Platelet Activation on Lung Function During Ex Vivo Lung Perfusion, Lung Transplantation, and the Role of Antiplatelet Therapy: A Narrative Review.

Background: Ischemia/reperfusion injury after lung transplantation is a significant cause of morbidity. In the realm of ex vivo lung perfusion (EVLP), inflammation, edema formation, and reduced compliance have limited the durability of EVLP. Previous evidence has suggested that platelet activation and thrombosis may play a role in both conditions.

Cysteine oxidation of a redox hub within complex I can facilitate electron transport chain supercomplex formation.

The mitochondrial electron transport chain (ETC) is a four complex unit that could be considered the most essential infrastructure within the mitochondria, as it primarily functions to generate the mitochondrial membrane potential (ΔΨm), which can then be utilized for ATP synthesis or heat production. Another important aspect of ETC function is the generation of mitochondrial reactive oxygen species (mtROS), which are essential physiologic signaling mediators that can be toxic to the cell if their levels become too high. Currently, it remains unresolved how a highly utilized and functioning ETC can sense excessive mtROS generation and adapt, to enhance ΔΨm.

Evaluating the Prevalence of Optimal Neurodevelopmental Outcome at 2 Years in Children Previously on Ventricular Assist Device Support.

Background: Literature reporting neurodevelopmental outcomes for patients who undergo ventricular assist device (VAD) therapy is limited to posttransplant cohorts. This study aims to determine the prevalence of optimal neurodevelopmental outcome and factors associated with nonoptimal outcome in patients implanted with a VAD at ≤15 months of age.

Methods: Patients followed by the Complex Pediatric Therapies Follow-Up Program were included in a prospective-inception cohort study if born between January 2006 and December 2022 and implanted with a VAD at ≤15 months of age.

A Systematic Review of Minimally Invasive Approaches to Surgical Atrial Septal Defect Repair.

Aim: Atrial septal defects (ASD) are the most common congenital cardiac malformations. Over the preceding decades, a host of minimally invasive and interventional techniques for ASD closure have emerged. Minimally invasive ASD (MIASD) repair utilises thoracotomies, endoscopic, robotic, and even beating heart approaches to facilitate MIASD repair.

Plasma-supplemented red cell concentrates as alternatives to whole blood in porcine ex vivo heart perfusion.

Background: Normothermic ex vivo organ perfusion holds promise for increasing the organ donor pool; however, standard use of autologous whole blood (WB) presents logistical and functional challenges. This study compared red cell concentrate (RCC)-, rejuvenated RCC-, and WB-based perfusates over a 4-hour ex vivo heart perfusion (EVHP) to assess blood quality and its impact on myocardial function.

Methods: Porcine WB was leukodepleted and hypothermically stored until perfusion.

The approach to placement of a continuous-flow intracorporeal ventricular assist device in small left ventricle.

Background: The HeartMate 3 (HM3) has become among the most widely utilized durable left ventricular (LV) assist devices (LVAD) owing to reduced rates of pump thrombosis, bleeding, and stroke. One limitation of the HM3 is its large size, which poses a challenge for implantation in smaller LVs. Herein, we describe a novel technique for durable LVAD implantation in patients with a small LV.

Cardiac allograft vasculopathy and the endothelial glycocalyx: a missing link?

Cardiac allograft vasculopathy (CAV) is a significant contributor to graft loss following heart transplantation, with a linear cumulative incidence over time. Both immune and non-immune risk factors are associated with the development of CAV, however, a cohesive mechanistic link between them is yet to be established. Immune and non-immune risk factors may be linked to CAV via disturbance of the endothelial glycocalyx (EGX), a protective vascular structure whose functions appear to be impaired in the context of CAV progression.

Severe primary graft failure: Are there lasting impacts? Analysis from the PHTS Database.

Background: Primary graft failure (PGF) is a leading cause of early morbidity and mortality after heart transplantation (HTx). PGF is secondary to graft ischemia and ischemia-reperfusion injuries to the cardiomyocytes and vasculature of the donor heart after transplantation. Longer-term outcomes after PGF are not well studied.

Evaluation of target temperature on effectiveness of myocardial preservation during hypothermic machine perfusion.

Background: Ex-situ heart perfusion (ESHP) has been proposed as an optimal method for preserving donated hearts prior to transplantation. Hypothermic oxygenated perfusion (HOP) is a simple method from a device design perspective, with enhanced safety compared to normothermic perfusion in the event of device failure. However, the optimal temperature for cardiac HOP has yet to be determined.

Protective effects of cyclosporine and its analog NIM-811 in a murine model of hepatic ischemia-reperfusion injury.

Background And Aim: The liver is susceptible to ischemia-reperfusion injury (IRI) during hepatic surgery, when the vessels are compressed to control bleeding, or liver transplantation, when there is an obligate period of ischemia. The hallmark of IRI comprises mitochondrial dysfunction, which generates reactive oxygen species, and cell death through necrosis or apoptosis. Cyclosporine (CsA), which is a well-known immunosuppressive agent that inhibits calcineurin, has the additional effect of inhibiting the mitochondrial permeability transition pore (mPTP), thereby, preventing mitochondrial swelling and injury.

The role of diagnostic modalities in differentiating hypertensive heart disease and hypertrophic cardiomyopathy: strategies in adults for potential application in paediatrics.

Hypertensive heart disease and hypertrophic cardiomyopathy both lead to left ventricular hypertrophy despite differing in aetiology. Elucidating the correct aetiology of the presenting hypertrophy can be a challenge for clinicians, especially in patients with overlapping risk factors. Furthermore, drugs typically used to combat hypertensive heart disease may be contraindicated for the treatment of hypertrophic cardiomyopathy, making the correct diagnosis imperative.

Negative Pressure Ventilation Ex-Situ Lung Perfusion Preserves Porcine and Human Lungs for 36-Hours.

Introduction: Preclinically, 24-hour continuous Ex-Situ Lung Perfusion (ESLP) is the longest duration achieved in large animal models and rejected human lungs. Here, we present our 36-hour Negative Pressure Ventilation (NPV)-ESLP protocol applied to porcine and rejected human lungs.

Methods: Five sets of donor domestic pig lungs (45-55 kg) underwent 36-hour NPV-ESLP.

Subnormothermic Machine Perfusion of Neonatal and Small-Sized Pediatric Donor Hearts.

Donor heart machine perfusion enables avoidance of prolonged cold ischemia, however the optimal temperature is yet to be elucidated. Given that maintenance of temperature beyond ambient levels demands significant energy, we sought to determine the suitability of room-temperature perfusion preservation of neonatal/pediatric-sized (5-20 kg) piglet donor hearts. A custom device was fabricated suitable for this purpose, with continuous readout of perfusion pressure, flow rate, temperature, and oxygen saturation.

Mild Permissive Alkalosis Improves Outcomes in Porcine Negative Pressure Ventilation Ex-Situ Lung Perfusion.

Background: Ex-Situ Lung Perfusion (ESLP) employs a membrane deoxygenator and mixed (N/O/CO) or pure sweep gas (CO) to target venous blood gas composition with physiologic pCO and pH. Clinically, mild permissive alkalosis counteracts elevated pulmonary vascular resistance (PVR) to improve perfusion. Increased PVR and pulmonary artery pressure (PAP) during ESLP mirrors rising pro-inflammatory cytokines.

Mitral Valve Repair in Patients with Chronic Kidney Disease: Long-Term Outcomes and Cardiac Remodeling.

Objectives: Literature examining mitral valve repair (MVr) outcomes in patients with chronic kidney disease (CKD) is largely limited to short-term outcomes and percutaneous approaches. This study is the first to present long-term outcomes of mortality and morbidity with paired cardiac remodeling data from patients with CKD undergoing surgical MVr.

Design: A retrospective, observational, comparative study.

Risk factors for thromboembolic events in pediatric patients with ventricular assist devices.

Objective: Pediatric patients on ventricular assist devices (VAD) are at risk of thromboembolic (TE) complications. Our objective was to identify factors associated with TE events, including the role of initial anticoagulation strategy and device type in the pediatric VAD population.

Methods: This was a retrospective, single-center review (2005-2022) of children who were implanted with paracorporeal pulsatile (PP), paracorporeal continuous (PC), or a combination of devices.

First North American experience with the Berlin Heart EXCOR Active driver.

For smaller pediatric patients on ventricular assist devices, the Berlin Heart EXCOR remains the main form of durable support. It requires a connection to the external IKUS, which has limited portability and battery life. The new EXCOR Active mobile driving unit has a battery life of up to 13 hours.

Normothermic Perfusion is Superior to Cold Perfusion in Porcine Ex Situ Lung Perfusion.

Background: Cold ex situ lung perfusion (ESLP) has demonstrated improved preservation in small animal ESLP compared to normothermic ESLP and cold static preservation. We hypothesized that cold negative pressure ventilation (NPV)-ESLP would improve graft function in a porcine transplantation model.

Methods: Four perfusate temperatures were examined with 12 hours NPV-ESLP in a large animal transplantation model.

Optimizing Resuscitation of the Donation after Circulatory Death Heart by Mitochondrial Protection in a Female Porcine Model.

Background: Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death [DCD]). Using a translational porcine model of DCD, this study developed and evaluated a protocol based on cardioprotection by multidrug postconditioning to optimize resuscitation of DCD hearts during ex situ heart perfusion (ESHP).

Methods: Hearts of female pigs (45.

Relation of body mass index to long-term survival and cardiac remodelling for patients undergoing mitral valve replacement surgery.

Background And Aims: Studies have demonstrated that obesity is paradoxically associated with reduced mortality following cardiac surgery. However, these studies have treated various types of cardiac surgery as a single entity. With mitral valve (MV) surgeries being the fastest-growing cardiac surgical interventions in North America, the purpose of this study was to identify the impact of body mass index (BMI) on long-term survival and cardiac remodelling of patients undergoing MV replacement (MVR).

The Effects of Oxygen-Derived Free-Radical Scavengers During Normothermic Ex-Situ Heart Perfusion.

Oxidative stress occurs during ex-situ heart perfusion (ESHP) and may negatively affect functional preservation of the heart. We sought to assess the status of key antioxidant enzymes during ESHP, and the effects of augmenting these antioxidants on the attenuation of oxidative stress and improvement of myocardial and endothelial preservation in ESHP. Porcine hearts were perfused for 6 hours with oxygen-derived free-radical scavengers polyethylene glycol (PEG)-catalase or PEG-superoxide dismutase (SOD) or with naive perfusate (control).

Cyclosporine A Does Not Mitigate Liver Ischemia/Reperfusion Injury in an Ex Vivo Porcine Model of Donation After Circulatory Death.

BACKGROUND Ischemia/reperfusion injury (IRI) is an inherent problem in organ transplantation, owing to the obligate period of ischemia that organs must endure. Cyclosporine A (CsA), though better know as an immunosuppressant, has been shown to mitigate warm IRI in a variety of organ types, including the liver. However, there is little evidence for CsA in preventing hepatic IRI in the transplant setting.