Slow Heart Rate Research Articles

Embryonic morphological development is delayed in pregnancies ending in a spontaneous miscarriage

Is there a difference in embryonic morphological development between ongoing pregnancies and live pregnancies ending in a miscarriage? Embryonic morphological development, assessed by the Carnegie stages, is delayed in live pregnancies ending in a miscarriage compared to ongoing pregnancies. Pregnancies ending in a miscarriage tend to have smaller embryos and slower heart rates. Between 2010 and 2018, 644 women with singleton pregnancies, in the periconception period, were enrolled in a prospective cohort study with follow up until 1 year after delivery. A miscarriage was registered as a non-viable pregnancy before 22 weeks gestational age, defined by an absent heartbeat by ultrasound for a previously reported live pregnancy. Pregnant women with live singleton pregnancies were included and serial three-dimensional transvaginal ultrasound scans were performed. Embryonic morphological development was assessed by the Carnegie developmental stages and evaluated using virtual reality techniques. The embryonic morphology was compared to clinically used growth parameters (i.e. crown-rump length (CRL) and embryonic volume (EV)). Linear mixed models were used to evaluate the association between miscarriage and the Carnegie stages. Logistic regression with generalized estimating equations was used to calculate the odds of a miscarriage after a delay in Carnegie stages. Adjustments were made for potential confounders or covariates and include age, parity, and smoking status. A total of 611 ongoing pregnancies and 33 pregnancies ending in a miscarriage were included between 7 + 0 and 10 + 3 weeks gestational age, resulting in 1127 assigned Carnegie stages for evaluation. Compared to an ongoing pregnancy, a pregnancy ending in a miscarriage is associated with a lower Carnegie stage (βCarnegie = -0.824, 95% CI -1.190; -0.458, P < 0.001). A live embryo of a pregnancy ending in a miscarriage will reach the final Carnegie stage with a delay of 4.0 days compared to an ongoing pregnancy. A pregnancy ending in a miscarriage is associated with a smaller CRL (βCRL = -0.120, 95% CI -0.240; -0.001, P = 0.049) and EV (βEV = -0.060, 95% CI -0.112; -0.007, P = 0.027). The delay in Carnegie stage increases the odds of a miscarriage by 1.5% per delayed Carnegie stage (ORCarnegie = 1.015, 95% CI 1.002; 1.028, P = 0.028). We included a relatively small number of pregnancies ending in a miscarriage from a study population that is recruited from a tertiary referral centre. Furthermore, results of genetic testing on the products of the miscarriages or information on the karyotype of the parents were not available. Embryonic morphological development, assessed by the Carnegie stages, is delayed in live pregnancies ending in a miscarriage. In the future, embryonic morphology may be used to estimate the likelihood of a pregnancy continuing to the delivery of a healthy baby. This is of crucial importance for all women but in particular for those at risk of a recurrent pregnancy loss. As part of supportive care, both women and their partners may benefit from information on the prospective outcome of the pregnancy and the timely identification of a miscarriage. The work was funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. The authors declare no conflicts of interest. N/A.

Physiological role of SK channels in modulating cardiac repolarization: APD and dispersion at slow heart rate in long QT syndrome.

Long QT syndrome (LQTS) is a congenital disease associated with polymorphic ventricular tachycardia (pVT) and sudden cardiac death. The hallmarks of LQTS are early afterdepolarizations that initiate pVT and dispersion of repolarization allowing reentry formation. Small conductance Ca2+-activated K+ (SK) channels are directly gated by Ca2+ and provide feedback from Ca2+ to membrane voltage to accelerate cardiac repolarization, which may help normalizing LQTS. Using optical mapping, we examined the role of ISK in transgenic rabbit models of LQT1, LQT2, and LQT5 and found that enhancing ISK with NS309 consistently shortened APD, reduced APD dispersion, and suppressed pVT genesis universally in the three LQT rabbit models. Enhancement of ISK has a greater impact at longer cycle length, flattening restitution curves at slow heart rate where most pVTs occur in LQTS. We incorporated a six state ISK gating simulation combined with intrinsic rectification and divalent block into the Mahajan rabbit action potential model to investigate the role of ISK in suppressing LQT-related arrhythmias. Increasing levels of SK channel conductance (gSK) were able to shorten and reduce APD dispersion simulated by conductance gradients of gKs by ∼64% under LQT2 conditions and gtof by ∼70% in LQT1 conditions. Computer modeling indicates that ISK can reduce APD dispersion through two mechanisms; increased Ca2+ duration in the prolonged APD cells augment ISK to shorten long APD and lowering plateau Vm by ISK masks IKs heterogeneity by reducing IKs's role in repolarization. In conclusion, the Ca2+-dependent gating of ISK allows it to directly feedback on the APD especially when other K+ channels are not functional and to be a potential therapeutic target for LQTS.

Spatially discordant alternans occurring when cardiac tissue is paced alternatively from two sites.

Cardiac alternans are a precursor to arrhythmias. Spatially discordant alternans (SDA) in ventricles are especially arrhythmogenic as they can lead to ventricular tachycardia and fibrillation. Bidirectional ventricular tachycardia (BVT) is one of the rare arrhythmias. However, the underlying mechanism is still not clear. The normal electrical activity generated by the sinoatrial node propagates as an action potential wave in the heart. BVT occurs when the route of conduction changes in every other beat. In this study, we investigated the mechanism of BVT using mathematical models of cardiac tissue. The two-dimensional tissue was paced from two sites at a constant pacing cycle length. The stimulation site alternated every pacing cycle. We measured electrical alternans, which are defined as an alternating sequence of the action potential durations. We varied parameters in the model such as the distance between two sites and the pacing cycle length. We found that alternans amplitude was significantly amplified when the tissue was paced alternatively from two sites. SDA was formed even at slow heart rates. The alternans amplitude increased with the distance between the pacing sites. The nodal line was formed in the middle of the two pacing sites. This is arrhythmogenic since it can easily lead to a wave break that may initiate a spiral wave. Fast pacing with steep APD restitution is another mechanism of SDA. However, the nodal line is parallel to the wavefront. When tissue is paced rapidly and alternatively from two sites, APD distribution becomes more complex. Our study demonstrates that alternans can be formed by alternating pacing from two sites that mimics BVT.

Cyclosporine A induces hepatotoxicity in zebrafish larvae via upregulating oxidative stress

As a powerful immunosuppressant, cyclosporine A (CsA) is widely used clinically. However, it has been found to have many side effects including nephrotoxicity and neurotoxicity. Despite this, some patients cannot avoid using CsA during pregnancy and this can be detrimental to both the patient and the foetus. This study used zebrafish as a model animal to evaluate the hepatotoxic effects of CsA in zebrafish embryos. Zebrafish embryos cultured at 72 post-fertilization (hpf) were exposed to three concentrations of CsA at 2.5 mg/L, 5 mg/L, and 10 mg/L for 72 h. Liver developmental defects, smaller or missing swim bladder, slower heart rate, reduced body length, and delayed yolk sac absorption were observed. The level of oxidative stress (ROS) increased with the increase of CsA concentration. The indicators of related oxidative stress kinase activities including malondialdehyde (MDA), catalase (CAT) and SOD, all appeared to significantly increased. The use of astaxanthin (ATX) to inhibit oxidative stress was found to be useful for rescuing zebrafish hepatic development defects. Therefore, our results suggest that CsA induces zebrafish embryonic hepatic development defects by activating the oxidative stress. The study of CsA-induced hepatic development defects of zebrafish embryos is helpful for clinical evaluation of the safety of CsA and enables the search for new use without side effects.

Developmental toxicity of the emerging contaminant cyclophosphamide and the integrated biomarker response (IBRv2) in zebrafish.

The safety of cyclophosphamide (CP) in the early developmental stages is not studied yet; it is important to study the responses at these stages because they might have relevance to CP-administered humans. We studied the developmental toxicity of CP by analysing physiological, morphological, and oxidative stress, neurotransmission enzymes, gene expression and histological endpoints in zebrafish embryos/larvae. The study lasted for 120 hpf at environmentally relevant concentrations of CP. No visible alterations were noticed in the control group. Delayed hatching, slow heart rate, yolk sac oedema, pericardial oedema, morphological deformities, the incompetence of oxidative stress biomarkers, excessive generation of ROS, apoptosis, inhibition of neurotransmitters and histopathological anomalies were observed in CP-treated groups. These alterations were found to be concentration- and duration-dependent effects for physiological and morphological endpoints, whereas concentration-dependent effects were antioxidants, ROS, apoptosis and histological endpoints. Biomarkers and gene expression were standardised using the integrated biomarker response-IBRv2 index. The IBRv2 index showed a concentration-dependent behaviour. A non-lethal developmental and teratogenic effect was observed in CP-treated zebrafish embryos/larvae at the studied concentrations. The studied biomarkers are sensitive, and the responses are interrelated; thus, their responses are useful to assess veiled and unseen hazards of pharmaceuticals.

Diagnóstico pré-natal de bloqueio atrioventricular total secundário à lúpus materno: relato de caso

This report describes the case of a newborn with congenital complete atrioventricular (AV) block diagnosed antenatally belonging to a mother diagnosed with lupus erythematosus during pregnancy based on an echocardiogram ordered to investigate a finding of slow fetal heart rate. Pregnancy was terminated at 36 weeks with a cesarean section indicated due to preeclampsia. Neonatal resuscitation protocols and vasoactive drugs did not increase the newborn’s heart rate to above 100 beats per minute. The newborn had a pacemaker implanted 20 days after birth and recovered well. He was discharged without other measures to maintain heart rate. The disease was attributed to previously undiagnosed maternal systemic lupus erythematosus (SLE), which was investigated once the fetus was diagnosed with complete AV block. The success of the procedure derived from an accessible prenatal care program and an efficient public healthcare system.

The efficacy and safety of pre-emptive methoxamine infusion in preventing hypotension by in elderly patients receiving spinal anesthesia: A PRISMA-compliant protocol for systematic review and meta-analysis.

Hypotension is frequent after spinal anesthesia, especially in elderly patients. Whether pre-emptive methoxamine infusion is effective and safe to prevent spinal anesthesia-induced hypotension is still a controversial issue, to dress this knowledge lack, we performed a systemic review and meta-analysis to evaluated it. Elderly patients undergoing spinal anesthesia. Administration of methoxamine prior to spinal anesthesia. We searched PUBMED, Cochrane Library, EMBASE, China National Knowledge Infrastructure, Wanfang Database, and VIP Database, Chinese BioMedical Literature & Retrieval System from January 1st 1978 to February 28th 2022. Primary outcomes of interests included hemodynamic parameters, such as systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate. Secondary outcomes of interests included the incidence of intraoperative hypotension, bradycardia, nausea and vomiting, vasopressors requirement, intraoperative blood loss. For continuous or dichotomous variables, treatment effects were calculated as weighted mean difference or odds ratio, respectively. Our search yielded 8 randomized controlled trials including 480 patients, and 240 patients were allocated into methoxamine group and 240 into control group. Meta-analysis demonstrated that pre-emptive methoxamine infusion in preventing hypotension by in elderly patients receiving spinal anesthesia had higher blood pressures, lower heart rates. Compared with the control group, the incidence of perioperative hypotension in elderly patients was lower, and elderly patients had less requirement for vasopressor in methoxamine group. This meta-analysis demonstrated that pre-emptive methoxamine infusion in elderly patients receiving spinal anesthesia can improve blood pressure, slow down heart rate, reduce the incidence of hypotension and requirement for vasopressor. However, these findings should be interpreted rigorously. Further well-conducted trials are required to confirm this.

Benomyl-induced development and cardiac toxicity in zebrafish embryos.

Benomyl is a highly effective broad-spectrum fungicide widely used worldwide to control vegetable, fruit, and oil crop diseases. However, the mechanism of its toxicity to aquatic organisms and humans remains unknown. In this study, zebrafish were used to determine the toxicity of benomyl. It was found to be highly toxic, with a 72-h post-fertilization (hpf) lethal concentration 50 (LC50) of 1.454mg/L. Benomyl induced severe developmental toxicity, including shorter body length, slower heart rate, and a reduced yolk absorption rate. Benomyl also increased oxidative stress in zebrafish, especially in the heart and head, as well as increasing malondialdehyde (MDA) content and decreasing catalase (CAT) and superoxide dismutase (SOD) activities. This indicates that benomyl induced reactive oxygen species (ROS) production and cell membrane peroxidation in vivo. Acridine orange (AO) staining and apoptosis factor detection further indicated that benomyl induced apoptosis in zebrafish. Overall, these findings demonstrate that benomyl disrupts cellular homeostasis by activating oxidative stress in zebrafish, resulting in an imbalance of cardiac development-related gene expression and apoptosis, which causes severe developmental toxicity and cardiac dysfunction. This study evaluated the in vivo toxicity of benomyl, which is a potential threat to aquatic organisms and humans. Possible toxicity mechanisms are explored, providing a valuable reference for the safe use of benomyl.

Effects of haloxyfop-p-methyl on the developmental toxicity, neurotoxicity, and immunotoxicity in zebrafish

Pesticides are extensively used in agricultural production, and their residues in soil, water, and agricultural products have become a threat to aquatic ecosystem. In this study, the toxicity of haloxyfop-p-methyl, an aryloxyphenoxypropionate herbicide was studied using the model animal zebrafish. The development of zebrafish larvae was affected by haloxyfop-p-methyl including spinal deformities, decreased body length, slow heart rate, and large yolk sac area. Behavior analysis revealed that behavior activity of larvae was weakened significantly including shortened displacement distance, reduced swimming speed, increased angular speed winding degrees, in accordance with higher AChE activity. Besides, exposure to haloxyfop-p-methyl could induce oxidative stress companied by the increased intents of ROS, MDA and increased activities of CAT and SOD. In immunotoxicity, haloxyfop-p-methyl not only reduced the innate immune cells such as neutrophils and macrophages, but also affected T cells mature in thymus. Furthermore, haloxyfop-p-methyl could induce neutrophils apoptosis, accompanied with the upregulation of the expression of proapoptotic protein such as Bax and P53 and the downregulation of the expression of antiapoptotic protein Bcl-2. In addition, haloxyfop-p-methyl could induce the expression of Jak, STAT and proinflammatory cytokine genes (IFN-γ, TNF-α, and IL-8). These results indicate that haloxyfop-p-methyl induces developmental toxicity, neurotoxicity, and immunotoxicity in zebrafish, providing a perspective on the toxicological mechanism of haloxyfop-p-methyl in teleosts.

Abstract 13309: Specific Deletion of Microrna1’S Biophysical Action Causes a Functional Deterioration of the Heart and Increases the Vulnerability to Arrhythmias

MicroRNAs (miRs) are involved in most biological events via a broadly-recognized RNA interference (RNAi) mechanism. miR1, encoded by miR1-1 and miR1-2 genes, is the predominant miRs of the heart and plays a critical role in heart development and cardiac diseases. Previous studies of miRs have focused on the canonical RNAi mechanism. Recently, we discovered a novel biophysical action of miR and found that miR1 physically binds to Kir2.1 and directly suppresses the inward rectifier potassium current (I K1 ). However, the physiological significance of this newly-discovered biophysical action of miR remains unknown. Importantly, we found that a human single nucleotide polymorphism (hSNP)-hSNP14A/G (rs776480338), in which the 14th nucleotide of miR1 is mutated from A to G, specifically disrupts this biophysical action while maintaining its RNAi function. We then created a single nucleotide mutation of hSNP14A/G on mouse miR1-1 and miR1-2 genes by CRISPR/Cas9 technology and have successfully developed 14G-mutated homozygous transgenic mice (14G-Homo), in which the biophysical function of miR1 is specifically removed while the RNAi function is maintained. We found that 14G-Homo mice had higher mortality than wild-type (WT) mice. Echocardiogram showed that, compared to WT hearts, adult 14G-homo heart (2-month age) had significantly lower ejection fraction and fractional shortening with a thinner wall of the left ventricle, which became more severe at the age of 6 months; some mice developed severe heart failure. Surface ECG showed that 14G-Homo hearts had a slower heart rate and the prolonged QRS interval and QT interval. Optical mapping revealed a slower conduction velocity in the 14G-Homo heart with high inducibility of ventricular arrhythmias. Patch clamping of isolated ventricular cardiomyocytes showed that, compared to WT cells, 14G-homo cardiomyocytes had an increased amplitude and prolonged duration of action potential with bigger I K1 and L-type calcium currents. In conclusion, our discoveries demonstrate that the biophysical action of miR1 is deeply involved in maintaining the homeostasis of the heart. Specific deletion of the biophysical function causes a functional deterioration of the heart and increases the vulnerability to arrhythmias.

Enantioselective toxic effects of the novel chiral antifungal agrochemical penthiopyrad in the early life stage of zebrafish (Danio rerio)

Penthiopyrad was extensively applied in agricultural production, however, the toxicities information of the penthiopyrad enantiomers on early life stages of aquatic organism were limited. This study investigated the enantioselective toxicity of penthiopyrad on the early life stage of zebrafish by acute toxicity, sublethal toxic effects and the mRNA relative expression levels of genes related to succinate dehydrogenase, cardiac development, and lipid metabolism. The results showed that the 96-h-LC50 of penthiopyrad racemate and enantiomers to zebrafish embryos were Rac-: 2.784 mg/L; R-(−)-: 3.528 mg/L; S-(+)-: 1.882 mg/L. Penthiopyrad exposure induced autonomous movement abnormalities, slowed heart rate and delayed hatching in zebrafish embryos, and caused developmental toxic effects such as pericardial edema and yolk sac edema. The mRNA relative expression levels results showed that penthiopyrad exposure induced significant enantioselectivity effect for the expression of the Sdha, Pr1 and Nkx2.5 with a 1.94–4.98-fold difference between different enantiomers, and significantly affected succinate dehydrogenase (energy metabolism), lipid metabolism and cardiac development-related genes expression. In general, S-(+)-penthiopyrad induced higher toxic effects in zebrafish embryos, and mitochondrial dysfunction may be an important cause of abnormal development. This study contributed to improve the comprehensive risk assessment and enantiomeric research system of penthiopyrad to early life stage of zebrafish.

Molecular and Functional Remodeling of Superior and Inferior SAN in a Rat Model of HCM.

Recently, our laboratory presented functional and molecular evidence for the presence of 2 competing sinoatrial node (SAN) pacemakers in healthy human and rat hearts. Anatomically localized near the superior vena cava and inferior vena cava, the superior and inferior SANs (sSAN and iSAN, respectively) preferentially control fast and slow normal heart rates. However, only 1 dominant pacemaker, primarily the sSAN, was functional in the failing rat heart with hypertrophic cardiomyopathy. This study aimed to determine the transcriptional basis of functional silencing of 1 of 2 dominant pacemakers in failing rat hearts. Ascending aortic constriction was performed on 1-week-old male Sprague-Dawley rat pups to induce left ventricular hypertrophy and heart failure. The dominant pacemaker was anatomically mapped in adult (10-12weeks old) healthy and failing rat hearts using optical mapping in isolated right atrial tissue preparations. RNA sequencing was used to identify regional sSAN/iSAN gene expression differences between healthy and failing rat hearts. In all failing rat hearts optically mapped in this study (n=4), only the sSAN pacemaker was functional, while the iSAN was silent. Compared to healthy rat hearts, a total of 3,640 genes were downregulated, and 4,518 genes were upregulated in failing rat hearts. The functional quiescence of the iSAN in these failing rat hearts may be explained by their downregulation of sodium, potassium, and calcium ion channels as well as their downregulation of specific structural genes, including ankyrin, titin, and myosin heavy chain. Moreover, the iSAN showed predominant downregulation of several key transcription factors such as Tbx5, Tbx3, Shox2, and Smad9. Pressure-overload-induced heart failure resulted in significant downregulation of critical transcription factors, ion channels, and structural transcripts of the iSAN, which could explain the functional silencing of the iSAN in failing rat hearts.

Sensitivity Analysis of Cardiac Alternans and Tachyarrhythmia to Ion Channel Conductance Using Population Modeling.

Action potential duration (APD) alternans, an alternating phenomenon between action potentials in cardiomyocytes, causes heart arrhythmia when the heart rate is high. However, some of the APD alternans observed in clinical trials occurs under slow heart rate conditions of 100 to 120 bpm, increasing the likelihood of heart arrhythmias such as atrial fibrillation. Advanced studies have identified the occurrence of this type of APD alternans in terms of electrophysiological ion channel currents in cells. However, they only identified physiological phenomena, such as action potential due to random changes in a particular ion channel's conductivity through ion models specializing in specific ion channel currents. In this study, we performed parameter sensitivity analysis via population modeling using a validated human ventricular physiology model to check the sensitivity of APD alternans to ion channel conductances. Through population modeling, we expressed the changes in alternans onset cycle length (AOCL) and mean APD in AOCL (AO meanAPD) according to the variations in ion channel conductance. Finally, we identified the ion channel that maximally affected the occurrence of APD alternans. AOCL and AO meanAPD were sensitive to changes in the plateau Ca2+ current. Accordingly, it was expected that APD alternans would be vulnerable to changes in intracellular calcium concentration.

Slowing Heart Rate Protects Against Pathological Cardiac Hypertrophy.

We aimed to determine the pathophysiological impact of heart rate (HR) slowing on cardiac function. We have recently developed a murine model in which it is possible to conditionally delete the stimulatory heterotrimeric G-protein (Gαs) in the sinoatrial (SA) node after the addition of tamoxifen using cre-loxP technology. The addition of tamoxifen leads to bradycardia. We used this approach to examine the physiological and pathophysiological effects of HR slowing. We first looked at the impact on exercise performance by running the mice on a treadmill. After the addition of tamoxifen, mice with conditional deletion of Gαs in the SA node ran a shorter distance at a slower speed. Littermate controls preserved their exercise capacity after tamoxifen. Results consistent with impaired cardiac capacity in the mutants were also obtained with a dobutamine echocardiographic stress test. We then examined if HR reduction influenced pathological cardiac hypertrophy using two models: ligation of the left anterior descending coronary artery for myocardial infarction and abdominal aortic banding for hypertensive heart disease. In littermate controls, both procedures resulted in cardiac hypertrophy. However, induction of HR reduction prior to surgical intervention significantly ameliorated the hypertrophy. In order to assess potential protein kinase pathways that may be activated in the left ventricle by relative bradycardia, we used a phospho-antibody array and this revealed selective activation of phosphoinositide-3 kinase. In conclusion, HR reduction protects against pathological cardiac hypertrophy but limits physiological exercise capacity.

Central autonomic network alterations in male endurance athletes

Physical exercise causes marked adjustments in brain function and the cardiovascular system. Brain regions of the so-called central autonomic network (CAN) are likely to show exercise-related alterations due to their involvement in cardiac control, yet exercise-induced CAN changes remain unclear. Here we investigate the effects of intensive exercise on brain regions involved in cardiac autonomic regulation using resting-state functional connectivity (rsFC). We explored rsFC of six core regions within CAN, namely ventromedial prefrontal cortex, dorsolateral anterior cingulate cortex, left/right amygdala, and left/right anterior insula, in 20 endurance athletes and 21 non-athletes. We showed that athletes had enhanced rsFC within CAN and sensorimotor areas compared to non-athletes. Likewise, we identified two networks with increased rsFC encompassing autonomic and motor-related areas using network-based statistics analysis. In addition, rsFC displayed an inverse relationship with heart rate, where the stronger rsFC in athletes correlates with their slower heart rate. Despite this significant relationship, mediation analysis revealed that heart rate is a weak mediator of the effect of intensive physical training on rsFC. Our findings prove that physical exercise enhances brain connectivity in central autonomic and sensorimotor networks and highlight the close link between brain and heart.

Insulin Therapy Increases the Risk of Hypokalemia and Arrhythmia in Diabetic Patients with Coronary Heart Disease: A Retrospective Study in Wahidin Sudirohusodo General Hospital

Background: Cardiovascular disease is the most common cause of morbidity and mortality in diabetic patients. Patients with Diabetes Mellitus (DM) often require insulin therapy to control hyperglycemia, yet, it is associated with the risk of hypokalemia and dysrhythmia. Objectives: To evaluate the prevalence and the risk of hypokalemia and arrhythmia due to insulin therapy in DM patients with Coronary Heart Disease (CHD) comorbidity. Material and Methods: The study was conducted retrospectively based on medical record data from January 2021 to December 2021 in Wahidin Sudirohusodo general hospital. The inclusion criteria include the out-hospital patients diagnosed with DM with CHD comorbidity. The patients were divided into 2 groups, those who received insulin and those who received oral antidiabetic drugs (OAD). Hypokalemia was defined if an electrolyte characterized by a low serum potassium concentration with a normal range of 3.5 – 5.0 mEq/L. Arrhythmia was defined if abnormal changes in a regular heartbeat, including an irregular heartbeat, a skipped heartbeat, a fast heart rate (tachycardia), or a slow heart rate (bradycardia). Results: The data were obtained from 322 patients’ medical record, 161 was treated with insulin, and 161 received OAD. The insulin-treated patients had a significantly lower blood potassium level compared to the OAD group. The insulin group had 63,40% incidents of hypokalemia, while in the OAD group only 16,80% experienced hypokalemia (p&lt;0.05). The presence of arrhythmia was detected in 63,40 % of insulin-treated patients, while only 29,80% had arrhythmia in the OAD group (p&lt;0,05). Conclusions: Insulin Therapy in DM patients with coronary heart disease can increase the incidence of hypokalemia, which may result in arrhythmia in patients with coronary heart disease.

Evaluation of the effect of green tea and its constituents on embryo development in a zebrafish model.

As one of the most popular beverages, green tea has attracted much interest for its beneficial effects on human health. However, the toxicity of green tea and its underlying mechanism are still poorly understood. Here, we evaluated the effect of green tea and its constituents on development by exposing zebrafish embryos to them. Morphologic results demonstrated that 0.1% and 0.2% green tea increased mortality, delayed epiboly of gastrulation, and shortened body length. Green tea altered the expression pattern of dlx3, cstlb, myod, and papc and decreased the expression levels of wnt5 and wnt11, suggesting that green tea disturbed convergence and extension movement through the downregulation of wnt5 and wnt11. The increased expression of the dorsal gene chordin and reduced expression of wnt8 and its target genes vox and vent in embryos exposed to 0.1% and 0.2% green tea indicated that green tea could affect dorsoventral differentiation by inhibiting the wnt8 signaling pathway. Additionally, green tea could inhibit epiboly progression by disrupting F-actin organization or removing F-actin in vegetal yolks during gastrulation. However, no malformation was caused by exposure to the five catechins and gallic acid individually. The mixture of constituents showed a similar effect to green tea solution on the embryos, such as smaller eyes and head, shorter body length, and slower heart rate, which indicated that the effect of green tea solution on embryo development was mainly due to the comprehensive effect of multiple components in the green tea solution.

Cardiac implantable electronic devices: an overview for primary care.

Cardiac rhythm management (CRM) is the treatment of arrhythmias. Arrhythmias can cause a range of symptoms including palpitations, dizzy spells, blackouts, and sudden cardiac arrest. Contemporary management of arrhythmia may involve cardiac implantable electronic devices (CIEDs) and catheter ablation.1 CIEDs are used to manage slow and fast heart rates, and in the treatment of selected patients with heart failure. Types of CIED include permanent pacemakers (PPMs), implantable cardioverter defibrillators (ICDs), and cardiac resynchronisation therapy (CRT) devices. CIEDs are usually implanted under the skin, with one to three leads threaded down a vein to connect to the heart.1 ### PPMs: types and what they do

Diastolic flow in the left ventricular outflow tract - A normal physiological and underappreciated echocardiographic finding.

Diastolic waveforms in the left ventricular outflow tract (LVOT) are commonly observed with Doppler echocardiography. The incidence and mechanism are not well described. This was a retrospective observational study of 186 adult patients, athletes and non-athletes, free of known cardiac disease, presenting for comprehensive transthoracic echocardiography at a research institute. We aimed to evaluate the incidence and echocardiographic associations between LVOT diastolic waveforms. Left ventricular outflow tract early to mid-diastolic waveforms were present in 100% of athletes and 95% of non-athletes. The LVOT diastolic velocity time integral was larger in athletes than non-athletes with a mean 8.3 cm (95% CI (7.6-8.9)) vs. 5.1 cm (4.4-5.9) (P < 0.0001). Multivariate predictors of this diastolic waveform were age (P = 0.002), slower heart rate (P = 0.035), higher stroke volume (P = 0.003), large mitral E (P = 0.019) and higher E/e' (P = 0.015). An LVOT early diastolic wave is a normal physiological finding. It is related to a flow vortex redirecting diastolic mitral inflow around anterior mitral valve leaflet into the LVOT. Early to mid-diastolic LVOT waves are present in almost all patients but more prominent in young athletes than non-athletes. Diastolic LVOT waves increase with younger age, slower heart rate, larger stroke volume and enhanced diastolic function.

Molecularly defined circuits for cardiovascular and cardiopulmonary control.

The sympathetic and parasympathetic nervous systems powerfully regulate internal organs1, but the molecular and functional diversity of their constituent neurons and circuits remains largely unknown. Here we use retrograde neuronal tracing, single-cell RNA sequencing, optogenetics, and physiological experiments to dissect the cardiac parasympathetic control circuit in mice. We show that cardiac-innervating neurons in the brainstem nucleus ambiguus (Amb) are comprised of two molecularly, anatomically, and functionally distinct subtypes. One we call ACV (ambiguus cardiovascular) neurons (~35 neurons per Amb), define the classical cardiac parasympathetic circuit. They selectively innervate a subset of cardiac parasympathetic ganglion neurons and mediate the baroreceptor reflex, slowing heart rate and atrioventricular node conduction in response to increased blood pressure. The other, ACP (ambiguus cardiopulmonary) neurons (~15 neurons per Amb) innervate cardiac ganglion neurons intermingled with and functionally indistinguishable from those innervated by ACV neurons, but surprisingly also innervate most or all lung parasympathetic ganglion neurons; clonal labeling shows individual ACP neurons innervate both organs. ACP neurons mediate the dive reflex, the simultaneous bradycardia and bronchoconstriction that follows water immersion. Thus, parasympathetic control of the heart is organized into two parallel circuits, one that selectively controls cardiac function (ACV circuit) and another that coordinates cardiac and pulmonary function (ACP circuit). This new understanding of cardiac control has implications for treating cardiac and pulmonary diseases and for elucidating the control and coordination circuits of other organs.