Alterations In Cardiac Electrophysiology Research Articles

Recovery of cardiac electrophysiological alterations by heart rate complexity based on multiscale entropy following liver transplantation

Autonomic nervous dysfunction is a known cardiac sequalae in patients with end-stage liver disease and is associated with a poor prognosis. Heart rate analysis using nonlinear models such as multiscale entropy (MSE) or complexity may identify marked changes in these patients where conventional heart rate variability (HRV) measurements do not. To investigate the application of heart rate complexity (HRC) based on MSE in liver transplantation settings. Thirty adult recipients of elective living donor liver transplantation were enrolled. HRV parameters using conventional HRV analysis and HRC analysis were obtained at the following time points: (1) 1 day before surgery, (2) postoperative day (POD) 7, (3) POD 14, (4) POD 90, and (5) POD 180. Preoperatively, patients with MELD score ≥ 25 had significantly lower HRC compared to patients with lower MELD scores. This difference in HRC disappeared by POD 7 following liver transplantation and subsequent analyses at POD 90 and 180 continued to show no significant difference. Our results indicated a significant negative correlation between HRC based on MSE analysis and liver disease severity preoperatively, which may be more sensitive than conventional linear HRV analysis. HRC in patients with MELD score ≧ 25 improved over time and became comparable to those with MELD < 25 as early as in 7 days.

Exposure to real ambient particulate matter inflicts cardiac electrophysiological disturbances, vascular calcification, and mitochondrial bioenergetics decline more than diesel particulate matter: consequential impact on myocardial ischemia-reperfusion injury.

Particulate matter (PM) present in the air sample comprises different sizes and is derived from multiple sources, in particular from diesel engines. In the present study, we assessed the cardiotoxic effect of PM2.5 from real ambient air sample and diesel vehicular exhaust from a specific location and compared it with SRM-2975. Female Wistar rats were exposed to PM2.5 from real ambient PM (RA_PM), diesel particulate matter (DPM), and SRM-2975 for 3h daily for 21 days followed by cardiotoxicity assessment. Twenty-one days of daily PM2.5 exposure induced hypertrophy, vascular calcification, and alterations in cardiac electrophysiology, where the changes were more prominent in the animals exposed to RA_PM. The gross pathological changes were supported by altered mitochondrial function and increased oxidative stress in the myocardium. To evaluate the cardiac responsive ability, isolated rat hearts were subjected to ischemia-reperfusion injury (IR), and the results showed significantly low recovery in the RA_PM-exposed rat hearts. Chemical analysis of PM2.5 by ICPMS from different sources indicated the presence of additional metals like Cr, Ni, Ga, As, Rb, Cd, Ba, La, and Ce in the RA_PM sample. Additionally, the chelation of metals in the RA_PM enhanced the cell viability of H9c2 cells when compared to the non-chelated sample. Based on the above observations, we conclude that PM2.5 from the ambient air sample exhibited higher cardiovascular toxicity than DPM, emphasizing the contribution of non-diesel components of PM2.5 and the need for a comprehensive approach to tackle the PM2.5 in the air sample.

Adenovirus increases arrhythmia susceptibility during acute cardiac infection

Myocarditis is responsible for 42% of sudden cardiac death in young adults, yet mechanisms underlying virally induced arrhythmia remain elusive. Adenovirus is a leading etiological agent of myocarditis but species‐specificity has limited development of animal disease models. Normal electrical impulse propagation in the heart is achieved through intercellular coupling via gap junctions, composed primarily of connexin43 (Cx43). Changes in Cx43 expression, localization, and/or function underlie the arrhythmias of sudden cardiac death. Given that gap junctions also propagate innate and adaptive antiviral immune responses, we hypothesized that adenovirus would target Cx43 to facilitate replication. Our prior work has demonstrated that Cx43 expression and function are indeed reduced rapidly during adenoviral infection limiting gap junction communication in human epithelial and cardiac cells. We are now employing a recently described cardiotropic strain of mouse adenovirus, MAdV‐3, to develop our work into whole animal studies and investigate virally‐induced alterations in cardiac electrophysiology and the molecular mechanisms of the resulting arrhythmogenic substrate. Adult mice were inoculated with MAdV‐3 and sampled after 7 days to model acute cardiac infection. We find MAdV‐3 viral genomes are specifically enriched in heart tissue, confirming cardiotropism. No cardiomyopathy was apparent by echocardiography or histopathology, consistent with human acute myocarditis patients. We find reductions in cardiac ion channel and connexin mRNA transcript levels after infection, and at the protein level, Cx43 is phosphorylated at residues known to reduce function. Ex vivo optical mapping experiments illustrate decreased conduction velocity in infected hearts. Turning to primary adult mouse cardiomyocytes, we detect prolonged action potential duration and impaired K+ current in infected cells by patch clamping. Confocal and super‐resolution localization microscopy of infected cardiac tissue and isolated cardiomyocytes reveals remodeling of gap junctions with alterations in complexing with scaffolding proteins and other ion channels at the cell‐cell junction. Finally, employing human iPSC‐derived cardiomyocytes and human adenovirus type‐5, we find increased Cx43 phosphorylation and, using optical mapping, perturbation of intercellular coupling during infection, just as we see with MAdV‐3. Our data demonstrate that reduced cellular coupling and ion channel function during adenoviral infection generates an arrhythmogenic substrate prior to an appreciable immune response or cardiomyopathy development. MAdV‐3 infection therefore provides a novel model of cardiac infection and myocarditis and provides physiologically relevant insight into mechanisms of virally‐induced arrhythmias.

Frontal plane QRS-T angle in the monitoring of intravenous amiodarone infusion for pharmacological cardioversion of acute atrial fibrillation.

Intravenous amiodarone infusion is effective and widely used treatment for pharmacological cardioversion of recent-onset atrial fibrillation (Af). Although amiodarone may trigger various alterations in cardiac electrophysiology and electrocardiography (ECG), the impact of amiodarone treatment on frontal plane QRS-T angle remains unclear. Frontal plane QRS-T angle is the angle between the depolarization and repolarization axes and indicates instability in the cardiac cellular electrophysiology. Therefore, the present study aimed to investigate whether intravenous amiodarone infusion has effect on frontal plane QRS-T angle in patients with acute Af. A total of 179 patients with acute-onset Af who underwent pharmacological cardioversion with intravenous amiodarone infusion were included into the study. Patients with successful and failed pharmacological cardioversion were compared regarding pre- and post-treatment frontal plane QRS-T angle. At the end of the amiodarone infusion, sinus rhythm was restored in 112 (62.6%) patients, whereas Af was persisted in 67 (37.4%) patients. Despite the similar frontal plane QRS-T angle at baseline (59.6°±21.73°vs.60.4°±25.67°, p=0.822), patients with failed pharmacological cardioversion had significantly higher post-treatment frontal plane QRS-T angle compared to patients with successful pharmacological cardioversion (68.8°±21.71°vs.58.6°±25.15° p<0.001). Furthermore, multivariate analysis demonstrated that post-treatment increased frontal plane QRS-T angle was found to be an independent predictor of failure of pharmacological cardioversion with amiodarone infusion (OR:1.233, 95% CI:1.147-1.919, p=0.024). Amiodarone may significantly affect the frontal plane QRS-T angle. As a parameter that can be easily calculated from automated ECG recordings, frontal plane QRS-T angle may be useful in the monitoring of intravenous amiodarone treatment.

Zinc Oxide Nanoparticles Induce Mitochondrial Biogenesis Impairment and Cardiac Dysfunction in Human iPSC-Derived Cardiomyocytes.

BackgroundZinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanomaterials in a variety of fields such as industrial, pharmaceutical, and household applications. Increasing evidence suggests that ZnO NPs could elicit unignorable harmful effect to the cardiovascular system, but the potential deleterious effects to human cardiomyocytes remain to be elucidated. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been increasingly used as a promising in vitro model of cardiomyocyte in various fields such as drug cardiac safety evaluation. Herein, the present study was designed to elucidate the cardiac adverse effects of ZnO NPs and explore the possible underlying mechanism using hiPSC-CMs.MethodsZnO NPs were characterized by transmission electron microscopy and dynamic light scattering. The cytotoxicity induced by ZnO NPs in hiPSC-CMs was evaluated by determination of cell viability and lactate dehydrogenase release. Cellular reactive oxygen species (ROS) and mitochondrial membrane potential were measured by high-content analysis (HCA). Mitochondrial biogenesis was assayed by detection of mtDNA copy number and PGC-1α pathway. Moreover, microelectrode array techniques were used to investigate cardiac electrophysiological alterations.ResultsWe demonstrated that ZnO NPs concentration- and time-dependently elicited cytotoxicity in hiPSC-CMs. The results from HCA revealed that ZnO NPs exposure at low-cytotoxic concentrations significantly promoted ROS generation and induced mitochondrial dysfunction. We further demonstrated that ZnO NPs could impair mitochondrial biogenesis and inhibit PGC-1α pathway. In addition, ZnO NPs at insignificantly cytotoxic concentrations were found to trigger cardiac electrophysiological alterations as evidenced by decreases of beat rate and spike amplitude.ConclusionOur findings unveiled the potential harmful effects of ZnO NPs to human cardiomyocytes that involve mitochondrial biogenesis and the PGC-1α pathway that could affect cardiac electrophysiological function.

Flecainide-Induced Brugada Syndrome in a Patient With Skeletal Muscle Sodium Channelopathy: A Case Report With Critical Therapeutical Implications and Review of the Literature

Skeletal muscle sodium channelopathies are a group of neuromuscular disorders associated with mutations in the SCN4A gene. Because principal sodium channel isoforms expressed in the skeletal muscles and the heart are distinct one from the other, this condition usually spares cardiac functioning. Nonetheless, evidence on a possible link between skeletal muscle and cardiac sodium channelopathies has emerged in recent years. To date, eight patients bearing pathogenetic mutations in the SCN4A gene and manifesting cardiac electrophysiological alterations have been reported in literature. Among these patients, three presented a phenotype compatible with Brugada syndrome. We report the case of a 29-year-old patient affected by non-dystrophic myotonia associated with a p.G1306E mutation in the SCN4A gene, who presented symptoms of syncope and palpitation after the introduction of flecainide as an anti-myotonic agent. ECG and ajmaline challenge were consistent with the diagnosis of Brugada syndrome, leading to the implantation of a cardioverter defibrillator. No mutation in causative genes for Brugada syndrome was detected. Mexiletine treatment reduced myotonia without any cardiac adverse events. This case report highlights the clinical relevance of the recognition of cardiac electrophysiological alterations in skeletal muscle sodium channelopathies. The discovery of a possible pathogenetic linkage between skeletal muscle and cardiac sodium channelopathies may have significant implications in patients' management, also in light of the fact that class 1C anti-arrhythmics are potential triggers for life-threatening arrhythmias in patients with Brugada syndrome.

Genetic analysis of sick sinus syndrome in a family harboring compound CACNA1C and TTN mutations.

Sick sinus syndrome (SSS) is a sinus node dysfunction characterized by severe sinus bradycardia. SSS results in insufficient blood supply to the brain, heart, kidneys, and other organs and is associated with the increased risk of sudden cardiac death. Bradyarrhythmia appears in the absence of any associated cardiac pathology and displays a genetic legacy. The present study identified a family with primary manifestation of sinus bradycardia (five individuals) along with early repolarization (four individuals) and atrial fibrillation (one individual). Targeted exome sequencing was used to screen exons and adjacent splice sites of 61 inherited arrhythmia-associated genes, to detect pathogenic genes and variant sites in the proband. Family members were sequenced by Sanger sequencing and protein functions predicted by Polyphen-2 software. A total of three rare variants were identified in the family, including two missense variants in calcium voltage-gated channel subunit alpha1 C (CACNA1C) (gi:193788541, NM_001129843), c.1786G>A (p.V596M) and c.5344G>A (p.A1782T), and one missense variant in titin (TTN) c.49415G>A (p.R16472H) (gi:291045222, NM_003319). The variants p.V596M and p.R16472H were predicted to be deleterious and resulted in alterations in the amino acid type and sequence of the polypeptide chain, which may partially or completely inactivate the encoded protein. The comparison of literature, gene database, and pedigree phenotype analysis suggests that p.V596M or p.R16472H variants are pathogenic. The complex overlapping variants at three loci lead to a more severe phenotype in the proband, and may increase the susceptibility of individuals to atrial fibrillation. The simultaneous occurrence of V596M and R16472H may increase the severity of early repolarization. Various family members may have carried heterozygous mutants of p.A1782T and p.R16472H due to genetic heterogeneity, however did not exhibit clinical signs of cardiac electrophysiological alterations, potentially attributable to the low vagal tone. To the best of the author's knowledge, this is the first study to suggest the involvement of the novel missense CACNA1C c.1786G>A and TTN c.49415G>A variants in the inheritance of symptomatic bradycardia and development of SSS.

An integrative appraisal of mechano-electric feedback mechanisms in the heart

Mechanically-induced alterations in cardiac electrophysiology are referred to as mechano-electric feedback (MEF), and play an important role in electrical regulation of cardiac performance. The influence of mechanical stress and strain on electrophysiology has been investigated at all levels, however the role of MEF in arrhythmia remains poorly understood. During the normal contraction of the heart, mechano-sensitive processes are an implicit component of cardiac activity. Under abnormal mechanical events, stretch-activated mechanisms may contribute to local or global changes in electrophysiology (EP). While such mechanisms have been hypothesised to be involved in mechanically-initiated arrhythmias, the details of these mechanisms and their importance remain elusive.We assess the theoretical role of stretch mechanisms using coupled models of cellular electrophysiology and sarcomere contraction dynamics. Using models of single ventricular myocytes, we first investigated the potential MEF contributions of stretch-activated currents (SAC), and stretch-induced myofilament calcium release, to test how strain and fibrosis may alter cellular electrophysiology. For all models investigated, SACs were alone not sufficient to create a pro-arrhythmic perturbation of the action potential with stretch. However, when combined with stretch-induced myofilament calcium release, the action potential could be shortened depending on the timing of the strain. This effect was highly model dependent, with a canine epicardial EP model being the most sensitive.These model results suggest that known mechanisms of mechano-electric coupling in cardiac myocyte may be sufficient to be pro-arrhythmic, but only in combination and under specific strain patterns.

Modulation of heart rate and heart rate variability by n-3 long chain polyunsaturated fatty acids: Speculation on mechanism(s)

Heart rate (HR) and heart rate variability (HRV) are valuable markers of health. Although the underlying mechanism(s) are controversial, it is well documented that n-3 long chain polyunsaturated fatty acid (LCPUFA) intake improves HR and HRV in various populations. Autonomic modulation and/or alterations in cardiac electrophysiology are commonly cited as potential mechanisms responsible for these effects. This article reviews existing evidence for each and explores a separate mechanism which has not received much attention but has scientific merit. Based on presented evidence, it is proposed that n-3 LCPUFAs affect HR and HRV directly by autonomic modulation and indirectly by altering circulating factors, both dependently and independently of the autonomic nervous system. The evidence for changes in cardiac electrophysiology as the mechanism by which n-3 LCPUFAs affect HR and HRV needs strengthening.

Cardiac electrophysiological alterations and clinical response in cardiac resynchronization therapy with a defibrillator treated patients affected by metabolic syndrome.

Metabolic syndrome (MS) is a multifactorial disease that can affect clinical outcomes in patients treated by Cardiac Resynchronization Therapy with a defibrillator (CRT-d).Ninety-one patients received a CRT-d. According to clinical diagnosis, the study population was divided into 46 MS (cases) versus 45 no MS (controls) patients. These patients were followed by clinical, instrumental assessment, and device telemetric interrogations at follow-up. The design of the study was to evaluate the functionality of the CRT-d leads, the arrhythmic events, the CRT-d response, and the clinical outcomes at follow-up.At follow-up, there was a statistical significant difference, comparing MS versus no MS patients regarding the sensing, pacing, and impedance thresholds of the right atrium, right ventricle, and left ventricle leads. There was a statistically significant difference in the percentage of CRT-d responders comparing MS (n = 16, 51%) versus no MS (n = 40, 77%) patients (P = 0.017). MS may be predictive for hospitalization for heart failure worsening (hazard ratio 0.327, 95% confidence interval 0.096–0.943, P = 0.044) in CRT-d patients.MS is a complex multifactorial disease that may affect the functionality of CRT-d leads, the CRT-d response, and clinical outcomes in failing heart patients. These parameters may be detectable by follow-up monitoring.

Aging in the Cardiovascular System: Lessons from Hutchinson-Gilford Progeria Syndrome.

Aging, the main risk factor for cardiovascular disease (CVD), is becoming progressively more prevalent in our societies. A better understanding of how aging promotes CVD is therefore urgently needed to develop new strategies to reduce disease burden. Atherosclerosis and heart failure contribute significantly to age-associated CVD-related morbimortality. CVD and aging are both accelerated in patients suffering from Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder caused by the prelamin A mutant progerin. Progerin causes extensive atherosclerosis and cardiac electrophysiological alterations that invariably lead to premature aging and death. This review summarizes the main structural and functional alterations to the cardiovascular system during physiological and premature aging and discusses the mechanisms underlying exaggerated CVD and aging induced by prelamin A and progerin. Because both proteins are expressed in normally aging non-HGPS individuals, and most hallmarks of normal aging occur in progeria, research on HGPS can identify mechanisms underlying physiological aging.

Electrophysiologic and cellular characteristics of cardiomyocytes after X-ray irradiation

The aim of this study was to investigate possible effects of ionizing irradiation on the electrophysiological functionality of cardiac myocytes in vitro. Primary chicken cardiomyocytes with spontaneous beating activity were irradiated with X-rays (dose range of 0.5–7Gy). Functional alterations of cardiac cell cultures were evaluated up to 7 days after irradiation using microelectrode arrays. As examined endpoints, cell proliferation, apoptosis, reactive oxygen species (ROS) and DNA damage were evaluated. The beat rate of the cardiac networks increased in a dose-dependent manner over one week. The duration of single action potentials was slightly shortened. Additionally, we observed lower numbers of mitotic and S-phase cells at certain time points after irradiation. Also, the number of cells with γH2AX foci increased as a function of the dose. No significant changes in the level of ROS were detected. Induction of apoptosis was generally negligibly low.This is the first report to directly show alterations in cardiac electrophysiology caused by ionizing radiation, which were detectable up to one week after irradiation.

Myocyte Stretch Slows Cardiac Conduction by a Caveolae-Dependent Increase in Sarcolemmal Capacitance

Alterations in cardiac electrophysiology by mechanical perturbations have been long observed, however the cellular basis for these changes remains poorly understood. Most studies have focused on pro-arrhythmic consequences of stretch-activated currents (SAC). However, alterations in cardiac conduction that can create an arrhythmogenic substrate have also been observed even in the presence of SAC blockade. We tested the hypotheses that stretch slows conduction by increasing cell membrane capacitance via recruitment and sarcolemmal integration of caveolae and found that: (1) Conduction slowing occurred with stretch in both (a) pressure-loaded mouse hearts and (b) biaxially-stretched micropatterned murine cardiomyocyte monolayers, (2) Inhibition of stretch-activated currents had no effect on this slowing in both models, (3) Slowing was abrogated by caveolae depletion in both models, using cav3-knockout mice or incubation with 1 mM MβCD, (4) Stretch significantly increased cell membrane capacitance and time constant in single wild-type, but not caveolae-depleted cells, and (5) These effects on cell membrane capacitance and conduction slowing concide with recruitment and integration of caveolae by stretch. Together, these data suggest that myocyte stretch promotes recruitment and integration of caveolae and causes slowing of cardiac conduction by increasing cell membrane capacitance.

Cardiac electrophysiological alterations in heart/muscle-specific manganese-superoxide dismutase-deficient mice: prevention by a dietary antioxidant polyphenol.

Cardiac electrophysiological alterations induced by chronic exposure to reactive oxygen species and protective effects of dietary antioxidant have not been thoroughly examined. We recorded surface electrocardiograms (ECG) and evaluated cellular electrophysiological abnormalities in enzymatically-dissociated left ventricular (LV) myocytes in heart/muscle-specific manganese-superoxide dismutase-deficient (H/M-Sod2 −/−) mice, which exhibit dilated cardiomyopathy due to increased oxidative stress. We also investigated the influences of intake of apple polyphenols (AP) containing mainly procyanidins with potent antioxidant activity. The QRS and QT intervals of ECG recorded in H/M-Sod2 −/− mice were prolonged. The effective refractory period in the LV myocardium of H/M-Sod2 −/− mice was prolonged, and susceptibility to ventricular tachycardia or fibrillation induced by rapid ventricular pacing was increased. Action potential duration in H/M-Sod2 −/− LV myocytes was prolonged, and automaticity was enhanced. The density of the inwardly rectifier K+ current (I K1) was decreased in the LV cells of H/M-Sod2 −/− mice. The AP intake partially improved these electrophysiological alterations and extended the lifespan in H/M-Sod2 −/− mice. Thus, chronic exposure of the heart to oxidative stress produces a variety of electrophysiological abnormalities, increased susceptibility to ventricular arrhythmias, and action potential changes associated with the reduced density of I K1. Dietary intake of antioxidant nutrients may prevent oxidative stress-induced electrophysiological disturbances.

Overt and Latent Cardiac Effects of Ozone Inhalation in Rats: Evidence for Autonomic Modulation and Increased Myocardial Vulnerability

Background: Ozone (O3) is a well-documented respiratory oxidant, but increasing epidemiological evidence points to extrapulmonary effects, including positive associations between ambient O3 concentrations and cardiovascular morbidity and mortality.Objective: With preliminary reports linking O3 exposure with changes in heart rate (HR), we investigated the hypothesis that a single inhalation exposure to O3 will cause concentration-dependent autonomic modulation of cardiac function in rats.Methods: Rats implanted with telemeters to monitor HR and cardiac electrophysiology [electrocardiography (ECG)] were exposed once by whole-body inhalation for 4 hr to 0.2 or 0.8 ppm O3 or filtered air. A separate cohort was tested for vulnerability to aconitine-induced arrhythmia 24 hr after exposure.Results: Exposure to 0.8 ppm O3 caused bradycardia, PR prolongation, ST depression, and substantial increases in atrial premature beats, sinoatrial block, and atrioventricular block, accompanied by concurrent increases in several HR variability parameters that were suggestive of increased parasympathetic tone. Low-O3 exposure failed to elicit any overt changes in autonomic tone, heart rhythm, or ECG. However, both 0.2 and 0.8 ppm O3 increased sensitivity to aconitine-induced arrhythmia formation, suggesting a latent O3-induced alteration in myocardial excitability.Conclusions: O3 exposure causes several alterations in cardiac electrophysiology that are likely mediated by modulation of autonomic input to the heart. Moreover, exposure to low O3 concentrations may cause subclinical effects that manifest only when triggered by a stressor, suggesting that the adverse health effects of ambient levels of air pollutants may be insidious and potentially underestimated.

BISOPROLOL INHIBITS SODIUM CURRENT IN VENTRICULAR MYOCYTES OF RATS WITH DIASTOLIC HEART FAILURE

1. Changes in sodium currents (I(Na)) in heart failure contribute to cardiac electrophysiological alterations and, thereby, to ventricular arrhythmias. Bisoprolol has anti-arrhythmic effects, but its direct effect on I(Na) in cardiac cells remains unclear. Accordingly, in the present study we investigated the effects of bisoprolol on ventricular I(Na) in diastolic heart failure (DHF) and normal rats. 2. The DHF model was produced by abdominal aortic coarctation for 4 weeks and single ventricular myocytes were isolated by enzymatic dissociation. The electrophysiological actions of bisoprolol on I(Na) currents were investigated using a whole-cell patch-clamp technique. 3. The membrane capacitance of rats in the DHF group was significantly greater than that of the control group and the current-voltage curve was simultaneously shifted downward. Bisoprolol concentration-dependently decreased I(Na) in ventricular myocytes of both groups (at -45 mV), with IC(50) values of 19.53 +/- 0.06 and 40.78 +/- 0.03 micromol/L in the control and DHF groups, respectively. 4. In both groups, the current-voltage curves were shifted upwards, whereas activation potentials, peak currents and reversal potentials showed no significant changes. At -45 mV, the descent ratio of current densities in the DHF group was lower than that of the control group. In both groups, inactivation curves were shifted to more negative potentials, but activation curves and recovery curves were not altered. Changes in the half-inactivation voltage, V(0.5), and the slope of the inactivation curve, S, were similar for both groups. 5. In conclusion, bisoprolol concentration-dependently decreases I(Na) in ventricular myocytes of DHF and normal rats, which could be responsible, at least in part, for its anti-arrhythmic effects.

Nitric oxide and prostacyclin mediate coronary shear force-induced alterations in cardiac electrophysiology

Previous studies have shown that an increase in coronary flow or shear force enhances the oxygen consumption and contractility of myocardium (the “Gregg effect”). Recent studies have indicated that an increase in coronary shear force also affects atrioventricular conduction and ventricular repolarization. The mechanisms of “Gregg effect” and the shear force-induced alterations in cardiac electrophysiology are unclear. It has been proposed that the distension of the coronary arteries and the stretch of the surrounding myocytes may play a key role but this is not supported by the latest studies. Intracoronary perfusion increases coronary endothelial synthesis of nitric oxide and prostacyclin. Emerging evidence has indicated that both nitric oxide and prostacyclin prolong the action potential duration or effective refractory period in the in vitro and in vivo animal heart. We therefore hypothesized that shear force-induced alterations in cardiac function and electrophysiology are largely attributed to the enhanced endothelial release of nitric oxide and prostacyclin.

Nitric oxide and prostacyclin mediate coronary shear force-induced alterations in cardiac electrophysiology

Previous studies have shown that an increase in coronary flow or shear force enhances the oxygen consumption and contractility of myocardium (the “Gregg effect”). Recent studies have indicated that an increase in coronary shear force also affects atrioventricular conduction and ventricular repolarization. The mechanisms of “Gregg effect” and the shear force-induced alterations in cardiac electrophysiology are unclear. It has been proposed that the distension of the coronary arteries and the stretch of the surrounding myocytes may play a key role but this is not supported by the latest studies. Intracoronary perfusion increases coronary endothelial synthesis of nitric oxide and prostacyclin. Emerging evidence has indicated that both nitric oxide and prostacyclin prolong the action potential duration or effective refractory period in the in vitro and in vivo animal heart. We therefore hypothesized that shear force-induced alterations in cardiac function and electrophysiology are largely attributed to the enhanced endothelial release of nitric oxide and prostacyclin.

Basis for Ventricular Arrhythmias Accompanying Myocardial Infarction

Investigations during the past several decades have indicated that the occurrence of cardiac arrhythmias associated with a variety of pathological states is a result of alterations in the basic cellular electrophysiological properties of the heart. This tenet obviously applies to the arrhythmias that accompany myocardial infarction as well. However, a definite documentation of the alterations in cardiac electrophysiology that are responsible for such arrhythmias in humans is still lacking. At present, our understanding of these mechanisms is derived from the results of laboratory investigations on animals. In this article, we discuss our own and related views on the mechanisms for the ventricular arrhythmias accompanying myocardial infarction based on such investigations. Our own data and that of others, which provides the basis for these hypotheses, has been mostly derived from microelectrode studies on isolated superfused canine myocardium exposed to environmental conditions simulating the conditions believed to be present after an acute

Basis for ventricular arrhythmias accompanying myocardial infarction: alterations in electrical activity of ventricular muscle and Purkinje fibers after coronary artery occlusion.

Investigations during the past several decades have indicated that the occurrence of cardiac arrhythmias associated with a variety of pathological states is a result of alterations in the basic cellular electrophysiological properties of the heart. This tenet obviously applies to the arrhythmias that accompany myocardial infarction as well. However, a definite documentation of the alterations in cardiac electrophysiology that are responsible for such arrhythmias in humans is still lacking. At present, our understanding of these mechanisms is derived from the results of laboratory investigations on animals. In this article, we discuss our own and related views on the mechanisms for the ventricular arrhythmias accompanying myocardial infarction based on such investigations. Our own data and that of others, which provides the basis for these hypotheses, has been mostly derived from microelectrode studies on isolated superfused canine myocardium exposed to environmental conditions simulating the conditions believed to be present after an acute