in mice. The fourth chapter is dedicated to the pulmonary pathologies and the MRI with the hyperpolarized helium-3 to set up the ventilation lung imaging protocol under spontaneous mouse breathing conditions with fast MR sequences. The administration of the gas was accomplished by a mask allowing a non-invasive approach which is adapted to the longitudinal studies in mouseLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Longitudinal 3He and proton imaging of magnetite biodistribution in a rat model of instilled nanoparticles

International audienceEpidemiological and toxicological studies have provided evidence that accidentally inhaled nanosize ultrafine particles can induce chronic or acute health damage. MRI, being noninvasive, is able to assess the biodistribution and clearance of magnetically labeled nanoparticles induced by instillation or inhalation. We report He-3 and proton MRI follow-up of lung, liver, spleen, and kidney distribution of USPIO (ultrasmall superparamagnetic iron oxide) in a rat model. The sensitivity of the imaging technique to various concentrations of instilled magnetite suspension was first assessed in vivo (n = 12). A 2-week longitudinal imaging study was then performed on animals (n = 7) instilled with a 0.5 mg magnetite solution. Hypointense and void signal regions associated with intrapulmonary USPIO were observed in the He-3 ventilation images throughout the study, whereas no USPIO-related proton signal intensity changes were found. Intrapulmonary magnetite nanoparticle confinement was confirmed by ex vivo iron assay and histological analysis. This study demonstrates that combined 3 He and proton MRI enables noninvasive assessment of the distribution and clearance of magnetically labeled instilled nanoparticle

High-resolution contrast-enhanced MRI of atherosclerosis with digital cardiac and respiratory gating in mice.

International audienceAtherosclerosis initially develops predominantly at the aortic root and carotid origin, where effective visualization in mice requires efficient cardiac and respiratory gating. The present study sought to first compare the high-resolution MRI gating performance of two digital gating strategies using: 1) separate cardiac and respiratory signals (double-sensor); and 2) a single-sensor cardiorespiratory signal (ECG demodulation), and second, to apply an optimized processing technique to dynamic contrast-enhanced (CE) carotid origin vessel-wall imaging in mice. High-resolution MR mouse heart and aortic arch images were acquired by ECG signal detection, digital signal processing, and gating signal generation modeled using Simulink (MathWorks, USA). Double-sensor gating used a respiratory sensor while single-sensor gating used breathing-modulated ECG to generate a demodulated respiratory signal. Pre- and postcontrast T(1)-weighted images were acquired to evaluate vessel-wall enhancement with a gadolinium blood-pool agent (P792; Guerbet, France) at the carotid origin in vivo in ApoE(-/-) and C57BL/6 mice, using the optimized cardiorespiratory gating processing technique. Both strategies provided images with improved spatial resolution, less artifacts, and 100% correct transistor-to-transistor logic (TTL) signals. Image quality allowed vessel-wall enhancement measurement in all the ApoE(-/-) mice, with maximal (32%) enhancement 27 min postinjection. The study demonstrated the efficiency of both cardiorespiratory gating strategies for dynamic contrast-enhanced vessel-wall imaging

Cardiac glucose metabolism <i>in vivo</i> and <i>ex vivo</i>.

<p>Cardiac [³H]-2-deoxyglucose uptake was examined <i>in vivo</i> over a 30 min period (A). Additionally, cardiac glucose uptake (B), lactate production (C) and tissue lactate concentration (D) were measured directly in the Langendorff perfused hearts. Values are presented as mean ± SEM. *p<0.05 vs. vehicle.</p