evaluation of the whole heart function allowing selective investigation of the right and left heart.

. The aim was to demonstrate a reliable method to test the function of the whole heart. .

Excitation and contraction of cardiac muscle and coronary arteries of brain-dead pigs.

Excitability and contraction of cardiac muscle from brain-dead donors critically influence the success of heart transplantation. Membrane physiology, Ca-handling, and force production of cardiac muscle and the contractile properties of coronary arteries were studied in hearts of brain-dead pigs. Cardiac muscle and vascular function after 12 h brain death (decapitation between C2 and C3) were compared with properties of fresh tissue.

A novel nonlinear afterload for ex vivo heart evaluation: Porcine experimental results.

Background: Existing working heart models for ex vivo functional evaluation of donor hearts often use cardiac afterloads made up of discrete resistive and compliant elements. This approach limits the practicality of independently controlling systolic and diastolic aortic pressure to safely test the heart under multiple loading conditions. We present and investigate a novel afterload concept designed to enable such control.

Prevention of Ischemic Myocardial Contracture Through Hemodynamically Controlled DCD.

Purpose: Ischemic myocardial contracture (IMC) or "stone heart" is a condition with rapid onset following circulatory death. It inhibits transplantability of hearts donated upon circulatory death (DCD). We investigate the effectiveness of hemodynamic normalization upon withdrawal of life-sustaining therapy (WLST) in a large-animal controlled DCD model, with the hypothesis that reduction in cardiac work delays the onset of IMC.

Non-ischemic Heart Preservation via Hypothermic Cardioplegic Perfusion Induces Immunodepletion of Donor Hearts Resulting in Diminished Graft Infiltration Following Transplantation.

Many donor organs contain significant leukocyte reservoirs which upon transplantation activate recipient leukocytes to initiate acute rejection. We aimed to assess whether non-ischemic heart preservation via perfusion promotes immunodepletion and alters the inflammatory status of the donor organ prior to transplantation. Isolated porcine hearts underwent hypothermic, cardioplegic perfusion for 8 h.

Cold non-ischemic heart preservation with continuous perfusion prevents early graft failure in orthotopic pig-to-baboon xenotransplantation.

Background: Successful preclinical transplantations of porcine hearts into baboon recipients are required before commencing clinical trials. Despite years of research, over half of the orthotopic cardiac xenografts were lost during the first 48 hours after transplantation, primarily caused by perioperative cardiac xenograft dysfunction (PCXD). To decrease the rate of PCXD, we adopted a preservation technique of cold non-ischemic perfusion for our ongoing pig-to-baboon cardiac xenotransplantation project.

Author Correction: Consistent success in life-supporting porcine cardiac xenotransplantation.

In this Letter, Mayuko Kurome and Valeri Zakhartchenko have been added to the author list (affiliated with Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany). The author list and 'Author contributions' section have been corrected online; see accompanying Amendment.

Phase-controlled intermittent intratracheal insufflation of oxygen during chest compression-active decompression mCPR improves coronary perfusion pressure over continuous insufflation.

Purpose: It has previously been shown that continuous intratracheal insufflation of oxygen (CIO) is superior to intermittent positive pressure ventilation (IPPV) regarding gas exchange and haemodynamics. The purpose of this study was to investigate gas exchange and haemodynamics with a new technique of phase-controlled intermittent insufflation of oxygen (PIIO) compared to CIO.

Method: Twenty (20) pigs were used, stratified into two groups (CIO, PIIO), with 10 animals each.

Consistent success in life-supporting porcine cardiac xenotransplantation.

Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons.

Closed-Loop Prevention of Hypotension in the Heartbeating Brain-Dead Porcine Model.

Unlabelled: Objective: The purpose of this paper is to demonstrate feasibility of a novel closed-loop controlled therapy for prevention of hypertension in the heartbeating brain-dead porcine model.

Methods: Dynamic modeling and system identification were based on in vivo data. A robust controller design was obtained for the identified models.

Intact endothelial and contractile function of coronary artery after 8 hours of heart preservation.

Objectives: The aim of the study was to investigate if adequate preservation of coronary artery endothelium-dependent relaxation and contractility may be obtained after 8 hours of non-ischemic heart preservation.

Design: Porcine hearts were perfused for 8 hours at 8 °C, either in cycles of 15 minutes perfusion and 60 minutes non-perfusion, or by continuous perfusion. The perfusate consisted of a cardioplegic, hyperoncotic nutrition solution with oxygenated red cells, and the perfusion pressure was 20 mmHg.

Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours.

Objectives: The aim of this study was to demonstrate safe orthotopic transplantation of porcine donor hearts harvested 24 hours after brain death and preserved for 24 hours before transplantation.

Design: Circulatory normalization of brain dead (decapitated) pigs was obtained using a new pharmacological regimen (n = 10). The donor hearts were perfused at 8 °C in cycles of 15 min perfusion followed by 60 min without perfusion.

A novel, minimally invasive rat model of normothermic cardiopulmonary bypass model without blood priming.

Background: Cardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a novel, minimally invasive rat model of normothermic CPB model without blood priming.

MeCP2 suppresses nuclear microRNA processing and dendritic growth by regulating the DGCR8/Drosha complex.

Loss- and gain-of-function mutations of the X-linked gene MECP2 (methyl-CpG binding protein 2) lead to severe neurodevelopmental disorders in humans, such as Rett syndrome (RTT) and autism. MeCP2 is previously known as a transcriptional repressor by binding to methylated DNA and recruiting histone deacetylase complex (HDAC). Here, we report that MeCP2 regulates gene expression posttranscriptionally by suppressing nuclear microRNA processing.

Intrinsic epigenetic factors cooperate with the steroid hormone ecdysone to govern dendrite pruning in Drosophila.

Pruning that selectively removes unnecessary axons/dendrites is crucial for sculpting neural circuits during development. During Drosophila metamorphosis, dendritic arborization sensory neurons, ddaCs, selectively prune their larval dendrites in response to the steroid hormone ecdysone. However, it is unknown whether epigenetic factors are involved in dendrite pruning.

Manual versus mechanical cardiopulmonary resuscitation. An experimental study in pigs.

Background: Optimal manual closed chest compressions are difficult to give. A mechanical compression/decompression device, named LUCAS, is programmed to give compression according to the latest international guidelines (2005) for cardiopulmonary resuscitation (CPR). The aim of the present study was to compare manual CPR with LUCAS-CPR.

Organ bath in detecting the effect of one-hour warm ischemia on pulmonic arteries and bronchi from non-heart-beating donor lungs.

Background: Non-heart-beating donor lung has been a promising source of lung transplantation. Many studies on non-heart-beating donor lungs are based on animal lung transplantation. In this study, we assessed by organ bath the effect of one-hour warm ischemia on the non-heart-beating donor lung in terms of the integrity of contractile and relaxant functions and tissue structures of pulmonic arteries and bronchi.

Detection of bronchial function of NHBD lung following one-h warm ischemia by organ bath model.

This study investigated the feasibility and effects of organ bath to be used for detection of bronchial function of non-heart-beating donor (NHBD) lung after 1-h warm ischemia. Sixteen Swedish pigs were divided into two groups randomly: heart-beating donor (HBD) group and NHBD with 1-h warm ischemia (NHBD-1 h) group. The bronchial rings whose lengths and inner diameters were both 1.

First human transplantation of a nonacceptable donor lung after reconditioning ex vivo.

Purpose: This article describes an ex vivo method to recondition and transplant rejected donor lungs.

Description: A 19-year-old man was brain dead after a traffic accident. A roentgenogram showed bilateral lung contusion.

In vivo validation of the coincidence of the peak and end of the T wave with full repolarization of the epicardium and endocardium in swine.

Objectives/background: Previous in vitro studies have suggested full repolarization of the epicardium coincides with the peak of the T wave (T(peak)) and that of the M cells coincides with the end of the T wave (T(end)). However, in vivo validation of the theory is lacking.

Methods: Monophasic action potentials (MAPs) were recorded using the CARTO mapping system from 51 +/- 10 epicardial sites and 64 +/- 9 endocardial sites of the left ventricle in 10 pigs and from 41 +/- 4 epicardial sites and 53 +/- 2 endocardial sites of the right ventricle in two of the 10 pigs.

QT dispersion failed to estimate the global dispersion of ventricular repolarization measured using monophasic action potential mapping technique in swine and patients.

The aim of this study was to evaluate whether the QT dispersion measured from 12-lead electrocardiogram (ECG) can estimate the global dispersion of ventricular repolarization (DVR) measured using a monophasic action potential (MAP) mapping technique. Monophasic action potentials were recorded from 75 +/- 12 left ventricular sites in 10 pigs and from 48 +/- 16 left or right ventricular sites in 15 patients using the CARTO mapping system. The maximum DVRs in both end-of-repolarization and MAP duration among all the mapped sites were calculated and termed as global DVR for each measurement.

Continuous intratracheal insufflation of oxygen improves the efficacy of mechanical chest compression-active decompression CPR.

The aim of the present study was to compare the efficacy of intratracheal continuous insufflation of oxygen (CIO) with intermittent positive pressure ventilation (IPPV) regarding gas exchange and haemodynamics during mechanical chest compression-active decompression cardiopulmonary resuscitation (mCPR) provided by the LUCAS device. Ventricular fibrillation (VF) was induced electrically and ventilation was discontinued in 16 pigs, mean body weight 23 kg (range 22-27 kg). They were randomized into two groups (CIO versus IPPV).

The critical importance of minimal delay between chest compressions and subsequent defibrillation: a haemodynamic explanation.

Outcome after prehospital defibrillation remains dire. The aim of the present study was to elucidate the pathophysiology of cardiac arrest and to suggest ways to improve outcome. Ventricular fibrillation (VF) was induced in air-ventilated pigs, after which ventilation was withdrawn.

Transplantation of lungs from non-heart-beating donors after functional assessment ex vivo.

Background: If lungs from patients dying of heart attacks are to serve as donor organs in a safe way, their function should be properly assessed before transplantation. The aim of this study was to investigate donor lung function evaluation in a realistic large animal model.

Methods: Twelve 60-kg pigs were used.