Effect of Diabetes on Nitric Oxide Metabolism During Cardiac Surgery

The metabolism of nitric oxide (NO) during cardiac surgery is unclear. We studied the effect of diabetes on NO metabolism during cardiac surgery in 40 subjects (20 with diabetes and 20 without diabetes). The patients were randomized to receive an infusion of physiological saline or nitroglycerin (GTN) at 1 g kg–1 min–1 starting 10 min before the initiation of cardiopulmonary bypass and then continuing for a period of 4 h. Blood and urine samples were collected at several time points for up to 8 h. NO metabolites were determined by the measurement of nitrate/nitrite (NOx, mol/mmol creatinine) and cyclic guanosine monophosphate (cGMP, nmol/mmol creatinine) in plasma and urine. Plasma insulin levels were also determined at selected time points. Plasma NOx levels before surgery were significantly elevated in the group with diabetes compared with the group without diabetes (P < 0.001), and values were further increased during surgery in the former (P 0.005) but not in the latter (P 0.8). The greater plasma NOx values in patients with diabetes were matched by commensurate elevations in plasma cGMP levels (P 0.01). Interestingly, infusion of GTN, an NO donor, significantly reduced plasma NOx (P < 0.001) and its urine elimination (P < 0.001) in patients with diabetes without reducing plasma cGMP levels (P 0.89). Cardiac surgery increased plasma insulin in patients with and without diabetes; this increase was delayed by the infusion of GTN, but it was not related to the changes in NO production. In conclusion, NO production during cardiac surgery is increased in patients with diabetes, and this elevation can be blunted by the infusion of GTN in a rapid and reversible manner

Meeting Report on the International Conference of ECMO-Life Support for Pakistan in 21st Century held May 11-12, 2017, Lahore

Extracorporeal membrane oxygenation support (ECMO) is indicated in severe heart or lung failure with 80 percent or more risk of mortality. In experienced centers, overall survival to discharge ranges from 40 percent in cardiac arrest with extracorporeal cardiopulmonary resuscitation (ECPR) to 70 percent for respiratory failure in adults. Overall survival in children is about 80 percent and newborns with severe lung injury can recover to normal function following prolonged ECMO support, thus, re-defining irreversible lung injury. In the future, ECMO will be automatically controlled with care out of the Intensive care units (ICU) or at home. The International Conference of ECMO-Life Support for Pakistan in 21st Century which was recently held in Lahore, Pakistan on May 11 - 12, 2017. It was to bring together the best of cardiothoracic and vascular surgeons, heart failure cardiologist, adult and pediatric intensivists, pulmonologists, anaesthetists, cardiovascular nurses, postgraduate trainees, para-medical staff, perfusionists, ambulance cardiac first responders and cardiovascular scientists for thought provoking evidence based discussions on the direction and flow of ECMO technology for Pakistan and the Developing World in the next decade. The aim of this conference was to share knowledge on ECMO technologies, advancements and their impact on the health capacity building

Neutrophil Gelatinase-associated Lipocalin as a Marker of Postoperative Acute Kidney Injury Following Cardiac Surgery in Patients with Preoperative Kidney Impairment.

IntroductionAcute kidney injury (AKI) is a serious complication of cardiac surgery. The current 'gold standard' for determining AKI is change in serum creatinine and urine output, however, this change occurs relatively late after the actual injury occurs. Identification of new biomarkers that detect early AKI is required. Recently, new biomarkers, such as the NephroCheck® Test and AKIRisk have also been tested and found to be good indicators of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in paediatric patients but has displayed varied results in adult populations, particularly post cardiac surgery. The aim of this study was to assess the value of urinary NGAL as a biomarker of AKI in patients with pre-existing renal impairment (eGFR >15ml/min to eGFRMethodsA post-hoc analysis of urinary NGAL concentrations from 125 patients with pre-existing kidney impairment, who participated in a randomised trial of haemofiltration during cardiac surgery, was undertaken. Urinary NGAL was measured using ELISA at baseline, post-operatively and 24 and 48 hours after surgery, and serum creatinine was measured pre and postoperatively and then at 24, 48, 72 and 96 hours as routine patient care. NGAL concentrations were compared in patients with and without AKI determined by changes in serum creatinine concentrations. A Kaplan-Meier plot compared survival for patients with or without AKI and a Cox proportional hazards analysis was performed to identify factors with the greatest influence on survival.ResultsFollowing surgery, 43% of patients developed AKI (based on KDIGO definition). Baseline urinary NGAL was not found to be significantly different between patients that did and did not develop AKI. Urinary NGAL concentration was increased in all patients following surgery, regardless of whether they developed AKI and was also significant between groups at 24 (p=0.003) and 48 hours (p156ng/mL also strongly predicted 7-year survival. However, additive EuroSCORE, age, current smoking and post-operative antibiotics usage were distinctly significantly more predictive of 7-year survival as compared with postoperative urinary NGAL at 48 hours >156ng/mL.ConclusionsOur study demonstrated that postoperative urinary NGAL levels at 48 hours postsurgery strongly predicts the onset or severity of postoperative AKI based on KDIGO classification in patients with preoperative kidney impairment and were also strongly related to 7-year survival

Website design: Technical, social and medical issues for self-reporting by elderly patients

There is growing interest in the use of the Internet for interacting with patients, both in terms of healthcare information provision and information gathering. In this paper we examine the issues in designing healthcare websites for elderly users. In particular this paper uses a year-long case study of the development of a web-based system for self-reporting of symptoms and quality of life with a view to examine the issues relating to website design for elderly users. The issues identified included the technical, social and medical aspects of website design for elderly users. The web-based system developed was based upon the EQ5D health-status questionnaire, a commonly used tool for patient self-reporting of quality of life, and the more specific CROQ (coronary revascularisation outcome questionnaire) questionnaire. Currently self-reporting is generally administered in the form of paper-based questionnaires to be completed in the out-patient clinic, or at home. There are a variety of issues relating to elderly users that imply that websites for elderly patients may involve different design considerations to other types of websites

An Intervention for Pulmonary Rehabilitators to Develop a Social Identity for Patients Attending Exercise Rehabilitation: A Feasibility and Pilot Randomised Control Trial Protocol

Background: Chronic obstructive pulmonary disease (COPD) is a degenerative condition that can impair health related quality of life (HRQoL). A number of self-management interventions, employing a variety of behavioural change techniques (BCTs), have been adopted to improve HRQoL for COPD patients. However, a lack of attention has been given to group management interventions with an emphasis on incorporating BCTs into rehabilitators practice. This study aims to pilot and feasibly explore a social identity group- management intervention, delivered by COPD rehabilitation staff to patients attending exercise pulmonary rehabilitation. Doing so will help inform the plausibility of the intervention before conducting a full trial to evaluate its effectiveness to improve HRQoL. Methods: This is a two center, randomized cross-over controlled trial. Two pulmonary rehabilitation centres based in the UK will be randomly allocated to two treatment arms (standard care and intervention). Outcome measurements relating to HRQoL and social identity will be completed pre and post exercise rehabilitation. Focus group interviews will be conducted at the end of exercise rehabilitation to capture participants’ contextualised experiences of the intervention. COPD rehabilitators will undertake semi-structured interviews at the end of the trial to garner their holistic perspectives of intervention fidelity and implementation. Discussion: This is the first study to adopt a social identity approach to develop a rehabilitator-led, group management intervention for COPD patients attending exercise pulmonary rehabilitation. The results of this study will provide evidence for the feasibility and sample size requirements to inform a larger study, which can ascertain the intervention’s effectiveness for improving HRQoL for COPD patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02288039. Date 31st October 2014

Impact of a community-based cardiovascular disease service intervention in a highly deprived area

Objective: To examine the effects on emergency hospital admissions, length of stay and emergency re-admissions of providing a consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service, based in a highly deprived area in the North West of England. Methods: A longitudinal matched controlled study using difference-in-differences analysis compared the change in outcomes in the intervention population, to the change in outcomes in a matched comparison population that had not received the intervention, five years before and after implementation. The outcomes were emergency hospitalisations, length of inpatient stay, and re-admission rates for cardiovascular disease (CVD). Results: Findings show that the intervention was associated with 66 fewer emergency CVD admissions per 100,000 population per year [95% CI 22.13 to 108.98] in the post-intervention period, relative to the control group. No significant measurable effects on length of stay or emergency re-admission rates were observed. Conclusion: This consultant-led, community-based cardiovascular diagnostic, treatment and rehabilitation service, was associated with a lower rate of emergency hospital admissions in a highly disadvantaged population. Similar approaches could be an effective component of strategies to reduce unplanned hospital admissions

Post-operative atrial fibrillation: a maze of mechanisms

Post-operative atrial fibrillation (POAF) is one of the most frequent complications of cardiac surgery and an important predictor of patient morbidity as well as of prolonged hospitalization. It significantly increases costs for hospitalization. Insights into the pathophysiological factors causing POAF have been provided by both experimental and clinical investigations and show that POAF is ‘multi-factorial’. Facilitating factors in the mechanism of the arrhythmia can be classified as acute factors caused by the surgical intervention and chronic factors related to structural heart disease and ageing of the heart. Furthermore, some proarrhythmic mechanisms specifically occur in the setting of POAF. For example, inflammation and beta-adrenergic activation have been shown to play a prominent role in POAF, while these mechanisms are less important in non-surgical AF. More recently, it has been shown that atrial fibrosis and the presence of an electrophysiological substrate capable of maintaining AF also promote the arrhythmia, indicating that POAF has some proarrhythmic mechanisms in common with other forms of AF. The clinical setting of POAF offers numerous opportunities to study its mechanisms. During cardiac surgery, biopsies can be taken and detailed electrophysiological measurements can be performed. Furthermore, the specific time course of POAF, with the delayed onset and the transient character of the arrhythmia, also provides important insight into its mechanisms

Re-Visiting Glutamate Toxicity: Implications of Monosodium Glutamate Consumption on Glutamate Metabolism and Metabolic Syndrome

Around a quarter of the world’s population is estimated to have metabolic syndrome (metS) which is a major risk factor for type II diabetes, cardiovascular disease and death. While the neurotoxicity of monosodium glutamate (MSG) has long been ruled out, recent trends suggest that excessive MSG intake may be associated with metS. Considering that some enzymes involved in glutamate metabolism predict early onset of metS, and that glutamate is involved in gluconeogenesis, energy production, insulin secretion and fatty acid synthesis and that it creates a perfect environment for the activation of mTOR, which subsequently leads to cell growth and autophagy inhibition, we propose that altered glutamate metabolism plays a central role in the cellular deregulation that leads to the development of metS. While recent studies have highlighted the role of aminotransferase enzymes and glutamine-recycling in metabolic syndrome, here we extend upon these concepts and provide fundamental mechanisms through which altered glutamate metabolism as a result of increased MSG consumption may play a role in the pathogenesis of metS. We propose that excessive MSG consumption leads to metS development via mechanisms involving deregulated glutamate metabolism and this is manifested through changes in glutamate metabolic enzymes and glutamate derived metabolites. Understanding whether MSG plays a role in the pathogenesis of metS is important for policy makers in food additive regulations as this may allow the prevention of debilitating diseases associated with metS. Furthermore, understanding the mechanisms involved in altered glutamate metabolism may provide important targets for diagnosing, preventing and treating metS