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Background The electro-hydraulically actuated Carmat total artificial heart (C-TAH) is designed to replace the heart in patients with end-stage heart failure, either as bridge to transplant or destination therapy. It provides pulsatile flow and contains bio-prosthetic blood contacting materials. A clinical feasibility study was conducted to evaluate the C-TAH safety and performance. Methods Hospitalized patients, at imminent risk of death from irreversible biventricular failure despite optimal medical management, and not eligible for transplant or eligible but on extracorporeal life support, were enrolled. The primary endpoint was 30-days survival. Results Four patients were implanted with the C-TAH, three as destination therapy (ages 76, 68, 74) and one as bridge to transplant (age 58). They had implant times of 74, 270, 254 and 20 days respectively. All patients were free from hemolysis, clinical neurologic events, clinical evidence of thrombus and device-related infections. Hemodynamic and physical recovery allowed two patients to be discharged home for a cumulative duration of 7 months. The anticoagulation management strategy comprised initial unfractionated heparin, from postoperative day 2, followed by low molecular weight heparin and aspirin. An increased D-dimer level was observed in all patients during months 1 to 4. Temporary suspension of heparin anticoagulation resulted in thrombocytopenia and increased fibrin monomer, reversed by resuming anticoagulation with heparin. Causes of death were device-related (2 cases), respiratory failure and multi-organ failure. Conclusions Preliminary clinical results with the C-TAH demonstrated good safety and performance profiles in patients suffering from biventricular failure, which need to be confirmed in a pivotal study. [ABSTRACT FROM AUTHOR]

Background: The development of artificial hearts in patients with end-stage heart disease have been confronted with the major issues of thromboembolism or haemorrhage. Since valvular bioprostheses are associated with a low incidence of these complications, we decided to use bioprosthetic materials in the construction of a novel artificial heart (C-TAH). We report here the device characteristics and its first clinical applications in two patients with end-stage dilated cardiomyopathy. The aim of the study was to evaluate safety and feasibility of the CARMAT TAH for patients at imminent risk of death from biventricular heart failure and not eligible for transplant.Methods: The C-TAH is an implantable electro-hydraulically actuated pulsatile biventricular pump. All components, batteries excepted, are embodied in a single device positioned in the pericardial sac after excision of the native ventricles. We selected patients admitted to hospital who were at imminent risk of death, having irreversible biventricular failure, and not eligible for heart transplantation, from three cardiac surgery centres in France.Findings: The C-TAH was implanted in two male patients. Patient 1, aged 76 years, had the C-TAH implantation on Dec 18, 2013; patient 2, aged 68 years, had the implantation on Aug 5, 2014. The cardiopulmonary bypass times for C-TAH implantation were 170 min for patient 1 and 157 min for patient 2. Both patients were extubated within the first 12 postoperative hours and had a rapid recovery of their respiratory and circulatory functions as well as a normal mental status. Patient 1 presented with a tamponade on day 23 requiring re-intervention. Postoperative bleeding disorders prompted anticoagulant discontinuation. The C-TAH functioned well with a cardiac output of 4·8-5·8 L/min. On day 74, the patient died due to a device failure. Autopsy did not detect any relevant thrombus formation within the bioprosthesis nor the different organs, despite a 50-day anticoagulant-free period. Patient 2 experienced a transient period of renal failure and a pericardial effusion requiring drainage, but otherwise uneventful postoperative course. He was discharged from the hospital on day 150 after surgery with a wearable system without technical assistance. After 4 months at home, the patient suffered low cardiac output. A change of C-TAH was attempted but the patient died of multiorgan failure.Interpretation: This preliminary experience could represent an important contribution to the development of total artificial hearts using bioprosthetic materials.Funding: CARMAT SA. [ABSTRACT FROM AUTHOR]

Purpose: Recently, dietary supplementation with inorganic nitrate (NO3-) has been proposed to endurance athletes to increase their performance. However, it has been suggested that an excess of NO3- might be harmful. The present study analyzed the effect of NO3- supplementation on kidney function. Methods: Thirteen young male subjects performed a 20-min cycling exercise at 85% of the maximal oxygen capacity. Seven days before exercise, the subjects ingested either a placebo (PI) or 450 mg of potassium nitrate (PN) per day. Venous blood samples and urine collections were collected before and immediately after exercise and after 60 min of recovery. Glomerular filtration rates (GFR) and clearances (Cl) were calculated from serum content and urine output for creatinine (Cm), albumin (Alb), and urea. Results: Under resting conditions, GFR and all clearance measures did not differ between PI and PN. Immediately after exercise, GFR remained stable in both PI and PN, whereas Cl-urea decreased significantly (P < 0.05) in PI (-44%) and PN (-49%). Alb urine outputs were enhanced by 18- to 20-fold in PI and PN, respectively (P < 0.05). After the recovery period, GFR remained enhanced under PI conditions, whereas Cl-urea returned to initial values in placebo and nitrate supplementation. Alb output and Cl-Alb remained enhanced under PN conditions. Conclusion: These results mainly indicate that dietary nitrate supplementation over a week does not induce any specific kidney function modifications either at rest or during sustained submaximal exercise as compared with PL [ABSTRACT FROM AUTHOR]

β-Alanine (BA) supplementation has become an ergogenic aid amongst competitive athletes to augment intramuscular carnosine content, leading to higher buffer capacity and exercise performance. We investigated 27 regularly trained young males and females who were randomly allocated either to placebo (PL) or BA ingestion for 8 weeks. Every single day, BA or PL (4.0-5.6 g day) supplements were ingested by participants and associated with a strong plyometric high-intensity training (two sessions per week during the 8 weeks). Before and after training, maximal jump heights were recorded during squat jump (SJ) and countermovement jump (CMJ) and an index of fatigue was recorded as a mean height of 45 consecutive CMJ. Blood lactate was measured at rest, after completing the fatigue test and every 5 min thereafter up to 30 min recovery. After plyometric training, SJ and CMJ were increased, respectively, by 8.8 and 6.4 % in PL group and 9.9 and 11.0 % in BA group ( p < 0.01, no difference between groups). Blood lactate reached a maximal value of 9.4 ± 1.6 mmol l in PL group, and 10.3 ± 1.3 mmol l in BA group, with a slight better performance in the fatigue test (+8.6 %, p ≤ 0.01) for BA group as compared to PL group. To conclude, 2-month β-alanine supplementation resulted in a slight improvement of explosive force after 45 maximal consecutive jumps in young athletes. However, the practical adequacy of supplementation remains questionable in an active and healthy population. [ABSTRACT FROM AUTHOR]

This paper proposes an ex ante evaluation of the willingness to adopt agro-ecological innovations aimed at reducing pesticide use for banana production in the French West Indies. Four innovative systems, including intercropping, improved fallow and new pest-tolerant varieties, are proposed to a sample of 607 planters, with innovation and policy attributes calibrated from a bio-economic farm model. The model interacts technological and economic innovation attributes with farmer individual factors, and allows for a dual source of unobserved heterogeneity. We estimate a system of random coefficient Logit models, to obtain marginal values of innovation traits that can be useful for targeting farm types with appropriate innovations and designing policies for securing agricultural revenue. [Copyright &y& Elsevier]

This study examines the effect of a change in fascicle length on motor unit recruitment and discharge rate in the human tibialis anterior during shortening and lengthening contractions that involved a similar change in torque. The dorsiflexor torque and the surface and intramuscular electromyograms (EMGs) from the tibialis anterior were recorded in eight subjects. The behaviour of the same motor unit ( n= 63) was compared during submaximal shortening and lengthening contractions performed at a constant velocity (10 deg s−1) with the dorsiflexor muscles over a 20 deg range of motion around the ankle neutral position. Muscle fascicle length was measured non-invasively using ultrasonography. Motor units that were active during a shortening contraction were always active during the subsequent lengthening contraction. Furthermore, additional motor units ( n= 18) of higher force threshold that were recruited during the shortening contraction to maintain the required torque were derecruited first during the following lengthening contraction. Although the change in fascicle length was linear ( r2 > 0.99), and similar for both shortening and lengthening contractions, modulation of discharge rate differed during the two contractions. Compared with an initial isometric contraction at short (11.9 ± 2.4 Hz) or long (11.7 ± 2.2 Hz) muscle length, discharge rate increased only slightly and stayed nearly constant throughout the lengthening contraction (12.6 ± 2.0 Hz; P < 0.05) whereas it augmented progressively and more substantially during the shortening contraction, reaching 14.5 ± 2.5 Hz ( P < 0.001) at the end of the movement. In conclusion, these observations indicate a clear difference in motor unit discharge rate modulation with no change in their recruitment order between shortening and lengthening contractions when performed with a similar change in muscle fascicle length and torque. [ABSTRACT FROM AUTHOR]

Objective: Although high intensity physical activities may represent a great proportion of the total energy expenditure in active people, only sparse studies have investigated the accuracy of wearable monitors to assess activity related energy expenditure (AEE) during high intensity exercises. Therefore, the purpose of the present study was to investigate the accuracy of the Actiheart, a light portable monitor estimating AEE based on heart rate (HR) and activity counts (ACT), during two popular activities (running and cycling) performed at high intensities. The benefit of an individual calibration of the HR-AEE relationship established during a preliminary maximal test was also evaluated. Methods: AEE was estimated in eighteen active adults (4 women and 14 men; 25 ± 4 yr) with indirect calorimetry using a respiratory gas analysis system (reference method) and the Actiheart during 5-min running and cycling at 60, 75 and 85% of maximal oxygen uptake (VO2max) previously determined during a maximal test performed on a treadmill or cycle ergometer. For the Actiheart, AEE was estimated either using the group or individual calibrated equations available in the dedicated software, and their respective HR, ACT or combined HR/ACT algorithms. Results: When the HR algorithm was used for cycling and the HR or HR/ACT algorithms for running, AEE measured by the Actiheart increased proportionally to exercise intensity from 60 to 85% VO2max (P<0.001). Compared to indirect calorimetry, the Actiheart group calibrated equations slightly to moderately underestimated (3 to 20%) AEE for the three exercise intensities (P<0.001). Accuracy of AEE estimation was greatly improved by individual calibration of the HR-AEE relationship (underestimation below 5% and intraclass correlation coefficient [ICC]: 0.79–0.93) compared to group calibration (ICC: 0.64–0.79). Conclusion: The Actiheart enables to assess AEE during high intensity running and cycling when the appropriate algorithm is applied. Since an underestimation was present for group calibration, an individual and sport-specific calibration should be performed when a high accuracy is required. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the efficacy of a new strength training method on strength gain, hypertrophy, and neuromuscular fatigability.Methods: The training exercise consisted of elbow flexion against a load of ~ 70% of one repetition maximal (1RM). A new method (3/7 method) consisting of five sets of an increasing number of repetitions (3 to 7) during successive sets and brief inter-set intervals (15 s) was repeated two times after 150 s of recovery and compared to a method consisting of eight sets of six repetitions with an inter-set interval of 150 s (8 × 6 method). Subjects trained two times per week during 12 weeks. Strength gain [1RM load and maximal isometric voluntary contraction (MVC)], EMG activity of biceps brachii and brachioradialis, as well as biceps' brachii thickness were measured. Change in neuromuscular fatigability was assessed as the maximal number of repetitions performed at 70% of 1RM before and after training.Results: Both 3/7 and 8 × 6 methods increased 1RM load (22.2 ± 7.4 and 12.1 ± 6.6%, respectively; p < 0.05) and MVC force (15.7 ± 8.2 and 9.5 ± 9.5%; p < 0.05) with a greater 1RM gain (p < 0.05) for the 3/7 method. Normalized (%Mmax) EMG activity of elbow flexors increased (p < 0.05) similarly (14.5 ± 23.2 vs. 8.1 ± 20.5%; p > 0.05) after both methods but biceps' brachii thickness increased to a greater extent (9.6 ± 3.6 vs. 5.5 ± 3.7%; p < 0.05) for the 3/7 method. Despite subjects performing more repetitions with the same absolute load after training, neuromuscular fatigability increased (p < 0.05) after the two training methods.Conclusion: The 3/7 method provides a better stimulus for strength gain and muscle hypertrophy than the 8 × 6 method. [ABSTRACT FROM AUTHOR]

Presents a study that investigated whether computer-assisted surgical instruments could minimize the difficulties experienced in heart operations which use long instruments that must go through small orifices or ports. The advantages of the a system developed by Intuitive Surgical Inc.; Study findings; Conclusions.

Discusses a study of the role of HLA-G molecules in graft rejection and acceptance among heart transplant patients. HLA-Gs protection of the fetus from maternal rejection by natural-killer cells; Assessment of HLA-G expression in endomyocardial biopsies; Support for the hypothesis that HLA-G may be activated during transplantation.

The Aeson® total artificial heart (A-TAH) has been developed as a total heart replacement for patients at risk of death from biventricular failure. We previously described endothelialization of the hybrid membrane inside A-TAH probably at the origin of acquired hemocompatibility. We aimed to quantify vasculogenic stem cells in peripheral blood of patients with long-term A-TAH implantation. Four male adult patients were included in this study. Peripheral blood mononuclear cells were collected before A-TAH implantation (T0) and after implantation at one month (T1), between two and five months (T2), and then between six and twelve months (T3). Supervised analysis of flow cytometry data confirmed the presence of the previously identified Lin−CD133+CD45− and Lin−CD34+ with different CD45 level intensities. Lin−CD133+CD45−, Lin−CD34+CD45− and Lin−CD34+CD45+ were not modulated after A-TAH implantation. However, we demonstrated a significant mobilization of Lin−CD34+CD45dim (p = 0.01) one month after A-TAH implantation regardless of the expression of CD133 or c-Kit. We then visualized data for the resulting clusters on a uniform manifold approximation and projection (UMAP) plot showing all single cells of the live Lin− and CD34+ events selected from down sampled files concatenated at T0 and T1. The three clusters upregulated at T1 are CD45dim clusters, confirming our results. In conclusion, using a flow cytometry approach, we demonstrated in A-TAH-transplanted patients a significant mobilization of Lin−CD34+CD45dim in peripheral blood one month after A-TAH implantation. Using a flow cytometry approach, we demonstrated in A-TAH transplanted patients a significant mobilization of Lin−CD34+CD45dim in peripheral blood one month after A-TAH implantation. This cell population could be at the origin of newly formed endothelial cells on top of hybrid membrane in Carmat bioprosthetic total artificial heart. [ABSTRACT FROM AUTHOR]

Choosing the optimal aortic valve prosthesis for middle-aged patients (late 40s to early 60s) with aortic stenosis presents a challenge. The available options all have substantial drawbacks that must be considered in the decision-making process. Current data indicate that there is little or no difference in survival between mechanical and bioprosthetic aortic valve replacement in middle-aged patients at 10-15 years after surgery. Patients who receive a mechanical valve replacement have an annual risk of major hemorrhagic or embolic events of 2-4% per year for life compared with about 1% per year for patients who have a bioprosthetic valve. However, bioprostheses are associated with an increasing risk of structural valve degeneration from 10 years postimplantation, and most patients will require reoperation if they survive much longer than a decade. The mortality risk associated with reoperation is similar to that of primary surgery for most patients, and does not seem to impact on the 15-year survival in this patient group. The Ross procedure, in which the aortic valve is replaced with a pulmonary autograft, can provide improved freedom from morbidity, but operative mortality is probably double that of isolated aortic valve replacement and most patients will require reoperation. Informed patient choice is the most important factor in deciding which valve to use, with biological valves increasingly favored over mechanical valves in middle-aged patients. [ABSTRACT FROM AUTHOR]

Given the negative environmental effects of conventional agricultural techniques, the need for biodiversity-friendly agriculture systems that rely more on ecosystem services and less on chemical inputs is becoming increasingly urgent. In this paper, we focus on crop protection strategies that are alternatives to the use of pesticides. Diversification of the plant component of agricultural areas at different space and time scales has been presented as a powerful socio-economic and agro-ecological mechanism for the sustainable control of pests. Our interdisciplinary group of scientific experts examined the literature on the ecological effects of plant diversification on pests and their natural enemies, as well as the social science literature on the conditions for farmers to adopt the corresponding practices, to assess the potential offered by plant diversification. We developed a conceptual framework that connects the agro-ecological and socio-economic components of an agricultural landscape in a dynamic loop accounting for interactions among elements at different spatial and temporal scales and their feedback effects. This article presents this framework and illustrates its application to the case of wheat production and protection. By explicitly connecting each level of agro-ecological organization with the potential socio-economic drivers and limitations underpinning the adoption and implementation of plant diversification in landscapes, this framework makes it possible to analyse the synergies and antagonisms between different modes of diversification and the conditions of their deployment. Exploring this framework is a prerequisite to the identification of opportunities and key feed-back loops for designing diversification strategies that unlock the agro-ecological potential of future production systems. We conclude that there is a need for interdisciplinary research in experimental landscapes involving farmers and other local stakeholders to design sustainable future agricultural landscapes that deliver high levels of biological control services. [ABSTRACT FROM AUTHOR]

Estimates of abundance and survivorship provide quantifiable measures to monitor populations and to define and understand their conservation status. This study investigated changes in abundance and survival rates of fin whales (Balaenoptera physalus) in the northern Gulf of St. Lawrence in the context of anthropogenic pressures and changing environmental conditions. A long‐term data set, consisting of 35 years of photo‐identification surveys and comprising more than 5,000 identifications of 507 individuals, formed the basis of this mark–recapture study. Based on model selection using corrected Akaike Information Criterion, the most parsimonious Cormack–Jolly–Seber model included a linear temporal trend in noncalf apparent survival rates with a sharp decline in the last 5 years of the study and a median survival rate of 0.946 (95% confidence interval (CI) 0.910–0.967). To account for capture heterogeneity due to divergent patterns of site fidelity, agglomerative hierarchical cluster analysis was employed to categorize individuals based on their annual and survey site fidelity indices. However, the negative trend in survivorship remained and was corroborated by a significant decline in the estimated super‐population size from 335 (95% CI 321–348) individuals in 2004–2010 to 291 (95% CI 270–312) individuals in 2010–2016. Concurrently, a negative trend was estimated in recruitment to the population, supported by a sharp decrease in the number of observed calves. Ship strikes and changes in prey availability are potential drivers of the observed decline in fin whale abundance. The combination of clustering methods with mark–recapture represents a flexible way to investigate the effects of site fidelity on demographic variables and is broadly applicable to other individual‐based studies. [ABSTRACT FROM AUTHOR]

The article discusses the importance of implementing an effective strategy for addressing rheumatic heart disease scourge and to access life-saving cardiac surgery in developing the world. Topics discussed include requirement of treating and preventing rheumatic heart disease (RHD), the impact of the human immunodeficiency virus, and requirement of creating an international working group.

OBJECTIVES: Surgical mortality and long-term outcomes are important considerations when determining strategies for multiple reoperations on the aortic valve (AV). With the rise of percutaneous valve-in-valve, we sought to evaluate the current outcomes of conventional surgery for AV reoperation, focusing first on the effect of the number of previous AV interventions with a subsequent analysis of the risk factors for adverse outcomes. METHODS: From January 2007 to December 2016, 316 consecutive patients underwent an open redo operation (replacement) on their AV at a single centre. It was the first AV reintervention in 263 patients (Group 1), second in 42 patients (Group 2) and third or more in 11 patients (Group 3). RESULTS: There were 230 men and 86 women, with a median age of 58 (Q1-Q3: 46-70) years. Structural valve deterioration (SVD) of the bioprosthesis (n = 136, 44%), endocarditis (n = 57, 18%) and prosthetic valve dehiscence (n = 41, 13%) were the most common reasons for reintervention. Overall, in-hospital mortality was 7.3%: 7.2% in Group 1, 4.76% in Group 2 and 18.2% in Group 3 (P = 0.233) and ranged from 3.7% for SVD to 14.0% when endocarditis was the reason for reintervention. Higher preoperative New York Heart Association (NYHA) class (III/IV) [odds ratio (OR) 15.9, P = 0.011], injury during re-entry (OR 16.9, P = 0.015), endocarditis (OR 3.7, P = 0.038) and concomitant mitral valve replacement (OR 5.6, P = 0.006) were independent risk factors for in-hospital mortality. Survival at 8 years was 79.0 ± 3.0% for the entire cohort and 88.4 ± 3.2% for re-replacement after SVD. CONCLUSIONS: Multiple AV reoperations carry an acceptable risk of early postoperative mortality, particularly for isolated valve replacements of SVD. [ABSTRACT FROM AUTHOR]

Background: After myocardial infarction (MI), mitral valve (MV) tethering stimulates adaptive leaflet growth, but counterproductive leaflet thickening and fibrosis augment mitral regurgitation (MR), doubling heart failure and mortality. MV fibrosis post-MI is associated with excessive endothelial-to-mesenchymal transition (EMT), driven by transforming growth factor (TGF)-β overexpression. In vitro, losartan-mediated TGF-β inhibition reduces EMT of MV endothelial cells.Objectives: This study tested the hypothesis that profibrotic MV changes post-MI are therapeutically accessible, specifically by losartan-mediated TGF-β inhibition.Methods: The study assessed 17 sheep, including 6 sham-operated control animals and 11 with apical MI and papillary muscle retraction short of producing MR; 6 of the 11 were treated with daily losartan, and 5 were untreated, with flexible epicardial mesh comparably limiting left ventricular (LV) remodeling. LV volumes, tethering, and MV area were quantified by using three-dimensional echocardiography at baseline and at 60 ± 6 days, and excised leaflets were analyzed by histopathology and flow cytometry.Results: Post-MI LV dilation and tethering were comparable in the losartan-treated and untreated LV constraint sheep. Telemetered sensors (n = 6) showed no significant losartan-induced changes in arterial pressure. Losartan strongly reduced leaflet thickness (0.9 ± 0.2 mm vs. 1.6 ± 0.2 mm; p < 0.05; 0.4 ± 0.1 mm sham animals), TGF-β, and downstream phosphorylated extracellular-signal-regulated kinase and EMT (27.2 ± 12.0% vs. 51.6 ± 11.7% α-smooth muscle actin-positive endothelial cells, p < 0.05; 7.2 ± 3.5% sham animals), cellular proliferation, collagen deposition, endothelial cell activation (vascular cell adhesion molecule-1 expression), neovascularization, and cells positive for cluster of differentiation (CD) 45, a hematopoietic marker associated with post-MI valve fibrosis. Leaflet area increased comparably (17%) in constrained and losartan-treated sheep.Conclusions: Profibrotic changes of tethered MV leaflets post-MI can be modulated by losartan without eliminating adaptive growth. Understanding the cellular and molecular mechanisms could provide new opportunities to reduce ischemic MR. [ABSTRACT FROM AUTHOR]

This study investigated the effect of protein supplementation enriched in leucine on muscle hypertrophy and strength gain in response to a 6-month strength training programme of the plantar flexor muscles in older adults (aged over 60 yr). To this end, changes in neuromuscular parameters were compared between two groups (matched for age, sex and initial maximal strength) that trained twice a week for 24 weeks, with one group receiving a protein supplementation enriched with leucine (supplementation group, n = 12), and another group receiving a placebo (control group, n = 13) that provided subjects with a similar energy intake that the protein supplementation. Muscle thickness and pennation angle of gastrocnemius medialis were used as indices of muscle hypertrophy. Maximal strength and associated electromyographic activity of leg muscles, and voluntary activation (assessed by the interpolated twitch technique) were recorded. Peak torque in response to 3-pulse train delivered to the tibial nerve was also recorded. After training, muscle thickness (+ 8.4%) and pennation angle (+ 13.4%) were increased, regardless of training groups (p < 0.05). Maximal plantar flexion strength (+ 28.2%) and voluntary activation (+ 29.5%) increased to the same extent for both training groups. Peak torque evoked by 3-pulse train increased similarly between training groups (+ 13.4%, p < 0.001). Regardless of protein supplementation, results obtained in twelve subjects indicate that muscle hypertrophy mainly occurred in the last 12 weeks of the programme. Our results suggest that protein supplementation enriched in leucine neither potentiated the neuromuscular adaptations to strength training, nor influenced the time course of these adaptations in older adults. [ABSTRACT FROM AUTHOR]

Background: In patients with myocardial infarction (MI), leaflet tethering by displaced papillary muscles induces mitral regurgitation (MR), which doubles mortality. Mitral valves (MVs) are larger in such patients but fibrosis sets in counterproductively. The investigators previously reported that experimental tethering alone increases mitral valve area in association with endothelial-to-mesenchymal transition.Objectives: The aim of this study was to explore the clinically relevant situation of tethering and MI, testing the hypothesis that ischemic milieu modifies mitral valve adaptation.Methods: Twenty-three adult sheep were examined. Under cardiopulmonary bypass, the papillary muscle tips in 6 sheep were retracted apically to replicate tethering, short of producing MR (tethered alone). Papillary muscle retraction was combined with apical MI created by coronary ligation in another 6 sheep (tethered plus MI), and left ventricular remodeling was limited by external constraint in 5 additional sheep (left ventricular constraint). Six sham-operated sheep were control subjects. Diastolic mitral valve surface area was quantified by 3-dimensional echocardiography at baseline and after 58 ± 5 days, followed by histopathology and flow cytometry of excised leaflets.Results: Tethered plus MI leaflets were markedly thicker than tethered-alone valves and sham control subjects. Leaflet area also increased significantly. Endothelial-to-mesenchymal transition, detected as α-smooth muscle actin-positive endothelial cells, significantly exceeded that in tethered-alone and control valves. Transforming growth factor-β, matrix metalloproteinase expression, and cellular proliferation were markedly increased. Uniquely, tethering plus MI showed endothelial activation with vascular adhesion molecule expression, neovascularization, and cells positive for CD45, considered a hematopoietic cell marker. Tethered plus MI findings were comparable with external ventricular constraint.Conclusions: MI altered leaflet adaptation, including a profibrotic increase in valvular cell activation, CD45-positive cells, and matrix turnover. Understanding cellular and molecular mechanisms underlying leaflet adaptation and fibrosis could yield new therapeutic opportunities for reducing ischemic MR. [ABSTRACT FROM AUTHOR]

Mitral valve disease is a frequent cause of heart failure and death. Emerging evidence indicates that the mitral valve is not a passive structure, but--even in adult life--remains dynamic and accessible for treatment. This concept motivates efforts to reduce the clinical progression of mitral valve disease through early detection and modification of underlying mechanisms. Discoveries of genetic mutations causing mitral valve elongation and prolapse have revealed that growth factor signalling and cell migration pathways are regulated by structural molecules in ways that can be modified to limit progression from developmental defects to valve degeneration with clinical complications. Mitral valve enlargement can determine left ventricular outflow tract obstruction in hypertrophic cardiomyopathy, and might be stimulated by potentially modifiable biological valvular-ventricular interactions. Mitral valve plasticity also allows adaptive growth in response to ventricular remodelling. However, adverse cellular and mechanobiological processes create relative leaflet deficiency in the ischaemic setting, leading to mitral regurgitation with increased heart failure and mortality. Our approach, which bridges clinicians and basic scientists, enables the correlation of observed disease with cellular and molecular mechanisms, leading to the discovery of new opportunities for improving the natural history of mitral valve disease. [ABSTRACT FROM AUTHOR]

Key points There is a long-standing concern that creatine supplementation could be associated with cancer, possibly by facilitating the formation of carcinogenic heterocyclic amines (HCAs)., This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, does not cause a significant increase in HCA formation., HCAs detection was unrelated to creatine supplementation. Diet was likely to be the main factor responsible for HCAs formation after either placebo ( n = 6) or creatine supplementation ( n = 3)., These results directly challenge the recently suggested biological plausibility for the association between creatine use and risk of testicular germ cell cancer., Abstract Creatine supplementation has been associated with increased cancer risk. In fact, there is evidence indicating that creatine and/or creatinine are important precursors of carcinogenic heterocyclic amines (HCAs). The present study aimed to investigate the acute and chronic effects of low- and high-dose creatine supplementation on the production of HCAs in healthy humans (i.e. 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline (8-MeIQx), 2-amino-(1,6-dimethylfuro[3,2-e]imidazo[4,5-b])pyridine (IFP) and 2-amino-3,4,8-trimethylimidazo[4,5- f]quinoxaline (4,8-DiMeIQx)). This was a non-counterbalanced single-blind crossover study divided into two phases, in which low- and high-dose creatine protocols were tested. After acute (1 day) and chronic supplementation (30 days), the HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx were assessed through a newly developed HPLC-MS/MS method. Dietary HCA intake and blood and urinary creatinine were also evaluated. Out of 576 assessments performed (from 149 urine samples), only nine (3 from creatine and 6 from placebo) showed quantifiable levels of HCAs (8-MeIQx: n = 3; 4,8-DiMeIQx: n = 2; PhIP: n = 4). Individual analyses revealed that diet rather than creatine supplementation was the main responsible factor for HCA formation in these cases. This study provides compelling evidence that both low and high doses of creatine supplementation, given either acutely or chronically, did not cause increases in the carcinogenic HCAs PhIP, 8-MeIQx, IFP and 4,8-DiMeIQx in healthy subjects. These findings challenge the long-existing notion that creatine supplementation could potentially increase the risk of cancer by stimulating the formation of these mutagens. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular research is the main shaper of clinical evidence underpinning decision making, with its cyclic progression of junior researchers to mature faculty members. Despite efforts at improving cardiovascular research training, several unmet needs persist. We aimed to appraise current perceptions on cardiovascular research training with an international survey. Methods and Results: We administered a 20-closed-question survey to mentors and mentees belonging to different international institutions. A total of 247 (12%) surveys were available (out of 2,000 invitations). Overall, mentees and mentors were reasonably satisfied with the educational and research resources. Significant differences were found analyzing results according to gender, geographic area, training and full-time researcher status. Specifically, women proved significantly less satisfied than men, disclosed access to fewer resources and less support from mentors (all P<0.05). People working in institutions not located in North America or Northern/Central Europe were significantly less satisfied and disclosed much less support (both P<0.05). Those in training reported limited opportunities for collaboration (P = 0.009), and non-full-time researchers disclosed more limited access to tutors and formal grant writing training (both P<0.05). Conclusions: Several potential biases appear to be present in the way training in cardiovascular research is provided worldwide, including one against women. If confirmed, these data require proactive measures to decrease discriminations and improve the cardiovascular research training quality. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The Carmat bioprosthetic total artificial heart (TAH) contains bioprosthetic blood-contacting surfaces, and is designed for orthotopic cardiac replacement. In preparation for clinical studies, we evaluated the TAH performance and its effects on end-organ function in an animal model. METHODS: Twelve female Charolais calves, 2-3 months of age and weighing 102-122 kg, were implanted with the TAH through a midsternotomy to ensure an adequate anatomic fit. The intended support duration was 4-10 days. Haematological values, creatinine, bilirubin and lactate levels were measured and mean arterial and central venous pressure, central venous oxygen saturation and TAH parameters were monitored. RESULTS: The calves were placed in a cage immediately postoperatively, and extubated on postoperative day 1 in most cases. Average support duration was 3 days, with 4 of 12 calves supported for 4, 4, 8 and 10 days. The initial procedures were used to refine surgical techniques and postoperative care. Pump output ranged from 7.3 to 10 l/min. Haemodynamic parameters and blood analysis were within acceptable ranges. No device failures occurred. No anticoagulation was used in the postoperative phase. The calves were euthanized in case of discomfort compromising the animal well-being, such as respiratory dysfunction, severe blood loss and cerebral dysfunction. Device explant analysis showed no thrombus formation inside the blood cavities. Histological examination of kidneys showed isolated micro-infarction in 2/12 animals; brain histology revealed no thromboembolic depositions. CONCLUSION: The Carmat bioprosthetic TAH implanted in calves up to 10 days provided adequate blood flow to organs and tissues. Low levels of haemolysis and no visible evidence of thromboembolic depositions in major organs and device cavities, without the use of anticoagulation, may indicate early-phase haemocompatibility of the TAH. [ABSTRACT FROM AUTHOR]

Objective Glomerular filtration rate (GFR) is part of routine medical practice for clinical assessment of kidney function in health and disease conditions, and is determined by measuring the clearance of creatinine (Cl-Crn) or estimated (eGFR) from equations using serum creatinine (Crn) or cystatin C (Cyst C). Crn and Cyst C methods obviate the need for urine collection but their reliability under non-resting conditions is uncertain. This study compared GFR determined by Cl-Crn, Crn and Cyst C methods under the conditions of rest and after exercise. Methods Twelve young male subjects performed a 30 min treadmill exercise at 80% of the maximal oxygen capacity. Venous blood samples and urine collections were collected before and after exercise and after recovery period. GFR rates were calculated from serum Crn and Cyst C equations, and Cl-Crn measured from serum and urine Crn output. Albumin was also determined for all samples. Results Under resting conditions, eGFR from Crn and Cyst C did not differ from Cl-Crn (p=0.39). Immediately after exercise, GFR decreased significantly, regardless of the method, but more so for Cl-Crn (-30.0%; p<0.05) compared with Crn (-18.2%) and Cyst C (-19.8%). After the recovery period, GFR determined by Cl-Crn was returned to initial values whereas Crn and Cyst C remained reduced. Although eGFR methods accurately estimate GFR at rest, those methods underestimated the change in GFR after acute exercise. Conclusions These results indicate that exercise-induced changes in GFR should be determined by Cl-Crn method. [ABSTRACT FROM AUTHOR]

OBJECTIVES Ventricular constraint devices made of polyester and nitinol have been used to treat heart failure patients. Long-term follow-up has not demonstrated significant benefits, probably due to the lack of effects on myocardial tissue and to the risk of diastolic dysfunction. The goal of this experimental study is to improve ventricular constraint therapy by associating stem cell intrainfarct implantation and a cell-seeded collagen scaffold as an interface between the constraint device and the epicardium. METHODS In a sheep ischaemic model, three study groups were created: Group 1: coronary occlusion without treatment (control group). Group 2: postinfarct ventricular constraint using a polyester device (Acorn CorCap). Group 3: postinfarct treatment with stem cells associated with collagen matrix and the polyester device. Autologous adipose mesenchymal stem cells cultured in hypoxic conditions were injected into the infarct and seeded into the collagen matrix. RESULTS At 3 months, echocardiography showed the limitation of left ventricular end-diastolic volume in animals both treated with constraint devices alone and associated with stem cells/collagen. In Group 3 (stem cell + collagen treatment), significant improvements were found in ejection fraction (EF) and diastolic function evaluated by Doppler-derived mitral deceleration time. In this group, histology showed a reduction of infarct size, with focuses of angiogenesis and minimal fibrosis interface between CorCap and the epicardium due to the interposition of the collagen matrix. CONCLUSIONS Myocardial infarction treated with stem cells associated with a collagen matrix and ventricular constraint device improves systolic and diastolic function, reducing adverse remodelling and fibrosis. The application of bioactive molecules and the recent development of nanobiotechnologies should open the door for the creation of a new semi-degradable ventricular support bioprosthesis, capable of controlled stability or degradation in response to physiological conditions of the left or right heart. [ABSTRACT FROM PUBLISHER]

Background-Undersized ring annuloplasty for ischemic mitral regurgitation (MR) is associated with variable results and >30% MR recurrence. We tested whether subvalvular repair by severing second-order mitral chordae can improve annuloplasty by reducing papillary muscle tethering. Methods and Results-Posterolateral myocardial infarction known to produce chronic remodeling and MR was created in 28 sheep. At 3 months, sheep were randomized to sham surgery versus isolated undersized annuloplasty versus isolated bileaflet chordal cutting versus the combined therapy (n = 7 each). At baseline, chronic myocardial infarction (3 months), and euthanasia (6.6 months), we measured left ventricular (LV) volumes and ejection fraction, wall motion score index, MR regurgitation fraction and vena contracta, mitral annulus area, and posterior leaflet restriction angle (posterior leaflet to mitral annulus area) by 2-dimensional and 3-dimensional echocardiography. All groups were comparable at baseline and chronic myocardial infarction, with mild to moderate MR (MR vena contracta, 4.6±0.1 mm; MR regurgitation fraction, 24.2±2.9%) and mitral annulus dilatation (P<0.01). At euthanasia, MR progressed to moderate to severe in controls but decreased to trace with ring plus chordal cutting versus trace to mild with chordal cutting alone versus mild to moderate with ring alone (MR vena contracta, 5.9±1.1 mm in controls, 0.5±0.08 with both, 1.0±0.3 with chordal cutting alone, 2.0±0.4 with ring alone; P<0.01). In addition, LV end-systolic volume increased by 108% in controls versus 28% with ring plus chordal cutting, less than with each intervention alone (P<0.01). In multivariate analysis, LV end-systolic volume and mitral annulus area most strongly predicted MR (r2=0.82, P<0.01). Conclusions-Comprehensive annular and subvalvular repair improves long-term reduction of both chronic ischemic MR and LV remodeling without decreasing global or segmental LV function at follow-up [ABSTRACT FROM AUTHOR]

Electrostimulation (ES) can be defined as a safe physical method to induce stem cell differentiation. The aim of this study is to evaluate the effectiveness of ES on bone marrow mesenchymal stem cells (BMSCs) seeded in collagen scaffolds in terms of proliferation and differentiation into cardiomyocytes. BMSCs were isolated from Wistar rats and seeded into 3D collagen type 1 templates measuring 25 x 25 x 6 mm. Bipolar in vitro ES was performed during 21 days. Electrical impedance and cell proliferation were measured. Expression of cardiac markers was assessed by immunocyto- chemistry. Viscoelasticity of collagen matrix was evaluated. Electrical impedance assessments showed a low resistance of 234±41 Ohms which indicates good electrical conductivity of collagen matrix. Cell proliferation at 570 nm as significantly increased in ES groups after seven day (ES 0.129±0.03 vs non-stimulated control matrix 0.06±0.01, P=0.002) and after 21 days, (ES 0.22±0.04 vs control 0.13±0.01, P=0.01). Immunocytoche mistry of BMSCs after 21 days ES showed positive stain- ing of cardiac markers, troponin I, connexin 43, sarcomeric alpha-actinin, slow myosin, fast myosin and desmin. Staining for BMSCs marker CD29 after 21 days was negative. Electrostimulation of cell-seeded collagen matrix changed stem cell morphology and biochemical characteristics, increasing the expression of cardiac markers. Thus, MSC-derived differentiated cells by electrostimulation grafted in biological scaffolds might result in a convenient tissue engineering source for myocardial diseases. [ABSTRACT FROM AUTHOR]

CD4+CD25+Foxp3+ regulatory T cells (Treg) have emerged as a dominant T cell population inhibiting anti-tumor effector T cells. Initial strategies used for Treg-depletion (cyclophosphamide, anti-CD25 mAb...) also targeted activated T cells, as they share many phenotypic markers. Current, ameliorated approaches to inhibit Treg aim to either block their function or their migration to lymph nodes and the tumor microenvironment. Various drugs originally developed for other therapeutic indications (anti-angiogenic molecules, tyrosine kinase inhibitors,etc) have recently been discovered to inhibit Treg. These approaches are expected to be rapidly translated to clinical applications for therapeutic use in combination with immunomodulators. [ABSTRACT FROM AUTHOR]

Increase in myofibrillar protein accretion can occur in the very early post-exercise period and can be potentiated by ingestion of essential amino acid (EAA). Furthermore, strength exercise induces important disturbances in protein turnover, especially in novice athletes. The purpose of this investigation was to evaluate the effects of an EAA supplementation on muscle mass, architecture and strength in the early stages of a heavy-load training programme. 29 young males trained during 12 weeks. They were divided into a placebo (PLA) (n = 14) group and an EAA group (n = 15). At baseline, daily food intake and nitrogenous balance were assessed with a food questionnaire over 7 days and two 24-h urine collections. The effect of training on muscle mass was assessed by anthropometric techniques. Muscle thickness and pennation angle were recorded by ultrasonography of the gastrocnemius medialis (GM). Maximal strength during squat and bench press exercises were tested on an isokinetic ergometer. Training resulted in significant increase in muscle mass and strength in both PLA and EAA groups. Positive linear regressions were found between nitrogen balance and increase in muscle mass in the PLA group (P < 0.01, r2 = 0.63) and between the initial strength and the increase in muscle strength in the EAA group (P <0.05, r2 = 0.29). EAA ingestion resulted in greater changes in GM muscle architecture. These data indicate that EAA supplementation has a positive effect on muscle hypertrophy and architecture and that such a nutritional intervention seems to be more effective in subject having lower nitrogen balance and/or lower initial strength. [ABSTRACT FROM AUTHOR]

Background: Although glutaraldehyde fixation is known to reduce immunogenicity and degeneration of heart valve bioprostheses, some degree of immunogenicity persists, which may trigger calcification. The aims of this study were to: (1) define the role of alpha-1,3-galactosyltransferase (α-Gal) antigen in valve calcification by comparing α-Gal–positive and α-Gal–deficient (GT-KO) pig pericardium; and (2) elucidate the role of human anti-Gal antibodies in the process of calcification and to determine the potential influence of different tissue-fixation techniques. Methods: Glutaraldehyde-treated pericardium from α-Gal–positive and GT-KO pigs, with or without pre-labeling with human anti-Gal antibodies, were implanted in rats during 1 month. Results: In glutaraldehyde-fixed pericardium, calcification levels were significantly lower in GT-KO pig pericardium (132.8 ± 5.8 μg/mg) as compared with α-Gal–positive pig pericardium (155.7 ± 7.1 μg/mg) (p < 0.015). In glutaraldehyde-fixed pig pericardium followed by a mix of formaldehyde, ethanol and Tween 80 (FET), the calcification levels were lower in GT-KO pig pericardium (0.35 ± 0.1 μg/mg) as compared with α-Gal–positive pig pericardium (4.6 ± 4.2 μg/mg). In glutaraldehyde-fixed pig pericardium + FET pre-incubated with human anti-Gal antibodies, calcification levels were significantly greater in α-Gal–positive pig pericardium (43.8 ± 8.5 μg/mg) as compared with GT-KO pig pericardium (5.7 ± 2.9 μg/mg) (p < 0.0001). Conclusions: This study demonstrates the role of α-Gal antigen and human α-Gal antibodies in the calcification process of valvular bioprostheses. It is suggested that GT-KO pig pericardium could be beneficial as a new source of material for heart valve bioprostheses. [Copyright &y& Elsevier]

Abstract: Objectives: Little is known regarding the mechanisms, the feasibility and the long-term results of re-repair in ‘posterior failure’ of a previous mitral valve repair performed for severe degenerative mitral regurgitation. We report our 16-year experience in redo surgery for late posterior failure of mitral valve repair in degenerative disease. Methods: From 1991 to 2004, 13 consecutive patients (10 males; median age: 65 years) were reoperated for late posterior failure of mitral valve repair. All patients had grade ≥3+ mitral regurgitation. Repair was mainly performed using Carpentier''s techniques. Results: Repair failure was due to posterior leaflet prolapse, leaflet retraction or leaflet dehiscence in eight (62%), three (23%) and two (15%) patients, respectively. Repair was performed in nine patients (69%). There was no perioperative death. During follow-up (median: 105 months; range: 40–170 months) one late death occurred in the mitral valve replacement group. One (11%) patient underwent mechanical mitral valve replacement 125 months after re-repair. Congestive heart failure occurred in one patient in each group. At the latest follow-up, all but one patient in the mitral valve repair group were in NYHA functional class I or II and all were in sinus rhythm. Doppler echocardiographic studies of the re-repaired valves (n =8) showed no or trivial, grade 1+ and grade 2+ residual mitral regurgitation in 6 (75%), 1 and 1 patients, respectively. Mean transmitral gradient was 3mmHg (2–8mmHg) and left ventricular ejection fraction was 59% (43–77%). Conclusion: In case of late posterior failure of mitral valve repair for severe degenerative, re-repair is feasible in about 70% of the patients with encouraging results at 10 years. [Copyright &y& Elsevier]

Abstract: Objective: Dynamic cardiomyoplasty (CMP) was proposed as a treatment for refractory heart failure; more than 2000 procedures have been performed worldwide. Heart transplantation was indicated afterwards in some CMP patients with recurrent heart failure symptoms. This study reviews the multicentric French experience with CMP followed by heart transplantation. Methods: From 1985 to 2007, 212 patients (mean age 53±11 years) with refractory heart failure (LVEF=22±9%, mean NYHA 3.2) underwent CMP in France. Heart transplantation was performed in 26 patients (12.3%), mean age: 51±11 years, within 2.3±3 years after CMP. Transplantation was indicated for persistent heart failure, i.e. no immediate improvement after CMP (19%) and for recurring heart failure (81%). Results: The surgical technique of heart transplantation following cardiomyoplasty presents few particularities. Routine extracorporeal bypass was instituted between the vena cavas and the ascending aorta. As in most of these patients the CMP procedure had been performed without the need of extracorporeal circulation, hearts were free of previous cannulations for cardiopulmonary bypass. The latissimus dorsi muscle flap was divided as far as possible inside the left pleural cavity and its vascular pedicle was obturated. The proximal portion of the muscle as well as the muscular pacing electrodes were kept in place in the pleural cavity. The adhesions between the flap and the heart were not released so as to achieve an en bloc resection of the heart and the muscle flap. During removal of the recipient''s heart, care was taken not to injure the left phrenic nerve that was frequently in tight relation with the latissimus dorsi muscle. Heart transplantation was then performed in a routine manner, the donor heart being anastomosed to remnant atria and great vessels. Mean follow-up was 5.5 years (longest 13.5 years). Survival at 10 years was 40% for early heart transplantation (done within 4 months of CMP) and 57% for transplantation performed at 3±2.8 years after CMP. Conclusions: Heart transplantation after CMP is technically feasible. Hospital mortality was higher when urgent transplantation was required. Long-term survival results are similar to those for primary heart transplantation. Cardiomyoplasty, when it fails, does not preclude transplantation, and when indicated, CMP could be considered as a biological bridge to heart transplantation. [Copyright &y& Elsevier]

Background: Pulmonary expression of heme oxygenase has been observed in multiple studies. This expression has been found beneficial in decreasing the severity of acute lung injury (ALI) post ischemia–reperfusion (I/R). The aim of this study was to assess the role of exogenous administration of the end-products of heme oxygenase reaction, carbon monoxide, and bilirubin, in the severity of ALI. Study design: We compared five groups of rats (n = 7/group) including a sham group and four I/R of the lower extremities by clamping the abdominal aorta for 2 h followed by reperfusion for 2 h. The four I/R groups included a control group, one pretreated with bilirubin (50 μmol/kg IV), another with inhaled carbon monoxide (CO) (250 ppm), and the last pretreated with both. The severity of ALI has been evaluated by a histological assay grading neutrophilic infiltration, as well as a study of the microvascular permeability using the Evans blue. Results: The administration of CO prevented pulmonary microvascular permeability alteration noted after I/R of the lower limbs (pulmonary content of Evans blue: 141 ± 23 μg/g of tissue in the isolated I/R group versus 68 ± 34 μg/g of tissue in CO group; P < 0.001). Histologically CO administration inhibited neutrophilic sequestration observed after I/R. On the other hand, treatment by bilirubin alone (50 μmol/kg IV) did not modify the extent of pulmonary injury. Conclusion: Exogenous administration of carbon monoxide by inhalation at low doses prevented ALI post-I/R in this model. [Copyright &y& Elsevier]

Aims: We compared two procedures for local myocardial treatment: transepicardial versus transendocardial catheter injection. Transepicardial injections were performed under direct surgical visualization whereas transendocardial injections were performed using electrophysiological guidance. Methods: A left ventricle (LV) myocardial infarction (MI) was surgically created in 14 sheep. At 3 months, gadolinium was injected IV followed by the injection of super paramagnetic iron oxide (SPIO) into MI. Animals were divided in two groups: transepicardial injection (Group I) versus transendocardial (Group II) using “Cell-Fix” catheter injection. This catheter was developed to identify by electrophysiology the infarcted area and to stabilize injections suctioning the device to the endocardium. Postgadolinium delayed-enhancement magnetic resonance imaging (MRI) was performed to stain the infarct size. SPIO injections were used to assess the magnitude of the treated area. The ratio between SPIO black stained treatment areas and white gadolinium stained infarcted areas was calculated using MRI. Results: The electrophysiological recordings by the catheter for the MI versus normal LV wall were: R wave amplitude 4.16 versus 12.08 mV (P = 0.003), slew rate (slope of the signal) 0.36 V/s versus 1.04 V/s (P = 0.008). The ratio of the SPIO diffusion into the MI was 41.2 ± 8.1% for surgical and 63.7 ± 8.2% for percutaneous endocardial injections (P = 0.0132). Conclusion: MRI allows evaluation of the extent of local myocardial treatments. The differences shown between epicardial and endocardial injections concerning the distribution of SPIO can be justified by the methodology of injection and by a more precise MI detection by electrophysiology. In conclusion, electrophysiological recordings to guide injections is superior to direct surgical visualization in terms of injecting into infarcted tissue. [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to assess whether post-myocardial infarction (MI) in-scar transplantation of skeletal myoblasts (SM) could reduce chronic ischemic mitral regurgitation (MR) by decreasing left ventricular (LV) remodeling. Background: Extensive work has confirmed the relationship between ischemic MR and post-myocardial infarction (MI) remodeling of the LV. Methods: An infero-posterior MI was created in 13 sheep, thereby resulting in increasing MR. Two months post-MI, the animals were randomized and in-scar injected with expanded autologous SM (n = 6, mean: 251 × 106 cells) or culture medium only (n = 7). Three-dimensional echocardiography was performed at baseline, before transplantation, and for two months thereafter (sacrifice), with measurements of LV end-diastolic and end-systolic volumes (ESV), ejection fraction (EF), MR stroke volume, and leaflet tethering distance; wall motion score index (WMSi) was assessed by two-dimensional echo. Results: Measurements were similar between groups at baseline and before transplantation. At sacrifice, transplantation was found to have reduced MR progression (regurgitant volume change: −1.83 ± 0.32 ml vs. 5.9 ± 0.7 ml in control group, p < 0.0001) and tethering distance (−0.41 ± 0.09 cm vs. 0.44 ± 0.12 cm in control group, p < 0.001), with significant improvement of EF (2.01 ± 0.94% vs. −4.86 ± 2.23%, p = 0.02), WMSi (−0.25 ± 0.11 vs. 0.13 ± 0.03 in controls, p < 0.01) and a trend to a lesser increase in ESV (23.3 ± 3.5 ml vs. 35.4 ± 4.2 ml in control group, p = 0.055). Conclusions: Autologous skeletal myoblast transplantation attenuates mild-to-moderate chronic ischemic MR, which otherwise is progressive, by decreasing tethering distance and improving EF and wall motion score, thereby enhancing valve coaptation. These data shed additional light on the mechanism by which skeletal myoblast transplantation may be cardioprotective. [Copyright &y& Elsevier]

Background: Expression of inducible heme-oxygenase (HO-1) has been shown to be increased in various inflammatory disorders, which may confer a protective role. The aim of our study was to assess pulmonary expression of HO-1 after ischemia/reperfusion (I/R) of the lower limbs in rats. Materials and methods: We compared three groups of rats (n = 5/group): one Sham group, and two I/R groups (aorta cross-clamped for 2 h followed by 2 h of reperfusion), one of which pre-treated with Zn-protoporphyrin (Zn-PP), a competitive inhibitor of HO (50 μmol/kg, i.p.). At the end of experiment, lungs were harvested for determination of HO activity and HO-1 expression by Western blot and immunohistochemistry. Lung injury was assessed by bronchoalveolar lavage, histological study, and determination of the lung Evans Blue dye content, an index of microvascular permeability. Results: I/R of the lower limbs was responsible for acute lung injury (ALI), characterized by neutrophilic infiltration (87 ± 20 × 103 neutrophils/mm3, Sham group versus 191 ± 38 × 103 neutrophils/mm3, I/R group; P < 0.002) and an increase in lung Evans blue dye content: (74 ± 6 μg/g, Sham group versus 122 ± 48 μg/g, I/R group; P < 0.05). Pre-treatment with Zn-PP further increases the Evans Blue content (122 ± 48 μg/g, I/R group versus 179 ± 23 μg/g Zn-PP group P < 0.05) and the neutrophilic infiltration. Pulmonary heme-oxygenase activity, and HO-1 content were increased after I/R. (10.5 ± 12 pmol bilirubin/mg protein/h, Sham group versus 101.2 ± 66 pmol bilirubin/mg protein/h, I/R group; P < 0.02). Immunohistochemistry revealed that the expression of HO-1 was mainly localized to inflammatory cells. Conclusions: ALI following I/R of the lower limbs in rats is associated with an increase of pulmonary expression of HO-1, inhibition of this expression increase the severity of ALI. [Copyright &y& Elsevier]

Purpose: It has been claimed that oral creatine supplementation might have potential cytotoxic effects on healthy consumers by increasing the production of methylamine and formaldehyde. Despite this allegation, there has been no scientific evidence obtained in humans to sustain or disprove such a detrimental effect of this widely used ergogenic substance. Methods: Twenty young healthy men ingested 21 g of creatine monohydrate daily for 14 consecutive days. Venous blood samples and 24-h urine were collected before and after the 14th day of supplementation. Creatine and creatinine were analyzed in plasma and urine, and methylamine, formaldehyde, and formate were determined in 24-h urine samples. Results: Oral creatine supplementation increased plasma creatine content 7.2-fold (P < 0.001) and urine output 141-fold (P < 0.001) with no effect on creatinine levels. Twenty-four-hour urine excretion of methylamine and formaldehyde increased, respectively, 9.2-fold (P = 0,001) and 4.5-fold (P = 0.002) after creatine feeding, with no increase in urinary albumin output (9.78 ± 1.93 mg.24 h-1 before, 6.97 ± 1.15 mg.24 h-1 creatine feeding). Conclusion: This investigation shows that short-term, high-dose oral creatine supplementation enhances the excretion of potential cytotoxic compounds, but does not have any detrimental effects on kidney permeability. This provides indirect evidence of the absence of microangiopathy in renal glomeruli. [ABSTRACT FROM AUTHOR]

Objectives: Large animal experimental models of chronic heart failure (HF) permit repeated invasive assessment of cardiovascular function, and evaluation of new medical or surgical therapies. The existing models however fail to achieve stable and long-term HF. The aim of this study was to create a simple and stable chronic model of HF in goat, using both arteriovenous fistula and weekly intravenous doxorubicin injections.Methods: After a preliminary experiment on four goats receiving weekly 1 to 2 mg/kg of doxorubicin, six adult female goats, having had an arteriovenous fistula without signs or symptoms of heart failure, received weekly two different dosages of doxorubicin for 13 weeks: group A (n = 3) received 0.5 mg/kg and group B (n = 3) received 1 mg/kg. After a three-month period without medication, both groups received again 1 mg/kg for four weeks. Cardiac function was assessed by repeated electrocardiographic and echocardiographic examinations.Results: Four goats died during the medication period (one in group A, three in group B). During the period without medication a stable ventricular hypocontractility with left ventricular dilation was observed. Left ventricular dysfunction was more pronounced in group B, and was associated with clinical symptoms of HF.Conclusions: Arteriovenous fistula alone did not produce HF. Its association with doxorubicin injections provides a simple and stable chronic model of HF. This association allows reduction of the required doxorubicin dose and toxicity in animals and in the environment. Depending of the dose of doxorubicin, it is possible to obtain a model of heart dilatation and ventricular hypokinesia with or without clinical symptoms of HF, with a different mortality. [ABSTRACT FROM AUTHOR]

This study examines the incidence, predictors, and evolution of postoperative atrioventricular block (AVB) after mitral valve repair (MVR) in 115 consecutive patients using Carpentier’s technique (between November 1996 and April 1997). Postoperative AVB occurred in 27 patients (23%). Third-degree AVB was found in 7 patients (6%) in the immediate postoperative period, but in 4 it was transient, resolving partially or completely before the seventh postoperative day. Second-degree AVB (Mobitz type I) occurred in 4 patients (3%) immediately after operation and resolved in all before hospital discharge. Isolated first-degree AVB occurred in 16 patients (14%) and was permanent in 12. Neither the preoperative variables nor the mitral procedures including anterior versus posterior leaflet repair were related to postoperative AVB. A lesser systemic hypothermia during surgery was the only, modestly independent predictor of postoperative AVB (odds ratio 1.53; 95% confidence interval 1.04 to 2.25; p = 0.031). Three patients (2.6%) had permanent pacemaker implantation, on average 18 days after operation, and all had persistent third-degree AVB. With a mean follow-up of 3 years, no recurrence or worsening of conduction disturbances, no further pacemaker implantation, and no late deaths were observed. [Copyright &y& Elsevier]

Due to their numerous advantages, mainly in terms of patient benefit, mini-invasive robotically assisted interventions are gaining in importance in various surgical fields. However, this conversion has its own challenges that stem from both its novelty and complexity. In this paper we propose to accompany the surgeons in their transition, by offering an integrated environment that enables them to make better use of this new technology. The proposed system is patient-dependent, and enables the planning, validation, simulation, teaching and archiving of robotically assisted interventions. The approach is illustrated for a coronary bypass graft using the daVinciTM tele-operated robot. [Copyright &y& Elsevier]

Background: Facing young foreign polyvalvular rheumatic patients, for which long-term anticoagulation is not available, we have chosen to attempt triple valve repair procedures in order to avoid prosthetic implantation in this particular population suffering from triple valve disease. Methods: Twenty-one young rheumatic patients (mean age:11±4 years) underwent triple valve repair procedures including cusp extension on the aortic valve aortic between September, 1992 and December, 2000. Valvular pathology characteristics according to Carpentier''s classification included mitral insufficiency type III post+II ant (n=10), type III post (n=4), type II ant (n=2), mitral stenosis (n=5), type III aortic insufficiency (n=21), type I (n=13) and type III (n=8) tricuspid insufficiency. Results: Firstly, the mitral valve disease were corrected using Carpentier''s techniques of repair: prosthetic ring annuloplasty (n=16), commissurotomy (n=12), chord transposition (n=11) or shortening (n=4), papillary muscle sliding plasty (n=4) and pericardial patch leaflet enlargement (n=6). Secondly, aortic lesions were corrected using glutaraldehyde stabilized autologous pericardium triple cusps extension technique (n=21). Lastly, tricuspid repairs were always performed on beating hearts using commissurotomy (n=8), prosthetic ring (n=12) or other techniques (n=9) of annuloplasty. The operative mortality was 4.7% (one patient died). Echocardiograms before discharge showed grade I mitral insufficiency in seven patients and grade I aortic insufficiency in five patients. There was no late death during a mean follow-up of 51±31 months. Two patients underwent valvular redo surgery because of aortic and mitral plasty deterioration due to rheumatic disease progress. After 5 years, 90% of the patients were free from redo valvular surgery. Conclusions: In rheumatic patients, autologous pericardial patch extension of the aortic valve permitted widespread use of reconstructive surgery even in patients suffering from triple valve disease. Triple valve repair, in this particular challenging setting of patients, has provided satisfactory initial and mid-term results and could be considered as an interesting palliative surgical approach. [Copyright &y& Elsevier]

Reports on the identification of cells that may be responsible for the nonclassical HLA class I antigen HLA-G protein expression during the allogeneic reaction. Detection of soluble HLA-G5 in three combinations after mixed lymphocyte reaction (MLR); Potential agent for controlling allograft rejection; Effects of the HLA-G5 protein secreted during MLR.

The article reports on ways to prevent rheumatic heart disease and acute rheumatic fever which include the coordination to produce vaccine, improvement of the use of valve repair function, and the research on echocardiographic screening. Topics mentioned include the safety measures for rheumatic heart disease patients, the need to cooperate by organizations World Health Organization (WHO) and World Heart Federation, and the safety measures for surgical valve repair techniques.

Introduction: After 10 years of implantation, 20 to 30% of valvular bioprosthesis show signs of dysfunction mostly due to calcification. Hypothesis: Because of bioprosthesis valve endothelial recovery after implantation is link to hemocompatibility and non-thrombogenicity, we hypothesis that a disruption of endothelial recovery associated to a modification of endothelial/angiogenic circulating marker could be associated with valve bioprosthesis degeneration. Methods: This is a retrospective case-control study based on serum from 74 adult patients with degeneration of valve bioprosthesis operated in two academic centers between 1998 and 2016. The control group included 50 age- and gender-matched subjects without valve diseases. Levels of VEGF-A, PDGF-BB, Thrombospondin-1 (TSP-1), soluble endoglin (sENG), TGF-β1, soluble protein C endothelial receptor (sEPCR), soluble E-selectin and ultra-sensitive CRP were measured in all subjects. Results: A total of 74 patients with degenerative valve biosprothesis were included. The average age of patients was 60.3 years and 68.9% were men. Among patients 74.3% had a redux valvular surgery and 35 (47.3%) had a calcified bioprosthesis explanted. Median age of patients at implantation and median biosprothesis life expectancy were respectively 46.3 years and 13.7 years. There was no significant difference between the clinical characteristics and cardiovascular risk factors of patients with or without calcification of the explanted bioprosthesis. The univariate analysis showed significant decrease in VEGF-A (p=0.011), TSP-1 (p=0.048) and sEPCR levels (p=0.006) in patients with calcified bioprosthesis. After adjustment, only a level of sEPCR lower than 108 ng/mL was significantly associated with a risk of calcification of the degenerative bioprosthesis (OR: 0.2, 95% CI 0.03-0.41, p<0.001). Conclusions: The novel evidence of a possible value of the sEPCR as a biomarker of valve bioprosthesis calcification was presented. Our results suggested a link between endothelial marker, coagulation and calcification of bioprosthetic valve. [ABSTRACT FROM AUTHOR]

OBJECTIVES The CARMAT total artificial heart (TAH) is an implantable, electro-hydraulically driven, pulsatile flow device with four bioprosthetic valves. Its blood-pumping surfaces consist of processed bioprosthetic pericardial tissue and expanded polytetrafluorethylene (ePTFE), potentially allowing for the reduction of anti-coagulation. This pre-clinical study assessed the in vitro haemocompatibility of these surfaces. METHODS Coupons of pericardial tissue and ePTFE were placed in closed tubular circuits filled with 12.5 ml of fresh human blood exposed to the pulsatile flow at 120 ml/min for 4 h (37°C). Silicone- and heparin-coated polyvinyl chloride (PVC) tubes served as positive and negative controls, respectively. Fresh blood from six donors was used to fill four sets of 12 circuits. Blood samples were taken at baseline and from each circuit after 4 h. Coupons of materials were examined with scanning electron microscopy. RESULTS The platelet count was 202 ± 45 × 109 l−1 at baseline. Four hours after circulation, the platelet counts were 161 ± 30 × 109 l−1 (compared with baseline, P = 0.0207) for pericardial tissue, 162 ± 35 × 109 l−1 (P = 0.0305) for ePTFE and 136 ± 42 × 109 l−1 for positive controls (P = 0.0021). Baseline plasma fibrinogen was 2.9 ± 0.5 mg/dl compared with 3.0 ± 0.5 mg/dl for pericardial tissue and 3.1 ± 0.7 mg/dl for ePTFE, indicating no marked fibrinogen consumption. Thromboxane B2 levels for positive controls were 33.3 ± 8.7 ng/ml compared with 16.2 ± 11.5 ng/ml for pericardial tissue (P = 0.0015) and 15.2 ± 4.7 ng/ml for ePTFE (P < 0.0001). Platelet adhesion was 2.87 ± 1.01 × 109 cm−2 for positive controls compared with 1.06 ± 0.73 × 109 cm−2 for pericardial tissue (P < 0.0001) and 0.79 ± 0.75 × 109 cm−2 for ePTFE (P < 0.0001). Thrombin–antithrombin III complex levels were 3.8 ± 0.5 μg/ml for positive controls compared with 1.9 ± 0.9 for pericardial tissue (P < 0.0001) and 2.1 ± 1.0 for ePTFE (P < 0.0001). With an electro-microscopic examination at ×600, only small depositions of platelets, erythrocytes and fibrin were noticed on the pericardial tissue samples and ePTFE samples. Silicone surfaces showed marked areas of thrombi, and PVC tubings a thin protein layer. CONCLUSIONS Haemocompatibility of the TAH blood-contacting surfaces was confirmed by in vitro studies showing a limited consumption of fibrin, limited thromboxane B2 release and platelet adhesion, and minor blood cell depositions on the surfaces. These results will be validated in clinical studies, with the aim of reducing anti-coagulation when using the CARMAT TAH. [ABSTRACT FROM AUTHOR]

Examines gene mapping for autosomal dominant myxomatous mitral-valve prolapse (MMVP) to chromosome 16p11.2 to p12.1. Identification of genes in the heterogeneous group of diseases; Characteristics of MMVP; Abnormality of the mitral-valve structure.