M Karck

Ex vivo coronary angiography of a donor heart in the organ care system.

The international demand for donor hearts for transplantation is steadily increasing. Thus, longer transportation distances and explantation from sites with limited abilities for preexplantation diagnostics have to be considered. The development of the Organ Care System® (OCS) (TransMedics, Andover, MA, USA) may extend the extracorporeal period, with the possibility to constantly evaluate and interact during organ transport. One of the potential advantages of the OCS® is the ability to even perform coronary angiography of the donor heart, if a preexplantation angiography evaluation is not possible at the donor hospital and if significant evidence for coronary artery disease in the donor heart becomes known, because of the donors medical history or after palpation of sclerotic coronary ostia. In this report, we present the first ex vivo coronary angiography evaluation of a potential donor heart that was performed in the OCS®. Upon explantation of the donor heart, sclerosis of the left coronary artery was palpated. After reaching the implantation site, a coronary angiography was performed by placing the OCS® on a catheterization table and inserting a 6F sheath into the access site of the OCS®. A 6F guide catheter was used to intubate the left coronary ostium. Injection of contrast agent led to strong contrast for visualization of the left coronary system. This procedure allowed sufficient assessment of the coronary arteries, which showed a slight diffuse sclerosis without any significant stenosis. This report demonstrates the advantage of the OCS® in the complex assessment of donor hearts after explantation. While the donor heart is still in the OCS®, not only is it possible to measure metabolic parameters and pressures, but even coronary angiography is feasible. With the increasing international demand for donor organs, such ex vivo examinations might play a more important role, because longer transportation distances can be accepted and organs from suboptimal donors without preexplantation diagnostics may be considered at donor sites with limited diagnostic options.

Treatment of Brain-Dead Donor Rats with Dimethyloxalylglycine Improves Both Donor and Graft Left-Ventricular Function after Heart Transplantation

Introduction: Cardiac transplantation is the most effective treatment of end-stage heart failure. Brain dead (BD) donors are currently the only reliable source for cardiac grafts. However, hemodynamic instability and cardiac dysfunction have been demonstrated in BD donors and this could therefore also affect posttransplant graft function. Hypothesis: Based upon the protective effect of Prolyl-Hydroxylase (PHD)-Hypoxia Inducible Factor (HIF)-1 pathway against ischemia/reperfusion injury (IRI), we tested the hypothesis that treatment of BD donor rats with the non-selective PHD inhibitor dimethyloxalylglycine (DMOG) results in a better graft heart condition in recipients after heterotopic transplantation. Methods: Lewis rats were injected with one shot DMOG (30 mg/kg i.v.) (n = 7) or equal volume of physiological saline (n = 7) and maintained BD for 5h by a subdurally placed and inflated balloon catheter. Controls were sham-operated (n = 11). Then, hearts were explanted, stored in cold preservation solution, heterotopically transplanted and after 1.5h reperfusion left-ventricular (LV) graft function was evaluated in vivo. Myocardial histological and molecular biological analyses were performed. Results: BD was associated with decreased LV function. DMOG treatment of BD animals resulted in better load-independent contractility and end-diastolic stiffness parameters (ESPVR E´max (mmHg/µl): BD+DMOG: 3.7 ± 0.6 vs BD: 3.1 ± 0.5; EDPVR (mmHg/µl): BD+DMOG: 0.13 ± 0.03 vs BD: 0.31 ± 0.06 p < 0.05). Following transplantation, DMOG treatment of BD donors significantly improved the altered LV systolic and diastolic function (at 80µL volume dP/dtmax (mmHg/s): BD+DMOG: 2284 ± 213 vs BD: 1854 ± 124 p < 0.05; dP/dtmin (mmHg/s): BD+DMOG: 1586 ± 183 vs BD: 1154 ± 74, p < 0.05; Tau-W (ms): BD+DMOG: 33 ± 4 vs BD: 43 ± 9 p < 0.05). Significantly lower myocardial inflammatory cell infiltration and necrosis were detected along with, significantly lower DNA-strand breakage in the DMOG treated BD group compared with BD group. Conclusions: Pre-treatment of BD heart donors with DMOG resulted in a significantly better LV graft function after transplantation. These results support the view that preconditioning of BD donors through the activation of HIF-1 pathway has a protective role against myocardial IRI after transplantation.

Constrictive Pericarditis in the Presence of Remaining Remnants of a Left Ventricular Assist Device in a Heart Transplanted Patient

Constrictive pericarditis (CP) is a severe subform of pericarditis with various causes and clinical findings. Here, we present the unique case of CP in the presence of remaining remnants of a left ventricular assist device (LVAD) in a heart transplanted patient. A 63-year-old man presented at the Heidelberg Heart Center outpatient clinic with progressive dyspnea, fatigue, and loss of physical capacity. Heart transplantation (HTX) was performed at another heart center four years ago and postoperative clinical course was unremarkable so far. Pharmacological cardiac magnetic resonance imaging (MRI) stress test was performed to exclude coronary ischemia. The test was negative but, accidentally, a foreign body located in the epicardial adipose tissue was found. The foreign body was identified as the inflow pump connection of an LVAD which was left behind after HTX. Echocardiography and cardiac catheterization confirmed the diagnosis of CP. Surgical removal was performed and the epicardial tubular structure with a diameter of 30 mm was carefully removed accompanied by pericardiectomy. No postoperative complications occurred and the patient recovered uneventfully with a rapid improvement of symptoms. On follow-up 3 and 6 months later, the patient reported about a stable clinical course with improved physical capacity and absence of dyspnea.

Transfemoral biopsy--a routine procedure after orthotopic heart transplantation for dilated cardiomyopathy in a patient with persistent left superior vena cava and hypoplastic right superior vena cava.

INTRODUCTION The increasing number of end stage heart failure patients has caused a high number of transplant candidates, including patients with concomitant other cardiac abnormalities. Congenital heart failure can exhibit changes in a variety of anatomic landmarks, and performing heart transplantation in this setting can be challenging. Monitoring for possible rejection is done via intramyocardial biopsies. Here the difficulties arise from variations in anatomic structures. BACKGROUND We present a case of a persistent left superior vena cava discovered intraoperatively during heart transplantation. The patient was a 45-year-old man who underwent transplantation for a severely reduced left ventricular function, along with a high left ventricular end-diastolic pressure and and end stage heart failure. DISCUSSION In previous cases, the biopsy was performed by means of left-sided transjugular venous access. Bearing the well-known complications in mind, we chose the transfemoral access so we could take biopsies postoperatively. Biopsies in patients with persistent left vena cava should routinely be performed using the transfemoral access.

The novel synthetic serine-protease inhibitor CU2010 dose-dependently reduces postoperative blood loss and improves postischemic recovery myocardial and endothelial function

Objective: Serine-protease inhibitors such as aprotinin reduce perioperative blood loss and may improve post pump cardiac performance due to their anti-inflammatory properties. After the „aprotinin era“, we investigated the efficacy of the novel synthetic serine-protease inhibitor CU2010 on blood loss and reperfusion injuryin a canine model. Methods: 36 dogs were divided into six groups: control, aprotinin (Hammersmith scheme), and CU2010 (0.5, 0.83, 1.25 and 1.66mg/kg). All animals underwent 90-minute cardiopulmonary bypass with 60 minutes of hypothermic cardioplegic arrest. Endpoints were blood loss during the first two hours after protamin, recovery of myocardial contractility (slope of the end-systolic pressure volume relationship, Ees), coronary blood flow and vascular reactivity. Results: CU2010 dose-dependently reduced blood loss comparble to aprotinin (Figure 1, *p<0.05). While aprotinin did not influence myocardial function CU2010 improved the recovery of Ees (control: 60±6 vs. aprotinin: 73±7 vs. CU2010: 102±8%, p<0.05). Coronary blood flow (52±4 vs. 88±7 vs. 96±7%, p<0.05) and response to acethylcholine (44±6 vs. 77±7 vs. 81±6%, p<0.05) was improved by both aprotinin and CU2010. Conclusions: The novel serine-protease inhibitor CU2010 significantly reduce blood loss comparable to aprotinin. Furthermore, it led to a significantly improved postischemic recovery of myocardial and endothelial function.

Development of a biological cardiac pacemaker using gene therapy in a preclinical model

Objective: When cardiac atrioventricular nodal cells are damaged by disease, the implantation of a cardiac pacemaker becomes necessary. Several limitations and problems of artificial pacemakers have emerged during the past decades. In children and newborn babies with arrhythmia, initial size mismatch and their growth can pose a problem. Lead extraction and infections have additional risks. The aim of our study was the development of a biological cardiac pacemaker by in-vivo adenoviral transfection of ventricular cardiomyocytes in a large animal model with the gene encoding for Adenylate-Cyclase type VI (ACVI) in order to increase the intracellular concentration of cAMP and intrinsic rhythmic rate of the transfected cells, enabling ectopic pacing from the injection site. Methods: Using an adenoviral vehicle, the Adenylate Cyclase gene was injected into the free wall of the left ventricle of adult pigs via anterolateral thoracotomy. The control group received the same amount of β-Galactosidase reporter genes. After 12 days, the animals under went fluoroscopy and the AV-node was interventionally ablated with simultaneous three-dimensional cardiac mapping using the ENSITE®-system in order to locate the origin of the escape rhythm. Results: All animals treated with the ACVI gene exhibited an escape rhythm which originated in the left ventricle while the animals of the control group all had a right-ventricular escape rhythm. Western blot analysis confirmed a significantly higher expression of ACVI at the site of gene injection. Conclusions: Gene therapy for transformation of ventricular cardiomyocytes into pacemaker cells may open a new perspective for the treatment of atrioventricular block.