Direct Cardiac Compression Devices to Augment Heart Biomechanics and Function.

The treatment of end-stage heart failure has evolved substantially with advances in medical treatment, cardiac transplantation, and mechanical circulatory support (MCS) devices such as left ventricular assist devices and total artificial hearts. However, current MCS devices are inherently blood contacting and can lead to potential complications including pump thrombosis, hemorrhage, stroke, and hemolysis. Attempts to address these issues and avoid blood contact led to the concept of compressing the failing heart from the epicardial surface and the design of direct cardiac compression (DCC) devices. We review the fundamental concepts related to DCC, present the foundational devices and recent devices in the research and commercialization stages, and discuss the milestones required for clinical translation and adoption of this technology.

Retrospective analysis of factors associated with outcome in veno-venous extra-corporeal membrane oxygenation.

BACKGROUND: The outcome of Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) in acute respiratory failure may be influenced by patient-related factors, center expertise and modalities of mechanical ventilation (MV) during ECMO. We determined, in a medium-size ECMO center in Switzerland, possible factors associated with mortality during VV-ECMO for acute respiratory failure of various etiologies. METHODS: We retrospectively analyzed all patients treated with VV-ECMO in our University Hospital from 2012 to 2019 (pre-COVID era). Demographic variables, severity scores, MV duration before ECMO, pre and on-ECMO arterial blood gases and respiratory variables were collected. The primary outcome was ICU mortality. Data were compared between survivors and non-survivors, and factors associated with mortality were assessed in univariate and multivariate analyses. RESULTS: Fifty-one patients (33 ARDS, 18 non-ARDS) were included. ICU survival was 49% (ARDS, 39%; non-ARDS 67%). In univariate analyses, a higher driving pressure (DP) at 24h and 48h on ECMO (whole population), longer MV duration before ECMO and higher DP at 24h on ECMO (ARDS patients), were associated with mortality. In multivariate analyses, ECMO indication, higher DP at 24h on ECMO and, in ARDS, longer MV duration before ECMO, were independently associated with mortality. CONCLUSIONS: DP on ECMO and longer MV duration before ECMO (in ARDS) are major, and potentially modifiable, factors influencing outcome during VV-ECMO.

[Monitoring respiratory mechanics in ventilated patients: a bedside approach]. / Monitorage de la mécanique respiratoire chez le patient ventilé : comment procéder au lit du malade.

In clinical practice, the term respiratory mechanics usually refers to the concept of compliance and resistance of the respiratory system. In ventilated patients, measurements of compliance and resistance can be performed at the bedside using the ventilator (end- inspiratory and end-expiratory occlusions). Those measurements allow caregivers to monitor pulmonary disorders and evaluate treatment effectiveness. In case of sudden change in compliance or resistance, the variation of flow and pressure curves displayed on the ventilator screen helps to narrow down the differential diagnosis. This article defines what are compliance and resistance and how to calculate and use them at the bedside.

Le terme « mécanique respiratoire ¼ se rapporte souvent, en pratique, aux concepts de compliance et résistance du système respiratoire. Chez un patient ventilé, les mesures de compliance et de résistance s'effectuent à l'aide du ventilateur (occlusion télé-inspiratoire et télé-expiratoire). Ces mesures permettent de suivre l'évolution d'une atteinte pulmonaire ou l'efficacité d'un traitement administré. En cas de changement brusque de compliance ou de résistance, l'analyse des variations des courbes affichées sur l'écran du ventilateur permet d'élaborer un diagnostic différentiel rapidement. Cet article de synthèse décrit les concepts de compliance et résistance du système respiratoire, la façon de les calculer et de les utiliser au lit du malade.

[Classic ventilatory modes for invasive mechanical ventilation]. / Modes ventilatoires de base en ventilation mécanique invasive.

Invasive mechanical ventilation is part of the daily practice of the intensivist and anesthetist. The comprehensive knowledge of ventilatory modes is mandatory for managing the ventilated patients. The objective of this article is to explain the characteristics of the barometric and volumetric modes and the differences between controlled, assist-controlled, and assisted ventilation. The most common modes (volume and pressure assist-control, dual modes and pressure support) are described in detail. Parameters that must be set and those that must be monitored in each mode are also described. Finally, suggestions for initial settings are provided in order to offer the reader unfamiliar with mechanical ventilation a practical decision-making aid.

La ventilation mécanique invasive est un outil indispensable à la pratique de l'intensiviste et de l'anesthésiste. La connaissance des modes ventilatoires est nécessaire pour la prise en charge des patients ventilés. L'objectif de cet article est, d'une part, de distinguer les caractéristiques des modes barométriques et volumétriques, et de comprendre les différences entre les modes contrôlé, assisté-contrôlé et assisté et, d'autre part, de distinguer les paramètres qui doivent être réglés de ceux qui doivent être monitorés. Les modes les plus utilisés (volume contrôlé, pression contrôlée, modes mixtes et aide inspiratoire) font l'objet d'une description détaillée. Des suggestions de réglages initiaux sont proposées pour ces modes afin d'offrir au lecteur peu familier avec la ventilation mécanique une aide décisionnelle pratique.

Hyperoxia during extracorporeal cardiopulmonary resuscitation for refractory cardiac arrest is associated with severe circulatory failure and increased mortality.

BACKGROUND: High levels of arterial oxygen pressures (PaO2) have been associated with increased mortality in extracorporeal cardiopulmonary resuscitation (ECPR), but there is limited information regarding possible mechanisms linking hyperoxia and death in this setting, notably with respect to its hemodynamic consequences. We aimed therefore at evaluating a possible association between PaO2, circulatory failure and death during ECPR. METHODS: We retrospectively analyzed 44 consecutive cardiac arrest (CA) patients treated with ECPR to determine the association between the mean PaO2 over the first 24 h, arterial blood pressure, vasopressor and intravenous fluid therapies, mortality, and cause of deaths. RESULTS: Eleven patients (25%) survived to hospital discharge. The main causes of death were refractory circulatory shock (46%) and neurological damage (24%). Compared to survivors, non survivors had significantly higher mean 24 h PaO2 (306 ± 121 mmHg vs 164 ± 53 mmHg, p < 0.001), lower mean blood pressure and higher requirements in vasopressors and fluids, but displayed similar pulse pressure during the first 24 h (an index of native cardiac recovery). The mean 24 h PaO2 was significantly and positively correlated with the severity of hypotension and the intensity of vasoactive therapies. Patients dying from circulatory failure died after a median of 17 h, compared to a median of 58 h for patients dying from a neurological cause. Patients dying from neurological cause had better preserved blood pressure and lower vasopressor requirements. CONCLUSION: In conclusion, hyperoxia is associated with increased mortality during ECPR, possibly by promoting circulatory collapse or delayed neurological damage.

Use of D-glucose-fenpiclonil conjugate as a potent and specific inhibitor of sucrose carriers.

Until now, specific inhibitors of sucrose carriers were not available. This led us to study the properties of the recently synthesized D-glucose-fenpiclonil conjugate (D-GFC). This large amphiphilic glucoside exhibited an extremely low phloem systemicity in contrast to L-amino acid-fenpiclonil conjugates. Using Ricinus seedlings, the effect of D-GFC on 0.5 mM [14C]sucrose (Suc), 3-O-[3H]methylglucose, and [3H]glutamine uptake by cotyledon tissues was compared with that of p-chloromercuribenzenesulfonic acid (PCMBS). D-GFC dramatically inhibited H+-Suc symport at the same concentrations as PCMBS (0.5 and 1 mM), but in contrast to the thiol reagent, it did not affect 3-O-methylglucose and glutamine transport, nor the acidification of the incubation medium by cotyledon tissues. Similarly, 0.5 mM D-GFC inhibited active Suc uptake by Vicia faba leaf tissues and by Saccharomyces cerevisiae cells transformed with AtSUC2, a gene involved in Suc phloem loading in Arabidopsis, by approximately 80%. The data indicated that D-GFC was a potent inhibitor of Suc uptake from the endosperm and of Suc phloem loading. It is the first chemical known to exhibit such specificity, at least in Ricinus, and this property permitted the quantification of the two routes involved in phloem loading of endogenous sugars after endosperm removal.

Soft robotic platform for progressive and reversible aortic constriction in a small-animal model.

Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to enable control over both disease progression and reversal, hindering their clinical relevance. Here, we describe a method for progressive and reversible aortic banding based on an implantable expandable actuator that can be finely tuned to modulate aortic banding and debanding in a rat model. Through catheterization, imaging, and histologic studies, we demonstrate that our platform can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leveraged soft robotics to enable noninvasive aortic debanding, demonstrating that these changes can be partly reversed because of cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this animal model could elucidate fundamental mechanisms of cardiac remodeling and optimize timing of intervention for pressure overload.

Soft robotic platform for controlled, progressive and reversible aortic constriction in a small animal model.

Our understanding of cardiac remodeling processes due to left ventricular pressure overload derives largely from animal models of aortic banding. However, these studies fail to simultaneously enable control over disease progression and reversal, hindering their clinical relevance. Here, we describe a method for controlled, progressive, and reversible aortic banding based on an implantable expandable actuator that can be finely controlled to modulate aortic banding and debanding in a rat model. Through catheterization, imaging, and histologic studies, we demonstrate that our model can recapitulate the hemodynamic and structural changes associated with pressure overload in a controllable manner. We leverage the ability of our model to enable non-invasive aortic debanding to show that these changes can be partly reversed due to cessation of the biomechanical stimulus. By recapitulating longitudinal disease progression and reversibility, this model could elucidate fundamental mechanisms of cardiac remodeling and optimize timing of intervention for pressure overload.

An implantable soft robotic ventilator augments inspiration in a pig model of respiratory insufficiency.

Severe diaphragm dysfunction can lead to respiratory failure and to the need for permanent mechanical ventilation. Yet permanent tethering to a mechanical ventilator through the mouth or via tracheostomy can hinder a patient's speech, swallowing ability and mobility. Here we show, in a porcine model of varied respiratory insufficiency, that a contractile soft robotic actuator implanted above the diaphragm augments its motion during inspiration. Synchronized actuation of the diaphragm-assist implant with the native respiratory effort increased tidal volumes and maintained ventilation flow rates within the normal range. Robotic implants that intervene at the diaphragm rather than at the upper airway and that augment physiological metrics of ventilation may restore respiratory performance without sacrificing quality of life.

Soft robotic patient-specific hydrodynamic model of aortic stenosis and ventricular remodeling.

Aortic stenosis (AS) affects about 1.5 million people in the United States and is associated with a 5-year survival rate of 20% if untreated. In these patients, aortic valve replacement is performed to restore adequate hemodynamics and alleviate symptoms. The development of next-generation prosthetic aortic valves seeks to provide enhanced hemodynamic performance, durability, and long-term safety, emphasizing the need for high-fidelity testing platforms for these devices. We propose a soft robotic model that recapitulates patient-specific hemodynamics of AS and secondary ventricular remodeling which we validated against clinical data. The model leverages 3D-printed replicas of each patient's cardiac anatomy and patient-specific soft robotic sleeves to recreate the patients' hemodynamics. An aortic sleeve allows mimicry of AS lesions due to degenerative or congenital disease, whereas a left ventricular sleeve recapitulates loss of ventricular compliance and diastolic dysfunction (DD) associated with AS. Through a combination of echocardiographic and catheterization techniques, this system is shown to recreate clinical metrics of AS with greater controllability compared with methods based on image-guided aortic root reconstruction and parameters of cardiac function that rigid systems fail to mimic physiologically. Last, we leverage this model to evaluate the hemodynamic benefit of transcatheter aortic valves in a subset of patients with diverse anatomies, etiologies, and disease states. Through the development of a high-fidelity model of AS and DD, this work demonstrates the use of soft robotics to recreate cardiovascular disease, with potential applications in device development, procedural planning, and outcome prediction in industrial and clinical settings.

The Right Ventricle in COVID-19.

Infection with the novel severe acute respiratory coronavirus-2 (SARS-CoV2) results in COVID-19, a disease primarily affecting the respiratory system to provoke a spectrum of clinical manifestations, the most severe being acute respiratory distress syndrome (ARDS). A significant proportion of COVID-19 patients also develop various cardiac complications, among which dysfunction of the right ventricle (RV) appears particularly common, especially in severe forms of the disease, and which is associated with a dismal prognosis. Echocardiographic studies indeed reveal right ventricular dysfunction in up to 40% of patients, a proportion even greater when the RV is explored with strain imaging echocardiography. The pathophysiological mechanisms of RV dysfunction in COVID-19 include processes increasing the pulmonary vascular hydraulic load and others reducing RV contractility, which precipitate the acute uncoupling of the RV with the pulmonary circulation. Understanding these mechanisms provides the fundamental basis for the adequate therapeutic management of RV dysfunction, which incorporates protective mechanical ventilation, the prevention and treatment of pulmonary vasoconstriction and thrombotic complications, as well as the appropriate management of RV preload and contractility. This comprehensive review provides a detailed update of the evidence of RV dysfunction in COVID-19, its pathophysiological mechanisms, and its therapy.

Deep Neural Network to Accurately Predict Left Ventricular Systolic Function Under Mechanical Assistance.

Characterizing left ventricle (LV) systolic function in the presence of an LV assist device (LVAD) is extremely challenging. We developed a framework comprising a deep neural network (DNN) and a 0D model of the cardiovascular system to predict parameters of LV systolic function. DNN input data were systemic and pulmonary arterial pressure signals, and rotation speeds of the device. Output data were parameters of LV systolic function, including end-systolic maximal elastance (E max,lv ), a variable essential for adequate hemodynamic assessment of the LV. A 0D model of the cardiovascular system, including a wide range of LVAD settings and incorporating the whole spectrum of heart failure, was used to generate data for the training procedure of the DNN. The DNN predicted E max,lv with a mean relative error of 10.1%, and all other parameters of LV function with a mean relative error of <13%. The framework was then able to retrieve a number of LV physiological variables (i.e., pressures, volumes, and ejection fraction) with a mean relative error of <5%. Our method provides an innovative tool to assess LV hemodynamics under device assistance, which could be helpful for a better understanding of LV-LVAD interactions, and for therapeutic optimization.

Simple equations to predict the effects of veno-venous ECMO in decompensated Eisenmenger syndrome.

Adult patients with uncorrected congenital heart diseases and chronic intracardiac shunt may develop Eisenmenger syndrome (ES) due to progressive increase of pulmonary vascular resistance, with significant morbidity and mortality. Acute decompensation of ES in conditions promoting a further increase of pulmonary vascular resistance, such as pulmonary embolism or pneumonia, can precipitate major arterial hypoxia and death. In such conditions, increasing systemic oxygenation with veno-venous extracorporeal membrane oxygenation (VV-ECMO) could be life-saving, serving as a bridge to treat a potential reversible cause for the decompensation, or to urgent lung transplantation. Anticipating the effects of VV-ECMO in this setting could ease the clinical decision to initiate such therapeutic strategy. Here, we present a series of equations to accurately predict the effects of VV-ECMO on arterial oxygenation in ES and illustrate this point by a case of ES decompensation with refractory hypoxaemia consecutive to an acute respiratory failure due to viral pneumonia.

Auxinic herbicide conjugates with an α-amino acid function: Structural requirements for biological activity on motor cells.

Two Fabaceae exhibiting rapid osmocontractile pulvinar movements were used in this study because this activity is modified by natural auxin and dramatically by 2,4D. A short chain with a carboxylic group being required for auxinic properties, a critical point to analyze is whether the recently synthesized proherbicide ε-(2,4-dichlorophenoxyacetyl)-L-Lys (2-4D-L-Lys) maintains some biological activity despite the increase in length of the chain and the substitution of the carboxyl group by an α-amino acid function. No trace of 2,4D could be detected in the pulvinar tissues treated for 1 h with 2,4D-L-Lys. Complementary approaches (electrophysiology, pH measurements, use of plasma membrane vesicles) suggest that it was less efficient than 2,4D to activate the plasma membrane H+-ATPase (PM-H+-ATPase). However, it modified the various ion-driven reactions of Mimosa pudica and Cassia fasciculata pulvini in a similar way as 2,4D. Additionally, it was much more effective than fusicoccin to inhibit seismonastic movements of M. pudica leaves and, at low concentrations, to promote leaflet opening in dark, indicating that its mode of action is more complex than the only activation of the PM-H+-ATPase. Various substitutions on 2,4D-L-Lys affected its activity in correlation with the molecular descriptor "halogen ratio" of these derivatives. Conjugation with D-Lys also led to a decrease of pulvinar reaction, suggesting that 2,4D-Lys maintains the main signaling properties of 2,4D involved in pulvinar movements providing that the terminal zwitterion is in a suitable orientation. Our data guide future investigations on the effect of 2,4D and 2,4D-L-Lys on the vacuolar pump activity of motor cells.

Implementation and Calibration of a Deep Neural Network to Predict Parameters of Left Ventricular Systolic Function Based on Pulmonary and Systemic Arterial Pressure Signals.

The evaluation of cardiac contractility by the assessment of the ventricular systolic elastance function is clinically challenging and cannot be easily obtained at the bedside. In this work, we present a framework characterizing left ventricular systolic function from clinically readily available data, including systemic and pulmonary arterial pressure signals. We implemented and calibrated a deep neural network (DNN) consisting of a multi-layer perceptron with 4 fully connected hidden layers and with 16 neurons per layer, which was trained with data obtained from a lumped model of the cardiovascular system modeling different levels of cardiac function. The lumped model included a function of circulatory autoregulation from carotid baroreceptors in pulsatile conditions. Inputs for the DNN were systemic and pulmonary arterial pressure curves. Outputs from the DNN were parameters of the lumped model characterizing left ventricular systolic function, especially end-systolic elastance. The DNN adequately performed and accurately recovered the relevant hemodynamic parameters with a mean relative error of less than 2%. Therefore, our framework can easily provide complex physiological parameters of cardiac contractility, which could lead to the development of invaluable tools for the clinical evaluation of patients with severe cardiac dysfunction.

Intrarachidial Misplacement of a Venous Stent for Iliofemoral Deep Vein Thrombosis.

INTRODUCTION: Complications due to venous thrombectomy and iliofemoral stenting in a patient with May-Thurner syndrome are reported. REPORT: The patient presented with a third episode of deep vein thrombosis (DVT). A computed tomography (CT) scan confirmed the clinical suspicion of left iliofemoral vein thrombosis. After thrombectomy and stenting, the patient complained of left foot paralysis. CT showed the misplaced stent to be in the intrarachidial space. Surgical removal of the stent and new endovascular stenting resulted in complete recovery. DISCUSSION: This is the first description of this kind of complication after stenting of the left iliofemoral vein. Peri-operative Xray appeared to confirm correct placement of the stent via bilateral femoral venous access. Is a profile control image necessary in patients with an important collateral venous network including large veins?

Vectorizing agrochemicals: enhancing bioavailability via carrier-mediated transport.

Systemicity of agrochemicals is an advantageous property for controlling phloem sucking insects, as well as pathogens and pests not accessible to contact products. After the penetration of the cuticle, the plasma membrane constitutes the main barrier to the entry of an agrochemical into the sap flow. The current strategy for developing systemic agrochemicals is to optimize the physicochemical properties of the molecules so that they can cross the plasma membrane by simple diffusion or ion trapping mechanisms. The main problem with current systemic compounds is that they move everywhere within the plant, and this non-controlled mobility results in the contamination of the plant parts consumed by vertebrates and pollinators. To achieve the site-targeted distribution of agrochemicals, a carrier-mediated propesticide strategy is proposed in this review. After conjugating a non-systemic agrochemical with a nutrient (α-amino acids or sugars), the resulting conjugate may be actively transported across the plasma membrane by nutrient-specific carriers. By applying this strategy, non-systemic active ingredients are expected to be delivered into the target organs of young plants, thus avoiding or minimizing subsequent undesirable redistribution. The development of this innovative strategy presents many challenges, but opens up a wide range of exciting possibilities. © 2018 Society of Chemical Industry.

Vectorization of agrochemicals: amino acid carriers are more efficient than sugar carriers to translocate phenylpyrrole conjugates in the Ricinus system.

Producing quality food in sufficient quantity while using less agrochemical inputs will be one of the great challenges of the twenty-first century. One way of achieving this goal is to greatly reduce the doses of plant protection compounds by improving the targeting of pests to eradicate. Therefore, we developed a vectorization strategy to confer phloem mobility to fenpiclonil, a contact fungicide from the phenylpyrrole family used as a model molecule. It consists in coupling the antifungal compound to an amino acid or a sugar, so that the resulting conjugates are handled by active nutrient transport systems. The method of click chemistry was used to synthesize three conjugates combining fenpiclonil to glucose or glutamic acid with a spacer containing a triazole ring. Systemicity tests with the Ricinus model have shown that the amino acid promoiety was clearly more favorable to phloem mobility than that of glucose. In addition, the transport of the amino acid conjugate is carrier mediated since the derivative of the L series was about five times more concentrated in the phloem sap than its counterpart of the D series. The systemicity of the L-derivative is pH dependent and almost completely inhibited by the protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP). These data suggest that the phloem transport of the L-derivative is governed by a stereospecific amino acid carrier system energized by the proton motive force.

Vectorisation of agrochemicals via amino acid carriers: influence of the spacer arm structure on the phloem mobility of phenylpyrrole conjugates in the Ricinus system.

BACKGROUND: Excessive agrochemical use poses significant threats to environmental safety and human health. Reducing pesticide use without reducing yield is necessary for sustainable agriculture. Therefore, we developed a vectorisation strategy to enhance agrochemical delivery through plant amino acid carriers. RESULTS: In addition to a fenpiclonil conjugate recently described, three new amino acid conjugates were synthesised by coupling fenpiclonil to an l-α-amino acid. Phloem mobility of these conjugates, which exhibit different structures of the spacer arm introduced between fenpiclonil and the α-amino acid function, was studied using the Ricinus model. Conjugate L-14, which contains a triazole ring with the shortest amino acid chain, showed the best phloem systemicity among the four conjugates. By contrast, removing the triazole ring in the spacer arm did not improve systemicity. L-14 exhibited phloem systemicity at all reported pH values (pH values from 5.0 to 6.5) of the foliar apoplast, while acidic derivatives of fenpiclonil were translocated only at pH values near 5.0. CONCLUSION: The conjugates were recognised by a pH-dependent transporter system and translocated at distance in the phloem. They exhibited a broader phloem systemicity than fenpiclonil acidic derivatives within the pH value range of the foliar apoplast. © 2017 Society of Chemical Industry.

Acidic derivatives of the fungicide fenpiclonil: effect of adding a methyl group to the N-substituted chain on systemicity and fungicidal activity.

A new acidic derivative of the fungicide fenpiclonil was synthesized containing a methyl group on the alpha-position of the carboxyl function of N-carboxymethyl-3-cyano-4-(2,3-dichlorophenyl)pyrrole. The phloem mobility of the resulting N-(1-carboxyethyl)-3-cyano-4-(2,3-dichlorophenyl)pyrrole was comparable with that of the former compound, but was higher at external pH 5.0. Unlike the derivatives previously synthesized, it was comparable with fenpiclonil in its fungicidal activity against the pathogenic fungus Eutypa lata.