Heart Work Research Articles

Investigation on heat stress of construction workers in summer in Chongqing, China

The heat stress of workers at construction sites in Chongqing, China, was studied in this paper. The investigation included measurement of environmental parameters, measurement of physiological parameters, questionnaire survey and tracking record of their self-regulation of the behaviour. Scaffolder, carpenter, porter, plasterer and handymen were taken as the main research subjects. Five subjects were selected daily to conduct a questionnaire survey and to measure their physiological parameters, 60 construction workers were investigated. The results show that in sizzling summer, the average effective Wet Bulb Globe Temperature (WBGTeff) is 35.8 ° C. Under these circumstances, workers are in a poor working environment based on some Chinese and international standards. During the experiment, the researchers recorded the work behaviour and self-regulation of workers. It is found that the average heart rate of workers with different job is significantly different, and the average metabolic rate of handymen is significantly lower than that of piling rig workers. Different type of workers should be protected by different protection rules to avoid suffering heat injury.

Walking activity during ambulant cardiac rehabilitation is related to maximum working capacity, age, and smoking behavior.

BackgroundA total of 6,500 to 8,000 steps per day are recommended for cardiovascular secondary prevention. The aim of this research was to examine how many steps per day patients achieve during ambulant cardiac rehabilitation (CR), and if there is a correlation between the number of steps and physical and cardiological parameters.MethodsIn all, 192 stable CR patients were included and advised for sealed pedometry. The assessed parameters included maximum working capacity and heart rate, body mass index (BMI), New York Heart Association (NYHA) class, ejection fraction (EF), coronary artery disease status, beta-blocker medication, age, sex, smoking behavior, and laboratory parameters. A regularized regression approach called least absolute shrinkage and selection operator (LASSO) was used to detect a small set of explanatory variables associated with the response for steps per day. Based on these selected covariates, a sparse additive regression model was fitted.ResultsThe model noted that steps per day had a strong positive correlation with maximum working capacity (P=0.001), a significant negative correlation with higher age (P=0.01) and smoking (smoker: P<0.05; ex-smoker: P=0.01), a positive correlation with high-density lipoprotein (HDL), and a negative correlation with beta-blockers. Correlation between BMI and walking activity was nonlinear (BMI 18.5–24: 7,427±2,730 steps per day; BMI 25–29: 6,448±2,393 steps/day; BMI 30–34: 6,751±2,393 steps per day; BMI 35–39: 5,163±2,574; BMI >40: 6,077±1,567).ConclusionWalking activity during CR is reduced in patients who are unfit, older, smoke, or used to smoke. In addition to training recommendations, estimated steps per day during CR could be seen as a baseline orientation that helps patients to stay generally active or even to increase activity after CR.

Isolated perfused working hearts provide valuable additional information during phenotypic assessment of the diabetic mouse heart.

Although murine models for studying the development of cardiac dysfunction in diabetes mellitus are well established, their reported cardiac phenotypes vary. These reported divergences may, in addition to the severity of different models, also be linked to the methods used for cardiac functional assessment. In the present study, we examined the functional changes using conventional transthoracic echocardiography (in vivo) and isolated heart perfusion techniques (ex vivo), in hearts from two mouse models; one with an overt type 2 diabetes (the db/db mouse) and one with a prediabetic state, where obesity was induced by a high-fat diet (HFD). Analysis of left ventricular function in the isolated working hearts from HFD-fed mice, suggested that these hearts develop diastolic dysfunction with preserved systolic function. Accordingly, in vivo examination demonstrated maintained systolic function, but we did not find parameters of diastolic function to be altered. In db/db mice, ex vivo working hearts showed both diastolic and systolic dysfunction. Although in vivo functional assessment revealed signs of diastolic dysfunction, the hearts did not display reduced systolic function. The contrasting results between ex vivo and in vivo function could be due to systemic changes that may sustain in vivo function, or a lack of sensitivity using conventional transthoracic echocardiography. Thus, this study demonstrates that the isolated perfused working heart preparation provides unique additional information related to the development of cardiomyopathy, which might otherwise go unnoticed when only using conventional echocardiographic assessment.

Pressure-volume analysis in athyroid patients off and on thyroxine supplementation: a pilot study.

Thyroid hormone importantly affects the cardiovascular system. However, evaluation of stroke volume (SV) and its determinants is confounded by variations in volume status that occur along different thyroid states. This study applied the pressure‐volume (PV) framework to obtain relatively load‐independent estimates of cardiac function in hypothyroidism as compared to euthyroidism. Ten athyroid patients were assessed echocardiographically after 4 weeks in deep hypothyroid state, and again after supplementation with oral Levothyroxine (LT4) for 3 months. Thyroid hormone levels were assessed and noninvasive pressure‐volume (PV) analysis based on dedicated repeated echocardiograms was performed. Changes were assessed using paired tests. Results are presented as medians and interquartile ranges. Hypothyroidism was associated with reduced stroke volume (SV: 67.6 ± 17 vs. 75.7 ± 20.6 mL, P = 0.024), preload (end‐diastolic volume, EDV: 122.6 ± 32.5 vs. 135.7 ± 33.6 mL, P = 0.004), and contractility (end‐systolic elastance, E es: 1.7 ± 0.33 vs. 2.58 ± 1.33 mmHg/mL, P = 0.01). Afterload was constant (effective arterial elastance, E a: 1.66 ± 0.32 vs. 1.79 ± 0.52 mmHg/mL, P = 0.43) and the total energy spent was lower (PVA∙HR: 86.7 ± 28 vs. 110.9 ± 32.1 J, P = 0.04). Hemodynamic manifestations of frank hypothyroidism in humans are characterized by reduced preload and contractility, and unchanged total afterload. LT4 therapy increased work efficiency and heart rate, but not the net energy expenditure. Noninvasive PV analysis may be useful to follow‐up different thyroid states.

Hands‐on or Heads‐up? Strategic Foresight as the Heart of the Board's Work

Jannice Moore is president of The Governance Coach, a Calgary, Alberta, Canada–based firm that specializes in Policy Governance consultation and coaching. In this article, Moore looks at the interplay between strategic planning, strategic thinking, and, ultimately, strategic foresight.

Empagliflozin Increases Cardiac Energy Production in Diabetes: Novel Translational Insights Into the Heart Failure Benefits of SGLT2 Inhibitors

SGLT2 inhibitors have profound benefits on reducing heart failure and cardiovascular mortality in individuals with type 2 diabetes, although the mechanism(s) of this benefit remain poorly understood. Because changes in cardiac bioenergetics play a critical role in the pathophysiology of heart failure, the authors evaluated cardiac energy production and substrate use in diabetic mice treated with the SGTL2 inhibitor, empagliflozin. Empagliflozin treatment of diabetic db/db mice prevented the development of cardiac failure. Glycolysis, and the oxidation of glucose, fatty acids and ketones weremeasured in the isolated working heart perfused with 5 mmol/l glucose, 0.8 mmol/l palmitate, 0.5 mmol/l ß-hydroxybutyrate (ßOHB), and 500 μU/ml insulin. In vehicle-treated db/db mice, cardiac glucose oxidation rates were decreased by 61%, compared with control mice, but only by 43% in empagliflozin-treated diabetic mice. Interestingly, cardiac ketone oxidation rates in db/db mice decreased to 45% of the rates seen in control mice, whereas a similar decrease (43%) was seen in empagliflozin-treated db/db mice. Overall cardiac adenosine triphosphate (ATP) production rates decreased by 36% in db/db vehicle-treated hearts compared with control mice, with fatty acid oxidation providing 42%, glucose oxidation 26%, ketone oxidation 10%, and glycolysis 22% of ATP production in db/db mouse hearts. In empagliflozin-treated db/db mice, cardiac ATP production rates increased by 31% compared with db/db vehicle-treated mice, primarily due to a 61% increase in the contribution of glucose oxidation to energy production. Cardiac efficiency (cardiac work/O2 consumed) decreased by 28% in db/db vehicle-treated hearts, compared with control hearts, and empagliflozin did not increase cardiac efficiency per se. Because ketone oxidation was impaired in db/db mouse hearts, the authors determined whether this contributed to the decrease in cardiac efficiency seen in the db/db mouse hearts.Addition of 600 μmol/l ßOHB to db/db mouse hearts perfused with5mmol/l glucose, 0.8 mmol/l palmitate, and100 μU/ml insulin increased ketone oxidation rates, butdidnotdecrease either glucose oxidation or fatty acid oxidation rates. The presence of ketones did not increase cardiac efficiency, but did increase ATP production rates, due tothe additional contribution ofketoneoxidation to energy production. The authors conclude that empagliflozin treatment is associatedwithanincrease in ATP production, resulting in an enhanced energy status of the heart.

Cardiac branched-chain amino acid oxidation is reduced during insulin resistance in the heart.

Recent studies have proposed that elevated branched-chain amino acids (BCAAs) may induce insulin resistance (IR) in muscle secondary to increased BCAA oxidation inhibiting glucose oxidation (GO) and fatty acid oxidation (FAO). However, BCAA oxidation rates have not been assessed in muscle IR, and cardiac FAO rates are actually already elevated in obesity-associated IR. We therefore directly examined cardiac BCAA oxidation in mice fed a high-fat diet (HFD) to induce insulin resistance to better understand the role of cardiac BCAA oxidation in cardiac IR. BCAA oxidation, GO, FAO, and glycolysis were measured in isolated working hearts from mice fed either a low-fat diet (LFD) or HFD for 10 wk. Insulin stimulation of cardiac GO and inhibition of FAO were blunted in HFD mice, resulting in a marked increase in FAO contribution to ATP production compared with LFD mice hearts (71.2% vs. 37.1%, respectively). Surprisingly, cardiac BCAA oxidation rate was reduced in HFD compared with LFD mice (33.5 ± 3.4 vs. 56.7 ± 7.1 nmol·min-1·g dry wt-1, respectively, P < 0.05, n = 9/group). In addition, BCAA oxidation contributed ~1% of the ATP production of the heart, and, as a result, alterations in BCAA oxidation could not significantly impact either GO or FAO rates. However, the decrease in BCAA oxidation was accompanied by an increase in BCAA concentration and impaired insulin signaling. These results suggest that cardiac IR is not due to an increase in BCAA oxidation and subsequent inhibition of GO and FAO. Rather, we propose that an inhibition of BCAA oxidation rate contributes to IR by leading to increased BCAA concentration, which negatively impacts insulin signaling.

Abstract 255: Mechanical Stretch is Not a Major Cause of Ectopic Activation During Early Stage Regional Ischemia in an Isolated Left-Ventricular Working Heart Model

Background: Acute regional ischemia is a leading cause of death. Ectopic beats may initiate ventricular arrhythmias in the first hour after coronary occlusion; however, the origin of these beats remains poorly understood. Some studies suggest that abnormal mechanical stretch at the ischemic border zone may contribute to the initiation of ectopy. If mechanical stretch plays a major role in triggering ectopic beats, we therefore expect: I , left ventricular working (LVW) hearts will have higher frequency of post-occlusion ectopic activity than non-beating (NB) hearts; II , in LVW hearts, ectopic beats will arise from ventricular sites undergoing mechanical stretch. Methods and Results: Isolated pig hearts were assigned to NB or LVW groups (8 per group) and prepared for Langendorff or LVW perfusion, respectively. Contraction of NB hearts was suppressed with 10 μM blebbistatin. Acute regional ischemia was induced by LAD occlusion. Using a newly developed optical mapping system, electrical activity and mechanical deformation were simultaneously recorded from 0 to 60 minutes after LAD occlusion. Mechanical stretch (positive strain in 2 principal directions) was observed in the ischemic and border zones of LVW but not NB hearts (Figure, Panel A). There was no significant difference in the number of ectopic events in LVW hearts compared to NB hearts (58±35 vs. 32±36, p=0.17). Of the 45 ectopic events that originated from the LV mapping region in LVW hearts, &lt;20% (6) were from sites that underwent mechanical stretch in the prior cardiac cycle (Figure, Panel B). Conclusion: Mechanical stretch does not play a major role in triggering ectopic beats in early acute regional ischemia in this model.

Abstract 274: Regulation of Myocardial Ketone Body Oxidation Capacity by Increased Protein O-GlcNAcylation in Diabetic Heart

Diabetes increases the risk of heart failure independently of underlying coronary artery disease. Perturbations in myocardial substrate utilization have been proposed to contribute to the pathogenesis of cardiac dysfunction. However, the exact mechanisms linking impaired substrate utilization to disease progression remain elusive. Compared to the well-established roles of glucose and fatty acids metabolism in cardiac physiology and pathology, the importance of ketone body (KB) metabolism is less well understood. Several findings suggest the importance of KB in the cardiac health and disease. More recently, two independent studies have simultaneously demonstrated increased reliance on KB utilization by the failing heart in the absence of diabetes. Despite these observations, our understanding of the importance of KB metabolism in a diabetic heart is incomplete. Interestingly, our findings from the hearts of streptozotocin-induced diabetic mice confirmed elevated cardiac β-hydroxybutyrate (a major KB) levels and transcriptional suppression of Oxct1 gene expression that encodes for SCOT (succinyl-CoA:3-oxoacid CoA transferase; a rate limiting enzyme of KB oxidation), consistent with a mismatch between KB availability and utilization. To determine a specific role for glucose delivery in this regulation we used an inducible transgenic mouse model with cardiac-restricted expression of the glucose transporter 4 (GLUT4; mG4H). Interestingly, mG4H mice had reduced cardiac SCOT protein levels and oxidation of KB in isolated working heart suggesting that glucose is sufficient to regulate the ketone metabolic pathway. Hyperglycemia associated with diabetes alter protein function via post-translational O -GlcNAcylation. Interestingly, we found that myocardial SCOT expression was also reduced in a third mouse model with increased cardiac O -GlcNAc levels (overexpression of a dominant negative form of O -GlcNAcase, which normally removes O -GlcNAc; dnOGAh) suggesting that increased protein O -GlcNAcylation is directly involved. Collectively, these studies establish a novel role of glucose and its downstream regulator, O -GlcNAc, in attenuation of KB metabolism in the diabetic heart.

The cardiac ryanodine receptor, but not sarcoplasmic reticulum Ca2+-ATPase, is a major determinant of Ca2+ alternans in intact mouse hearts

Sarcoplasmic reticulum (SR) Ca2+ cycling is governed by the cardiac ryanodine receptor (RyR2) and SR Ca2+-ATPase (SERCA2a). Abnormal SR Ca2+ cycling is thought to be the primary cause of Ca2+ alternans that can elicit ventricular arrhythmias and sudden cardiac arrest. Although alterations in either RyR2 or SERCA2a function are expected to affect SR Ca2+ cycling, whether and to what extent altered RyR2 or SERCA2a function affects Ca2+ alternans is unclear. Here, we employed a gain-of-function RyR2 variant (R4496C) and the phospholamban-knockout (PLB-KO) mouse model to assess the effect of genetically enhanced RyR2 or SERCA2a function on Ca2+ alternans. Confocal Ca2+ imaging revealed that RyR2-R4496C shortened SR Ca2+ release refractoriness and markedly suppressed rapid pacing-induced Ca2+ alternans. Interestingly, despite enhancing RyR2 function, intact RyR2-R4496C hearts exhibited no detectable spontaneous SR Ca2+ release events during pacing. Unlike for RyR2, enhancing SERCA2a function by ablating PLB exerted a relatively minor effect on Ca2+ alternans in intact hearts expressing RyR2 WT or a loss-of-function RyR2 variant, E4872Q, that promotes Ca2+ alternans. Furthermore, partial SERCA2a inhibition with 3 μm 2,5-di-tert-butylhydroquinone (tBHQ) also had little impact on Ca2+ alternans, whereas strong SERCA2a inhibition with 10 μm tBHQ markedly reduced the amplitude of Ca2+ transients and suppressed Ca2+ alternans in intact hearts. Our results demonstrate that enhanced RyR2 function suppresses Ca2+ alternans in the absence of spontaneous Ca2+ release and that RyR2, but not SERCA2a, is a key determinant of Ca2+ alternans in intact working hearts, making RyR2 an important therapeutic target for cardiac alternans.

A neuronal role of the Alanine-Serine-Cysteine-1 transporter (SLC7A10, Asc-1) for glycine inhibitory transmission and respiratory pattern

The Alanine-Serine-Cysteine-1 transporter (SLC7A10, Asc-1) has been shown to play a role in synaptic availability of glycine although the exact mechanism remains unclear. We used electrophysiological recordings and biochemical experiments to investigate the role of Asc-1 transporter in glycinergic transmission in the brainstem respiratory network. Using both the Asc-1 substrate and transportable inhibitor D-isoleucine (D-Ile), and the non-transportable Asc-1 blocker Lu AE00527 (Lu), we found that D-Ile reduces glycinergic transmission and increases glycine release via hetero-exchange, whereas Lu has no acute effect on glycinergic synaptic transmission. Furthermore, D-Ile increases the frequency and reduces amplitude of the phrenic nerve activity in the arterially-perfused working heart brainstem preparation. These results suggest a role of Asc-1 in modulating presynaptic glycine levels that can impact on the respiratory network.

Missed Opportunities: What can be learnt from EPs’ experiences at SEN tribunals?

ABSTRACTThis article explores the experiences of eight Educational Psychologists (EPs) in the UK who acted as expert witnesses at Special Educational Needs and Disability Tribunals (SENDIST) hearings in the last 12 months on behalf of their employing Local Authority (LA). A thematic analysis of semi-structured interviews with all eight EPs indicated two super-ordinate themes related to process and professional role. This included challenges with the quality of instructions, information sharing and a failure of mediation. An overarching theme suggested a sense of dissonance related to EPs’ perceived professional role as co-constructors of solutions, and the demands placed upon them by the adversarial appeals process. This paper explores possible ways in which to refocus the EP role in tribunals in order to support LAs to manage the appeals process more effectively. Furthermore, it is suggested that Educational Psychology Services should consider developing a formal commissioned role with LAs that positions mediation at the heart of EP tribunal work.

Mobile cloud computing for ECG telemonitoring and real-time coronary heart disease risk detection

Abstract Advancement in healthcare technologies and biomedical equipment leads to accurate diagnosis of heart related diseases. The major challenges associated with telehealthcare technologies are complex computational requirement and large amount of data processing in continuous monitoring. Mobile cloud computing approach is presented in this work to overcome the issues involved in ECG telemonitoring. Mobile cloud approach is superior to telehealth monitoring techniques due to the access to centralized cloud data and report delivery to mobile phones. In this work, ECG telemonitoring and coronary heart disease (CHD) risk assessment are combined using mobile cloud computing approach. CHD risk is identified using feature extraction and adaptive neuro fuzzy inference system (ANFIS) based classification. In feature extraction process, R-peaks are detected using wavelet transform to find heart rate variability (HRV) of the ECG signal. Various HRV parameters are extracted and applied to ANFIS classifier which employs adaptive feature selection to evaluate CHD risk. Since the mobile cloud approach deals with large amount of data, 160 files of MIT–BIH arrhythmia database has been used in this work for the assessment of CHD risk. ECG signal data are classified into two categories (normal and CHD risky) using ANFIS classifier. The classifier performance is evaluated and comparison is established with other similar classifiers.

Child protection decision-making: social workers’ perceptions

ABSTRACTDecision-making is located at the heart of social work as a core professional activity, because much of what social workers do concerns decisions about future courses of action. Drawing on elements of the learning together systems model and Falkov’s Systemic Family Model, this study investigated social workers’ perceptions regarding how child protection decisions are made. Evidence was drawn from a constructivist–-interpretivist qualitative research design, involving 16 semi-structured interviews with qualified and experienced social workers and 20 direct, non-participant observations of child protection meetings. Evidence from the study suggests that professionals and family members do not rely entirely on the guidance on the threshold criterion of the likelihood and significance of risk of harm when making decisions. Instead, they use discretionary intuition and analytical judgement, involving multidimensional criteria which includes consensus between professionals and with family members; individual professional’s state of mind; other agencies and professionals’ priorities as well as external factors such as the availability of resources. Conclusion can be drawn that existing guidance on decision-making is inadequate, hence the discretionary use of a combination of intuitive heuristics and analytical thinking in a complementary manner. This study, therefore, contributes to considerable conceptual clarity regarding the complex child protection decision-making process.

Contribution of SGLT1 in cardiac glucose uptake

The sodium-glucose transporter 1 (SGLT1) has been identified as the major SGLT isoform expressed in the heart. The exact role of this transporter in the heart is still unknown. Several authors have postulated a role on glucose transport using phlorizin as a specific inhibitor of SGLT transporters. However, high concentrations of phlorizin have been used in these studies and questions remain towards its potential effects on facilitated glucose transporters (GLUTs). Indeed, phlorizin has a similar structure to phloretin, GLUT-specific inhibitor and it could be hydrolyzed into phloretin acting on glucose transport independently of SGLT transporters. The aim of this study is to determine the contribution of SGLT1 transporter on glucose uptake in hearts and the impact of phlorizin on this uptake. We studied glucose uptake in vitro (cardiomyocytes), ex vivo (whole working hearts) and in vivo with SGLT1 WT and KO mice using 2- 3 [H]-glucose. Different phlorizin concentrations were tested to determine its impact on glucose uptake. We showed that glucose uptake was similar in SGLT1 WT and KO mice in basal, hyperglycemic and insulin-stimulated conditions. Moreover, we observed that high concentrations of phlorizin (10 −3 M) completely inhibit glucose uptake in cardiomyocytes subjected to insulin stimulation and that this inhibition was similar in WT and KO SGLT1 mice. An inhibition was also found at lower concentration of phlorizin (10 −4 M) to a lesser extent. The contribution of SGLT1 in glucose uptake in the heart is marginal compared to facilitate glucose uptake. At least at high concentrations, phlorizin inhibits glucose uptake independently of SGLT1 questioning the use of this compound to study SGLT-dependent glucose uptake.

Comparative study of perfusion medium impact on hemodynamics of ex vivo swine hearts perfused in the biventricular working model

Large animal ex vivo biventricular working hearts are a recent breakthrough in the scientific experimental community. This model allows a greater insight into intrinsic cardiac electrophysiology and hemodynamic function without interference from autonomous nervous system. Perform a comparative study between different perfusion mediums and their impact on intrinsic hearts hemodynamics. Pig hearts were excised with the pericardium. Cardiac arrest was induced in vivo by infusion of cold cardioplegic solution into the aortic root, followed by a rapid excision and immersion in a cold 0.9% saline solution. Some hearts were perfused with autologous blood (1.5 diluted in 10L Tyrode's solution). The aorta, pulmonary artery, pulmonary veins and vena cava were cannulated and remaining vessels were sutured. Hearts were placed on the setup and perfused at fixed pre- and afterloads. All hearts were perfused with Tyrode's solution with BSA and fatty acids (FA) (group 1), or BSA/FA and blood (group 2) or blood (group 3). An increased aortic flow was observed in hearts perfused with blood without (+110%, P < 0.05) and with BSA/FA (+50%, non-significant) compared to BSA/FA group. A drop was noted in LV and RV minimum pressure (−75 to 100%), end diastolic pressure (−40 to 80%) and dP/dtmin (−50%) in hearts perfused with blood ± BSA/FA compared to BSA/FA only. dP/dtmax did not change in LV, but increased in the RV (+120–60% in blood ± BSA/FA groups). All hearts perfused with BSA/FA ± blood displayed a lower heart rate than hearts perfused with blood without BSA/FA ( P < 0.05). This study shows significant advantages the addition of blood has on the ex vivo heart hemodynamics, especially for diastolic parameters, leading to a better maintenance of function during perfusion. Limitation of edema and a better oxygen carrying capacity of blood help reduce localised ischemia by improving the overall perfusion of the myocardium.

Uncoupling of glycolysis from glucose oxidation accompanies the development of heart failure with preserved ejection fraction

BackgroundAlterations in cardiac energy metabolism contribute to the development and severity of heart failure (HF). In severe HF, overall mitochondrial oxidative metabolism is significantly decreased resulting in a reduced energy reserve. However, despite the high prevalence of HF with preserved ejection fraction (HFpEF) in our society, it is not clear what changes in cardiac energy metabolism occur in HFpEF, and whether alterations in energy metabolism contribute to the development of contractile dysfunction.MethodsWe directly assessed overall energy metabolism during the development of HFpEF in Dahl salt-sensitive rats fed a high salt diet (HSD) for 3, 6 and 9 weeks.ResultsOver the course of 9 weeks, the HSD caused a progressive decrease in diastolic function (assessed by echocardiography assessment of E’/A’). This was accompanied by a progressive increase in cardiac glycolysis rates (assessed in isolated working hearts obtained at 3, 6, and 9 weeks of HSD). In contrast, the subsequent oxidation of pyruvate from glycolysis (glucose oxidation) was not altered, resulting in an uncoupling of glucose metabolism and a significant increase in proton production. Increased glucose transporter (GLUT)1 expression accompanied this elevation in glycolysis. Decreases in cardiac fatty acid oxidation and overall adenosine triphosphate (ATP) production rates were not observed in early HF, but both significantly decreased as HF progressed to HF with reduced EF (i.e. 9 weeks of HSD).ConclusionsOverall, we show that increased glycolysis is the earliest energy metabolic change that occurs during HFpEF development. The resultant increased proton production from uncoupling of glycolysis and glucose oxidation may contribute to the development of HFpEF.

Argon preconditioning enhances postischaemic cardiac functional recovery following cardioplegic arrest and global cold ischaemia.

Previous studies demonstrated that preconditioning with argon gas provided a marked reduction in inflammation and apoptosis and increased myocardial contractility in the setting of acute myocardial ischaemia-reperfusion (IR). There is substantial evidence that myocardial IR injury following cardioplegic arrest is associated with the enhancement of apoptosis and inflammation, which is considered to play a role in cardiac functional impairment. Therefore, the present study was designed to clarify whether preconditioning with argon gas enhances recovery of cardiac function following cardioplegic arrest. Sprague-Dawley rats were anaesthetized and ventilated and allocated to (i) the control group (control IR, n = 10) and (ii) the in vivo group (argon IR), which received 3 cycles of argon (50% argon, 21% oxygen and 29% nitrogen, n = 10) administered for 5 min interspersed with 5 min of a gas mixture (79% nitrogen and 21% oxygen). The hearts were excised and then evaluated in an erythrocyte-perfused isolated working heart system. Cold ischaemia (4°C) for 60 min was induced by histidine-tryptophan-ketoglutarate cardioplegia, followed by 40 min of reperfusion. Cardiac functional parameters were assessed. In left ventricular tissue samples, the expressions of extracellular-regulated kinase (ERK1/2), AKT serine/threonine kinase (Akt), jun N-terminal kinase (JNK), endothelial nitric oxide synthase (eNOS) and HMGB1: high-mobility group box 1 (HMGB1) protein were assessed by western blot, and high-energy phosphates were evaluated by high-performance liquid chromatography. At the end of reperfusion, the rats preconditioned with argon showed significantly enhanced recovery of cardiac output (101 ± 6% vs 87 ± 11%; P < 0.01), stroke volume (94 ± 4% vs 80 ± 11%; P = 0.001), external heart work (100 ± 6% vs 81 ± 13%; P < 0.001) and coronary flow (90 ± 13% vs 125 ± 21%; P < 0.01) compared with the control IR group. These results were accompanied by a significant increase in the levels of myocardial phosphocreatine (23.71 ± 2.07 µmol/g protein vs the control IR group, 13.50 ± 4.75; P = 0.001) and maintained adenosine triphosphate levels (13.62 ±1.89 µmol/g protein vs control IR group adenosine triphosphate: 10.08 ± 1.94 µmol/g; P = 0.017). Additionally, preconditioning with argon markedly reduced the activation of JNK (0.11 ± 0.01 vs 0.25 ± 0.03; P = 0.005) and the expression of HMGB1 protein (0.52 ± 0.04 vs 1.5 ± 0.10; P < 0.001) following reperfusion. Preconditioning with argon enhanced cardiac functional recovery in rat hearts arrested with histidine-tryptophan-ketoglutarate cardioplegia, thereby representing a potential novel cardioprotective approach in cardiac surgery.

Cardiac-Specific Deletion of Pyruvate Dehydrogenase Impairs Glucose Oxidation Rates and Induces Diastolic Dysfunction.

Obesity and type 2 diabetes (T2D) increase the risk for cardiomyopathy, which is the presence of ventricular dysfunction in the absence of underlying coronary artery disease and/or hypertension. As myocardial energy metabolism is altered during obesity/T2D (increased fatty acid oxidation and decreased glucose oxidation), we hypothesized that restricting myocardial glucose oxidation in lean mice devoid of the perturbed metabolic milieu observed in obesity/T2D would produce a cardiomyopathy phenotype, characterized via diastolic dysfunction. We tested our hypothesis via producing mice with a cardiac-specific gene knockout for pyruvate dehydrogenase (PDH, gene name Pdha1), the rate-limiting enzyme for glucose oxidation. Cardiac-specific Pdha1 deficient (Pdha1Cardiac−/−) mice were generated via crossing a tamoxifen-inducible Cre expressing mouse under the control of the alpha-myosin heavy chain (αMHC-MerCreMer) promoter with a floxed Pdha1 mouse. Energy metabolism and cardiac function were assessed via isolated working heart perfusions and ultrasound echocardiography, respectively. Tamoxifen administration produced an ~85% reduction in PDH protein expression in Pdha1Cardiac−/− mice versus their control littermates, which resulted in a marked reduction in myocardial glucose oxidation and a corresponding increase in palmitate oxidation. This myocardial metabolism profile did not impair systolic function in Pdha1Cardiac−/− mice, which had comparable left ventricular ejection fractions and fractional shortenings as their αMHC-MerCreMer control littermates, but did produce diastolic dysfunction as seen via the reduced mitral E/A ratio. Therefore, it does appear that forced restriction of glucose oxidation in the hearts of Pdha1Cardiac−/− mice is sufficient to produce a cardiomyopathy-like phenotype, independent of the perturbed metabolic milieu observed in obesity and/or T2D.

Communication at the heart of effective group work

Nursing students conducted a study into the meaning of group work. Based on the experience they gained from their practice placements, as well as their trip organised as part of their optional learning unit, they scrutinised the conditions favourable to the effective functioning of a working group and the pitfalls to avoid. It equipped them with useful references with which to approach their first job.