Empagliflozin (EMPA), an inhibitor of sodium-glucose co-transporter 2 (SGLT2), significantly reduces cardiovascular mortality and heart failure hospitalisation in both diabetic and non-diabetic patients. The mechanism underlying this improvement in clinical outcome remains unclear as SGLT2 is not expressed in the heart. Previous studies have found that EMPA inhibits the sodium hydrogen exchanger, which is activated during and after induction of myocardial ischaemia. To investigate if acute administration of EMPA reduces myocardial infarct (MI) size. C57BL/6 mice underwent permanent ligation of the left anterior descending coronary artery to induce MI. Following surgery and before withdrawal of anaesthesia, animals were randomised to receive saline (N=11) or EMPA (10 mg/kg) by intraperitoneal (IP, N=13) administration. Compared with a saline control, IP administration of EMPA resulted in a significant (49%) reduction in infarct size (8.9±5.6 vs 17.3±4.1, respectively; p<0.001) as a percentage of left ventricular area An acute single bolus dose of IP EMPA is cardioprotective, as evidenced by an attenuation of cardiac infarct size. The benefit of EMPA in reducing MI size indicates its potential clinical use as an adjunctive therapy in patients suffering acute MI, particularly those without access to immediate reperfusion therapy.

Background:Posttransplant immunosuppression in kidney transplant recipients is associated with an increased risk of developing cutaneous squamous cell carcinoma (CSCC), contributing to significant morbidity and mortality. Various dermatological and immunosuppression modulation strategies have been identified that may reduce the risk of CSCC, both in primary and secondary prevention settings. Recent recommendations have provided consensus regarding dermatological approaches to prevent CSCC. Comparable transplant nephrology recommendations to guide immunosuppression modulation for CSCC prevention are currently lacking, leading to marked variation in practice. Methods:To address this knowledge gap, 46 international transplant nephrology experts participated in a 3-round Delphi survey to develop consensus recommendations for CSCC secondary prevention based on the actinic damage and skin cancer index stages of CSCC. Results:The panel of experts reached consensus to consider a change in immunosuppression after multiple low-risk invasive CSCC (stage 5a, 1/y >3 y) and encouraged collaboration with dermatology to optimize dermatologic preventative care after the first CSCC. There was also consensus to prioritize azathioprine modification where this is present in an immunosuppressive regimen. Conclusions:This study provides the first international consensus recommendations for management of immunosuppression in kidney transplant recipients at discrete stages of CSCC. Additional prospective studies are necessary to determine the optimal management of immunosuppression in this patient population. These recommendations have been endorsed by the Board of the American Society of Transplantation.

Purpose: To describe a novel case of donor-derived scedosporium infection following kidney transplantation presenting as endogenous endophthalmitis. Observations: A 69 year-old male presented with right eye pain and redness for 3 days following deceased donor kidney transplant one month prior. Initial exam showed counting fingers vision, 4+ anterior chamber cell, hypopyon, dense vitritis, and a large white macular lesion. A vitreous tap and inject was performed with intravitreal vancomycin, ceftazidime, and voriconazole. The patient was admitted to the for systemic antimicrobials where infectious workup revealed a psoas abscess and a perinephric donor kidney fluid collection with biopsy of the fluid yielding positive Scedosporium spp. Given his multifocal systemic infection, recent transplantation, and immunosuppression requirements, a review of the donor history was performed and revealed evidence of systemic Scedosporium infection. A diagnosis of donor-derived Scedosporium infection was made. The other transplant centers where the other organs from this donor were used were contacted and each of their recipients were screened, however, no other donor-derived infections were found. Conclusions and importance: Donor derived scedosporium infections can have devastating ophthalmologic and systemic complications in solid organ transplant recipients. Further efforts are warranted to better screen for the risk for deceased donor fungal infections during transplant organ evaluation.

Purpose: Heart transplantation from donation after circulatory death (DCD) donors has expanded the donor pool. Global experience with older DCD donor hearts is limited. In January 2018 our unit increased the DCD donor heart age limit from 40yrs to 55yrs. In this study we review the outcomes of heart transplants (HTs) from younger (age <40 yrs) versus older DCD heart donors (age >40yrs).

The outcomes for patients implanted with left ventricular assist devices are continuously improving as demonstrated by recent studies. However, options for durable biventricular support remain limited with the Syncardia total artificial heart being the only FDA approved device available. BiVACOR is a future device featuring a magnetically levitated impeller that supports pulsatile flow. This study discusses the pump implant process in a series of acute large animals.

Venkata, Varsha Reddy Pothula; Warburton, Karen M.; Kamal, Jeanne; Glass, William F.; Doyle, Alden M. Author Information

Purpose: Hypothermic machine perfusion (HMP) is an emerging method of donor organ preservation.Its application for heart transplantation is currently being studied in a clinical trial.Due to the limited ability to assess graft quality during HMP, a reliable prognostic biomarker is needed for quality assessment and prediction of heart function after implantation.This study was designed to identify prognostic biomarkers during HMP of porcine hearts using a multitargeted approach.Methods: A total of 7 slaughterhouse porcine hearts were subjected to 4 hours HMP, followed by 4 hours of normothermic machine perfusion (NMP) for functional assessment.Perfusate samples were collected at baseline and after 4 hours of HMP, for analysis of damage markers and cell-free DNA.Additionally, an Olink Organ Damage T96 panel was performed, after which proteins of interest were identified based on a significant change in expression between baseline and 4 hours HMP.Prognostic value of each protein of interest was determined by correlating expression values at the end of HMP with cardiac function after 4 hours of NMP using Spearman's R. Results: Both ammonia (r=0.8571;P=0.0238) and troponin-I (r=0.7857;P=0.0480) were positively correlated with cardiac index, while lactate (r=-0.8108;P=0.0381) was negatively correlated with coronary flow index.Both mitochondrial and nuclear cell-free DNA displayed a decrease in expression during HMP and showed no significant correlation with cardiac function.Olink data revealed that YES1 was negatively correlated with cardiac index (r=-0.8571;P=0.0238), coronary flow (r=-0.7857;P=0.0480) and coronary flow index (r=-0.8571;P=0.0238).Conclusion: Our study identifies YES1 as a potential prognostic biomarker when assessed during HMP, as reflected by the negative correlation with cardiac function.Future research into the translational value of YES1 and the involved physiological pathways is needed.Furthermore, troponin-I expression during HMP shows an interesting inverse correlation with functional outcome.We hypothesize that the increased troponin-I values during HMP are reflective of improved wash-out of damage markers due to better preserved microvasculature.This might explain the improved function of hearts with high troponin-I expression during HMP.

Purpose In DCD heart transplantation an asystolic warm ischemic time (aWIT) of >15mins is associated with increased ECMO requirement for primary graft dysfunction. Increasing aWIT tolerance could improve the number/quality of hearts transplanted. Hi1a (a funnel-web spider derived Acid-Sensing Ion Channel 1a inhibitor) has shown cardioprotective promise in pre-clinical studies. We investigate in a porcine model if adding Hi1a to DCD hearts could improve aWIT tolerance. Methods Hearts were retrieved from Landrace pigs utilizing a direct-procurement DCD protocol with varying aWIT prior to cardioplegia and ante/post-mortem pharmacological interventions. All groups received St.Thomas Cardioplegia. Groups include: i.) 0mins aWIT with antemortem heparin(control, n=4); ii.) 20min aWIT with no ante/post-mortem pharmacological intervention(n=3); iii.) 20min aWIT with antemortem heparin and post-mortem tirofiban(n=3); iv.) 20min aWIT with antemortem heparin, cardioplegia & blood collection bag supplemented with Hi1a, and, post-mortem tirofiban(n=3). The isolated pig heart was then subject to: 1hr of ex-situ normothermic Langendorff reperfusion, followed by 1hr of working-mode assessment. Following this a left atrial pressure (LAP) challenge was performed with aortic flows measured to assess LV contractility in response to set left atrial pressures. Results Image 1 surmises LAP challenge results. After exposure to 20mins of aWIT, only hearts supplemented with cardioplegia containing Hi1a and perfused utilizing a blood collection reservoir containing Hi1a generated a Starling response on par with the control group (exposed to 0mins aWIT) (p=0.996, Two-way ANOVA). Groups exposed to 20mins aWIT without Hi1a performed significantly worse (p<0.001, Two-way ANOVA). Conclusion Adding Hi1a to cardioplegia & the blood collection reservoir enables isolated pig hearts to tolerate 20mins of aWIT in a DCD retrieval protocol. This warrants further exploration in the setting of DCD heart preservation.