Publications by authors named "Christophe Jayle"

75 Publications

In vitro differentiation of W8B2 human cardiac stem cells: gene expression of ionic channels and spontaneous calcium activity.

Cell Mol Biol Lett 2020 Nov 5;25(1):50. Epub 2020 Nov 5.

University of Poitiers Signalisation et Transports Ioniques Membranaires, EA7349, Poitiers Cedex 09, France.

Background: Human cardiac stem cells expressing the W8B2 marker (W8B2 CSCs) were recently identified and proposed as a new model of multipotent CSCs capable of differentiating into smooth muscle cells, endothelial cells and immature myocytes. Nevertheless, no characterization of ion channel or calcium activity during the differentiation of these stem cells has been reported.

Methods: The objectives of this study were thus to analyze (using the TaqMan Low-Density Array technique) the gene profile of W8B2 CSCs pertaining to the regulation of ion channels, transporters and other players involved in the calcium homeostasis of these cells. We also analyzed spontaneous calcium activity (via the GCaMP calcium probe) during the in vitro differentiation of W8B2 CSCs into cardiac myocytes.

Results: Our results show an entirely different electrophysiological genomic profile between W8B2 CSCs before and after differentiation. Some specific nodal genes, such as Tbx3, HCN, ICaT, L, KV, and NCX, are overexpressed after this differentiation. In addition, we reveal spontaneous calcium activity or a calcium clock whose kinetics change during the differentiation process. A pharmacological study carried out on differentiated W8B2 CSCs showed that the NCX exchanger and IP3 stores play a fundamental role in the generation of these calcium oscillations.

Conclusions: Taken together, the present results provide important information on ion channel expression and intrinsic calcium dynamics during the differentiation process of stem cells expressing the W8B2 marker.
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http://dx.doi.org/10.1186/s11658-020-00242-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646077PMC
November 2020

Myocardial infarction revealed a giant right coronary artery aneurysm.

J Card Surg 2019 Dec 15;34(12):1651-1652. Epub 2019 Nov 15.

Department of Thoracic and Cardiovascular Surgery, Cardio-Vascular Center, University Hospital of Poitiers, Poitiers, France.

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http://dx.doi.org/10.1111/jocs.14357DOI Listing
December 2019

Thoracic Endometriosis and Hepatothorax.

Ann Thorac Surg 2019 12 23;108(6):e415. Epub 2019 Jul 23.

Department of Thoracic and Cardiovascular Surgery, Cardio-vascular Center, Poitiers University Hospital, Poitiers, France.

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http://dx.doi.org/10.1016/j.athoracsur.2019.05.082DOI Listing
December 2019

Dissecting Thoracic Aneurysm in Takayasu Arteritis With Concomitant Tuberculosis.

Ann Thorac Surg 2020 02 27;109(2):e119-e121. Epub 2019 Jun 27.

Department of Thoracic and Cardiovascular Surgery, Cardio-vascular Center, University Hospital of Poitiers, Poitiers, France.

We present a case of dissecting aneurysm of ascending aorta in a 15-year-old patient secondary to Takayasu arteritis with concomitant tuberculosis, with an emphasis on multimodality imaging findings and to illustrate preoperative and postoperative medical management. Antituberculosis therapy, high-dose corticosteroids, antiplatelet therapy, and β-blockers were administrated during the initial active phase. The patient presented with acute chest pain 3 months after medical therapy initiation. We performed an ascending aorta and aortic arch replacement with branched Dacron grafts. Only a handful of similar, but not identical, cases of Takayasu arteritis with concomitant tuberculosis leading to aortic dissection have been described previously.
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http://dx.doi.org/10.1016/j.athoracsur.2019.05.014DOI Listing
February 2020

A high-resolution ICP-MS method for the determination of 38 inorganic elements in human whole blood, urine, hair and tissues after microwave digestion.

Talanta 2019 Jul 20;199:228-237. Epub 2019 Feb 20.

Plateforme de spectrométrie de masse MasSpecLab, INSERM UMR 1173, UFR Simone Veil - Santé, Université Versailles Saint Quentin, Université Paris Saclay, Montigny le Bretonneux, France; Laboratoire de toxicologie, Hôpital Raymond Poincaré, AP-HP, Garches, France.

Inductively coupled plasma-mass spectrometry (ICP-MS) is currently the reference method for the determination of inorganic elements, and has many applications in healthcare and the environmental field. The objective of the present study was to develop and validate a high-resolution ICP-MS method for the simultaneous quantification of 38 elements in samples of human whole blood, urine, hair and tissues after microwave mineralization. The samples were incubated with nitric acid, hydrogen peroxide and internal standards prior to microwave mineralization for 25 min. The analysis was performed with an Element XR ICP-MS and validated using commercial reference standards (whole blood, urine, and hair) and in-house quality control samples. The 38 elements were detected in low-, medium- or high-resolution mode, depending on interferences and sensitivity. The lower and upper limits of quantification were adjusted for each element. The method was linear for all elements (correlation coefficient >0.996), and the inter- and intraday precision values (coefficient of variation) were below 15%. Samples from a clinical trial were used to confirm the high-resolution ICP-MS method's suitability for the assessment of patient samples.
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http://dx.doi.org/10.1016/j.talanta.2019.02.068DOI Listing
July 2019

Defining the optimal duration for normothermic regional perfusion in the kidney donor: A porcine preclinical study.

Am J Transplant 2019 03 17;19(3):737-751. Epub 2018 Sep 17.

INSERM U1082, (IRTOMIT), Poitiers, France.

Kidneys from donation after circulatory death (DCD) are highly sensitive to ischemia-reperfusion injury and thus require careful reconditioning, such as normothermic regional perfusion (NRP). However, the optimal NRP protocol remains to be characterized. NRP was modeled in a DCD porcine model (30 minutes of cardiac arrest) for 2, 4, or 6 hours compared to a control group (No-NRP); kidneys were machine-preserved and allotransplanted. NRP appeared to permit recovery from warm ischemia, possibly due to an increased expression of HIF1α-dependent survival pathway. At 2 hours, blood levels of ischemic injury biomarkers increased: creatinine, lactate/pyruvate ratio, LDH, AST, NGAL, KIM-1, CD40 ligand, and soluble-tissue-factor. All these markers then decreased with time; however, AST, NGAL, and KIM-1 increased again at 6 hours. Hemoglobin and platelets decreased at 6 hours, after which the procedure became difficult to maintain. Regarding inflammation, active tissue-factor, cleaved PAR-2 and MCP-1 increased by 4-6 hours, but not TNF-α and iNOS. Compared to No-NRP, NRP kidneys showed lower resistance during hypothermic machine perfusion (HMP), likely associated with pe-NRP eNOS activation. Kidneys transplanted after 4 and 6 hours of NRP showed better function and outcome, compared to No-NRP. In conclusion, our results confirm the mechanistic benefits of NRP and highlight 4 hours as its optimal duration, after which injury markers appear.
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http://dx.doi.org/10.1111/ajt.15063DOI Listing
March 2019

Modulation of cellular membrane properties as a potential therapeutic strategy to counter lipointoxication in obstructive pulmonary diseases.

Biochim Biophys Acta Mol Basis Dis 2018 09 28;1864(9 Pt B):3069-3084. Epub 2018 Jun 28.

Laboratoire Coopératif "Lipotoxicity and Channelopathies - ConicMeds", Université de Poitiers, 1, rue Georges Bonnet, Poitiers, France. Electronic address:

Maintaining the equilibrium between saturated and unsaturated fatty acids within membrane phospholipids (PLs) is crucial to sustain the optimal membrane biophysical properties, compatible with selective organelle-based processes. Lipointoxication is a pathological condition under which saturated PLs tend to accumulate within the cell at the expense of unsaturated species, with major impacts on organelle function. Here, we show that human bronchial epithelial cells extracted from lungs of patients with Obstructive Pulmonary Diseases (OPDs), i. e. Cystic Fibrosis (CF) individuals and Smokers, display a characteristic lipointoxication signature, with excessive amounts of saturated PLs. Reconstitution of this signature in cellulo and in silico revealed that such an imbalance results in altered membrane properties and in a dramatic disorganization of the intracellular network of bronchial epithelial cells, in a process which can account for several OPD traits. Such features include Endoplasmic Reticulum-stress, constitutive IL8 secretion, bronchoconstriction and, ultimately, epithelial cell death by apoptosis. We also demonstrate that a recently-identified lipid-like molecule, which has been shown to behave as a "membrane-reshaper", counters all the lipointoxication hallmarks tested. Altogether, these insights highlight the modulation of membrane properties as a potential new strategy to heal and prevent highly detrimental symptoms associated with OPDs.
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http://dx.doi.org/10.1016/j.bbadis.2018.06.021DOI Listing
September 2018

Medicoeconomic analysis of lobectomy using thoracoscopy versus thoracotomy for lung cancer: a study protocol for a multicentre randomised controlled trial (Lungsco01).

BMJ Open 2017 06 15;7(6):e012963. Epub 2017 Jun 15.

Department of Thoracic and Cardiovascular Surgery, CHU Dijon, Dijon, France.

Introduction: In the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact.

Methods And Analysis: The French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients.

Ethics And Dissemination: The protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals.

Trial Registration Number: NCT02502318.
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http://dx.doi.org/10.1136/bmjopen-2016-012963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541439PMC
June 2017

Subcutaneous cardioverter defibrillator has longer time to therapy but is less cardiotoxic than transvenous cardioverter defibrillator. Study carried out in a preclinical porcine model.

Europace 2018 05;20(5):873-879

CHU Poitiers, Service de Cardiologie, 2 rue de la Milétrie, Poitiers 86021, France.

Aims: Totally subcutaneous implantable cardioverter defibrillator (S-ICD) delivers higher shock energy and can have longer time to therapy compared to transvenous implantable cardioverter defibrillator (T-ICD). Aim of the study was to compare time to therapy and to investigate cardiac, cerebral and systemic injuries of S-ICD and T-ICD shocks delivered after ventricular fibrillation (VF) induction.

Methods And Results: Fourteen pigs were randomly implanted with a S-ICD (n = 7) or a T-ICD (n = 7). Five VF episodes were induced in each pig. For each VF episode, up to two shocks could be delivered by the T-ICD or the S-ICD to terminate the arrhythmia. Cardiac, systemic, and cerebral toxicity were monitored. Mean time to therapy was longer in the S-ICD group compared to the T-ICD group (19[18; 23] s vs. 9 [7; 10] s; P = 0.001, respectively). High-sensitivity troponin T levels were significantly higher in the T-ICD group from 1 to 24 h after the procedure (P ≤ 0.02). Creatine phosphokinase activity levels were significantly higher in the S-ICD group, at 3, 6, and 24 h after the procedure (P ≤ 0.05). Lactate levels were not significantly different between groups. S100 protein level was similar in both groups at 1 h after the procedure and then decreased in the T-ICD group compared to the S-ICD group (P = 0.04).

Conclusions: Time to therapy in S-ICD was twice as long as for T-ICD, but didn't induce relevant brain injury. Conversely, S-ICD shocks were less cardiotoxic than T-ICD shocks.
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http://dx.doi.org/10.1093/europace/eux074DOI Listing
May 2018

Medical and Economic Evaluation of FOREseal Bioabsorbable Reinforcement Sleeves Compared With Current Standard of Care for Reducing Air Leakage Duration After Lung Resection for Malignancy: A Randomized Trial.

Ann Surg 2017 01;265(1):45-53

*Department of Thoracic Surgery, Paris Center University Hospital, Paris Descartes University, Paris, France †Department of Thoracic Surgery, Poitiers University Hospital, Poitiers, France ‡Department of Thoracic Surgery, Limoges University Hospital, Limoges, France §Department of Thoracic Surgery, Institute Mutualiste Montsouris, Paris, France ||Department of Thoracic Surgery, Bichat University Hospital, Paris Diderot University, Paris, France ¶Department of Thoracic Surgery, St Etienne University Hospital, St Etienne, France #Department of Thoracic Surgery, Dijon University Hospital, Dijon, France **Department of Thoracic Surgery, Lyon University Hospital, Bron, France ††Department of Thoracic Surgery, Grenoble University Hospital, Grenoble, France ‡‡Department of Thoracic Surgery, Tours University Hospital, Tours, France §§Department of Thoracic Surgery, Nancy University Hospital, Nancy, France ||||Department of Thoracic Surgery, Clinique du Cedre, Rouen, France ¶¶Department of Biostatistics, Paris West University Hospital, Paris, France ##Department of Public Health and Medical Economy, Paris Center University Hospital, Paris, France ***Department of Thoracic Surgery, Paris West University Hospitals, AP-HP, Paris Descartes University, Paris, France.

Objective: The objective of this study was to determine the efficacy of alginate staple-line reinforcement of fissure openings as compared with stapling alone, with or without tissue sealant or glue, in reducing the incidence and duration of air leakage after pulmonary lobectomy for malignancy.

Summary Background Data: No randomized trial evaluating alginate staple-line reinforcement has been performed to date.

Methods: The Staple-line Reinforcement for Prevention of Pulmonary Air Leakage study was a multicenter randomized trial, with blinded evaluation of endpoints. Patients over 18 years of age scheduled for elective open lobectomy or bilobectomy for malignancy were eligible for enrollment. At thoracotomy, patients were deemed ineligible if an unanticipated pneumonectomy was indicated, or if air leakage occurred after the liberation of pleural adhesions. Otherwise, if the fissure was incomplete or the lung had an emphysematous appearance, patients were randomized to either standard management or interventional procedure consisting of fissure opening with linear cutting staplers buttressed with paired alginate sleeves (FOREseal). The number of eligible patients necessary in each randomization arm was estimated to be 190, and an outcomes analysis was performed on an intention-to-treat basis.

Results: Of the 611 patients consented to study enrollment, 380 met the inclusion criteria and were randomized. Based on an intention-to-treat analysis, the primary endpoint of air leak duration was not different between the 2 groups: 1 day (range: 0-2 d) in the FOREseal group and 1 day (range: 0-3 d) in the control group (P = 0.8357). In addition, the 2 groups were similar in terms of the proportion of patients presenting with prolonged air leakage (7.8% in the FOREseal group vs 11.3% in the control group, P = 0.264) and the average duration of chest drainage (P = 0.107). Procedure costs were comparable for both groups.

Conclusions: FOREseal did not demonstrate a significant advantage over standard treatment alone.
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http://dx.doi.org/10.1097/SLA.0000000000001687DOI Listing
January 2017

A functional tandem between transient receptor potential canonical channels 6 and calcium-dependent chloride channels in human epithelial cells.

Eur J Pharmacol 2015 Oct 8;765:337-45. Epub 2015 Aug 8.

Laboratoire Signalisation et Transports Ioniques Membranaires, Université de Poitiers-CNRS, Pôle Biologie Santé, 1 rue Georges Bonnet, 86073 Poitiers Cedex 9, France. Electronic address:

TRPC6 plays important human physiological functions, notably in artery and arterioles constriction, in regulation of vascular volume and in bronchial muscle constriction. It is implicated in pulmonary hypertension, cardiovascular disease, and focal segmental glomerulosclerosis and seems to play a role in cancer development. Previously, we identified Guanabenz, an α2-adrenergic agonist used for hypertension treatment (Wytensin®), as an activator of calcium-dependent chloride channels (CaCC) in human Cystic Fibrosis (CF) nasal epithelial cells by transiently increasing [Ca2+]i via an influx of extracellular Ca2+. In this study, using assays to measure chloride channel activity, we show that guanabenz is an activator of CaCC in freshly dissociated human bronchial epithelial cells from three CF patients with various genotypes (F508del/F508del, F508del/R1066C, F508del/H1085R). We further characterised the effect of guanabenz and show that it is independent of α-adrenergic receptors, is inhibited by the TRPC family inhibitor SKF-96365 but not by the TRPV family inhibitor ruthenium red. Using western-blotting, Ca2+ measurements and iodide efflux assay, we found that TRPC1 siRNA has no effect on guanabenz induced responses whereas TRPC6 siRNA prevented the guanabenz-dependent Ca2+ influx and the CaCC-dependent activity stimulated by guanabenz. In conclusion, we show that TRPC6 channel is pivotal for the activation of CaCC by guanabenz through a α2-adrenergic-independent pathway in human airway epithelial cells. We suggest propose a functional coupling between TRPC6 and CaCC and guanabenz as a potential TRPC6 activator for exploring TRPC6 and CaCC channel functions and corresponding channelopathies.
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http://dx.doi.org/10.1016/j.ejphar.2015.08.005DOI Listing
October 2015

Flail chest in polytraumatized patients: surgical fixation using Stracos reduces ventilator time and hospital stay.

Biomed Res Int 2015 1;2015:624723. Epub 2015 Feb 1.

Thoracic and Cardiac Surgery Unit, Poitiers University Hospital, 2 rue de la Milétrie, 86000 Poitiers, France.

Objectives: Conservative management of patients with flail chest is the treatment of choice. Rib fracture repair is technically challenging; however, with the advent of specially designed molding titanium clips, surgical management has been simplified. Surgical stabilization has been used with good outcomes. We are reporting on our institutional matched-case-control study.

Methods: Between April 2010 and April 2011, ten polytraumatized patients undergoing rib stabilization for flail chest were matched 1 : 1 to 10 control patients by age ±10 years, sex, neurological or vertebral trauma, abdominal injury, and arm and leg fractures. Surgery was realized in the first 48 hours.

Results: There were no significant differences between groups for matched data and prognostic scores: injury severity score, revised trauma score, and trauma injury severity score. Ventilator time (142 ± 224 versus 74 ± 125 hours, P = 0.026) and overall hospital stay (142 ± 224 versus 74 ± 125 hours, P = 0.026) were significantly lower for the surgical group after adjustment on prognostic scores. There was a trend towards shorter ICU stay for operative patients (12.3 ± 8.5 versus 9.0 ± 4.3 days, P = 0.076).

Conclusions: Rib fixation with Stracos is feasible and decreases the length of ventilation and hospital stay. A multicenter randomized study is warranted so as to confirm these results and to evaluate impact on pulmonary function status, pain, and quality of life.
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http://dx.doi.org/10.1155/2015/624723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4331314PMC
December 2015

Primary cardiac lymphoma complicated by cardiogenic shock: successful treatment with chemotherapy delivered under extracorporeal membrane oxygenation support.

Eur J Cardiothorac Surg 2015 Dec 10;48(6):968-70. Epub 2015 Feb 10.

Department of Cardio-thoracic Surgery, University Hospital of Poitiers, Poitiers, France.

Primary cardiac lymphomas (PCLs) are rare in immunocompetent patients. Their clinical presentation is highly variable and in case of cardiogenic shock, death is often inevitable with a diagnosis made post-mortem. We report the case of a 65-year old immunocompetent man with cardiogenic shock requiring emergent extracorporeal membrane oxygenation (ECMO). Soon after, a diagnosis of PCL was given and chemotherapy was delivered under ECMO support. The patient was progressively weaned from the mechanical support. Six months later, he had fully recovered.
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http://dx.doi.org/10.1093/ejcts/ezv031DOI Listing
December 2015

The low PLC-δ1 expression in cystic fibrosis bronchial epithelial cells induces upregulation of TRPV6 channel activity.

Cell Calcium 2015 Jan 18;57(1):38-48. Epub 2014 Nov 18.

Laboratoire Signalisation et Transports Ioniques Membranaires ERL 7368 CNRS, Université de Poitiers, 86073 Poitiers, France. Electronic address:

Increase of Ca(2+) influx in Cystic Fibrosis (CF) cells has been reported to be related to Transient Receptor Potential Canonical (TRPC6) channel, which is implicated in a functional coupling with Cystic Fibrosis Transmembrane conductance Regulator (CFTR). Several members of the Transient Receptor Potential Vanilloid (TRPV) channels family have already been described as emerging target for respiratory diseases. Two specific isoforms, TRPV5 and TRPV6 are of particular interest in the context of CF Ca(2+) homeostasis as they are highly selective toward Ca(2+) and constitutively activated. Thus, we investigated the involvement of these channels in Ca(2+) influx in CF and non-CF human bronchial epithelial cell lines. 16HBE14o-, CFBE41o- cell lines, primary human airway epithelial cells (hAEC) and freshly isolated human airway epithelial cells from CF and non-CF individuals were used. We showed that both channels are expressed in CF and non-CF cells and constitutive Ca(2+) influx was significantly higher (85%) in cells from CF individuals compared to cells from non-CF ones. Using the selective inhibitor of TRPV6 channel SOR-C27 and a siRNA strategy, our results revealed that TRPV6 was mostly involved in the increase of Ca(2+) influx. TRPV6 channel is negatively regulated by the PLC-PIP2 pathway. We measured the Ca(2+) influx in the presence of the non-specific PLC inhibitor, U73122, in non-CF human bronchial epithelial cells. Ca(2+) influx was increased by 33% with U73122 and this increase was largely reduced in the presence of SOR-C27. PLC inhibition in CF cells by U73122 had no effect on Ca(2+) influx. These results showed that PLC-PIP2 pathway is dysregulated in CF cells and leads to the increase of TRPV6 activity. The regulation of TRPV6 by PLC-PIP2 pathway implicates the specific PLC isoform, PLC-δ1. Immunoblot experiments revealed that expression of PLC-δ1 was decreased by 70% in CF cells. TRPV6 activity was normalized but not the level of expression of PLC-δ1 protein after F508del-CFTR rescue by low temperature for 48 h or treated for 24 h by 10 μM VX-809 in CF cells. This study revealed TRPV6 and PLC-δ1 as critical actor of Ca(2+) homeostasis in CF human bronchial epithelial cells.
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http://dx.doi.org/10.1016/j.ceca.2014.11.005DOI Listing
January 2015

Partial aortic valve replacement: a new and simple approach for endocarditis.

Ann Thorac Surg 2014 Oct;98(4):e101-2

Department of Cardiothoracic Surgery, University Hospital of Poitiers, Poitiers, France.

We describe the replacement of a single cusp in two patients with severe aortic regurgitation due to endocarditis with a one third stentless bioprosthesis, with excellent results in both.
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http://dx.doi.org/10.1016/j.athoracsur.2014.07.041DOI Listing
October 2014

Left ventricular outflow tract obstruction secondary to accessory mitral valve tissue: a multimodality imaging approach.

Eur Heart J 2014 Dec 4;35(48):3464. Epub 2014 Sep 4.

Service de Cardiologie, Centre Hospitalier de Poitiers, Poitiers, France.

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http://dx.doi.org/10.1093/eurheartj/ehu297DOI Listing
December 2014

Development of a preclinical model of donation after circulatory determination of death for translational application.

Transplant Res 2014 14;3:13. Epub 2014 Jun 14.

INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; GH Pitié-Salpêtrière, AP-HP, Service d'Urologie et de transplantation rénale, Paris F-75013, France ; UPMC Université Paris VI, Paris F-75013, France.

Background: Extracorporeal membranous oxygenation is proposed for abdominal organ procurement from donation after circulatory determination of death (DCD). In France, the national Agency of Biomedicine supervises the procurement of kidneys from DCD, specifying the durations of tolerated warm and cold ischemia. However, no study has determined the optimal conditions of this technique. The aim of this work was to develop a preclinical model of DCD using abdominal normothermic oxygenated recirculation (ANOR). In short, our objectives are to characterize the mechanisms involved during ANOR and its impact on abdominal organs.

Methods: We used Large White pigs weighing between 45 and 55 kg. After 30 minutes of potassium-induced cardiac arrest, the descending thoracic aorta was clamped and ANOR set up between the inferior vena cava and the abdominal aorta for 4 hours. Hemodynamic, respiratory and biochemical parameters were collected. Blood gasometry and biochemistry analysis were performed during the ANOR procedure.

Results: Six ANOR procedures were performed. The surgical procedure is described and intraoperative parameters and biological data are presented. Pump flow rates were between 2.5 and 3 l/min. Hemodynamic, respiratory, and biochemical objectives were achieved under reproducible conditions. Interestingly, animals remained hemodynamically stable following the targeted protocol. Arterial pH was controlled, and natremia and renal function remained stable 4 hours after the procedure was started. Decreased hemoglobin and serum proteins levels, concomitant with increased lactate dehydrogenase activity, were observed as a consequence of the surgery. The serum potassium level was increased, owing to the extracorporeal circulation circuit.

Conclusions: Our ANOR model is the closest to clinical conditions reported in the literature and will allow the study of the systemic and abdominal organ impact of this technique. The translational relevance of the pig will permit the determination of new biomarkers and protocols to improve DCD donor management.
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http://dx.doi.org/10.1186/2047-1440-3-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082279PMC
July 2014

Amniotic fluid-derived mesenchymal stem cells prevent fibrosis and preserve renal function in a preclinical porcine model of kidney transplantation.

Stem Cells Transl Med 2014 Jul 5;3(7):809-20. Epub 2014 May 5.

INSERM U1082, Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers, France; CHU de Poitiers, Poitiers, France; INSERM U935, Poitiers and Villejuif, France; INSERM U935, Esteam Pluripotent Stem Cell Core Facility and Ingestem Infrastructure, Université Paris Sud XI, Villejuif, France; INRA, UE1372 GenESI, Plateforme Ibisa, Surgères, France.

It is well known that ischemia/reperfusion injuries strongly affect the success of human organ transplantation. Development of interstitial fibrosis and tubular atrophy is the main deleterious phenomenon involved. Stem cells are a promising therapeutic tool already validated in various ischemic diseases. Amniotic fluid-derived mesenchymal stem cells (af-MSCs), a subpopulation of multipotent cells identified in amniotic fluid, are known to secrete growth factors and anti-inflammatory cytokines. In addition, these cells are easy to collect, present higher proliferation and self-renewal rates compared with other adult stem cells (ASCs), and are suitable for banking. Consequently, af-MSCs represent a promising source of stem cells for regenerative therapies in humans. To determine the efficiency and the safety of af-MSC infusion in a preclinical porcine model of renal autotransplantation, we injected autologous af-MSCs in the renal artery 6 days after transplantation. The af-MSC injection improved glomerular and tubular functions, leading to full renal function recovery and abrogated fibrosis development at 3 months. The strong proof of concept generated by this translational porcine model is a first step toward evaluation of af-MSC-based therapies in human kidney transplantation.
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http://dx.doi.org/10.5966/sctm.2013-0186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073821PMC
July 2014

Cystic fibrosis bronchial epithelial cells are lipointoxicated by membrane palmitate accumulation.

PLoS One 2014 19;9(2):e89044. Epub 2014 Feb 19.

Signalisation et Transports Ioniques Membranaires, ERL CNRS 7368, Université de Poitiers, Poitiers, France.

The F508del-CFTR mutation, responsible for Cystic Fibrosis (CF), leads to the retention of the protein in the endoplasmic reticulum (ER). The mistrafficking of this mutant form can be corrected by pharmacological chaperones, but these molecules showed limitations in clinical trials. We therefore hypothesized that important factors in CF patients may have not been considered in the in vitro assays. CF has also been associated with an altered lipid homeostasis, i. e. a decrease in polyunsaturated fatty acid levels in plasma and tissues. However, the precise fatty acyl content of membrane phospholipids from human CF bronchial epithelial cells had not been studied to date. Since the saturation level of phospholipids can modulate crucial membrane properties, with potential impacts on membrane protein folding/trafficking, we analyzed this parameter for freshly isolated bronchial epithelial cells from CF patients. Interestingly, we could show that Palmitate, a saturated fatty acid, accumulates within Phosphatidylcholine (PC) in CF freshly isolated cells, in a process that could result from hypoxia. The observed PC pattern can be recapitulated in the CFBE41o(-) cell line by incubation with 100 µM Palmitate. At this concentration, Palmitate induces an ER stress, impacts calcium homeostasis and leads to a decrease in the activity of the corrected F508del-CFTR. Overall, these data suggest that bronchial epithelial cells are lipointoxicated by hypoxia-related Palmitate accumulation in CF patients. We propose that this phenomenon could be an important bottleneck for F508del-CFTR trafficking correction by pharmacological agents in clinical trials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089044PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929646PMC
January 2015

ANO1 contributes to angiotensin-II-activated Ca2+-dependent Cl- current in human atrial fibroblasts.

J Mol Cell Cardiol 2014 Mar 9;68:12-9. Epub 2014 Jan 9.

ERL CNRS 7368, Université de Poitiers, 1 rue Georges Bonnet, 86022 Poitiers Cedex, France. Electronic address:

Cardiac fibroblasts are an integral part of the myocardial tissue and contribute to its remodelling. This study characterises for the first time the calcium-dependent chloride channels (CaCC) in the plasma membrane of primary human atrial cardiac fibroblasts by means of the iodide efflux and the patch clamp methods. The calcium ionophore A23187 and Angiotensin II (Ang II) activate a chloride conductance in cardiac fibroblasts that shares pharmacological similarities with calcium-dependent chloride channels. This chloride conductance is depressed by RNAi-mediated selective Anoctamine 1 (ANO1) but not by Anoctamine 2 (ANO2) which has been revealed as CaCC and is inhibited by the selective ANO1 inhibitor, T16inh-A01. The effect of Ang II on anion efflux is mediated through AT1 receptors (with an EC50 = 13.8 ± 1.3 nM). The decrease of anion efflux by calphostin C and bisindolylmaleimide I (BIM I) suggests that chloride conductance activation is dependent on PKC. We conclude that ANO1 contributes to CaCC current in human cardiac fibroblasts and that this is regulated by Ang II acting via the AT1 receptor pathway.
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http://dx.doi.org/10.1016/j.yjmcc.2013.12.027DOI Listing
March 2014

Abnormal origin of the right coronary artery in a patient with left ventricular non-compaction.

Eur J Cardiothorac Surg 2014 Sep 8;46(3):506. Epub 2014 Jan 8.

Department of Cardio-thoracic Surgery, University Hospital of Poitiers, Poitiers, France.

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http://dx.doi.org/10.1093/ejcts/ezt591DOI Listing
September 2014

Aortic root replacement in a patient with left ventricular noncompaction.

Ann Thorac Surg 2014 Jan;97(1):e1-3

Department of Cardiothoracic Surgery, University Hospital of Poitiers, Poitiers, France.

We describe the case of a 57-year-old woman with noncompaction of the left ventricle and regurgitant bicuspid aortic valve who presented with progressive congestive heart failure and was successfully treated with aortic root replacement. The long-term outcome for these patients is poor because of progressive left ventricular impairment, increased rates of life-threatening arrhythmias, and intraventricular thrombi. To our knowledge, only 3 patient with noncompaction of the left ventricle has been reported to have undergone aortic valve replacement for severely regurgitant bicuspid aortic valve. Herein, we describe a patient with noncompaction of the left ventricle who underwent successful mechanical aortic root replacement.
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http://dx.doi.org/10.1016/j.athoracsur.2013.08.017DOI Listing
January 2014

TachoSil to prevent postoperative pericardial adhesions.

Ann Thorac Surg 2014 Jan;97(1):378-9

Department of Cardiothoracic Surgery, University Hospital of Poitiers, 2 Rue de la Milétrie, 86021 Poitiers cedex, France.

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http://dx.doi.org/10.1016/j.athoracsur.2013.06.075DOI Listing
January 2014

Post-myocardial infarction ventricular septal defect.

J Card Surg 2013 Nov 17;28(6):721-2. Epub 2013 Oct 17.

Department of Cardio-Thoracic Surgery, University Hospital of Poitiers, Poitiers, France.

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http://dx.doi.org/10.1111/jocs.12228DOI Listing
November 2013

eComment. Prevention of sternal wound infection.

Interact Cardiovasc Thorac Surg 2013 Aug;17(2):382-3

Department of Cardio-Thoracic Surgery, University Hospital of Poitiers, Poitiers, France.

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http://dx.doi.org/10.1093/icvts/ivt275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715213PMC
August 2013

eComment. Pleiotropic effects of statins after cardiac surgery.

Interact Cardiovasc Thorac Surg 2013 Aug;17(2):352

Department of Cardio-Thoracic Surgery, University Hospital of Poitiers, Poitiers, France.

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http://dx.doi.org/10.1093/icvts/ivt235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3715205PMC
August 2013

Synthesis and biological evaluations of a monomethylauristatin E glucuronide prodrug for selective cancer chemotherapy.

Eur J Med Chem 2013 Sep 25;67:75-80. Epub 2013 Jun 25.

Université de Poitiers, UMR-CNRS 7285, Institut de Chimie des Milieux et des Matériaux de Poitiers (IC2MP), Groupe "Systèmes Moléculaires Programmés", 4 rue Michel Brunet, 86022 Poitiers, France.

We developed a glucuronide prodrug of the potent monomethylauristatin E (MMAE). This prodrug is significantly less toxic than the parent drug. However, in the presence of β-glucuronidase the prodrug leads to the efficient release of MMAE thereby triggering a subnanomolar cytotoxic activity against several cancer cell lines. Preliminary in vivo experiments conducted in C57BL/6 mice bearing a subcutaneous murine Lewis Lung Carcinoma (LLC) demonstrated the potential of this targeting system for the selective treatment of solid tumors.
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http://dx.doi.org/10.1016/j.ejmech.2013.06.037DOI Listing
September 2013

Bronchorelaxation of the human bronchi by CFTR activators.

Pulm Pharmacol Ther 2014 Feb 1;27(1):38-43. Epub 2013 Jul 1.

Institut de Physiologie et Biologie Cellulaires CNRS FRE3511, Université de Poitiers, Poitiers, France. Electronic address:

The airway functions are profoundly affected in many diseases including asthma, COPD and cystic fibrosis (CF). CF the most common lethal autosomal recessive genetic disease is caused by mutations of the CFTR (Cystic Fibrosis transmembrane Conductance Regulator) gene, which normally encodes a multifunctional and integral membrane cAMP regulated and ATP gated Cl(-) channel expressed in airway epithelial cells. Using human lung tissues obtained from patients undergoing surgery for lung cancer, we demonstrated that CFTR participates in bronchorelaxation. Using human bronchial smooth muscle cells (HBSMC), we applied iodide influx assay to analyze the CFTR-dependent ionic transport and immunofluorescence technique to localize CFTR proteins. Moreover, the relaxation was studied in isolated human bronchial segments after pre-contraction with carbachol to determine the implication of CFTR in bronchodilation. We found in HBSMC that the pharmacology and regulation of CFTR is similar to that of its epithelial counterpart both for activation (using forskolin/genistein or a benzo[c]quinolizinium derivative) and for inhibition (CFTR(inh)-172 and GPinh5a). With human bronchial rings, we observed that whatever the compound used including salbutamol, the activation of muscular CFTR leads to a bronchodilation after constriction with carbachol. Altogether, these observations revealed that CFTR in the human airways is expressed in bronchial smooth muscle cells and can be pharmacologically manipulated leading to the hypothesis that this ionic channel could contribute to bronchodilation in human.
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http://dx.doi.org/10.1016/j.pupt.2013.06.008DOI Listing
February 2014

eComment. Multiple approaches for sternal dehiscence.

Interact Cardiovasc Thorac Surg 2013 Jun;16(6):723-4

Department of Cardio-Thoracic Surgery, University Hospital of Poitiers, Poitiers, France.

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http://dx.doi.org/10.1093/icvts/ivt139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653497PMC
June 2013

Late postcardiotomy sternal dehiscence: a simple approach using Stratos® system.

J Card Surg 2013 Nov 9;28(6):632-4. Epub 2013 May 9.

Department of Cardio-thoracic Surgery, University Hospital of Poitiers, Poitiers, France.

Management of late sternal dehiscence is challenging and time consuming. Although numerous techniques exist including rewiring and titanium plates screwing to stabilize the sternum, we describe an alternative technique by using four titanium clips and one connecting bar.
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http://dx.doi.org/10.1111/jocs.12123DOI Listing
November 2013
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