PP Intervals Research Articles

Analysis of the correlations between ECG components in adolescents both before and after exposure to different types of physical stress in the Subarctic winter conditions

BACKGROUND: Adaptive responses to harsh environmental conditions of the Arctic may vary not only among adults, but also among children and adolescents. These compensatory reactions are influenced by the predominant type of regulation of the autonomic nervous system. The myocardium and its electrical properties play a significant role in determining how individuals adapt to to environmental conditions. AIM: To study correlations between PP and TR intervals in adolescents in adolescents undergoing the clinostatic test and the Martinet test during the winter season. MATERIAL AND METHODS: Twenty cardiac cycles were recorded in 22 adolescents aged 15–16 years in the II standard lead, both at baseline and after conducting the clinostatic and Martinet tests. Durations of the RR and TR intervals were measured and used for the analysis. Statistical processing of the data was performed using the MS Excel tables. RESULTS: Based on both individual and group data analysis, it has been observed that the duration of RR and TR increases during the clinostatic test, while it decreases during the Martinet test. The extent of these changes in RR and TR varies between the two tests. Specifically, the RR:TR ratios are 1:3.5 during the clinostatic test and 1:2.5 during the Martinet test. These findings suggest a higher likelihood of parasympathetic influences on the electrical properties of the myocardium during the clinostatic test, and sympathetic influences during the Martinet test. CONCLUSION: Duration of RR and TR intervals increased by 25% and 85%, respectively, in response to the clinostatic test. Conversely, after the Martinet test, the duration of both intervals decreased by 15% and 38%, respectively. These findings suggest that the changes in the duration of RR and TR intervals are influenced by the parasympathetic and sympathetic divisions of the autonomic nervous system, under different types of physical stress. Further research should be conducted in other seasons, particularly during transitional periods such as spring and autumn, to better understand the electrical properties of the myocardium under physical stress.

The causal relationship between sarcopenia-related traits and ECG indices - A mendelian randomization study

BackgroundSarcopenia is a common geriatric condition closely associated with cardiovascular diseases and other health issues. This study aims to investigate the causal relationship between sarcopenia-related traits and electrocardiogram(ECG) indices. MethodsWe conducted a comprehensive analysis utilizing summary data from genome-wide association studies (GWAS) associated with sarcopenia-related traits, including hand grip strength, lean body mass, and walking pace. ECG indices included PR interval, PP interval, ST duration, QRS duration and T wave duration. The primary analytical method employed was the inverse variance-weighted method (IVW). ResultsAccording to our study findings, we identified a significant association between sarcopenia-related traits and ECG indices. Specifically, we observed a positive correlation between increased muscle mass and certain ECG indices. For instance, increased limb muscle mass (including left arm, right arm, left leg, and right leg) was associated with prolonged PR interval and QRS duration. This suggests that enhancing muscle mass may impact the timing of cardiac electrical activity. Additionally, increased whole-body fat-free mass showed similar associations with cardiac electrical activity. ConclusionSarcopenia-related traits have a unidirectional causal relationship with ECG indices, indicating that sarcopenia affects cardiac electrical activity.

Исследование соотношений между показателями ритмической активности сердца человека

The purpose of this article was to determine the correlations between the electrical and mechanical parameters of the rhythmic activity of the heart (HRA) in humans taking into account age and the effect of functional loads. Materials and methods. The research involved 146 people of both sexes aged between two hours after birth and 92 years, who were examined using functional tests that differed depending on the age of the subjects. Electrocardiogram (ECG) and heart rate (HR) parameters were recorded in the standard lead II using the Poly-Spectrum ECG system (Neurosoft, Ivanovo). Results. Correlations between HRA parameters can be traced from the first hours of post-embryogenesis throughout the rest of a person’s life. The data obtained indicate a dependence of HRA on the age and on the effect of functional tests, as well as confirm the proposition that there is an inverse relationship between HR dynamics and the dynamics of myocardial electrical parameters. ECG recordings at birth indicate that the correlations between ECG and HR are formed as early as in the prenatal period. Their correlations in people aged between 70 and 92 years indicate a strain associated with the wear and tear of the body’s functional systems. HR and ECG parameters are based on the electrical properties of the myocardium, which are significantly affected by the autonomic nervous system (ANS). A linear range of correlations between HR and ECG intervals was compiled. The maximum values of the duration of the PP interval and TP segment correspond to the minimum HR values. With an increase in HR from 40 to 80 beats/min, the duration of the TP segment decreases twoto three-fold. With HR reaching 120 ± 5 beats/min, the duration of the TP segment drops to zero. Since the increase in HR continues further in response to functional tests, it is obvious that at this stage the process is provided only by the neurohumoral components of the ANS. Due to the maximum variability of the duration of the TP segment, its most important role in the organization of HRA is emphasized.

Effect of Head-Up/-Down Tilt on ECG Segments and Myocardial Temporal Dispersion in Healthy Subjects.

The head-up/-down tilt test acutely modifies the autonomic nervous system balance throughout a deactivation of the cardiopulmonary reflexes. The present study examines the influence of head-up/-down tilt on a number of ECG segments. A total of 20 healthy subjects underwent a 5 min ECG and noninvasive hemodynamic bio-impedance recording, during free and controlled breathing, lying at (a) 0°; (b) -45°, tilting up at 45°, and tilting up at 90°. Heart rate variability power spectral analysis was obtained throughout some ECG intervals: P-P (P), P-Q (PQ), PeQ (from the end of P to Q wave), Q-R peak (QR intervals), Q-R-S (QRS), Q-T peak (QTp), Q-T end (QTe), STp, STe, T peak-T end (Te), and, eventually, the TeP segments (from the end of T to the next P waves). Results: In all study conditions, the Low Frequency/High FrequencyPP and LFPP normalized units (nu) were significantly lower than the LF/HFRR and LFRRnu, respectively. Conversely, the HFPP and HFPPnu were significantly higher in all study conditions. STe, QTp, and QTe were significantly related to the PP and RR intervals, whereas the T wave amplitude was inversely related to the standard deviations of all the myocardial repolarization variables and to the left ventricular end-systolic volume (LVEDV). The T wave amplitude diminished during head-up tilt and significantly correlated with the LVEDV.

Occam's Razor: Two Arrhythmias in a Single Heart?

Occam's Razor: Two Arrhythmias in a Single Heart?

A Novel Quantitative Electrocardiography Strategy Reveals the Electroinhibitory Effect of Tamoxifen on the Mouse Heart.

Tamoxifen, a selective estrogen receptor modulator, was initially used to treat cancer in women and more recently to induce conditional gene editing in rodent hearts. However, little is known about the baseline biological effects of tamoxifen on the myocardium. In order to clarify the short-term effects of tamoxifen on cardiac electrophysiology of myocardium, we applied a single-chest-lead quantitative method and analyzed the short-term electrocardiographic phenotypes induced by tamoxifen in the heart of adult female mice. We found that tamoxifen prolonged the PP interval and caused a decreased heartbeat, and further induced atrioventricular block by gradually prolonging the PR interval. Further correlation analysis suggested that tamoxifen had a synergistic and dose-independent inhibition on the time course of the PP interval and PR interval. This prolongation of the critical time course may represent a tamoxifen-specific ECG excitatory-inhibitory mechanism, leading to a reduction in the number of supraventricular action potentials and thus bradycardia. Segmental reconstructions showed that tamoxifen induced a decrease in the conduction velocity of action potentials throughout the atria and parts of the ventricles, resulting in a flattening of the P wave and R wave. In addition, we detected the previously reported prolongation of the QT interval, which may be due to a prolonged duration of the ventricular repolarizing T wave rather than the depolarizing QRS complex. Our study highlights that tamoxifen can produce patterning alternations in the cardiac conduction system, including the formation of inhibitory electrical signals with reduced conduction velocity, implying its involvement in the regulation of myocardial ion transport and the mediation of arrhythmias. A Novel Quantitative Electrocardiography Strategy Reveals the Electroinhibitory Effect of Tamoxifen on the Mouse Heart（Figure 9）. A working model of tamoxifen producing acute electrical disturbances in the myocardium. SN, sinus node; AVN, atrioventricular node; RA, right atrium; LA, left atrium; RV, right ventricle; LV, left ventricle.

PO-02-031 FEASIBILITY OF NONINVASIVE TRAGAL STIMULATION TO ASSESS VAGAL TONE DURING CARDIONEUROABLATION

There is increasing evidence that cardioneuroablation (CNA) can be an effective treatment for patients with atrial fibrillation and vasovagal syncope. The optimal procedural endpoint for CNA is unknown but elimination of response to invasive vagal stimulation has been utilized. To characterize the ability of transcutaneous tragal stimulation to non-invasively assess vagal tone before and after CNA as a potential procedural endpoint. We conducted a prospective, single center study in patients undergoing CNA as part of an ablation for atrial fibrillation. Transcutaneous tragal stimulation (left, right, then bilateral) was performed using Parasym vagal stimulator (20Hz, up to 42mA, up to 10 seconds) to identify vagal response. Positive response was defined as >2 seconds ventricular asystole, AV block or >10% increase in P-P or R-R interval. Stimulation was performed at baseline and repeated immediately following the CNA portion of the procedure. Among 19 patients, 9(47%) were male, median age was 70.7 years (IQR 66.9-70.7), median CHA2DS2Vasc score was 3(IQR 2.5-4). Atrial fibrillation was paroxysmal in 13 patients (68%), 11 patients (58%) were on antiarrhythmic therapy and 6 patients (32%) had prior ablations for atrial fibrillation. Response to bilateral stimulation was noted in 2 patients and only to left tragal stimulation in 1 patient. The response in these patients was a median increase in the PP interval by 350ms (IQR 310 – 370) or 31% (IQR 29 – 44) without an increase in the PR interval noted in any patient. No response to stimulation was seen after CNA in these 3 patients. Among all patients, median heart rate (HR) increase after CNA was 19 bpm (IQR 14-36, p=0.0001) and the PR interval decreased by a median of 15ms (IQR 9.5-41, p=0.0024). Changes in HR and PR interval was seen in both patients with tragal stimulation response (HR increase median 26 bpm and PR decrease median 36ms) and without response to tragal stimulation (HR increase median 15 bpm and PR decrease median 14 ms). High output tragal stimulation was inconsistently able to produce identifiable increase in vagal tone. When identified, elimination of response may be a reliable indicator of effective CNA, however the low response rate limits its utility. The poor efficacy observed may be due to the limited tragal innervation of the vagus nerve and alternative stimulation sites, such as the auditory canal should be considered.Tabled 1Table 1Baseline Characteristicsn=19Age (years) median (IQR)70.7 years (67-73.3)Male gender n (%)9 (47%)Prior historyHypertension n (%)14 (73%)Obstructive Sleep Apnea n (%)4 (21%)Diabetes n (%)5 (26%)Congestive Heart Failure n (%)3 (15%)Coronary artery disease n (%)7 (37%)Cerebrovascular disease n (%)1 (5%)Peripheral arterial disease n (%)2 (10%)CHA2DS2Vasc median (IQR)3 (2.5-4)Atrial Fibrillation detailsParoxysmal n (%)13 (69%)Persistent n (%)6 (32%)Vagally mediated AF n (%)8 (42%)Coexisting Atrial Flutter n (%)6 (32%)Antiarrhythmic drugs11 (58%)Prior ablation n (%)6 (32%)Echocardiographic featuresLeft Ventricular Ejection Fraction (%) median (%)60 (55-65)Normal Left atrial size n (%)4 (21%)Severe Left atrial dilatation n (%)1 (5%)Tragal Stimulation responseLeft tragal response n (%)1 (5%)Bilateral tragal response n (%)2 (10%)ΔPP interval pre-ablation (msec) median (IQR)350ms (IQR 310 – 370)Post Cardioneuroablation responseΔHeart rate post-ablation (bpm) median (IQR)18.5bpm (IQR 13.5 to 35.5)ΔPR interval post-ablation (msec) median (IQR)-15ms (IQR -9.5 to -41) Open table in a new tab

PO-04-033 CARDIONEUROABLATION IN A WOMAN WITH ICTAL-INDUCED CARDIAC ASYSTOLE

Ictal-induced cardiac bradyarrhythmia and asystole is a rare phenomenon. The exact mechanism of ictal-induced cardiac bradyarrhythmia and asystole remains unclear. It was postulated that stimulation of central autonomic network during ictal episode may trigger an abrupt burst of hypervagotonia. Prolonged episode of cardiac bradyarrhythmia and asystole may result in syncope or death due to impairment of cerebral perfusion. The role of cardioneuroablation (CNA) in this condition has not been well-described in the literature. To describe a case of successful CNA in a patient with ictal-induced bradyarrhythmia and asystole. n/a A 47-year-old female has a 1.5-year history of intractable focal epilepsy and COVID-19 infection. She started having multiple episodes of seizures following a mild COVID-19 infection. Electroencephalogram (EEG) and brain MRI revealed right temporal onset seizures without structural lesions. Due to ongoing uncontrolled seizures with multiple semiologies despite multiple anti-epileptic drugs, she was admitted to Epilepsy Monitoring Unit for seizure classification. Her ictal EEGs (Figure 1) showed onset of ictal rhythm in the right temporal region with episodes of severe sinus bradycardia (15-30 bpm) and sinus pauses (15-16 seconds). Telemetry tracings demonstrated PP interval slowing with PR interval prolongation prior to the pauses consistent with a vagally-mediated mechanism. Cardiac electrophysiology team recommended CNA for treating the episodes of ictal-induced bradyarrhythmia and asystole. 3D anatomic maps of the right atrium (RA) and left atrium (LA) were created using CARTO system (Biosense Webster). Right superior ganglionated plexus (RSGP) was localized with fractionation mapping and intracardiac echocardiography guidance. RSGP was targeted from the RA using an irrigated radiofrequency catheter with power limit of 25 W. Post-ablations of RSGP, her heart rate increased from 60 - 99 bpm. Additional lesions were delivered from the LA site but no additional heart rate increase was not seen. An implantable loop recorder was implanted post-ablation procedure. During follow-up of 8 months, she had recurrent focal epilepsy, but no bradyarrhythmias or asystole was noted on her loop recorder. Resting heart rates at long-term follow up were between 70 - 100 bpm. This case highlights the utility of CNA in patient with ictal-induced cardiac bradyarrhythmia and asystole. CNA may be an approach to avoid permanent pacemakers in this population.

PO-04-064 QUANTIFICATION OF AUTONOMIC MODULATION DURING SINGLE-SHOT PULMONARY VEIN ISOLATION WITH PULSED FIELD ABLATION

Additional ganglionated plexi (GPs) ablation beyond pulmonary vein isolation (PVI) has been associated with better outcomes after radiofrequency ablation. Because of the anatomical relationship between the major atrial GPs and the pulmonary veins, single-shot PVI with cryoballoon catheter ablation (CBA) has been demonstrated to concomitantly affect the GPs, as documented by intraprocedural vagal reactions and increased heart rates (HR) after ablation. The novel multispline pulsed field ablation catheter (PFA) is emerging as a safe and effective non-thermal single-shot alternative for PVI, with ablation selectivity for the cardiac tissue. To quantify the degree of parasympathetic denervation during single-shot PVI with PFA compared with CBA. We prospectively included consecutive patients undergoing autonomic modulation assessment with extracardiac vagal stimulation (ECVS) during single-shot PVI for paroxysmal AF with PFA and CBA. Patients with previous ablations were excluded. The response to ECVS was determined as the sinus pause following stimulation, measuring the maximum PP interval (sinus node response). Baseline and post-ablation responses to ECVS were collected and analysed. The degree of autonomic modulation in the two groups was assessed by evaluating the difference between pre- and post-ablation responses to ECVS. A total of 30 patients (PFA group, n=15 vs CBA group, n=15) were included in the analysis. Baseline patients’ characteristics were similar between the two groups (Table 1). Pre-ablation responses to ECVS were similar between the PFA and CBA groups (10757.3 ± 3155.2 ms vs. 11155.9 ± 2472.3 ms, p=0.70). Vagal reactions during PVI occurred more frequently with PFA than CBA (86.7% vs 20%, p=0.001), more commonly during left superior PVI. After PVI, the sinus pause following ECVS was significantly longer after PFA compared with CBA (9897.9 ± 2702.0 ms vs. 874.6 ± 213.6 ms; p<0.001, Figure 1). Despite similar baseline values, 24h post-ablation HR increased significantly more with CBA than PFA (14.0 ± 6.8 bpm vs. 1.8 ± 8.4 bpm, respectively; p<0.001). Single-shot PVI with PFA was associated with less autonomic modulation compared with CBA at ECVS testing. This is likely the result of cardiac tissue selectivity, with minimal effect on the autonomic nervous system. The clinical impact of reduced parasympathetic denervation of PFA on AF outcome is yet to be elucidated.

Electrocardiographic features of paradoxical ventriculophasic response

BackgroundParadoxical ventriculophasic response (P-VR), a rare entity, has not been fully investigated. This study sought to compare the electrocardiographic features of P-VR and typical ventriculophasic response (T-VR). MethodsThe 12‑lead electrocardiogram (ECG) data recorded before implantation of a cardiac implantable electronic device were analyzed in patients with greater than second-degree atrioventricular block (AVB). P-VR or T-VR was defined as present if the PP interval interposing a QRS complex was prolonged or shortened, respectively, by >3% compared with the preceding PP interval without a QRS complex when a QRS complex occurred within a span of 60% of the preceding PP interval. ResultsOf 95 patients (age 80 ± 9 years; 49 men) with heart block, 1868 instances (an instance was defined as a set of PP intervals without a QRS complex and the subsequent PP interval interposing a QRS complex) from 214 ECGs were analyzed: 894 instances from 122 ECGs in 64 patients with complete AVB (cAVB) and 974 instances from 92 ECGs in 43 patients with 2:1 AVB (12 showed both cAVB and 2:1 AVB). P-VR was observed in 48 patients (51%). The position of the interposed QRS complex relative to the preceding PP interval was earlier in P-VR than in T-VR. The PP interval was shorter in P-VR than in T-VR. ConclusionP-VR was present in >50% of patients and was affected by the position of the interposed QRS complex and the PP interval.

Cardiodiagnostics Based on Photoplethysmographic Signals.

The article presents a methodology to support the process of correct cardiodiagnostics based on cardio signals recorded with modern optical photoplethysmographic (PPG) sensor devices. An algorithm for preprocessing registered PPG signals and the formation of a time series for the analysis of heart rate variability is presented, which is an important information indicator in the diagnosis of cardiovascular diseases. In order to validate the proposed algorithm, an experimental scheme for synchronous recordings of PPG and electrocardiographic (ECG) signals and the study of the accuracy of the registered signals was created. The obtained results show high accuracy of the studied signals in terms of the following parameters: number of QRS complexes/pulse waves and mean RR intervals/PP intervals and the finding that the proposed algorithm is suitable for preprocessing PPG signals, as well as the possibility of interchangeable use of PPG and ECG. The results of the mathematical analysis of heart rate variability by applying linear methods (Time-Domain and Frequency-Domain) to two groups of people are presented: healthy controls and patients with cardiovascular disease (syncope). After determining the values of the parameters of the methods used, in order to distinguish healthy subjects from sick ones, statistical analysis was applied using t-test and Receiver Operating Characteristics (ROC) analysis. The obtained results show that the linear methods used are suitable for analysing the dynamics of PP interval series and for distinguishing healthy subjects from those with pathological diseases. The presented research and analyses can find applications in guaranteeing correctness and accuracy of conducting cardiodiagnostics in clinical practice.

INSIGHTS ON ATRIAL ELECTROCARDIOGRAM IN SINUS RHYTHM AND ATRIOVENTRICULAR BLOCK FOR IMPROVED CLINICAL DIAGNOSIS

Objective: This study aims to characterize P and Ta wave of Modified Limb Lead (MLL) Electrocardiogram (ECG) in Normal Sinus Rhythm (NSR) and Atrioventricular Block (AVB). Methods: ECGs were recorded using MLL configuration from 100 NSR volunteers (mean age 31 years, 35 women) and 20 male AVB patients (mean age 72 years). Amplitudes and durations of P, Ta wave, and PTa Interval (PTaI) were measured, plotted, and analyzed for both the groups. Results: P-wave amplitudes were larger in AVB, and also P, Ta waves correlated significantly in both groups with higher correlation in AVB (NSR: [Formula: see text]; AVB: [Formula: see text]). Ta-wave duration ([Formula: see text][Formula: see text]ms) was longer than P-wave duration ([Formula: see text][Formula: see text]ms) in AVB patients and was opposite to P-wave polarity in all the leads. PP Interval (PPI) correlated significantly with P wave (NSR: [Formula: see text]; AVB: [Formula: see text]), Ta wave ([Formula: see text]; [Formula: see text]), PTaI ([Formula: see text]; [Formula: see text]), and corrected PTaI ([Formula: see text]; [Formula: see text]). Conclusion: P-wave right axis shift leads to the higher P-wave amplitude in AVB which may be due to the advancing age and atrial chamber enlargement. In NSR, the duration of observable Ta wave was longer than P wave, whereas in AVB, the Ta wave duration was 3–3.5 times longer than P wave.

Вариабельность временных и амплитудных показателей ЭКГ у людей пожилого и старческого возраста

The purpose of this article was to determine the effect of the clinostatic test on the electrical properties of the myocardium in older adults leading an active lifestyle. Materials and methods. The study involved 38 people aged between 70 and 90 years living in a northern city (Syktyvkar, 61°N) and leading an active lifestyle. The indicators of the electrical properties of the cardiac muscle were determined before and after the clinostatic test. For this purpose, an ECG was recorded in the standard lead II in the standing and lying positions. Results. Using the method of paired comparisons, we showed a decrease in heart rate under the influence of the clinostatic test from 76 ± 10 beats/min to 64 ± 10 beats/min. The variability of ECG components according to pNN50 (the percentage of successive NN intervals differing from each other by more than 50 ms) in older adults in the standing position was, on average, two times lower than in the lying position. The PP interval increased from 0.81 ± 0.12 s (in the standing position) to 0.90 ± 0.10 s (in the lying position). The PT interval remained practically unchanged, staying at the level of (0.46 ± 0.07) – (0.49 ± 0.07) s. The TP segment grew from 0.35 to 0.42 ± 0.10 s. The RD amplitude was 1.04 ± 0.43 mV in the standing and 0.88 ± 0.30 mV in the lying position; the propagation rate of depolarization in the cardiac muscle was 245 ± 137 and 205 ± 106 mm/s, respectively. In addition, the paper discussed the mechanism of opposite reactions to the clinostatic test, i.e. increasing duration of cardiointervals and decreasing amplitude indicators. For citation: Irzhak L.I., Russkikh N.G., Parshukova A.N. Variability of Time and Amplitude ECG Indicators in Older Adults. Journal of Medical and Biological Research, 2021, vol. 9, no. 4, pp. 355–365. DOI: 10.37482/2687-1491-Z073

Angiotensin receptor-neprilysin inhibition by sacubitril/valsartan attenuates doxorubicin-induced cardiotoxicity in a pretreatment mice model by interfering with oxidative stress, inflammation, and Caspase 3 apoptotic pathway.

Doxorubicin (DOX) is a well-known cardiotoxic agent, whereas sacubitril/valsartan (Sac/Val) is an effective treatment option in heart failure. In this study, we aimed to evaluate the effect of Sac/Val on DOX-induced cardiotoxicity in pretreatment mice model. A total of 24 mice were equally classified into 4 groups; control group, DOX (20 mg/kg; fifth day), Sac/Val (80 mg/kg), and Sac/Val+DOX (Sac/Val was given from day one of the study before doxorubicin administration). Electrocardiography parameters, including durations of QRS, ST, QT, PP segment, and QT/PQ index were measured. Total antioxidant status (TAS), total oxidant status (TOS), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), IL-6, NT-proBNP concentrations, and Caspase 3 activity were evaluated. At the end of the 9-day study duration, QRS, ST, QT intervals, QT/PQ index and TAS, TOS, TNF-α, IL-1β, IL-6 levels were significantly higher in the DOX group than in the control group (p<0.001). Moreover, there were significant differences only in the PP interval when comparing the Sac/Val+DOX and control groups (p<0.001). QRS, ST, QT intervals, and QT/PQ index, TAS, TOS, TNF-α, IL-1β, IL-6 levels were significantly lower in the Sac/Val+ DOX group compared with the DOX group (p<0.001). Furthermore, NT-proBNP levels were lower in the Sac/Val+DOX group compared with the DOX group along with less Caspase 3 apoptosis. Sac/Val seems to be cardioprotective against DOX-induced cardiotoxicity in pretreatment mice model. These findings can be attributed to the antiarrhythmic, anti-inflammatory, antioxidant, and antiapoptotic effects of Sac/Val as shown in this study.

Understanding the molecular role of syndecan-1 in the regulation of caspase-6 during the progression of cardiac arrhythmia.

The role of caspase-6 in heart disease is not well understood, particularly with respect to cardiac arrhythmia. Also, the function of syndecan-1 in the stimulation of inflammation or a regenerative response after cardiac injury is unclear. Leptin receptor-deficient (C57BL/KS-leprdb/leprdb) mice were used in the present study. In addition to developing type 2 diabetes, they also develop initial- and end-stage cardiac arrhythmia after 5 and 8 months, respectively. The initial and end-stage arrhythmias were confirmed through progressive variations in the PP intervals observable in electrocardiograms. Histopathological images of the cardiac tissue exhibited scattered and loosened cardiac cells at the initial stage of cardiac arrhythmia, whereas tissue hardness and extensive structural changes in cardiomyocytes were evident at the end stage. At the molecular level, the progressive upregulation of caspase-6 was observed as the cardiac arrhythmia progressed. In the initial stage of arrhythmia, immunohistochemistry revealed that caspase-6 was expressed at the surface of cardiac cells, suggesting that caspase-6 targeted the extracellular matrix, leading to a loosening of the cardiac tissue structure. In the end stage of cardiac arrhythmia, caspase-6 expression was abundant in the cytoplasm, as well as at the cell surface, suggesting that caspase-6 may have cleaved intermediate filaments, paving the way for cellular morphological changes and apoptosis. Notably, syndecan-1 was upregulated 5.8-fold in the initial stage of cardiac arrhythmia, but downregulated at the end stage. Syndecan-1 may restrict the expression of caspase-6 in the initial stage of cardiac arrhythmia, while its downregulation at the end stage may allow destructive changes via caspase-6 overexpression. Furthermore, the knockdown of syndecan-1 using small interfering RNA enhanced the expression of caspase-6 in the cardiac tissue by factors of 1.8 and 1.2 at the initial and end stages of cardiac arrhythmia, respectively, compared with that in non-silenced cardiac tissue. Therefore, it may be concluded that syndecan-1 plays a major role in the regulation of caspase-6 during the pathological stages of cardiac arrhythmia.

ECG Intervals on Acute Carbon Monoxide Poisoning.

To evaluate the usability of electrocardiography (ECG) intervals in the diagnosis and treatment monitoring of acute carbon monoxide (CO) poisoning. An observational study. Department of Emergency Medicine, Kayseri City Hospital, Turkey, from November 2018 to May 2019. Each of 80 patients for study and control groups were prospectively included. For study group, pre- and post-treatment ECG intervals (P-wave and QRS complex periods, PP, PR, RR, QT, and QTc intervals) and carboxyhemoglobin (COHb) levels of the patients were evaluated. For control group, ECG intervals and COHb levels of the patients during admission to the Emergency Department were evaluated. As a result of the statistical analysis in which measurements of the study group and control group were compared, a statistically significant difference was found in the following values: pre-treatment group COHb level (p<0.001), PR interval (p=0.046), PP interval (p<0.001), QT interval (p<0.001), QTC interval (p=0.016), RR interval (p<0.001), and post-treatment group COHb level (p<0.001), PR interval (p=0.009), PP interval (p=0.041), QTC interval (p=0.010), and RR interval (p=0.036). QT interval values in the post-treatment group were similar to those of the control group (p=0.342). In the ROC analysis where the diagnostic performance of ECG intervals was evaluated, the area under the curve (AUC) scale was between 0.29 and 0.62. ECG intervals do not provide as much benefit as COHb measurement in the diagnosis of acute CO poisoning. However, the QT interval is a useful ECG interval in the treatment monitoring of acute CO poisoning. Key Words: Acute carbonmonoxide poisoning, ECG interval, QT interval, Emergency Department.

WWP2 and PPP1R3A are abnormally regulated in arrhythmia-induced cardiac damage.

The present work aimed to identify the roles of WWP2 (an E3 ubiquitin-protein ligase) and protein phosphatase 1 regulatory subunit 3A (PPP1R3A) in different pathological stages of cardiac arrhythmia development. Leptin-deficient mice (C57BLKS-Leprdb/Leprdb) were used for the development of initial and severe stages of cardiac arrhythmia. Histology, ECG, immunohistochemistry and Western blotting were used to analyse cardiac arrhythmia, WWP2 and PPP1R3A expression. Histopathological studies of 4-month-old mice showed cardiac degeneration, cellular lesions, and swollen tissue structure with loss of tissue elasticity, indicative of the initial condition of cardiac arrhythmia. The leptin-deficient 7-month-old mice showed cardiac tissue hardening with increased secretion of extracellular matrix. The development of initial- and severe-cardiac arrhythmia was further evident with electrocardiogram studies, which showed more PP interval variations as the disease progressed. At the molecular level, WWP2 showed marginal upregulation in the initial stages of arrhythmia and was predominantly expressed within nuclei. WWP2 was overexpressed 6.6-fold in the severe stage of cardiac arrhythmia and was spread throughout the tissue layer. Interestingly, PPP1R3A was significantly overexpressed in initial cardiac arrhythmia conditions, but was downregulated and restricted to more nuclear expression in advanced cardiac arrhythmia. Silencing of PPP1R3A, enhances the expression of WWP2 to 5.3-fold in initial stages, but remarkable variation not observed in advanced cardiac arrhythmia conditions. Our results suggest that PPP1R3A had a control over WWP2 in the initial stages of cardiac arrhythmia. In particular, PPP1R3A overexpression implies its potential protective effect in initial cardiac arrhythmia stages.

Stability analysis on the effects of heart rate variability and premature activation of atrial ECG dynamics using ARMAX model.

The cellular action potential of cardiac muscles generates Electrocardiogram (ECG) signals. Disturbances in cardiac cells are determined by analyzing the stability of ECG intervals. The PTa Interval (PTaI) of ECG represents the atrial Action Potential Duration (APD) and the evaluation of the causes of PTaI instability can predict the onset of arrhythmia. This study developed an Autoregressive Moving Average with Exogenous Input (ARMAX) model to explore the roles of Heart Rate Variability (HRV) and Premature Activation (PA) in PTaI dynamics using PTaI and PP Interval (PPI) as exogenous inputs. Minute ECG signals were collected from twenty Normal Sinus Rhythm (NSR) and ten Atrial Tachycardia (AT) volunteers. The EDAN PC ECG system was used in the Modified Limb Lead (MLL)configuration to evaluate instability. The instabilities of PTaI were found at the minimum model orders (Amin) of 10 and 11, in the NSR and AT groups, respectively. In the NSR group, the predominant reason for PTaI instability was HRV, whereas among AT patients, it was largely due to PA that preceded the onset of AT. The proposed model showed better prediction of PTaI with minimum Mean Square Error(MSE) between the measured and predicted PTa Intervals (PTaIs). The factor that led to PTaI instability in AT patients was found to be different from that of the NSR group. The frequency of PA (fPA) was found to contribute more in the AT than the NSR group. The developed ARMAX model was better in predicting instability of atrial ECG dynamics in both groups than other autoregressive models currently in use.

Effect of Blood Volume Shift Simulated via Head-up Tilt on Photoplethysmography Morphology.

PPG can provide information on cardiovascular responses to fluid shifts from upper to lower part of body under the condition of orthostatic stress. The current study investigated ability of PPG derived LVET and other PPG derived features to identify progressive central hypovolemia induced by head up tilt (HUT) and evaluated potential use of LVET as early noninvasive indicator of blood loss. Continuous finger PPG, blood pressure, and electrocardiography were recorded simultaneously during 5-minutes of baseline and HUT of 20°, 40°, and 60° from 15 participants (age: 26.5 ± 3 years; height: 177 ± 8 cm; weight: 72 ± 10 kg, mean ± SD). Beat-by-beat pulse rate (PR), systolic amplitude (SA), systolic time (ST), diastolic time (DT), and PP Interval (PPI) and Ratio of pulse rate over systolic amplitude (PR/SA) were derived for each stage. LVET was derived from each stage. Friedman test followed by post-hoc analysis using Tukey-HSD was conducted to highlight the significance of changes induced by HUT. Application of 60° HUT (i.e. moderate category simulated hypovolemia) resulted in a significant change in PR (80±3 bpm vs 68±3 bpm, p=0.0008), DT (264±7 ms vs 303±4 ms, p=0.0008), ST (110±6 ms vs 117±7 ms, p=0.02), PP interval (764±39 ms vs 869±25 ms, p=0.0045), PR/SA (112±16 vs 82±21, p=0.012) , SA (0.875± 0.2 vs 1.69±0.6, p=0.012) and LVET(292 vs 351ms,p=0.0008) compared to baseline. LVET has a strong association with the change in central blood volume and may be used as a sensitive early marker of progressive hypovolemia. The findings of the study support the hypothesis of differentiating simulated hypovolemia based on PPG alone. Keywords: Hypovolemia, HUT, LVET.

Aging-associated sinus arrest and sick sinus syndrome in adult zebrafish.

Because of its powerful genetics, the adult zebrafish has been increasingly used for studying cardiovascular diseases. Considering its heart rate of ~100 beats per minute at ambient temperature, which is very close to human, we assessed the use of this vertebrate animal for modeling heart rhythm disorders such as sinus arrest (SA) and sick sinus syndrome (SSS). We firstly optimized a protocol to measure electrocardiogram in adult zebrafish. We determined the location of the probes, implemented an open-chest microsurgery procedure, measured the effects of temperature, and determined appropriate anesthesia dose and time. We then proposed an PP interval of more than 1.5 seconds as an arbitrary criterion to define an SA episode in an adult fish at ambient temperature, based on comparison between the current definition of an SA episode in humans and our studies of candidate SA episodes in aged wild-type fish and Tg(SCN5A-D1275N) fish (a fish model for inherited SSS). With this criterion, a subpopulation of about 5% wild-type fish can be considered to have SA episodes, and this percentage significantly increases to about 25% in 3-year-old fish. In response to atropine, this subpopulation has both common SSS phenotypic traits that are shared with the Tg(SCN5A-D1275N) model, such as bradycardia; and unique SSS phenotypic traits, such as increased QRS/P ratio and chronotropic incompetence. In summary, this study defined baseline SA and SSS in adult zebrafish and underscored use of the zebrafish as an alternative model to study aging-associated SSS.