Low female participant representation in clinical trials is poorly understood. One postulated explanation is bias through imbalance in trial leadership gender. This study examined the association between staff and participant gender in an Australian cohort of two contemporary multicentre heart failure trials. Twelve Australian centres provided gender data. Participant, principal investigator, consenting investigator, and trial coordinator genders were recorded. Analysis was performed by Pearson Chi-squared testing via SPSS; p-values of <0.05 was considered significant. This study examined 179 participants: 37 women (20.7%) and 142 men (79.3%). The principal investigator was female at four sites (30%). The trial coordinator was female at 10 sites (83%). The consenting investigator was female for 78 subjects (43.6%) and male for 101 (56.4%). No association was found between principal investigator and participant gender (0.087; p=0.77) or consenting investigator and participant gender (0.002; p=0.96). There was a trend against female participation when the trial coordinator was female (3.07; p=0.08). Low female participant representation in clinical trials remains an important, poorly understood, and emotive issue. This study found no association between principal or consenting investigator, and participant gender. The signal for the consenting trial coordinator was unexpected and warrants further consideration. Further prospective analyses are needed to explore participant gender imbalance in clinical trials, including both reasons for "screen failures" and participants' reasons to decline enrolment.

Introduction: The Budyari Cardiology Outreach Program in Miller, Sydney was commenced in August 2014 to provide specialist Cardiology services for Aboriginal patients due to non-attendance rates of 40–50% in hospital outpatient clinics. The clinic comprises a Cardiologist, Cardiology AT, two registered nurses and an Aboriginal Health Education Officer. Methods: A retrospective cohort study of patient demographics, attendance rates and investigations was performed. Results: From August 2014 to December 2018, 99 patients attended. There were 323 appointments over 44 clinics, with 80.5% attendance rate. 40/99 patients were male with mean age 57.0 (range 16.8–85.5). Mean follow up was 11.5 months (range 0–3.9 years) and mean number of appointments per patient was 3 (range 1–9). Initial mean blood pressure was 129 ± 18/76 ± 10mmHg and BMI 33.7 ± 10.0kg/m2, which reduced by 6 ± 16/3 ± 12mmHg and 0.3 ± 2.0kg/m2. 21/99 patients were lost to follow-up and 5/99 died. Referrals were from GPs in 92/99 patients. Most common indications included investigation of chest pain (33%), dyspnoea (17%), palpitations (11%) and risk factor modification (10%). There were a high number of abnormal results including 39/99 abnormal ECGs, 1/23 ESTs, 29/70 echocardiograms, 4/20 Sestamibis, 1/4 CTCAs, 1/8 stress echocardiograms, 4/13 Holter monitors and 9/11 coronary angiograms. Three patients were referred for a pacemaker. Medication changes were made in 61/99 patients and 36/99 were referred to other specialist or allied health services. Only 1/46 current smokers ceased smoking. Conclusions: The program provides convenient and culturally appropriate specialist Cardiology care, resulting in high attendance rates. Future goals include successful intervention for smoking cessation and weight loss.

Withdrawal of life support (WOLS) in Donation after Circulatory Death (DCD) subjects the heart to an obligatory warm ischaemic injury. A comprehensive understanding of the haemodynamic and volumetric changes to the left (LV) and right (RV) ventricles during circulatory arrest will facilitate development of better techniques to preserve the heart. 12 Landrace pigs (60-65 kg) were subjected to WOLS while under deep general anesthesia, and observed until death. During this period, serial haemodynamic parameters were taken, consisting of mean arterial pressure (MAP), central venous pressure (CVP), pulmonary artery pressure (PAP) and left atrial pressure (LAP). Sonometric crystals were used to measure the volumetric changes of the LV (n=6) or RV (n=6) with direct measurement of corresponding ventricular pressure. Death was defined as equalisation of all pressures. Volumetric data were analysed using Sonolab and pressure volume loops generated. The early withdrawal period was marked by a rise in PAP and CVP but a drop in LAP in response to rapid desaturation of the subject (Figure). Volumetric measurements showed a gradual increase in overall RV volume, which remained elevated after death. LV, however, did not show significant volume change throughout the withdrawal period. RV at baseline was 162.32 ± ¬29.60 mL and 198.66 ± 56.51 mL at end of withdrawal, and 158.99 ± 52.20 mL and 169.18 ± 48.52 mL in the LV. WOLS is associated with rapid onset of profound hypoxemia and pulmonary vasoconstriction resulting in an acute increase in RV afterload and decrease in LV preload. Although the heart is subjected to global myocardial ischemia, hypoxia-induced vasoconstriction in the pulmonary vasculature places an additional stress on the RV and explains the disproportionate RV dilatation during WOLS.

Registry data show a higher rate of primary graft failure, one-year and long-term mortality in transplants from older donors; however, whilst organ donation rates remain low, we are forced to accept organs from older ‘marginal’ donors. Aged hearts are more susceptible to brain death (BD), ischemia and reperfusion injury (IRI). We aimed to develop strategies to protect the aging myocardium by adding pharmacological conditioning agents erythropoietin (E), glyceryl trinitrate (G), and zoniporide (Z) to standard cardioplegic solutions. Male Wistar rats aged 3, 12 and 18 months (n= 12 per group) underwent BD or sham procedure. Cardiac output (CO) was then assessed ex-vivo on a Langendorff Rig. The hearts were arrested and stored for 6 hours at 4ºC in Celsior. An additional six 18 month BD hearts were arrested and stored in Celsior supplemented with E, G and Z. Post-storage CO was assessed on a Langendorff rig. Coronary effluent lactate dehydrogenase (LDH) levels were compared and pro-survival kinases p-ERK, p-STAT 3 and p-AKT 1/2 were measured in the myocardium using Western Blots. Baseline CO adjusted for body weight (ml/min/g) was 73.1±8.2 (3m BD), 39.5±6.6 (12m sham), 38.5±8.2 (12m BD), 32.5±9.6 (18m sham) and 29.8±5.7 (18m BD) (p<0.0001, 3m vs. all other groups; p<0.01, 12m BD vs. 18m BD). The recovery of CO after 6 hours of hypothermic storage was significantly poorer in all 12 and 18 month hearts stored in Celsior compared with 3 month hearts (p<0.001, p<0.0001 respectively), Fig 1. Hearts stored in Celsior with E+G+Z had improved CO (p<0.05 cf 18 m BD and p=ns cf 3m and 12m hearts all stored in Celsior). LDH was lower and p-ERK higher in 18m BD hearts stored in Celsior +E+G+Z (p<0.05, p<0.01 respectively) Aged hearts show a significant decline in function following BD and IRI. While these hearts are presently suboptimal for use in cardiac transplantation, the use of pharmacological conditioning agents can improve myocardial protection and allow the use of aged hearts in transplantation.

The shortage of donors in cardiac transplantation may be alleviated by the use of allografts from donation after circulatory death (DCD) donors. We have previously shown that hearts exposed to 30 min warm ischemic time and then flushed with Celsior supplemented with agents that activate ischemic postconditioning pathways, show complete recovery on a blood-perfused ex vivo working heart apparatus. In this study, these findings were assessed in a porcine orthotopic heart transplant model. DCD hearts were preserved with either normothermic ex vivo perfusion (NEVP) using a clinically approved device, or with standard cold storage (CS) for 4 h. Orthotopic transplantation into recipient animals was subsequently undertaken. Five of six hearts preserved with NEVP demonstrated favorable lactate profiles during NEVP and all five could be weaned off cardiopulmonary bypass posttransplant, compared with 0 of 3 hearts preserved with CS (p < 0.05, Fisher's exact test). In conclusion, DCD hearts flushed with supplemented Celsior solution and preserved with NEVP display viability before and after transplantation. Viability studies of human DCD hearts using NEVP are warranted.

Donation after circulatory death (DCD) offers a potential additional source of cardiac allografts. We used a porcine asphyxia model to evaluate viability of DCD hearts subjected to warm ischemic times (WIT) of 20–40 min prior to flushing with Celsior (C) solution. We then assessed potential benefits of supplementing C with erythropoietin, glyceryl trinitrate and zoniporide (Cs), a combination that we have shown previously to activate ischemic postconditioning pathways. Hearts flushed with C/Cs were assessed for functional, biochemical and metabolic recovery on an ex vivo working heart apparatus. Hearts exposed to 20-min WIT showed full recovery of functional and metabolic profiles compared with control hearts (no WIT). Hearts subjected to 30- or 40-min WIT prior to C solution showed partial and no recovery, respectively. Hearts exposed to 30-min WIT and Cs solution displayed complete recovery, while hearts exposed to 40-min WIT and Cs solution demonstrated partial recovery. We conclude that DCD hearts flushed with C solution demonstrate complete recovery up to 20-min WIT after which there is rapid loss of viability. Cs extends the limit of WIT tolerability to 30 min. DCD hearts with ≤30-min WIT may be suitable for transplantation and warrant assessment in a transplant model.

Hearts from DCD donors are not used clinically due to concern of warm ischaemic injury. Our preclinical porcine studies have shown that, utilising a pharmacological post-conditioning strategy and ex vivo normothermic perfusion, warm ischaemic times (WIT) of ≤30 mins are tolerated with good recovery. We report the first two cases of human DCD donor heart resuscitation using this strategy. Donor 01 was a 62 y.o male with Guillain Barre Syndrome. WIT (b/w extubation & organ preservation) was 32 mins. Donor 2 was a 39 y.o male, with hypoxic encephalopathy (drug overdose). He was declared brain dead (BD), but subsequently exposed to 30 mins of WIT for the study. Post WIT, hearts were flushed with Celsior solution supplemented with post-conditioning agents. Hearts were reperfused on a modified Transmedics Organ Care System (OCS) device for 8 hrs, which allowed ex vivo beating heart assessment in working mode in addition to the standard resting mode. Functional & metabolic parameters were evaluated. The hearts were maintained in resting and working modes for 4 hours each. During resting perfusion, heart 1 had favourable lactate profiles (lactate extraction) suggestive of viable myocardium, however remained >5mmol/l. Heart 2 had an adverse lactate profile suggestive of ischaemic myocardium (Figure 1). In a working state, a left atrial pressure challenge was conducted. Heart 1 functioned better than Heart 2 (figure 1), with superior cardiac output and generated pressure. The inferiority of Heart 2 was likely the result of dual BD + DCD insult, decreased post-conditioning activation, and an undiagnosed patent foramen ovale. We report the first 2 DCD human hearts recovered on the OCS. Although these were not the ideal donors for DCD heart donation (donor 1 - age>50, WIT > 30 mins; Donor 2 - BD + DCD, PFO), both demonstrated viability and the potential for DCD cardiac allografts. Further studies of ideal criteria DCD donors are underway.

Heart and lung transplant recipients have one of the highest incidences of post-transplant lymphoproliferative disease (PTLD). There is still a paucity of data specific to this group of patients, in particular, on factors associated with improved survival and on the efficacy of newer therapeutic strategies. We conducted the largest analysis to date on heart (H), lung (L) and heart-lung (HL) transplant recipients with PTLD, in order to identify unique features of PTLD in thoracic organ transplant recipients, to identify specific prognostic factors and thereby improve treatment. 70 cases (H [43], L [21] and HL [6]) of PTLD were identified from a single institution between 1984-2011. Data were retrospectively analysed in detail for demographics, immunosuppression, rejection, treatment, response, complications and survival. Univariate and multivariate Cox regression analyses were performed to identify factors associated with survival outcomes. Univariate analysis identified poorer survival in patients > 50 years at diagnosis of PTLD (hazard ratio 2.22, p=0.004), bone marrow (BM) involvement (HR 5.34, p<0.001), serum albumin < 30g/l (HR 2.90, p=0.02) and Ann Arbor stage ≥ 3 (HR 2.78, p=0.001). Improved survival was associated with age between 18-50 years at PTLD diagnosis (HR 0.44, p=0.004) and when complete response (CR) was achieved after the initial course of treatment (HR 0.06, p<0.001). This analysis did not show prognostic significance for factors such as early (430U/l), anaemia (Hb <100g/l), allograft involvement (lung only) or treatment with rituximab (n=18). Multivariate analysis identified a significantly poorer prognosis in patients with BM involvement (HR 11.23, p<0.001) and serum albumin < 30g/l (HR 3.70, p=0.02) and significantly improved survival in those with CR after the initial course of treatment (HR 0.07, p<0.001). Three-year overall survival (OS) was 33% and 10-year OS 20% post-PTLD, consistent with figures quoted in the literature. This study is the first to identify prognostic markers unique to H, L and HL transplant recipients with PTLD. Hypoalbuminaemia and BM involvement are identified as significant markers of poorer survival post-PTLD, while CR after initial treatment is a significant marker of improved survival. Larger studies are required to determine the effects of rituximab on survival in this group of patients.

PurposeStatic cold storage of hearts from brain dead donors is still the mainstay in cardiac transplantation. The risk of ischaemia-reperfusion injury (IRI) and primary graft failure (PGF) are significant disadvantages of this method. We found that three ‘conditioning’ agents–Glyceryl trinitrate (G), Erythropoietin€ and Zoniporide (Z), when added to standard preservation solutions, attenuate IRI in rat hearts. We aimed to test their efficacy in hearts from brain dead rats in prolonged cold storage.Methods and MaterialsRats were subjected to brain death (BD) by inflation of a subdural embolectomy catheter. Invasive haemodynamic changes are shown in Figure 1. Cardiac function was assessed on an isolated working heart model (IWHM), then hearts arrested and preserved in Celsior for 1, 3 or 6 hours (n=6 each sub-group). Additional hearts from BD donors were arrested and stored for 3 or 6 hours using Celsior with G+E+Z (n=6 for 3h, 6h) and function re-assessed on an IWHM.ResultsBD hearts had inferior recovery of cardiac output (CO) cf with shams. Supplementing Celsior with G+E+Z significantly improved CO in BD hearts (p<0.0003 3h, 6h). Pathology analyses are underway.ConclusionsG, E & Z that activate ‘conditioning’ pathways significantly improve recovery of BD rat hearts after prolonged static cold storage. This data warrants assessing these strategies clinically. [figure 2] Static cold storage of hearts from brain dead donors is still the mainstay in cardiac transplantation. The risk of ischaemia-reperfusion injury (IRI) and primary graft failure (PGF) are significant disadvantages of this method. We found that three ‘conditioning’ agents–Glyceryl trinitrate (G), Erythropoietin€ and Zoniporide (Z), when added to standard preservation solutions, attenuate IRI in rat hearts. We aimed to test their efficacy in hearts from brain dead rats in prolonged cold storage. Rats were subjected to brain death (BD) by inflation of a subdural embolectomy catheter. Invasive haemodynamic changes are shown in Figure 1. Cardiac function was assessed on an isolated working heart model (IWHM), then hearts arrested and preserved in Celsior for 1, 3 or 6 hours (n=6 each sub-group). Additional hearts from BD donors were arrested and stored for 3 or 6 hours using Celsior with G+E+Z (n=6 for 3h, 6h) and function re-assessed on an IWHM. BD hearts had inferior recovery of cardiac output (CO) cf with shams. Supplementing Celsior with G+E+Z significantly improved CO in BD hearts (p<0.0003 3h, 6h). Pathology analyses are underway. G, E & Z that activate ‘conditioning’ pathways significantly improve recovery of BD rat hearts after prolonged static cold storage. This data warrants assessing these strategies clinically. [figure 2]

BACKGROUND: Heart and lung transplant recipients have among of the highest incidence rates of post-transplant lymphoproliferative disease (PTLD). Despite this, there is a paucity of data specific to this group. We collated data on heart, lung and heart lung transplant recipients with PTLD to identify disease features and prognostic factors unique to this group of patients.METHODS: Seventy cases of PTLD were identified from a single institution (41 heart, 22 lung, 6 heart lung and 1 heart kidney transplant) from 1984 to 2013. Demographics, immunosuppression, treatment, response, complications and survival data were analyzed. Uni- and multivariate Cox regression analyses were performed to identify prognostic factors.RESULTS: The incidence of PTLD was 7.59% in heart lung, 5.37% in heart and 3.1% in lung transplant recipients. Extranodal disease (82%) with diffuse large B-cell lymphoma (72%) was the most common presentation. Bone marrow involvement (13%) and central nervous system disease (3%) were uncommon. Heart transplant recipients had later onset of FTLD (> 1 year post-transplant), with less allograft involvement, compared with lung and heart lung recipients. Poor prognostic markers were bone marrow involvement (FIR 6.75, p < 0.001) and serum albumin <30 g/liter (HR 3.18, p = 0.006). Improved survival was seen with a complete response within 3 months of treatment (FIR 0.08, p < 0.001). Five-year overall survival was 29%.CONCLUSION: This analysis is the largest to date on PTLD in heart and lung transplant recipients. It provides a detailed analysis of the disease in this group of patients and identifies unique prognostic features to aid risk stratification and guide treatment allocation. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.

PurposeUtilising pharmacological ischaemic post-conditioning strategies, we demonstrated excellent functional recovery in DCD hearts following 30 minutes warm ischaemia time (WIT)1. The aim of this study was to assess recovery of these hearts post orthotopic transplantation (Tx) and using a clinically approved Organ Care System (Transmedics OCS) for preservation. We hypothesized that the Transmedics OCS would provide a platform to gauge the viability of DCD hearts beforeTx.Methods and MaterialsHearts were exposed to 30 mins WIT in a DCD asyphyxia porcine model, before being flushed with supplemented Celsior (glyceryl trinitrate (GTN), Erythropoietin (EPO) and Zoniporide – post-conditioning strategy). Hearts were explanted onto the Transmedics OCS (t=3.5 hrs), recovery assessed by evaluating cardiac rhythm, lactate extraction & overall lactate trends. Hearts deemed to be viable underwent orthotopic Tx.Results7 DCD hearts have been assessed to-date, all recovered to a sinus rhythm, 6/7 hearts had lactate profiles compatible with heart viability for transplantation. [figure 1] Excluding 2 recipient animals (malignant hyperthermia, CPB issues), remaining 4 transplanted hearts were successfully weaned off cardio-pulmonary bypass (CPB) on low dose inotropes. These hearts supported circulation (t=3 hrs) with good biventricular function.ConclusionsThe Transmedics OCS provides an excellent platform to assess DCD heart recovery following warm ischemia. Using a clinically applicable model, we have shown that DCD hearts with WIT ≤30 mins appear to be a viable source of additional organs in cardiac transplantation and warrant human studies. Utilising pharmacological ischaemic post-conditioning strategies, we demonstrated excellent functional recovery in DCD hearts following 30 minutes warm ischaemia time (WIT)1. The aim of this study was to assess recovery of these hearts post orthotopic transplantation (Tx) and using a clinically approved Organ Care System (Transmedics OCS) for preservation. We hypothesized that the Transmedics OCS would provide a platform to gauge the viability of DCD hearts beforeTx. Hearts were exposed to 30 mins WIT in a DCD asyphyxia porcine model, before being flushed with supplemented Celsior (glyceryl trinitrate (GTN), Erythropoietin (EPO) and Zoniporide – post-conditioning strategy). Hearts were explanted onto the Transmedics OCS (t=3.5 hrs), recovery assessed by evaluating cardiac rhythm, lactate extraction & overall lactate trends. Hearts deemed to be viable underwent orthotopic Tx. 7 DCD hearts have been assessed to-date, all recovered to a sinus rhythm, 6/7 hearts had lactate profiles compatible with heart viability for transplantation. [figure 1] Excluding 2 recipient animals (malignant hyperthermia, CPB issues), remaining 4 transplanted hearts were successfully weaned off cardio-pulmonary bypass (CPB) on low dose inotropes. These hearts supported circulation (t=3 hrs) with good biventricular function. The Transmedics OCS provides an excellent platform to assess DCD heart recovery following warm ischemia. Using a clinically applicable model, we have shown that DCD hearts with WIT ≤30 mins appear to be a viable source of additional organs in cardiac transplantation and warrant human studies.

Purpose Left heart failure is often complicated by pulmonary hypertension (T2PH), which can progress from ‘reactive' (RPH) to a'fixed' (FPH), significantly increasing morbidity and mortality. Continuous flow left ventricular assist devices (VAD) can reverse T2PH. We aimed to determine if treatment with VAD therapy improves morbidity and mortality in T2PH in both RPH and FPH. Methods and Materials All right heart catheters were analysed from Jan 2008 to Oct 2012 in our institution. Selection criteria: cardiac index 2.8 l/min/m 2 , pulmonary capillary wedge pressure>15mmHg, mean pulmonary arterial pressure>25mmHg, and transpulmonary gradient>15mmHg OR pulmonary vascular resistance (PVR)>3.0WU. FPH group had TPG>15 or PVR>3.0 after vasodilator challenge. Baseline and follow-up data were analysed. Results 62 patients had T2PH (15FPH, 47 RPH). 21 had VAD therapy (6FPH, 15RPH), and 41 medical therapy (9 FPH, 32 RPH). PVR was significantly reduced by VAD but not medical therapy [Table 1]. Cardiovascular admissions were reduced byVAD cf medical therapy (p Conclusions VAD therapy significantly improves survival in T2PH patients with RPH. Patients with FPH benefited from VAD therapy by having reduced hospital admissions but this study did not show a survival benefit. LVADMedicalFPH (n=6)RPH (n=15)FPH (n=9)RPH (n=32)NYHA4433INTERMACS1177002070036640110417465695-7003323PVR pre-treatment7.26.356.85.1PVR post-treatment3.82.116.24.6p-value (PVR change)

Introduction: Utilising pharmacological ischaemic post-conditioning strategies, we have demonstrated excellent cardiac functional recovery in DCD hearts following 30 min warm ischaemia time (WIT) [ [1] Cardiac Transplantation using hearts from Donation after Circulatory Death (DCD) Donors—a viable source of organs? Submitted abstract 65 ANZSCTS Annual Scientific Meeting 2012. Google Scholar ]. This has been validated on an ex-vivo construct in the laboratory. The aim of this study was to assess recovery of DCD hearts in a clinically approved Organ Care System – Transmedics OCS. This ex-vivo perfusion device allows assessment of marginal organs from brain dead donors prior to transplantation (Tx). We hypothesised that the Transmedics OCS would provide a suitable platform to gauge the viability of DCD hearts.

Introduction: New organ preservation strategies are being tested in research units worldwide in order to find ways to maximize the utility of available donor organs. In our laboratory we have previously assessed preservation strategies using an isolated working rat heart model (1,2). The major limitation of this is that it does not incorporate donor brain death (BD) and its consequent adverse impact on heart function. The aim of this study is to develop BD in donor rat which will enable us to assess the effectiveness of preservation strategies when BD is incorporated into the model. Methods: BD was induced in anesthetized rats by balloon inflation of a catheter introduced into the subdural space and confirmed by cessation of spontaneous respirations and absence of pedal and corneal reflexes. A Millar catheter was inserted into the right carotid artery for continuous monitoring of MAP during and after BD induction. Animals were intubated and ventilated during the experiments and observed for 1hr after induction of BD. Hearts were then excised and reperfused with Kreb's buffer at 37°C. Function of the isolated hearts were measured at working mode perfusion before and after the hearts were arrested and stored in Celsior solution at 4°C. Recovery of cardiac function after 1, 3, or 6hrs storage was compared between BD and non-BD hearts. Results: Significant increases in MAP were observed in all animals at the end of the balloon inflation (Fig 1). Pre-storage cardiac function of hearts from BD rats was not significantly different from hearts of non-BD rats (CO = 66±9.5 vs 65±7.6 ml/min). However, recovery of aortic flow after 6hrs storage was decreased in BD rat hearts (Fig 2). An increase of storage time from 1 to 6hrs has resulted in significant decreases in post-storage recovery of aortic flow (Fig 2).[Figure 1: Change of MAP during BD induction][Figure 2: Post-storage Recovery of Aortic Flow]Conclusions: Hearts from BD rats had inferior functional recoveries after storage compared to hearts from non-BD rats. Significantly reduced recovery of cardiac function was observed in BD hearts after 3hrs ischemic storage. We now successfully incorporate BD in our future experiments on cardiac preservation strategies. 1. Gao et al. Am J Transplant 2005;5:1820-26. 2. Gao et al. Transplantation. 2007;84 (3): 380-6.

Introduction: Utilisation of hearts from Donations after circulatory death (DCD) donors has been limited by fear of warm ischaemic damage. We aim to investigate the impact of varying periods of warm ischaemia on cardiac function in DCD hearts, and evaluate ischaemic post-conditioning strategies to limit warm ischaemic injury. Methods: Utilising a porcine DCD model, 3 warm ischaemic time (WIT) periods were evaluated. All hearts were antegrade flushed with Celsior solution after the designated period of warm ischaemia. Ischaemic post-conditioning was affected with the supplementation of Celsior with glyceryl trinitrate (GTN), erythropoietin (EPO), and zoniporide - this approach has been studied extensively in our laboratory1. (table 1)Hearts were explanted onto an isolated working heart circuit. Left heart performance was assessed for 4 hours - functional assessment (Cardiac Output, Coronary Flow, Left Atrial Pressure (LAP) vs Aortic Flow (AF) challenge), metabolic recovery (pH, lactate, myocardial oxygen consumption), and biochemical parameters (troponin, LDH) were evaluated. Results: When compared with control hearts, Group 1 hearts showed complete functional recovery, Group 2 had partial recovery and Group 3 had no recovery. Cardiac Output was inferior with Group 2 hearts (graph 1). The increase in AF in response to increased LAP was significantly blunted for Group 2 (p=0.05), when compared with control and Group 1. Group 2 hearts also remained more acidotic (p=0.03), had higher lactate levels (p=0.03), greater troponin release (p=0.03) and had non-significant trends towards higher LDH levels than control or Group 1 hearts. Following the supplementation of the preservation flush for 30 minute warm ischaemia hearts (Group 4) there was a significantly improved functional and biochemical recovery when compared with group 2 hearts (unsupplemented 30 minute warm ischaemia hearts). Comparing group 2 and group 4, group 4 had superior Cardiac Output (p < 0.01, see graph 1), higher coronary flows (p < 0.01), superior performance in the AF vs LAP challenge (p = 0.03), and decreased troponin release (p=0.05).Figure: [Graph 1]Conclusion: Hearts with a WIT of less than 20 minutes demonstrate excellent recovery, supporting the potential for DCD hearts in transplantation. The detrimental effects of warm ischaemia become evident beyond 20 minutes - here, ischaemc post-conditioning strategies aimed at mitigating ischaemia-reperfusion injury significantly improve cardiac recovery. With the utilization of such strategies in preserving cardiac function following 30 minutes of warm ischaemia, the potential for translation to clinical DCD heart transplantation is greatly strengthened and warrants further investigation.

Objectives: Pulmonary hypertension complicating left heart failure (LHF) is associated with increased morbidity and mortality. It limits suitability for orthotopic heart transplant and is associated with higher post-transplant mortality. The aim of this study was to determine if treatment with continuous flow left ventricular assist devices (LVADs) improves secondary pulmonary hypertension (20 PAH), thereby providing a bridge to heart transplantation.

Background: Ertapenem is a relatively new carbapenem with broad activity. There are however limited studies regarding its efficacy in bacteremic patients. We evaluated the in-vitro activity of Ertapenem against blood culture isolates (community onset and nosocomial) at a tertiary hospital. Methods: Bacteria isolated from blood cultures from hospitalized patients admitted to the National University Hospital, Singapore (Dec 2003–May 2004) were identified using the Vitek instrument (bioMerieux, NC) and Microbact 12A and 12B (Oxoid Australia). Gram-stain, catalase, coagulase (Pastorex Staph Plus, Bio-Rad, CA) and PYR disk testing were done for Staphylococcusand Streptococcus spp. Ertapenem susceptibilities were determined using the Kirby-Bauer disk method on cation-adjusted Mueller-Hinton plates according to the CLSI performance standards. Burkholderia pseudomallei (B. pseudomallei) isolates were further tested using the E-test (AB Biodisk, Sweden). Results: 333 blood stream isolates were studied, including 157 Enterobacteraciae (73 Extended spectrum beta-lactamase (ESBL) positive) and 29 isolates of B. pseudomallei. All 157 Enterobacteraciae isolates were Ertapenem susceptible. 26 B. pseudomallei strains were susceptible and 3 strains intermediate to Ertapenem by disk testing, but the E-test showed that only 5 of the 29 strains were susceptible (MIC≤2 mcg/ml). Of the non-fermenting gram- negatives, 26 of 64 isolates were susceptible (including 4/6 B. cepacia, 8/26 A. baumanii and 3/10 P. aeruginosa isolates). All isolates of S. maltophila (9/9) were resistant. Of the gram-positives, 2/2 L. monocytogenes and all S. viridans (5/5), beta-hemolytic Streptococci (11/11), S. pneumoniae (6/6), methicillin susceptible S. aureus (32/32) were susceptible. All 12 strains of penicillin susceptible E. faecalis were non-susceptible to Ertapenem, whilst 9 of the 10 B. fragilis strains tested were Conclusions: Ertapenem demonstrates excellent activity against enterobacteraciae including ESBL producing strains at our institution but is lacking against A. baumannii, P. aeruginosa, S. maltophilia and E. faecalis. It also has poor activity against B. pseudomallei and cannot be recommended as therapy for melioidosis.

SUMMARY Two hundred and four Salmonella enterica serotype Typhi (S. Typhi) isolates were collected from seven Asian countries during 2002–2004. Multidrug-resistant S. Typhi (resistant to ⩾3 antibiotics) was detected in 84 (41·2%) isolates and 142 (69·6%) showed reduced susceptibility to ciprofloxacin (minimum inhibitory concentration=0·125–1·0 mg/l). This study highlights the worsening situation of antimicrobial resistance of S. Typhi in Asia.

To further exert the technical advantages of face gears, high-end equipment puts forward the need for the long-life mass-machining of face gears. However, the commonly used technique of hard honing is more sensitive to installation errors and impact loads, and soft honing has insufficient removal ability to the margin, so the quality of the gear's life is difficult to guarantee. To solve this contradiction, this paper introduces a damper to honing and proposes a flexible honing method for face gears. First, to reveal the flexible honing mechanism, the tooth-surface model of face-gear honing is derived, and the mathematical model for face-gear flexible honing is established. Second, to clarify the influence of flexible honing parameters on the quality of the tooth surface, a roughness model of the honing surface is established, and the influence of flexible honing parameters on roughness is analyzed. Third, by analyzing the influence of roughness under the action of honing parameters on the stress of the tooth surface, the parameters for flexible honing are determined. Finally, the effectiveness of the method is verified by flexible honing machining and testing.