Cardiac Pump Function Research Articles

Protective effects of a modified apelin-12 and dinitrosyl iron complexes in experimental cardioplegic ischemia and reperfusion

The maintenance of nitric oxide (NO) bioavailability has been recognized as an important component of myocardial protection during cardiac surgery. This study was designed to evaluate the efficacy of using two NO-donating compounds in cardioplegia and reperfusion: (i) a modified peptide apelin-12 (MA12) that activates endothelial NO synthase (eNOS) and (ii) dinitrosyl iron complexes with reduced glutathione (DNIC-GS), a natural NO vehicle. Isolated perfused working rat hearts were subjected to normothermic global ischemia and reperfusion. St. Thomas' Hospital cardioplegic solution (STH) containing 140μM MA12 or 100μM DNIC-GS was used. In separate series, 140μM MA12 or 100μM DNIC-GS was administered at early reperfusion. Metabolic state of the hearts was evaluated by myocardial content of high-energy phosphates and lactate. Lactate dehydrogenase (LDH) activity in myocardial effluent was used as an index of cell membrane damage. Cardioplegia with MA12 or DNIC-GS improved recovery of coronary flow and cardiac function, and reduced LDH leakage in perfusate compared with STH without additives. Cardioplegic arrest with MA12 significantly enhanced preservation of high-energy phosphates and decreased accumulation of lactate in reperfused hearts. The overall protective effect of cardioplegia with MA12 was significantly greater than with DNIC-GS. The administration of MA12 or DNIC-GS at early reperfusion also increased metabolic and functional recovery of reperfused hearts. In this case, recovery of cardiac contractile and pump function indices was significantly higher if reperfusion was performed with DNIC-GS. The results show that MA12 and DNIC-GS are promising adjunct agents for protection of the heart during cardioplegic arrest and reperfusion.

Cardiogenic Shock.

Cardiogenic shock (CS) is a physiologic state in which cardiac pump function is inadequate to perfuse the tissues. If CS is not rapidly recognized and treated, tissue hypoperfusion can quickly lead to organ dysfunction and patient death. Evaluation of patients with suspected CS should include an electrocardiogram, chest radiograph, laboratory studies, and bedside echocardiogram. Initial resuscitation is directed toward restoring cardiac output and tissue perfusion. Mechanical circulatory support is indicated for patients with CS who do not respond to pharmacologic therapy. Ultimately, these patients should undergo emergent reperfusion therapy with either percutaneous coronary intervention or coronary artery bypass grafting.

Cardiovascular Function of Modern Pigs Does not Comply with Allometric Scaling Laws

Growing concerns have been expressed regarding cardiovascular performance in modern farm pigs, which has been proposed as a critical factor contributing to the reduced adaptability of modern pigs to stress. Here we tested the hypothesis that cardiac dimensions and pump function in modern heavy farm pigs are disproportionally low for their body weight, and investigated potential underlying mechanisms. The results from the present study indeed demonstrate disproportionally low values for stroke volume and cardiac output in pigs with bodyweights over 150 kg. Importantly, these low values were not the result of impaired left ventricular (LV) systolic contractile function, but were due to a disproportionally small LV end-diastolic volume. The latter was associated with changes in determinants of LV passive stiffness, including (i) an increase in LV myocardial collagen, (ii) a shift from the compliant N2BA titin isoform towards the stiff N2B, and (iii) a marked elevation of aortic blood pressure. Taken together, these results demonstrate reduced pumping capacity of the hearts of heavy modern pigs, due to structural abnormalities in the LV myocardium.

THE UNEXPECTED CARDIOPROTECTION BY EPIGENETIC FOODS

Epigenetic changes affect the gene expression profile of cells without altering the DNA sequence in response to different environmental stimuli, such as the diet. Several dietary plant compounds have the epigenetic ability to prevent both the onset and the progression of different diseases, including cardiovascular diseases that are one of the most common in the world. Heart failure following perioperative myocardial infarction is a complex clinical syndrome without cure, also affecting high-risk patients undergoing non-cardiac surgery. It is characterized by serious decay of cardiac pump function as a result of ongoing remodelling of the myocardium. Despite the increasing use of conventional medications has reduced the mortality of patients with myocardial infarction, the outcome remains unpredictable so far. The past three decades have witnessed incessant research aimed at protecting the adult myocardium against ischemic injury, but the development of effective strategies to prevent the maladaptive tissue remodelling is still a desirable achievement. Recent findings reveal that the dietary intake of natural bioactive components with known antioxidant activity improves the intercellular communication and increases the tolerance of both cardiomyocytes and coronary endothelial cells against the ischemic microenvironment. The Epigenetic activation of rescue genes prevents the decay of function of the abovementioned cardiac cells. Consequently, this scenario would reduce the myocardial accumulation of collagen responsible for the tightening of the heart walls. Whereas the noninvasive delivery of cardioprotectant epigenetic compounds through diet is a promising approach, regulatory mechanisms need to be unravelled.

Abstract 158: A Tether Containing a UBX Domain (TUG) Mediates Glucose Transporter Translocation in the Ischemic Heart

Introduction: The adaptive metabolic regulation of glucose and fatty acid in the heart plays a critical role in limiting cardiac damage caused by ischemia and reperfusion (I/R). TUG (tether containing a UBX domain, for GLUT4) can be cleaved to mobilize glucose transporter GLUT4 from intracellular vesicles to the cell surface in skeletal muscle and adipose in response to insulin stimulation. The energy sensor AMP-activated protein kinase (AMPK) plays an important cardioprotective role in response to ischemic insults by modulating GLUT4 translocation. Hypothesis: TUG is one of the downstream targets of AMPK in the heart. TUG could be phosphorylated by ischemic AMPK and cleaved to dissociate with GLUT4 and increase GLUT4 translocation in the ischemic heart. Methods: In vivo regional ischemia by ligation of left anterior coronary artery and ex vivo isolated mouse heart perfusion Langendorff system were used to test the hypothesis. Results: Antithrombin (AT) is an endogenous AMPK agonist in the heart and used to define the role of TUG in regulating GLUT4 trafficking during ischemia and reperfusion in the heart. AT showed its cardioprotective function through recovering cardiac pumping function and activating AMPK. The results showed that AMPK activation by AT treatment was through LKB1 and Sesn2 complex. Furthermore, the ex vivo heart perfusion data demonstrated that AT administration significantly increase GLUT4 translocation, glucose uptake, glycolysis and glucose oxidation during ischemia and reperfusion (p<0.05 vs . vehicle). Moreover, AT treatment increased abundance of a TUG cleavage product (42 KD) in response to I/R. The TUG protein was clearly phosphorylated by activated AMPK in HL-1 cardiomyocytes. The in vivo myocardial ischemia results demonstrated that ischemic AMPK activation triggers TUG cleavage and significantly increases GLUT4 translocation to the cell surface. Moreover, an augmented interaction between AMPK and TUG was observed during ischemia. Conclusions: Cardiac AMPK activation stimulates TUG cleavage and causes the dissociation between TUG and GLUT4 in the intracellular vesicles. TUG is a critical mediator that modulates cardiac GLUT4 translocation to cell surface and enhances glucose uptake by AMPK signaling pathway.

Evaluation of Resting Cardiac Power Output as a Prognostic Factor in Patients with Advanced Heart Failure

If the heart is represented by a hydraulic pump, cardiac power represents the hydraulic function of the heart. Cardiac pump function is frequently determined through left ventricular ejection fraction using imaging. This study aims to validate resting cardiac power output (CPO) as a predictive biomarker in patients with advanced heart failure (HF). One hundred and seventy-two patients with HF severe enough to warrant cardiac transplantation were retrospectively reviewed at a single tertiary care institution between September 2010 and July 2013. Patients were initially evaluated with simultaneous right-sided and left-sided cardiac catheter-based hemodynamic measurements, followed by longitudinal follow-up (median of 52 months) for adverse events (cardiac mortality, cardiac transplantation, or ventricular assist device placement). Median resting CPO was 0.54 W (long rank chi-square = 33.6; p < 0.0001). Decreased resting CPO (<0.54 W) predicted increased risk for adverse outcomes. Fifty cardiac deaths, 10 cardiac transplants, and 12 ventricular assist device placements were documented. The prognostic relevance of resting CPO remained significant after adjustment for age, gender, left ventricular ejection fraction, mean arterial pressure, pulmonary vascular resistance, right atrial pressure, and estimated glomerular filtration rate (HR, 3.53; 95% confidence interval, 1.66 to 6.77; p = 0.0007). In conclusion, lower resting CPO supplies independent prediction of adverse outcomes. Thus, it could be effectively used for risk stratification in patients with advanced HF.

Effects of human milk fortifier on premature infant's cardiac function

Objective To investigate the effects of human milk fortifier on premature infant's cardiac function. Methods From January 2014 to December 2016, sixty premature infants of paediatric preterm infants were selected from Daqing Longnan Hospital, Heilongjiang province. The random number table method was divided into 30 cases (milk feeding and strengthening agent) and the control group of 30 cases (pure milk feeding) .The heart rate of premature infant was measured before, during and after using human milk fortifier. After using human mike fortifier for 1 week, heart rate, electrocardiogram (p-wave duration, QRS wave duration, P-R interval, incidence of arrhythmia) , echocardiogram (LVEF, RVEF, E/A ratio of mitral and tricuspid valves) and myocardial enzymes (the quantity of AST, LDH, CK and CK-MB) were compared between experimental group and control group. Results The heart rate of premature infant during using human milk fortifier was significantly faster than those before and after using human milk fortifier and that of children in the control group (P 0.05) . Conclusions Human milk fortifier can increase the heart rate of premature infant, and has no harmful effect on cardiac electrical activity, pump function and myocardial enzymes. Key words: Infant, premature; Human milk fortifier; Cardiac function

A comprehensive review of the bioenergetics of fatty acid and glucose metabolism in the healthy and failing heart in nondiabetic condition.

The function of the heart is defined by its ability to deliver adequate cardiac output to meet the requirements of the body both at rest and with exertion. To fill this role, the heart demonstrates an impressive capacity to tightly regulate energy generation and consumption. Energy production and transfer within cardiac myocytes primarily relies on the process of oxidative phosphorylation. In the failing heart, there is an imbalance between the work of the cardiac system and the energy required to generate this work. This presence of this mismatch has given rise to the concept known as the energy starvation theory. This concept encapsulates observations such as perturbed substrate consumption, insufficient energy transfer and ingestion, reduced substrate and oxygen availability, and diminished energy production in the failing heart. Diminished available cellular energy may further result from a reduction in the biosynthesis of mitochondria and their protein synthesis and from global cellular architectural disarray. In essence, the energy starvation theory posits that cardiac pump function declines due to a reduction in oxygen and substrate availability, and thus leads to a total body starvation of systemic energy. This novel cognitive framework has led to encouraging new directions in a "metabolic therapeutic approach" for the failing heart.

Cardiac regenerative medicine: At the crossroad of microRNA function and biotechnology.

There is an urgent need to develop new therapeutic strategies to stimulate cardiac repair after damage, such as myocardial infarction. Already for more than a century scientist are intrigued by studying the regenerative capacity of the heart. While moving away from the old classification of the heart as a post-mitotic organ, and being inspired by the stem cell research in other scientific fields, mainly three different strategies arose in order to develop regenerative medicine, namely; the use of cardiac stem cells, reprogramming of fibroblasts into cardiomyocytes or direct stimulation of endogenous cardiomyocyte proliferation. MicroRNAs, known to play a role in orchestrating cell fate processes such as proliferation, differentiation and reprogramming, gained a lot of attention in this context the latest years. Indeed, several research groups have independently demonstrated that microRNA-based therapy shows promising results to induce heart tissue regeneration and improve cardiac pump function after myocardial injury. Nowadays, a whole new biotechnology field has been unveiled to investigate the possibilities for efficient, safe and specific delivery of microRNAs towards the heart.

Vinculin at the heart of aging.

With age, the heart and large arteries show decreased elasticity. In arteries, this results in increased resistance to cardiac pump function and increased workload against this resistance results in pathological cardiac hypertrophy (1). The left ventricle undergoes an increase in wall thickness and an overall expansion of left ventricular mass with age. At the cellular level, this overload results in an increase in cardiomyocyte dimension and decrease in cardiomyocyte number (2). In terms of the cardiac scaffold, collagen deposition increases in the aging heart, contributing to further stiffening of the myocardium (2). These factors altogether impact diastolic function of the heart, impairing the ability for proper relaxation and ventricular filling. Systolic function is not often affected with cardiac aging, based on the preserved ejection fraction and stroke volume associated with heart failure (3). The cytoskeleton encompasses a network of proteins associated with the sarcomere (titin, α-actinin), true cytoskeleton (desmin, actin), cell membrane (vinculin, dystrophin), and intercalated disc (ICD) (desmoplakin, connexin 43) that function to provide cell stability, as well as transmit and receive mechanical and chemical stimuli both within and between cells (4). During cardiac stress and failure, there are significant alterations in the expression of cardiomyocyte cytoskeletal proteins, including myosin and vinculin (4). Cytoskeletal alterations are also observed during cardiac aging (5). However the consequences of these alterations in disease and aging on mechanosensing, force transmission, and global heart function remain unknown. In the recent publication, “Vinculin network-mediated cytoskeletal remodeling regulates contractile function in the aging heart”, Kaushik et al . identify a protective role for vinculin in the aging heart. Their study exploits proteomic analysis of simian and murine ventricles as well as functional analysis of transgenic Drosophila models to highlight a major role for vinculin-mediated cytoskeletal remodeling in mechanotransmission during cardiac aging ( Figure 1 ).

Fear and disgust in women: Differentiation of cardiovascular regulation patterns

Both fear and disgust facilitate avoidance of threat. From a functional view, however, cardiovascular responses to fear and disgust should differ as they prepare for appropriate behavior to protect from injury and infection, respectively. Therefore, we examined the cardiovascular responses to fear and contamination-related disgust in comparison to an emotionally neutral state induced with auditory scripts and film clips in female participants. Ten emotion and motivation self-reports and ninecardiovascular response factors derived from 23 cardiovascular variables served as dependent variables. Self-reports confirmed the specific induction of fear and disgust. In addition, fear and disgust differed in their cardiovascular response patterning. For fear, we observed specific increases in factors indicating vasoconstriction and cardiac pump function. For disgust, we found specific increases in vagal cardiac control and decreases in myocardial contractility. These findings provide support for the cardiovascular specificity of fear and disgust and are discussed in terms of a basic emotions approach.

Acute Beneficial Effects of Muscular Counterpulsation in Patients with Coronary Heart Diseases.

This prospective pilot study was designed to investigate the acute hemodynamic effects and clinical applicability of muscular counterpulsation (MCP), a one-shot procedure for biomechanical circulatory support. The study included 17 consecutive patients with coronary artery disease (CAD) and impaired ejection fraction (EF ≤45%) who underwent elective coronary artery bypass grafting (CABG). Patients were divided into control ( n = 7) and treatment ( n = 10) groups. MCP was applied through adhesive skin electrodes to the thighs and calves with a battery-powered, portable, ECG-triggered device for 15 minutes prior to general anesthesia. Standard ECG and invasive hemodynamic data were obtained from all patients. MCP was well tolerated in all patients, with no complications. Patients receiving MCP exhibited better cardiac function as indicated by reduced systemic vascular resistance and an augmented cardiac stroke index (+10%), which was maintained over time. After inducing general anesthesia via endotracheal intubation, the treatment group exhibited a reduced after-load (systemic vascular resistance index -28% and mean arterial pressure -10%) with increased left ventricular efficiency (stroke index/left ventricular stroke work index, +22%). Our findings indicate that MCP method was safe and easy to use in this patient population. In conclusion, a one-shot application of MCP prior to anesthesia was associated with an improvement in cardiac pump function and myocardial contractility.

Non-invasively estimated left atrial stiffness is associated with short-term recurrence of atrial fibrillation after electrical cardioversion

BackgroundAs atrial stiffness (Kla) is an important determinant of cardiac pump function, better mechanical characterization of left atrial (LA) cavity would be clinically relevant. Pulmonary venous ablation is an option for atrial fibrillation (AF) treatment that offers a powerful context for improving our understanding of LA mechanical function. We hypothesized that a relation could be detected between invasive estimation of Kla and new non-invasive deformation parameters and traditional LA and left ventricular (LV) function descriptors, so that Kla can be estimated non-invasively. We also hypothesized that a non-invasive surrogate of Kla would be useful in predicting AF recurrence after cardioversion. MethodsIn 20 patients undergoing AF ablation, LA pressure–volume curves were derived from invasive pressure and echocardiographic images; Kla was calculated during ascending limb of V-loop as ΔLA pressure/ΔLA volume. 2D-speckle-tracking echocardiographic LA and LV longitudinal strains and volumes, ejection fraction (EF) and ventricular stiffness (Klv), as obtained from mitral deceleration time, were tested as non-invasive Kla predictors. In 128 sinus rhythm patients 1 month after electrical cardioversion for persistent AF, non-invasively estimated Kla (computed-Kla) was tested as predictor of recurrence at 6 months. ResultsTertiles of mean LA pressure correlated with increasing Kla (trend, p=0.06) and decreasing LA peak strain, LVEF, and LV longitudinal strain (p=0.029, p=0.019, and p=0.024). There were no differences in LA and LV volumes and Klv across groups. Multiple regression analysis identified LV longitudinal strain as the only independent predictor of Kla (p=0.014). Patients in highest quartile of computed-Kla (estimated as [log]=0.735+0.051×LV strain) tended to have highest AF recurrence rate (25%) as compared with remaining 3 quartiles (9%, 9%, 3%, p=0.09). ConclusionKla can be assessed invasively in patients undergoing AF ablation and it can be estimated non-invasively using LV strain. AF recurrence after cardioversion tends to be highest in highest quartile of computed-Kla.

Abstract 296: Loss of Trpc6 Function in Cardiomyocytes Improves Survival and Attenuates Progression of Cardiac Dysfunction After Mi

Ischemic heart disease (IHD) commonly culminates in myocardial infarction (MI), which causes cardiac myocyte death and depressed cardiac pump function. Surviving myocytes can usually maintain pump function by increasing Ca 2+ influx and contractility. However, elevated intracellular Ca 2+ also can activate pathological hypertrophic signaling that promotes cardiac dysfunction and progression into heart failure. Ca 2+ influx through Canonical Transient Receptor Potential (TRPC) channels has been classified as a potential source of hypertrophic signaling. Specifically, TRPC6 gene expression and biological activity is significantly upregulated in cardiac myocytes after MI. Our aim was to determine if TRPC6 loss of function is cardioprotective in MI mouse model. We performed an MI study on cardiac specific dominant negative (dn) TRPC6 transgenic mice that express 3 mutated amino acids (L678A-W680A) in the pore region, which disables TRPC6 channel function. In the course of 6 weeks post MI, dnTRPC6 mice had significantly greater survival (69.2%) than wild-type (WT) mice (47.5%). Cardiac function at 2 weeks post MI was decreased to the same extent in WT and dnTRPC6 mice. Ejection fraction (EF) in WT group was 30.6% vs. 57.1% and in dnTRPC6 EF was 31% vs. 61% (MI vs. sham, respectively). The EF in dnTRPC6 mice 6 weeks post MI suggested attenuation of heart failure progression compared to WT mice (32.5% vs. 26.5%, *P=0.05). Mice in the WT group demonstrated significant elevation in end diastolic and end systolic volumes (EDV and ESV) 6 weeks post MI, while dnTRPC6 had reduced end diastolic and end systolic volumes (116μL vs. 88μL and 106μL vs. 76μL, WT vs. dnTRPC6, EDV and ESV, respectively. ***P&lt;0.0001). Hypertrophy measures of heart weight to body weight ratio and heart weight to tibia length ratio were significantly reduced in dnTRPC6 mice 6 weeks post MI as opposed to WT mice (8.4 vs. 7.3 and 13.4 vs. 11.7, respectively *P&lt;0.05). Hypertrophic markers of ANP, BNP and βMHC followed similar downregulation trend in the dnTRPC6 mice. In conclusion, loss of TRPC6 function slows the progression of cardiac dysfunction and cardiac remodeling in the post MI heart.

Real-time monitoring of hypertrophy in HL-1 cardiomyocytes by impedance measurements reveals different modes of growth.

Hypertrophic growth is a response of the heart to increased mechanical load or physiological stress. Thereby, cardiomyocytes grow in length and/or width to maintain cardiac pump function. Major signaling pathways involved in cardiomyocyte growth and remodeling have been identified during recent years including calcineurin-NFAT and PI3K-Akt signaling. Modulation of these pathways is of certain interest for therapeutic treatment of cardiac hypertrophy. However, quantification and characterization of hypertrophy in response to different stimuli or modulators is difficult. This study aims to test different read-out systems for detection and quantification of differences in hypertrophic growth in response to prohypertrophic stimuli. Real-time impedance measurements allowed the detection of distinct differences in hypertrophic growth in response to endothelin, norepinephrine, phenylephrine or BIO, which were not observable by other methods such as flow cytometry. Endothelin treatment induced a rapid and strong peak in the impedance signal concomitant with a massive reorientation of the actin cytoskeleton. Changes in expression of hypertrophy-associated genes were detected and stabilization of β-catenin was identified as a common response to all hypertrophic stimuli used in this study. Hypertrophic growth was blocked by the PI3K/mTOR inhibitor PI-103.

Mitochondrial sirtuins in the heart.

Sirtuins (SIRTs) are NAD(+)-dependent enzymes that catalyze deacylation of protein lysine residues. In mammals, seven sirtuins have been identified, SIRT1-7. SIRT3-5 are mainly or exclusively localized within mitochondria and mainly participate in the regulation of energy metabolic pathways. Since mitochondrial ATP regeneration is inevitably linked to the maintenance of cardiac pump function, it is not surprising that recent studies revealed a role for mitochondrial sirtuins in the regulation of myocardial energetics and function. In addition, mitochondrial sirtuins modulate the extent of myocardial ischemia reperfusion injury and the development of cardiac hypertrophy and failure. Thus, targeting mitochondrial sirtuins has been proposed as a novel approach to improve myocardial mitochondrial energetics, which is frequently impaired in cardiac disease and considered an important underlying cause contributing to several cardiac pathologies, including myocardial ischemia reperfusion injury and heart failure. In the current review, we present and discuss the available literature on mitochondrial sirtuins and their potential roles in cardiac physiology and disease.

0281 : Protection of berries polyphenols in response to cardiac stress might involve other mechanisms than a mitochondrial direct action

Cardiovascular diseases (CVD) are the leading cause of death in the developing world. Epidemiological studies have shown a consistent relationship between the consumption of fruits and vegetables and a reduced risk of CVD susceptibility. Among mechanisms underlying the decline of cardiac pump function in heart failure (HF), chronic elevation of cAMP, protein post-translational modifications and mitochondrial dysfunction emerge as major contributing factors. Thus, (i) modulation of the cAMP-hydrolyzing phosphodiesterase (PDE) activity and (ii) maintaining a proper function of mitochondria to ensure cellular process metabolite synthesis, calcium homeostasis and cell death, can have a positive effect on the heart. The aim was to evaluate the contribution of polyphenols on the prevention of mitochondrial permeability transition, a process which can lead to cell death and on the modulation of cardiac PDE activity and cAMP levels ex vivo. Wistar rats were divided into 2 groups. In a first group, cardiac tissues were collected to isolate mitochondria and measure mitochondria transmembrane potential and matrix swelling induced by calcium (Ca2+) and tert- Butyl hydroperoxide (t-BHP). In the second group, hearts were excised and lysed to measure PDE activity. Large range of concentrations of polyphenols showed no mitochondrial pore transition protection in response to 50μMCa2+ mitochondria and to oxidative stress induced by tert-Butyl hydroperoxide (t-BHP). Experiments on cardiac PDEs are on-going and results will be compared to resveratrol, which has been shown to inhibit PDE 1, 3, and 4 in the heart. These results suggest that if these polyphenols metabolites have a cardioprotective effect in vivo, it might be rather mediated by an indirect effect on cardiac mitochondria such as modulation of PDE activity or others cellular targets. Further investigations will be performed to fully elucidate the targets of polyphenols effects. Funding (ANR and FCT-ANR) The author hereby declares no conflict of interest

Abstract P201: Ischemia with Mental Stress is Associated with Greater Left Ventricular Dyssynchrony

Introduction: Synchronized contraction of left ventricle (LV) is necessary for normal cardiac pump function. Delayed activation of LV segments, known as “dyssynchrony,” can result in systolic and diastolic function deterioration and clinical heart failure. The autonomic nervous system regulates LV conduction and is influenced by psychological stress. We used mental stress testing to examine the effects of psychological stress on LV dyssynchrony and assess whether patients who develop mental stress-induced myocardial ischemia (MSI), a condition associated with doubling of risk for mortality and cardiovascular events, have greater LV dyssynchrony at baseline and/or during stress as compared to MSI negative subjects. We compared results with a control condition of conventional physical (exercise/ pharmacological) stress. Methods: 660 patients with CAD underwent 99mTc[[Unable to Display Character: &amp;#8208;]]sestamibi myocardial perfusion imaging at rest and following both mental and physical stress. Dyssynchrony parameters, measured using the Emory Cardiac Toolbox software, included phase standard deviation (SD) and phase bandwidth; higher levels indicate higher desynchronized contraction. Ischemia with both conditions was blindly assessed by 2 independent readers, with consensus reading for any discordance. The Gensini score was calculated from angiographic data to assess CAD burden. Dyssynchrony data at baseline and during mental/physical stress were log-transformed for analyses. Results: Mean age was 63 years (SD: 9), 180 (27%) were females and 432 (66%) were whites. Overall, 108 (16%) subjects developed mental stress ischemia (MSI+), while 232 (35%) developed physical stress ischemia (PSI+). After adjusting for age, sex, race, traditional CAD risk factors, indicators of CAD burden, history of heart failure, and LV ejection fraction, at baseline MSI+ subjects compared with MSI- had 11% higher phase SD (95% CI: 1% to 19%), and 11% higher phase bandwidth (95% CI: 3% to 20%). PSI+ subjects compared with PSI- had a more modest and non-significant increase in phase SD (mean increase of 4%, 95% CI: -3% to 12%) and phase bandwidth (4%, 95% CI: -3% to 11%). The associations of MSI with baseline dyssynchrony was independent of PSI status. A similar association was noted between MSI and dyssyncrony during mental stress. Among the covariates, male sex (P=0.01), smoking (P=0.02), Gensini score (P=0.01), history of MI (P&lt;0.001), history of heart failure (P&lt;0.001), and LV ejection fraction (P&lt;0.001) were significantly associated with higher baseline dyssynchrony. Conclusion: MSI is associated with greater LV dyssynchrony at rest and during stress. Baseline LV dyssynchrony may be a marker of susceptibility to stress-induced ischemia possibly due to recurrent or chronic subclinical ischemia during daily life. LV dyssynchrony may be a potential mechanism for adverse cardiac events in patients with MSI.

Acute kidney injury among ST elevation myocardial infarction patients treated by primary percutaneous coronary intervention: a multifactorial entity.

Acute kidney injury is a frequent complication among ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), and is associated with adverse outcomes. While contrast nephropathy is considered the most important reason for worsening of renal function, recent data have suggested the role of other important factors among this specific patient population. In the present review, we examine the various factors leading to renal impairment in STEMI patients and place the findings in the context of this specific patient population in the era of primary PCI. These factors include contrast nephropathy, time to coronary reperfusion, cardiac pump function and hemodynamics as well as various inflammatory and metabolic markers.

Modeling our understanding of the His-Purkinje system

The His-Purkinje System (HPS) is responsible for the rapid electric conduction in the ventricles. It relays electrical impulses from the atrioventricular node to the muscle cells and, thus, coordinates the contraction of ventricles in order to ensure proper cardiac pump function. The HPS has been implicated in the genesis of ventricular tachycardia and fibrillation as a source of ectopic beats, as well as forming distinct portions of reentry circuitry. Despite its importance, it remains much less well characterized, structurally and functionally, than the myocardium. Notably, important differences exist with regard to cell structure and electrophysiology, including ion channels, intracellular calcium handling, and gap junctions. Very few computational models address the HPS, and the majority of organ level modeling studies omit it. This review will provide an overview of our current knowledge of structure and function (including electrophysiology) of the HPS. We will review the most recent advances in modeling of the system from the single cell to the organ level, with considerations for relevant interspecies distinctions.