Mitochondrial transplantation normalizes transcriptomic and proteomic shift associated with ischemia reperfusion injury in neonatal hearts donated after circulatory death.

Heart transplantation remains the ultimate treatment strategy for neonates and children with medically refractory end-stage heart failure and utilization of donors after circulatory death (DCD) can expand th donor pool. We have previously shown that mitochondrial transplantation preserves myocardial function and viability in neonatal swine DCD hearts to levels similar to that observed in donation after brain death (DBD). Herein, we sought to investigate the transcriptomic and proteomic pathways implicated in these phenotypic changes using ex situ perfused swine hearts.

Robotic right ventricle is a biohybrid platform that simulates right ventricular function in (patho)physiological conditions and intervention.

The increasing recognition of the right ventricle (RV) necessitates the development of RV-focused interventions, devices and testbeds. In this study, we developed a soft robotic model of the right heart that accurately mimics RV biomechanics and hemodynamics, including free wall, septal and valve motion. This model uses a biohybrid approach, combining a chemically treated endocardial scaffold with a soft robotic synthetic myocardium.

Biorobotic hybrid heart as a benchtop cardiac mitral valve simulator.

In this work, we developed a high-fidelity beating heart simulator that provides accurate mitral valve pathophysiology. The benchtop platform is based on a biorobotic hybrid heart that combines preserved intracardiac tissue with soft robotic cardiac muscle providing dynamic left ventricular motion and precise anatomical features designed for testing intracardiac devices, particularly for mitral valve repair. The heart model is integrated into a mock circulatory loop, and the active myocardium drives fluid circulation producing physiological hemodynamics without an external pulsatile pump.

Soft robotics-enabled large animal model of HFpEF hemodynamics for device testing.

Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular medicine, accounting for approximately 50% of all cases of heart failure. Due to the lack of effective therapies for this condition, the mortality associated with HFpEF remains higher than that of most cancers. Despite the ongoing efforts, no medical device has yet received FDA approval.

Mitochondrial transplantation preserves myocardial function and viability in pediatric and neonatal pig hearts donated after circulatory death.

Objective: Mitochondrial transplantation has been shown to preserve myocardial function and viability in adult porcine hearts donated after circulatory death (DCD) . Herein, we investigate the efficacy of mitochondrial transplantation for the preservation of myocardial function and viability in neonatal and pediatric porcine DCD heart donation.

Methods: Circulatory death was induced in neonatal and pediatric Yorkshire pigs by cessation of mechanical ventilation.

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.

Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists.

Kynurenic acid (KynA) is tissue protective in cardiac, cerebral, renal, and retinal ischemia models, but the mechanism is unknown. KynA can bind to multiple receptors, including the aryl hydrocarbon receptor, the a7 nicotinic acetylcholine receptor (a7nAChR), multiple ionotropic glutamate receptors, and the orphan G protein-coupled receptor GPR35. Here, we show that GPR35 activation was necessary and sufficient for ischemic protection by KynA.

Major Aortopulmonary Collateral Arteries Requiring Percutaneous Intervention Following the Arterial Switch Operation: A Case Series and Systematic Review.

Dextro transposition of the great arteries (d-TGA) is the most common critical congenital cardiac defect surgically treated in the neonatal period by arterial switch operation (ASO). Major aortopulmonary collaterals (MAPCAs) can be present in this population and may complicate the early postoperative period. Our aim was to review our institutional data and systematically review the available literature to provide further insight on the clinical significance of MAPCAs during the early postoperative course after ASO.

Tricuspid valve repair concomitant with the Norwood operation among babies with hypoplastic left heart syndrome.

Objectives: Among patients with hypoplastic left heart syndrome (HLHS), tricuspid valve regurgitation (TR) portends a poor prognosis. Our goal was to describe the outcomes of tricuspid valve reconstruction (TVR) concomitant with the Norwood operation and using two-dimensional echocardiography and evaluate the structural factors associated with successful functional correction.

Methods: We performed a retrospective, single-centre study of patients with HLHS undergoing TVR at the time of the Norwood operation.

The feasibility of mitral valve device foldoplasty: an in vivo study to evaluate durable retention.

Objectives: We have previously shown in experimental settings that a leaflet foldoplasty device reduces redundant leaflet area to re-establish mitral valve (MV) coaptation. The current study investigates the in vivo device retention and functional durability following foldoplasty.

Methods: The prototype is of superelastic nitinol formed into a 3-dimensional shape.

Importance of Preserved Tricuspid Valve Function for Effective Soft Robotic Augmentation of the Right Ventricle in Cases of Elevated Pulmonary Artery Pressure.

Purpose: In clinical practice, many patients with right heart failure (RHF) have elevated pulmonary artery pressures and increased afterload on the right ventricle (RV). In this study, we evaluated the feasibility of RV augmentation using a soft robotic right ventricular assist device (SRVAD), in cases of increased RV afterload.

Methods: In nine Yorkshire swine of 65-80 kg, a pulmonary artery band was placed to cause RHF and maintained in place to simulate an ongoing elevated afterload on the RV.

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion.

Acute kidney injury (AKI) is associated with higher risk for morbidity and mortality post-operatively. Ischemia-reperfusion injury (IRI) is the most common cause of AKI. To mimic this clinical scenario, this study presents a highly reproducible large animal model of renal IRI in swine using temporary percutaneous bilateral balloon-catheter occlusion of the renal arteries.

A Multi-Mode System for Myocardial Functional and Physiological Assessment during Ex Situ Heart Perfusion.

Ex situ heart perfusion (ESHP) has proven to be an important and valuable step toward better preservation of donor hearts for heart transplantation. Currently, few ESHP systems allow for a convenient functional and physiological evaluation of the heart. We sought to establish a simple system that provides functional and physiological assessment of the heart during ESHP.

Outcomes after the Fontan operation in the Middle East: A large Saudi Arabian single centre experience.

Background: Fontan outcomes data from large volume Middle Eastern Centres are lacking. We report our experience after the Fontan operation from a tertiary cardiac centre in Saudi Arabia.

Method: All 458 consecutive patients who had Fontan surgery 1986 through 2015 at the Prince Sultan Cardiac Centre, Riyadh [PSCC], Saudi Arabia, were evaluated for baseline, early and late post-operative outcomes and their uni and multivariate determinants.

An organosynthetic dynamic heart model with enhanced biomimicry guided by cardiac diffusion tensor imaging.

The complex motion of the beating heart is accomplished by the spatial arrangement of contracting cardiomyocytes with varying orientation across the transmural layers, which is difficult to imitate in organic or synthetic models. High-fidelity testing of intracardiac devices requires anthropomorphic, dynamic cardiac models that represent this complex motion while maintaining the intricate anatomical structures inside the heart. In this work, we introduce a biorobotic hybrid heart that preserves organic intracardiac structures and mimics cardiac motion by replicating the cardiac myofiber architecture of the left ventricle.

Autogenous mitochondria transplantation for treatment of right heart failure.

Background: Right ventricular hypertrophy and failure are major causes of cardiac morbidity and mortality. A key event in the progression to right ventricular hypertrophy and failure is cardiomyocyte apoptosis due to mitochondrial dysfunction. We sought to determine whether localized intramyocardial injection of autologous mitochondria from healthy muscle treats heart failure.

Mitochondrial transplantation for myocardial protection in ex-situ‒perfused hearts donated after circulatory death.

Background: Donation after circulatory death (DCD) offers an additional source of cardiac allografts, potentially allowing expansion of the donor pool, but is limited owing to the effects of ischemia. In this study, we investigated the efficacy of mitochondrial transplantation to enhance myocardial function of DCD hearts.

Methods: Circulatory death was induced in Yorkshire pigs (40-50 kg, n = 29) by a cessation of mechanical ventilation.

Mitochondrial transplantation by intra-arterial injection for acute kidney injury.

Acute kidney injury is a common clinical disorder and one of the major causes of morbidity and mortality in the postoperative period. In this study, the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury were investigated. Female Yorkshire pigs underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon catheters.

Dynamic Augmentation of Left Ventricle and Mitral Valve Function With an Implantable Soft Robotic Device.

Left ventricular failure is strongly associated with secondary mitral valve regurgitation. Implantable soft robotic devices are an emerging technology that enables augmentation of a native function of a target tissue. We demonstrate the ability of a novel soft robotic ventricular assist device to dynamically augment left ventricular contraction, provide native pulsatile flow, simultaneously reshape the mitral valve apparatus, and eliminate the associated regurgitation in an Short-term large animal model of acute left ventricular systolic dysfunction.

A geometrically adaptable heart valve replacement.

Congenital heart valve disease has life-threatening consequences that warrant early valve replacement; however, the development of a growth-accommodating prosthetic valve has remained elusive. Thousands of children continue to face multiple high-risk open-heart operations to replace valves that they have outgrown. Here, we demonstrate a biomimetic prosthetic valve that is geometrically adaptable to accommodate somatic growth and structural asymmetries within the heart.

A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy.

Mitochondrial dysfunction is the determinant insult of ischemia-reperfusion injury. Autologous mitochondrial transplantation involves supplying one's healthy mitochondria to the ischemic region harboring damaged mitochondria. The authors used in vivo swine to show that mitochondrial transplantation in the heart by intracoronary delivery is safe, with specific distribution to the heart, and results in significant increase in coronary blood flow, which requires intact mitochondrial viability, adenosine triphosphate production, and, in part, the activation of vascular K channels.

An Imaging Protocol to Discriminate Specialized Conduction Tissue During Congenital Heart Surgery.

We performed preclinical validation of intraoperative fiber-optic confocal microscopy (FCM) and assessed its safety and efficacy in an ovine model of the pediatric heart. Intraoperative imaging was performed using an FCM system (Cellvizio, Mauna Kea Technology, Paris, France) with specialized imaging miniprobe (GastroFlex UHD, Mauna Kea Technologies). Before imaging, we applied an extracellular fluorophore, sodium fluorescein, to fluorescently label extracellular space.

A leaflet plication clip is an effective surgical template for mitral valve foldoplasty.

Objectives: During mitral valve repair using the foldoplasty technique, correct judgement of the necessary dimensions and orientation of the leaflet fold is a critical but challenging step that can affect the chances of successful repair. In this study, we investigated whether a leaflet plication clip can be used to guide suture foldoplasty for posterior leaflet prolapse of the mitral valve.

Methods: Complete posterior leaflet prolapse was created in both in vivo and ex vivo pig hearts by severing the chordae supporting the middle scallop.

An Implantable Extracardiac Soft Robotic Device for the Failing Heart: Mechanical Coupling and Synchronization.

Soft robotic devices have significant potential for medical device applications that warrant safe synergistic interaction with humans. This article describes the optimization of an implantable soft robotic system for heart failure whereby soft actuators wrapped around the ventricles are programmed to contract and relax in synchrony with the beating heart. Elastic elements integrated into the soft actuators provide recoiling function so as to aid refilling during the diastolic phase of the cardiac cycle.

Soft robotic ventricular assist device with septal bracing for therapy of heart failure.

Previous soft robotic ventricular assist devices have generally targeted biventricular heart failure and have not engaged the interventricular septum that plays a critical role in blood ejection from the ventricle. We propose implantable soft robotic devices to augment cardiac function in isolated left or right heart failure by applying rhythmic loading to either ventricle. Our devices anchor to the interventricular septum and apply forces to the free wall of the ventricle to cause approximation of the septum and free wall in systole and assist with recoil in diastole.