Control Hearts Research Articles

Evaluation of the effect of carotid sinus blockade on hemodynamic stability in carotid surgery: A retrospective study.

This study assesses the effect of carotid sinus blockade applied with a local anesthetic on hemodynamic parameters during carotid endarterectomy (CEA) operations performed under general anesthesia. The medical records of patients who underwent CEA under general anesthesia between January 2020 and December 2022, were retrospectively reviewed. It was recorded whether the patients received carotid sinus block with 2 mL of 2% prilocaine. Intraoperative and 48-hour postoperative hemodynamic data were examined in the patients included in the study. A total of 129 patients were evaluated in the study, with 70 patients who received carotid sinus blockade (Group I) and 59 patients who did not receive blockade (Group II) during CEA. The comparison of heart rate variability immediately before clamping, immediately after clamping, and at 5, 10, and 20 minutes post-clamping indicated a significantly greater reduction in Group II compared to Group I (P < .05). In the postoperative period, the total dose of glyceryl trinitrate administered was 40.8 ± 31.9 mg in Group I and 53 ± 17.2 mg in Group II, showing a statistically significant difference (P = .001). Additionally, blood pressure measurements during this period were significantly higher in Group II than in Group I (P < .05). While the application of a local anesthetic during CEA appears to provide better intraoperative heart rate and postoperative blood pressure control, attributing these results solely to local anesthesia may not be entirely accurate. Hemodynamic instability observed during and after CEA is influenced by various factors.

Cost-effectiveness of digoxin versus beta blockers in permanent atrial fibrillation: the Rate Control Therapy Evaluation in Permanent Atrial Fibrillation (RATE-AF) randomised trial

BackgroundAtrial fibrillation (AF) is a major and increasing burden on health services. This study aimed to evaluate the cost-effectiveness of digoxin versus beta-blockers for heart rate control in patients with...

Mechanistic Insights into Melatonin's Antiarrhythmic Effects in Acute Ischemia-Reperfusion-Injured Rabbit Hearts Undergoing Therapeutic Hypothermia.

The electrophysiological mechanisms underlying melatonin's actions and the electrophysiological consequences of superimposed therapeutic hypothermia (TH) in preventing cardiac ischemia-reperfusion (IR) injury-induced arrhythmias remain largely unknown. This study aimed to unveil these issues using acute IR-injured hearts. Rabbits were divided into heart failure (HF), HF+melatonin, control, and control+melatonin groups. HF was induced by rapid right ventricular pacing. Melatonin was administered orally (10 mg/kg/day) for four weeks, and IR was created by 60-min coronary artery ligation and 30-min reperfusion. The hearts were then excised and Langendorff-perfused for optical mapping studies at normothermia, followed by TH. Melatonin significantly reduced ventricular fibrillation (VF) maintenance. In failing hearts, melatonin reduced the spatially discordant alternans (SDA) inducibility mainly by modulating intracellular Ca2+ dynamics via upregulation of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and calsequestrin 2 and attenuating the downregulation of phosphorylated phospholamban protein expression. In control hearts, melatonin improved conduction slowing and reduced dispersion of action potential duration (APDdispersion) by upregulating phosphorylated connexin 43, attenuating the downregulation of SERCA2a and phosphorylated phospholamban and attenuating the upregulation of phosphorylated Ca2+/calmodulin-dependent protein kinase II. TH significantly retarded intracellular Ca2+ decay slowed conduction, and increased APDdispersion, thereby facilitating SDA induction, which counteracted the beneficial effects of melatonin in reducing VF maintenance.

Comparison of the efficacy and safety of Landiolol and Esmolol in critically ill patients: a propensity score-matched study

BackgroundExcessive tachycardia is associated with impaired hemodynamics and worse outcome in critically ill patients. Previous studies suggested beneficial effect of β-blockers administration in ICU patients, including those with septic shock. However, comparisons in ICU settings are lacking. Our study aims to compare Landiolol and Esmolol regarding heart rate control and hemodynamic variables in general ICU patients.MethodsThis retrospective, observational study was conducted in a 56-bed ICU at a university hospital. A propensity score matching (PSM) was employed to balance baseline differences. Generalized estimating equations (GEE) were used to compare heart rate between two drugs. The primary outcome was heart rate control, while secondary outcomes included hemodynamic response, hospital length of stay (HLOS) and ICU length of stay (ICULOS).ResultsFrom June 2016 to December 2022, 438 patients were included after PSM, (292 in the Esmolol group and 146 the in Landiolol group). Baseline heart rate was similar between groups (Landiolol:120.0 [110.2, 131.0] bpm vs. Esmolol:120.0 [111.0, 129.0] bpm, p = 0.925). During 72 h. of β-blocker infusion, Landiolol reduced heart rate by 4.7 (1.3, 8.1) bpm, more than Esmolol (p = 0.007), while preserving a comparable proportion of patients able to stabilize vasopressor doses within the first 24 h. (82.9 vs. 80.8%, respectively, p = 0.596). Norepinephrine doses and lactate levels were similar between groups over 72 h., while the Landiolol group exhibited notably higher minimal ScvO2 levels (72% [63%, 78%] vs 68% [55%, 73%], respectively, p = 0.006) and a lower maximal PCO2 gap compared to the Esmolol group (7.0 [6.0, 9.0] vs. 8.0 [6.0, 10.0] mmHg, respectively, p = 0.040). Patients in the Landiolol group were observed to experience shorter HLOS than patients in the Esmolol group (26.5 [13.0, 42.0] vs 30.0 [17.0, 47.2] days, respectively, p = 0.044) and ICULOS (4.9 [2.8, 10.0] vs.6.7 [3.4, 13.1] days, respectively, p = 0.011).ConclusionLandiolol provides superior heart rate control in critically ill patients with tachycardia compared to Esmolol, without increasing vasopressor requirements during the first 24 h. Findings from ScvO2 levels and PCO2 gap suggest that Landiolol may exert less impact on cardiac output than Esmolol. Further studies, incorporating comprehensive hemodynamic monitoring, are warranted to clarify the clinical implications of heart rate control with β-blockers in ICU patients with tachycardia.

Integrated Management of Persistent Atrial Fibrillation.

The global incidence of atrial fibrillation is on the rise. Atrial fibrillation, a complex disease, heightens the likelihood of heart failure, stroke, and mortality, necessitating careful attention. Controlling heart rate and rhythm, addressing risk factors, and preventing strokes are fundamental in treating atrial fibrillation. Catheter ablation stands out as the primary approach for atrial fibrillation rhythm control. Nevertheless, the limited success rates pose a significant challenge to catheter ablation, particularly for persistent atrial fibrillation. Various adjunctive ablation techniques are currently under investigation to enhance the effectiveness of catheter ablation. This review provides an overview of the current state of the art and the latest optimized treatments for persistent atrial fibrillation in the areas of rhythm control, heart rate control, and risk factor management.

Association of Time in Target Range of Resting Heart Rate With Adverse Clinical Outcomes in Patients With Acute Coronary Syndromes After Percutaneous Coronary Intervention.

Heart rate (HR) has been proved to be associated with major adverse cardiovascular events (MACE) in Acute coronary syndrome patients. However, the threshold value and clinical significance of time in target of resting heart rate (TTR-HR) remain insufficiently elucidated. Our study aimed to evaluate the independent association between TTR-HR and cardiovascular outcomes in the follow-up study of ACS. A total of 1455 ACS patients who underwent percutaneous coronary intervention (PCI) and were admitted to 22 hospitals between 2019 and 2022 were enrolled and followed up for 12 months. MACE was defined as a composite of cardiac death, nonfatal recurrent myocardial infarction, ischemic-driven revascularization, and ischemic stroke. The association between TTR-HR and cardiovascular outcomes was assessed using Cox regression model. Compared to patients with TTR-HR 0-50% and >50%-75%, patients with TTR-HR > 75%-100% were older and less alcohol user, less likely to use diuretics and anti-diabetic drugs, these patients had less comorbidities of hyperlipidemia, diabetes, heart failure, and cardiac shock. After 12 months follow up, the incidence of MACE and composite endpoint but not mortality was higher in patients with TTR-HR 0-50% and >50%-75% than those with TTR-HR > 75%-100%. After multivariate adjustment, TTR-HR [hazard ratio = 2.11, 95% CI: 1.19-3.74, p = 0.01] was independently associated with composite endpoint. In summary, our study demonstrates that TTR-HR holds significant prognostic value, with TTR-HR > 75%-100% being independently associated with reduced composite endpoint risk in ACS patients following PCI. These findings emphasize the importance of effective heart rate control in ACS patients following PCI.

INFLUENCE OF AMBIENT TEMPERATURE ON THE CONTROL OF BODY POSTURE STABILITY IN PROFESSIONAL FIREFIGHTERS

Introduction. Stability of body posture is essential for ensuring safety and achieving highphysical performance. Firefighting, as a high-risk occupation, exposes professionals to factorsthat destabilize balance and posture, increasing the risk of falls and injuries. Extreme thermalenvironments are known to affect postural stability, which relies on dynamic neuromuscularcontrol influenced by vision, body temperature, and psychophysiological state.Objective. This study aims to assess the influence of ambient temperature on the control of bodyposture stability among professional firefighters. Specifically, it examines the role of visual controlin balance maintenance and explores coordination between the nervous and musculoskeletalsystems using posturographic measurements from a force plate (AccuGait). Additionally, thestudy investigates the relationships between posturographic parameters, heart rate (HR), heartrate variability (HRV) and body temperature. The impact of extreme thermal conditions –temperatures exceeding 35C and falling below 0C – on balance maintenance, dizziness, andbalance disorders is also analysed.Material and Methods. Seventeen healthy male volunteers (mean age 35.9 6.1 years, mean workexperience 10.7 5.5 years) were involved in the study. In the first phase, participants completeda survey containing general and detailed questions. They responded with “YES” or “NO” regardingtheir exposure to high temperatures (above 35C) and low temperatures (below 0C). In the secondphase, measurements were taken using the AccuGait force plate (AMTI, USA). Each participantperformed two 30-second trials. The first trial involved standing still on the force plate with openeyes (OE) and closed eyes (CE). Heart rate (HR) and heart rate variability (HRV) were monitoredusing a Polar H7 heart rate monitor and the EliteHRV application. Additionally, infrared photos ofall participants were taken using a FLIR C3X Compact thermal camera.Results. The study revealed that 89.7% of respondents reported experiencing dizziness duringexposure to high temperatures. Force plate testing confirmed excellent postural stability amongfirefighters in both open-eye (OE) and closed-eye (CE) trials. In the CE trial, an 18.9% increase in the average COP velocity (Avg Velocity) and a 19.3% increase in COP path length (Length)were observed. The average heart rate (HR) for the 17 participants was 79.9 15 beats per minute.A correlation was identified between HR and the average COP velocity, COP path length, andthe minimal COP deviation along the Y-axis (AP). The average heart rate variability (HRV) was56.4 8.8 ms, and HRV correlated with the maximum COP value on the Y-axis (AP) during theCE trial. The average corneal temperature was 34.4 1.5C. Statistical analysis was conductedusing Spearman’s rank correlation and the Wilcoxon signed-rank test.Conclusions. The risk of balance disturbances is higher when firefighters operate in hightemperatureenvironments (above 35C) as compared to low temperatures (below 0C). Theabsence of visual control does not compromise the stability of firefighters’ posture, reflecting theirexceptional neuromuscular coordination. The dynamics of muscle force activation in maintainingbody balance are influenced by visual control status and heart rate.

Comprehensive analysis of voluntary wheel training effects on neural control of the heart rate in rats

Aerobic physical training is used to prevent and correct many cardiovascular disorders. To study the effects of such physical exercise, various methods of training are used in rodents, among which voluntary wheel running is of particular interest, because it is close to the natural rat locomotion in terms of the pattern of motor activity and is devoid of stressful influence. The aim of this work was a comprehensive study of the effects of wheel running on the nervous control of heart rate (HR) in rats. At the age of 6 weeks, the animals were divided into two groups: training (TR, free access to wheels, n = 11) and sedentary control (CON, n = 12). After 6 weeks of training, ECG was recorded in freely moving rats using skin electrodes in baseline, after blockade of cardiac nervous influences and under air-jet stress (4 min). The effects of the autonomic nervous system were analyzed by administering a β1-adrenergic blocker and a peripherally acting M-cholinoceptor blocker, and by analyzing cardiac rhythm variability using spectral and wavelet analyses. TR group showed a decrease in the baseline HR level compared to the CON group. The decrease in HR upon administration of atenolol (2 mg/kg) did not differ between the groups, but methylatropine (1 mg/kg) caused a more significant increase in HR in the TR group than in the CON group. With the combined action of atenolol and methylatropine, HR levels did not differ between the groups. The rats of the TR group showed an increase in the contribution of high-frequency (0.75–3 Hz) oscillations to the total spectrum power of the RR interval. During air-jet stress, TR group showed a more pronounced increase in HR compared to the CON group. In addition, in the TR group, a decrease in the amplitude of HR high-frequency oscillations was observed during stress, while in the CON group, such a decrease was absent. Thus, the voluntary wheel running is accompanied in the rat by an increase in parasympathetic influences on the heart, which is manifested in an increase in respiratory sinus arrhythmia and in an increase in vagal influence on the resting HR level. Moderate bradycardia at rest provides the possibility of a more pronounced increase in HR during emotional stress because of the suppression of parasympathetic cardiac influences.

Changes in heart rate variability at rest and during exercise in patients after a stroke: a feasibility study

The aim of this study was to evaluate the feasibility of using a biofeedback-enhanced robotics-assisted tilt table (RATT) to investigate time- and intensity-dependent changes in heart rate variability (HRV) at rest and during heart rate-controlled exercise in patients recovering from a stroke. Twelve patients (age 55.3 years ± 15.6 years, 7 women) completed two separate measurement sessions. The first involved familiarization and system identification to determine parameters of a feedback system for automatic control of heart rate (HR). The second comprised 14 min of rest and 21 min of active exercise during which HR was held constant using feedback control to eliminate cardiovascular drift. HR data were collected using a chest-belt HR sensor, and raw RR intervals were employed for HRV analysis during periods of rest (0–7 min and 7–14 min) and exercise (5–13 min and 13–21 min). A biofeedback-enhanced, robotics-assisted tilt table can be successfully employed to perform heart rate-controlled exercises in patients after a stroke. All HRV metrics were substantially lower during exercise compared to rest. In the rest period, HRV values during 0–7 min were lower than during 7–14 min, in line with a slight HR decrease over the entire rest period. During exercise, HRV values during 5–13 min were higher than during 13–21 min, suggesting a time-dependent HRV decrease. All HRV metrics exhibited intensity- and time-dependent changes: higher HRV at rest and decreasing HRV over time. Understanding these HRV characteristics will support the development of heart rate-controlled exercise regimens and protocols for examining HRV changes during exercise in patients.

Lab-grown, 3D Extracellular Matrix Particles Improve Cardiac Function and Morphology in Myocardial Ischemia.

The promise of injection of extracellular matrix (ECM) from animal hearts as a treatment of myocardial ischemia has been limited by immune reactions and harsh ECM-damaging extraction procedures. We developed a novel method to produce lab-grown human 3D acellular ECM particles from human mesenchymal stem cells (MSCs) to mitigate product variability, immunogenicity, and preserve ECM architecture. We hypothesized that intramyocardial injection (I/M) of this novel ECM (dia ~200 microns) would improve cardiac function in a post-myocardial infarction (MI) murine model. WT mice aged 8-10 weeks underwent ligation of the LAD artery and I/M injection of 10 uL ECM or normal saline (n=10/group). Compared to control, ECM-treated hearts showed significant reduction in infarct size (p=0.04), increased capillary density in ischemic myocardium (p=0.01), and increased fractional shortening (FS) (p>0.05) on POD 14, 21, and 28 by echocardiography. There were no significant differences in immunogenic response as determined by TNF⍺, IL6, CD86, or CD163 levels (p>0.05 for all) in the hearts. Biodistribution of fluorophore-conjugated ECM demonstrated localized epifluorescence in the heart after I/M injection, without significant peripheral end organ epifluorescence. Proteomic analysis of ischemic and perfused myocardium from control and ECM-treated hearts using LC-MS/MS (n=3/group) detected significant changes in proteins involved in cardiomyocyte contractility and fatty acid metabolism. These findings suggest that 3D ECM particles induce recovery of ischemic myocardium, by upregulating protein networks involved in cellular contractility and metabolism. Taken together, 3D ECM particles represent a promising therapy for MI, and warrant confirmatory studies in a high-fidelity large animal model.

Effects of Gestational Diabetes Mellitus on Fetal Cardiac Morphology.

This study aims to investigate the possible effects of gestational diabetes mellitus (GDM) on fetal heart structure and the relationship of this effect with maternal blood sugar control. In this cross-sectional study, 19 women with GDM at 24-36 weeks of gestation (case group) and 21 healthy pregnant women at the same weeks of gestation (control group) were examined. Fetal heart structure was evaluated by ultrasonography; interventricular septum (IVS) thickness, right and left ventricular sphericity indices, global sphericity index (GSI) and cardio-thoracic ratio were also measured. In addition, mothers' HbA1c values (an indicator of blood sugar control) were recorded. An increase in IVS thickness was observed in the fetuses of mothers with GDM. A more rounded trend was observed in the right ventricular structure, but this did not create a significant difference. No significant relationship was found between maternal blood sugar control and fetal heart structure. This study examined the effects of gestational diabetes on fetal cardiac morphology and the relationship of this effect with maternal glycemic control. Babies of mothers with GDM had a significantly thicker interventricular septum. A more rounded trend was detected in the right ventricular structure. However, this change was not found to be statistically significant. In addition, no significant correlation was found between maternal glycemic control and fetal cardiac morphology.

Reassessing Ivabradine: Potential Benefits and Risks in Atrial Fibrillation Therapy.

Ivabradine has been identified as a funny current (If) inhibitor in the sinoatrial node (SAN) and is considered an advocated therapeutic agent in chronic heart failure and stable angina. This therapeutic agent has shown positive benefits in maintaining a reduction in heart rate while sustaining hemodynamic stability. Its clinical application is still evolving and the mechanism of action is becoming clearer daily. The use of this agent to manage atrial fibrillation (AF) has recently been brought under discussion. This study summarizes the mechanism of action of ivabradine and current evidence about the risk of new-onset AF and rate-lowering potential as a therapeutic option in patients suffering from AF. This review synthesizes findings from preclinical studies, case reports, and clinical trials that assess ivabradine's efficacy in controlling heart rate and its association with new-onset AF. Studies have shown that this medication may be beneficial in ventricular rate reduction in patients intolerant of first-line AF therapeutic options, including non-dihydropyridine calcium channel blockers and β-blockers. However, it is important to state that ivabradine-treated patients with cardiovascular diseases demonstrated an increased risk for new-onset AF compared with those patients who did not receive it. While ivabradine demonstrates promise as a therapeutic option for rate control in patients with AF, its use is accompanied by a notable risk of new-onset AF. Further studies should focus on optimal dosing strategies and long-term outcomes of ivabradine treatment in AF management.

Current Management of Uncomplicated Type B Aortic Dissection.

Aortic dissection is the most common thoracic aortic emergency and is associated with significant morbidity and mortality. Initial complications are dependent on reduction of sheer stress against the aortic wall to protect against rupture and minimize progression of the aortic wall injury. In patients with dissection starting at or distal to the left subclavian artery (Stanford type B), initial management includes strict blood pressure and heart rate control with monitoring for any complications such as malperfusion, rupture, or hemodynamic instability. Following the acute dissection event, survivors are faced with the lifelong need for blood pressure control and surveillance imaging to monitor for potential aortic deterioration leading to rupture or aneurysm formation. This review will discuss the latest recommendations for current management of uncomplicated type B aortic dissection including the evolving role of endovascular therapies.

The Impact of Methamphetamine on Liver Injury in Iraqi Male Addicts

Methamphetamine (METH) is a powerful stimulant that affects neurochemical processes controlling heart rate, appetite, blood pressure, body temperature, and wakefulness, making it highly susceptible to abuse. Liver enzymes such as ALT, AST, ALP, and GGT are crucial for liver function. Albumin, a protein synthesized by healthy liver cells, serves as an indicator of chronic liver disease. Additionally, hepatocytes produce bile acids, which are essential for the secretion of bile salts into the bile canaliculi. Disruption in this secretion results in the accumulation of bile salts in the canaliculi, leading to intrahepatic cholestasis. METH-induced liver toxicity involves disruptions in hepatic metabolism, oxidative stress, and increased body temperature, affecting cellular processes such as cell division and the cell cycle and potentially accelerating liver cell apoptosis. The study explores the link between liver toxicity and hepatocyte damage in Iraqi males suffering from addiction. This is a case-control study, conducted at Ibn-Rushed Psychiatric Hospital in Baghdad from July 2023 to February 2024, involved 196 males, with addiction durations exceeding 24 months with varying degrees of methamphetamine (METH) addiction. The study included 187 healthy male controls with no history of drug addiction. Participants were aged 18 to 40 years. Diagnosis was confirmed using a drug test screening card administered by a specialist. The study included liver function tests (ALT, AST, ALP, and GGT), total bilirubin, and albumin concentration assessments. Significant differences were observed between the addicts and controls, particularly a marked decrease in serum albumin concentration in the addicted males. The ROC curve classification model at various thresholds demonstrated that liver enzymes, especially ALT, ALP, and GGT, exhibited increased sensitivity to METH addiction. A histopathological examination was conducted on a deceased 38-year-old male who had a six-year history of chronic amphetamine addiction to confirm liver injury and the resulting elevation of liver enzymes. The findings of this study indicate that METH greatly affects liver function, suggested to the importance of following a preventative measures and effective treatment approaches for monitoring METH addiction progress.

P038 Autonomic cardiovascular control is unaffected in children referred for assessment of excessive daytime sleepiness.

Abstract Introduction There is conflicting evidence for impaired autonomic control of heart rate (HR) in adults with narcolepsy and idiopathic hypersomnolence (IH). Despite these conditions primarily being diagnosed around the age of puberty, there are limited studies in children. The present study investigated cardiovascular control using heart rate variability (HRV) and the extent of nocturnal HR dipping during sleep in children and adolescents with narcolepsy and IH. Methods All children having an overnight polysomnographic study followed by a multiple sleep latency test (MSLT) for investigation of excessive daytime sleepiness (EDS) between May 2010 to December 2023 were included: 28 children diagnosed with narcolepsy, 11 with IH and 26 subjectively sleepy children who did not meet the diagnostic criteria for either narcolepsy or IH. Each clinically-referred child was matched for age and sex with a control. Time domain and frequency domain HRV were calculated from ECG recorded at 512 Hz. Results There were no differences in either time domain or spectral analysis of HRV between clinical groups or between clinical groups and their control group. The expected sleep state differences in HRV were observed in all groups. There was also no difference in HR nocturnal dipping between groups. Conclusion Despite evidence for abnormal autonomic function in adults with narcolepsy and IH, our study did not identify any abnormalities in HR, HR control or nocturnal dipping of HR in children referred for assessment of EDS. This suggests that autonomic dysfunction may be a feature of these conditions that develops in later life.

Affective Touch in Preterm Infant Development: Neurobiological Mechanisms and Implications for Child-Caregiver Attachment and Neonatal Care.

Affective touch is crucial in infant development, particularly in regulating emotional, cognitive, and physiological processes. Preterm infants are often deprived of essential tactile stimulation owing to their early exposure to the external environment, which may affect long-term developmental outcomes. This review aimed to examine the neurobiological mechanisms of affective touch and highlight effective interventions, such as skin-to-skin contact (SSC) and kangaroo care (KC), to promote development in preterm infants. This review summarizes recent studies in the literature on affective touch, the role of C-tactile fibers, and the effects of tactile interventions in neonatal care. Studies were selected based on their relevance to the care and development of preterm infants, with a focus on physiological and neurodevelopmental outcomes. Key interventions, including SSC and massage therapy, are discussed in relation to their effectiveness in the neonatal intensive care unit (NICU). The results suggest that affective touch, mainly through activation of tactile C-fibers, improves caregiver-infant bonding, reduces stress responses, and supports neurodevelopment in preterm infants. Interventions such as SSC and KC have also been shown to improve physiological regulation in these infants, including heart rate, breathing, and temperature control while promoting emotional regulation and cognitive development. Affective touch is a key component of early development, particularly in preterm infants admitted to the NICU. Integrating tactile interventions such as SSC and KC into neonatal care practices may significantly improve long-term developmental outcomes. Future research should explore the epigenetic mechanisms underlying affective touch and further refine tactile interventions to optimize neonatal care.

A Swarm Based Integer and Fractional Order Heart Rate Controller for Cardiac Pacemaker

The heart's significant contribution is well known in the functioning of the human body. If it stops operating, the body shuts down systematically, which is known as cardiac arrest. The heart acts as a power supply that generates the electrical pulses which run through the entire body to supply energy to every organ. But in today's time, due to our unhealthy lifestyle, the functioning of the heart gets uneven, that it is unable to supply the regulated electrical pulses. This irregular supply of electrical pulses is known as arrhythmia. In order to overcome arrhythmia, the medical device pacemaker is invented to control the irregularities of the heart rate. The pacemaker generates the electrical pulses artificially when the heart is unable to respond at regular intervals. Many researchers have proposed several control techniques using PID controllers to improve the performance of such device called as artificial pacemaker. In this work an optimized system is designed for an artificial cardiac pacemaker to well perform so that the system can generate a controlled desire response through the incorporation of both integer and fractional order PID controller for better system performance with least errors. The applied integer and fractional order PID controllers are tuned using various classical tuning methods and the modern optimization technique such as particle swarm optimization (PSO) method to obtain a response with better dynamic and static performance. These implemented tuning methods offer a good control characteristic for the pacing rate of the cardiac pacemaker.

Hypothalamic Regulation of Cardiorespiratory Functions: Insights into the Dorsomedial and Perifornical Pathways.

The dorsomedial hypothalamus nucleus (DMH) plays a pivotal role in the orchestration of sympathetic nervous system activities. Through its projections to the brainstem and pontomedullary nuclei, it controls heart rate, contractility, blood pressure, and respiratory activity, such as timing and volumes. The DMH integrates inputs from higher brain centers and processes these signals in order to modulate autonomic outflow accordingly. It has been demonstrated to be of particular significance in the context of stress responses, where it orchestrates the physiological adaptations that are necessary for all adaptative responses. The perifornical region (PeF), which is closely associated with the DMH, also makes a contribution to autonomic regulation. The involvement of the PeF region in autonomic control is evidenced by its function in coordinating the autonomic and endocrine responses to stress, frequently in conjunction with the DMH. The DMH and the PeF do not function in an isolated manner; rather, they are components of a comprehensive hypothalamic network that integrates several autonomic responses. This neural network could serve as a target for developing therapeutic strategies in cardiovascular diseases.

Digoxin Loading Doses and Serum Digoxin Concentrations for Rate Control of Atrial Arrhythmias in Critically Ill Patients.

Intravenous (IV) digoxin loading dose recommendations for rate control of atrial arrhythmias in critically ill patients are not well studied. When using digoxin in the setting of atrial fibrillation/atrial flutter (AF/AFL), a loading dose (LD) in either a fixed-dose regimen, weight-based dose, or pharmacokinetic-based calculation to target a serum digoxin concentration (SDC) of 0.8-1.5 ng/mL is recommended. The objective of this study was to assess the safety and effectiveness of digoxin LD used in critically ill patients for rate control of AF/AFL and to assess the SDC achieved. This single center retrospective cohort study included patients who received IV digoxin and had a SDC drawn. The primary endpoint was the median SDC achieved after a digoxin LD. Secondary outcomes included the frequency of SDCs ≥1.5 ng/mL and heart rate (HR) control. A total of 92 patients were included. The median total LD of digoxin for the entire cohort was 11mcg/kg (750 mcg). For 61% of the cohort, the LD was distributed over six-hour intervals. The median SDC after completion of the IV digoxin LD was 1.3 ng/mL (0.9, 1.7). The incidence of supratherapeutic SDC was 36% for the total cohort. A target HR < 110 beats per minute within 24 hours from digoxin LD was achieved in 60% of the cohort. In conclusion, a median total digoxin LD of 750 mcg in critically ill patients with AF/AFL, targeting a SDC < 1.5ng/mL may be considered for acute rate control, taking into account drug-drug interactions in the cardiac intensive care unit. Future studies are necessary to confirm our findings.

Abstract 4138606: Toll-like Receptor 4 Signaling Establishes Trained Innate Immunity Through Interferon-Mediated Epigenetic Modifications Leading to Cardioprotection in a Stress-induced Cardiomyopathy Model

Introduction: The mechanisms responsible for establishing preconditioning-induced cardioprotection remain unknown. We have shown that a high dose of isoproterenol (ISO) induces cardioprotection against a second ISO dose in mice. The durability of protection and the lack of an innate immune response suggests trained immunity as a novel cardioprotective mechanism. Hypothesis: We hypothesize that cardioprotection is conferred through trained immunity, by interferon signaling downstream of necrotic cardiac material-mediated Toll-like receptor 4 (TLR4) activation. Methods: Wild-type C57BL/6J mice were intraperitoneally injected with TLR agonists or diluent, and challenged with 300 mg/kg ISO 7 days later. Mice were assessed by 2-D echocardiography, serum cardiac troponin levels, flow cytometry immune cell counts, and Multiome (single nuclei RNA+ATAC) sequencing. Results: The TLR4 agonist lipopolysaccharide (LPS) induced cardioprotection against ISO injury, with mice having enhanced survival (P=0.049) and no changes in cardiac troponin levels (P&gt;0.99), cardiac neutrophil influx (P&gt;0.99) or left ventricular motion (P=0.057) relative to baseline values before injury. Treating LPS-injected mice with β-glucan reversed the effects of LPS on immune cells and abolished cardioprotection. Multiome analysis of genes linked to chromatin peaks with increased accessibility in LPS+vehicle (protected) compared to LPS+β-glucan and diluent control (non-protected) hearts revealed the interferon pathway to be up-regulated across all major cell types. Modulation of interferon signaling with monoclonal antibodies against type 1+2 interferon receptors abolished cardioprotection in LPS-treated mice, whereas pre-treatment with recombinant type 1+2 interferons induced cardioprotection. Importantly, interferon-treated hearts shared similar chromatin accessibility features and enriched transcription factor motifs, including interferon-specific motifs, with LPS-protected hearts across cell types, particularly among non-cardiomyocytes. Conclusions: TLR4-induced interferon signaling is sufficient and in part necessary for cardioprotection against ISO injury. Moreover, our findings show that epigenetic modifications downstream of interferon signaling lead to cardioprotection consistent with trained innate immunity.