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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]

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]

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]

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]

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]

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]