Prolongation Of RR Interval Research Articles

Analysis of the Prognostic Impact of Heart Rate Deceleration Capacity on Type 2 Diabetes Mellitus with Ventricular Premature Contractions

At present, one of the greatest life-threatening risks for patients with type 2 diabetes is cardiovascular complications. According to relevant research, approximately 70% to 80% of these patients die due to cardiovascular disease. Compared to non-diabetic individuals, diabetic patients face a two- to four-fold higher risk of developing cardiovascular and cerebrovascular diseases, with vascular complications resulting in an average life expectancy reduction of about 12 years. Increasing evidence indicates that cardiovascular-related indicators become abnormal as early as the initial stages of type 2 diabetes. During this period, the likelihood of adverse cardiovascular events rises, and cardiac autonomic dysfunction (CAD) begins, disrupting the balance between the parasympathetic and sympathetic nervous systems and thereby increasing cardiovascular disease risk. Cardiac autonomic dysfunction is one of many severe complications, and ventricular premature contractions are common arrhythmias in patients with type 2 diabetes, often seen as key indicators of declining cardiac function. Continuous heart rate deceleration, observed as deceleration runs (DRs) in Holter ECGs, manifests as a gradual prolongation of consecutive RR intervals, an indicator useful in assessing cardiac autonomic neuropathy. Persistent hyperglycemia or pre-diabetic states are associated with coronary artery disease (CAD), and strict blood glucose control helps slow the progression of microvascular complications. HRV monitoring is an effective method for evaluating early-stage cardiovascular autonomic neuropathy (CAN), providing a quantitative assessment of autonomic function and aiding in diagnosing other vascular complications.

Oxidative damage and cardiotoxicity induced by 2-aminobenzothiazole in zebrafish (Danio rerio)

There is limited information available on cardiovascular toxicity of 2-Aminobenzothiazole (NTH), a derivative of benzothiazole (BTH) commonly used in tire production, in aquatic organisms. In the present study, the zebrafish embryos were exposed to varying concentrations of NTH (0, 0.05, 0.5, and 5 mg/L) until adulthood and the potential cardiovascular toxicity was assessed. NTH exposure resulted in striking aberrations in cardiac development, including heart looping failure and interference with atrioventricular canal differentiation. RNA-sequencing analysis indicated that NTH causes oxidative damage to the heart via ferroptosis, leading to oxygen supply disruption, cardiac malformation, and ultimately, zebrafish death. Quantitative real-time polymerase chain reaction (qPCR) analysis demonstrated the dysregulation of genes associated with early heart development, contraction, and oxidative stress. Additionally, reactive oxygen species accumulation and glutathione/malondialdehyde levels changes suggested a potential link between cardiac developmental toxicity and oxidative stress. In adult zebrafish, NTH exposure led to ventricular enlargement, decreased heart rate, reduced blood flow, and prolonged RR, QRS, and QTc intervals. To the best of our knowledge, this study is the first to provide evidence of cardiac toxicity and the adverse effects of ontogenetic NTH exposure in zebrafish, revealing the underlying toxic mechanisms connected with oxidative stress damage. These findings may provide crucial insights into the environmental risks associated with NTH and other BTHs.

High-dose Agomelatine Combined with Haloperidol Decanoate Improves Cognition, Downregulates MT2, Upregulates D5, and Maintains Krüppel-like Factor 9 But Alters Cardiac Electrophysiology.

Haloperidol decanoate (HD) has been implicated in cognitive impairment. Agomelatine (AGO) has been claimed to improve cognition. We aimed at investigating the effects of HD + low- or high-dose AGO on cognition, verifying the melatonergic/dopaminergic to the cholinergic hypothesis of cognition and exploring relevant cardiovascular issues in adult male Wistar albino rats. HD + high-dose AGO prolonged the step-through latency by +61.47% (P < 0.0001), increased the time spent in bright light by +439.49% (P < 0.0001), reduced the time spent in dim light by -66.25% (P < 0.0001), and increased the percent of alternations by +71.25% (P < 0.0001), despite the reductions in brain acetylcholine level by -10.67% (P < 0.0001). Neurodegeneration was minimal, while the mean power frequency of the source wave was reduced by -23.39% (P < 0.05). Concurrently, the relative expression of brain melatonin type 2 receptors was reduced by -18.75% (P < 0.05), against increased expressions of dopamine type 5 receptors by +22.22% (P < 0.0001) and angiopoietin-like 4 by +119.18% (P < 0.0001). Meanwhile, electrocardiogram (ECG) demonstrated inverted P wave, reduced P wave duration by -36.15% (P < 0.0001) and PR interval by -19.91% (P < 0.0001), prolonged RR interval by +27.97% (P < 0.05), increased R wave amplitude by +523.15% (P < 0.0001), and a depressed ST segment and inverted T wave. In rats administered AGO, HD, or HD+ low-dose AGO, Alzheimer's disease (AD)-like neuropathologic features were more evident, accompanied by extensive ECG and neurochemical alterations. HD + high-dose AGO enhances cognition but alters cardiac electrophysiology. SIGNIFICANCE STATEMENT: Given the issue of cognitive impairment associated with HD and the claimed cognitive-enhancing activity of AGO, combined high-dose AGO with HD improved cognition of adult male rats, who exhibited minimal neurodegenerative changes. HD+ high-dose AGO was relatively safe regarding triggering epileptogenesis, while it altered cardiac electrophysiology. In the presence of low acetylcholine, the melatonergic/dopaminergic hypothesis, added to angiopoietin-like 4 and Krüppel-like factor 9, could offer some clue, thus offering novel targets for pharmacologic manipulation of cognition.

Semaglutide attenuates pathological electrophysiological remodeling in diabetic cardiomyopathy via restoring Cx43 expression.

Semaglutide is a relatively new anti-hyperglycemic agent that was shown to carry cardioprotective potentials. However, the exact effects of semaglutide on diabetic cardiomyopathy (DCM) and their underlining mechanism remain unclear. This study aimed to evaluate the effects of semaglutide on myocardium injury and cardiac function in DCM mice and its potential mechanisms, with emphasis on its effects on Cx43 and electrophysiological remodeling. C57BL/6 mice were randomly divided into four groups: control group, semaglutide group, diabetes group, and diabetes + semaglutide treatment group. Type 1 diabetes were induced by intraperitoneal injection of streptozotocin. Mice in the semaglutide intervention group were injected subcutaneously with semaglutide (0.15 mg/kg) every week for 8 weeks. The blood glucose, cardiac function, oxidative stress markers, apoptosis, expression of Sirt1, AMPK, Cx43, and electrocardiogram of mice in each group were evaluated. Treatment with semaglutide alleviated glucose metabolism disorders and improved cardiac dysfunction in diabetic mice. In addition, semaglutide ameliorated the increase in oxidative stress and apoptosis in diabetic heart. Sirt1/AMPK pathway was activated after semaglutide treatment. Furthermore, diabetic mice showed reduced expression of Cx43 in the myocardium, accompanied by changes in electrocardiogram, including significantly prolonged RR, QRS, QT and QTc interval. Semaglutide treatment restored Cx43 expression and reversed the above-mentioned ECG abnormalities. Our research results showed that semaglutide protected against oxidative stress and apoptosis in diabetic heart, thereby improving cardiac function and electrophysiological remodelling in DCM mice, which may attribute to activation of Sirt1/AMPK pathway and restore of Cx43 expression.

Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease.

Chronic Chagas cardiomyopathy (CCC) results from infection with the protozoan parasite Trypanosoma cruzi and is a prevalent cause of heart disease in endemic countries. We previously found that cardiac fibrosis can vary widely in C3H/HeN mice chronically infected with T. cruzi JR strain, mirroring the spectrum of heart disease in humans. In this study, we examined functional cardiac abnormalities in this host:parasite combination to determine its potential as an experimental model for CCC. We utilised electrocardiography (ECG) to monitor T. cruzi-infected mice and determine whether ECG markers could be correlated with cardiac function abnormalities. We found that the C3H/HeN:JR combination frequently displayed early onset CCC indicators, such as sinus bradycardia and right bundle branch block, as well as prolonged PQ, PR, RR, ST, and QT intervals in the acute stage. Our model exhibited high levels of cardiac inflammation and enhanced iNOS expression in the acute stage, but denervation did not appear to have a role in pathology. These results demonstrate the potential of the C3H/HeN:JR host:parasite combination as a model for CCC that could be used for screening new compounds targeted at cardiac remodelling and for examining the potential of antiparasitic drugs to prevent or alleviate CCC development and progression.

Water Extract of Capsella bursa-pastoris Mitigates Doxorubicin-Induced Cardiotoxicity by Upregulating Antioxidant Enzymes

Doxorubicin (DOX), an effective chemotherapeutic drug, causes cardiotoxicity in a cumulative and dose-dependent manner. The aim of this study is to investigate the effects of hot-water extract of Capsella bursa-pastoris (CBW) on DOX-induced cardiotoxicity (DICT). We utilized H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells to evaluate the effects of CBW on DOX-induced cell death. Superoxide dismutase (SOD) levels, reactive oxygen species (ROS) production, and oxygen consumption rate were measured in H9c2 cells. C57BL/6 mice were treated with DOX and CBW to assess their impact on various cardiac parameters. Human-induced pluripotent stem-cell-derived cardiomyocytes were also used to investigate DOX-induced electrophysiological changes and the potential ameliorative effects of CBW. UPLC-TQ/MS analysis identified seven flavonoids in CBW, with luteolin-7-O-glucoside and isoorientin as the major compounds. CBW inhibited DOX-induced death of H9c2 rat cardiomyocytes but did not affect DOX-induced death of MDA-MB-231 human breast cancer cells. CBW increased SOD levels in a dose-dependent manner, reducing ROS production and increasing the oxygen consumption rate in H9c2 cells. The heart rate, RR interval, QT, and ST prolongation remarkably recovered in C57BL/6 mice treated with the combination of DOX and CBW compared to those in mice treated with DOX alone. Administration of CBW with DOX effectively alleviated collagen accumulation, cell death in mouse heart tissues, and reduced the levels of creatinine kinase (CK) and lactate dehydrogenase (LDH) in serum. Furthermore, DOX-induced pathological electrophysiological features in human-induced pluripotent stem-cell-derived cardiomyocytes were ameliorated by CBW. CBW may prevent DICT by stabilizing SOD and scavenging ROS. The presence of flavonoids, particularly luteolin-7-O-glucoside and isoorientin, in CBW may contribute to its protective effects. These results suggest the potential of CBW as a traditional therapeutic option to mitigate DOX-induced cardiotoxicity.

Influence of Age on Hyperoxia-Induced Cardiac Pathophysiology in Type 1 Diabetes Mellitus (T1DM) Mouse Model.

Mechanical ventilation often results in hyperoxia, a condition characterized by excess SpO2 levels (>96%). Hyperoxia results in changes in the physiological parameters, severe cardiac remodeling, arrhythmia development, and alteration of cardiac ion channels, all of which can point toward a gradual increase in the risk of developing cardiovascular disease (CVD). This study extends the analysis of our prior work in young Akita mice, which demonstrated that exposure to hyperoxia worsens cardiac outcomes in a type 1 diabetic murine model as compared to wild-type (WT) mice. Age is an independent risk factor, and when present with a major comorbidity, such as type 1 diabetes (T1D), it can further exacerbate cardiac outcomes. Thus, this research subjected aged T1D Akita mice to clinical hyperoxia and analyzed the cardiac outcomes. Overall, aged Akita mice (60 to 68 weeks) had preexisting cardiac challenges compared to young Akita mice. Aged mice were overweight, had an increased cardiac cross-sectional area, and showed prolonged QTc and JT intervals, which are proposed as major risk factors for CVD like intraventricular arrhythmias. Additionally, exposure to hyperoxia resulted in severe cardiac remodeling and a decrease in Kv 4.2 and KChIP2 cardiac potassium channels in these rodents. Based on sex-specific differences, aged male Akita mice had a higher risk of poor cardiac outcomes than aged females. Aged male Akita mice had prolonged RR, QTc, and JT intervals even at baseline normoxic exposure. Moreover, they were not protected against hyperoxic stress through adaptive cardiac hypertrophy, which, at least to some extent, is due to reduced cardiac androgen receptors. This study in aged Akita mice aims to draw attention to the clinically important yet understudied subject of the effect of hyperoxia on cardiac parameters in the presence of preexisting comorbidities. The findings would help revise the provision of care for older T1D patients admitted to ICUs.

Hydroxychloroquine induces long QT syndrome by blocking hERG channel

Abstract Objective In March 2022, more than 600 million cases of Corona Virus Disease 2019 (COVID-19) and about 6 million deaths have been reported worldwide. Unfortunately, while effective antiviral therapy has not yet been available, chloroquine (CQ)/hydroxychloroquine (HCQ) has been considered an option for the treatment of COVID-19. While many studies have demonstrated the potential of HCQ to decrease viral load and rescue patients’ lives, controversial results have also been reported. One concern associated with HCQ in its clinical application to COVID-19 patients is the potential of causing long QT interval (LQT), an electrophysiological substrate for the induction of lethal ventricular tachyarrhythmias. Yet, the mechanisms for this cardiotoxicity of HCQ remained incompletely understood. Materials and methods Adult New Zealand white rabbits were used for investigating the effects of HCQ on cardiac electrophysiology and expression of ion channel genes. HEK-293T cells with sustained overexpression of human-ether-a-go-go-related gene (hERG) K+ channels were used for whole-cell patch-clamp recordings of hERG K+ channel current (IhERG). Quantitative RT-PCR analysis and Western blot analysis were employed to determine the expression of various genes at mRNA and protein levels, respectively. Results electrocardiogram (ECG) recordings revealed that HCQ prolonged QT and RR intervals and slowed heart rate in rabbits. Whole-cell patch-clamp results showed that HCQ inhibited the tail current of hERG channels and slowed the reactivation process from inactivation state. HCQ suppressed the expression of hERG and hindered the formation of the heat shock protein 90 (Hsp90)/hERG complex. Moreover, the expression levels of connexin 43 (CX43) and Kir2.1, the critical molecular/ionic determinants of cardiac conduction thereby ventricular arrythmias, were decreased by HCQ, while those of Cav1.2, the main Ca2+ handling proteins, remained unchanged and SERCA2a was increased. Conclusion HCQ could induce LQT but did not induce arrhythmias, and whether it is suitable for the treatment of COVID-19 requires more rigorous investigations and validations in the future.

Diagnostic Efficiency of Ambulatory Electrocardiography in Atrial Fibrillation with Long RR Intervals

The current research was conducted to evaluate the diagnostic efficiency of ambulatory electrocardiography in atrial fibrillation with long RR intervals. A total of 80 patients with atrial fibrillation with long RR intervals shown by ambulatory electrocardiography who were hospitalized in our institution between January 2020 and December 2022 were recruited. The baseline patient profiles were recorded and the causative factors related to long RR intervals were analyzed. The patients were stratified into a study group (long RR intervals during sleep) and a control group (long RR intervals during non-sleep periods). The mean heart rate, number of prolonged RR episodes and prolonged RR intervals of patients were analyzed. Premature ventricular beats, ventricular escape, and crossover escape were risk factors for atrial fibrillation with long RR intervals (p<0.05). Significantly more patients showed long RR intervals during sleep than during non-sleep periods (p<0.05). Patients with long RR intervals during sleep had a higher heart rate and, fewer and shorter long RR intervals vs. those with long RR intervals during non-sleep periods (p<0.05). Ambulatory electrocardiography in the diagnosis of atrial fibrillation with long RR intervals provides rapid detection of the relevant causative factors and frequency of disease occurrence, thereby allowing accurate assessment of the patient’s condition and the implementation of appropriate therapeutic measures to effectively improve treatment outcomes.

Heart Rate Variability Reveals Altered Autonomic Regulation in Response to Myocardial Infarction in Experimental Animals.

The analysis of beating rate provides information on the modulatory action of the autonomic nervous system on the heart, which mediates adjustments of cardiac function to meet hemodynamic requirements. In patients with myocardial infarction, alterations of heart rate variability (HRV) have been correlated to the occurrence of arrhythmic events and all-cause mortality. In the current study, we tested whether experimental rodent models of myocardial infarction recapitulate dynamics of heart rate variability observed in humans, and constitute valid platforms for understanding mechanisms linking autonomic function to the development and manifestation of cardiovascular conditions. For this purpose, HRV was evaluated in two engineered mouse lines using electrocardiograms collected in the conscious, restrained state, using a tunnel device. Measurements were obtained in naïve mice and animals at 3–∼28 days following myocardial infarction, induced by permanent coronary artery ligation. Two mouse lines with inbred and hybrid genetic background and, respectively, homozygous (Homo) and heterozygous (Het) for the MerCreMer transgene, were employed. In the naïve state, Het female and male mice presented prolonged RR interval duration (∼9%) and a ∼4-fold increased short- and long-term RR interval variability, with respect to sex-matched Homo mice. These differences were abrogated by pharmacological interventions inhibiting the sympathetic and parasympathetic axes. At 3–∼14 days after myocardial infarction, RR interval duration increased in Homo mice, but was not affected in Het animals. In contrast, Homo mice had minor modifications in HRV parameters, whereas substantial (> 50%) reduction of short- and long-term RR interval variation occurred in Het mice. Interestingly, ex vivo studies in isolated organs documented that intrinsic RR interval duration increased in infarcted vs. non-infarcted Homo and Het hearts, whereas RR interval variation was not affected. In conclusion, our study documents that, as observed in humans, myocardial infarction in rodents is associated with alterations in heart rhythm dynamics consistent with sympathoexcitation and parasympathetic withdrawal. Moreover, we report that mouse strain is an important variable when evaluating autonomic function via the analysis of HRV.

Differential cardiotoxic electrocardiographic response to doxorubicin treatment in conscious versus anesthetized mice.

IntroductionDoxorubicin (DOX), an anticancer drug used in chemotherapy, causes significant cardiotoxicity. This study aimed to investigate the effects of DOX on mouse cardiac electrophysiology, in conscious versus anesthetized state.MethodsMale and female C57BL/6 mice were injected with saline, 20 or 30 mg/kg DOX. ECGs were recorded 5 days post‐injection in conscious and isoflurane anesthetized states. ECGs were analyzed using a custom MATLAB software to determine P, PR, QRS, QTc, and RR intervals as well as heart rate variability (HRV).ResultsECGs from the same mouse demonstrated P wave and QTc shortening as well as PR and RR interval prolongation in anesthetized versus conscious saline‐treated mice. ECG response to DOX was also modulated by anesthesia. DOX treatment induced significant ECG modulation in female mice alone. While DOX20 treatment caused decrease in P and QRS durations, DOX30 treatment‐induced QTc and RR interval prolongation in anesthetized but not in conscious female mice. These data suggest significant sex differences and anesthesia‐induced differences in ECG response to DOX. HRV measured in time and frequency domains, a metric of arrhythmia susceptibility, was increased in DOX20‐treated mice compared to saline.ConclusionsThis study for the first time identifies that the ECG response to DOX is modulated by anesthesia. Furthermore, this response demonstrated stark sex differences. These findings could have significant implications in clinical diagnosis of DOX cardiotoxicity.

Cardiomyocyte Deletion of Bmal1 Exacerbates QT- and RR-Interval Prolongation in Scn5a+/ΔKPQ Mice

Circadian rhythms are generated by cell autonomous circadian clocks that perform a ubiquitous cellular time-keeping function and cell type-specific functions important for normal physiology. Studies show inducing the deletion of the core circadian clock transcription factor Bmal1 in adult mouse cardiomyocytes disrupts cardiac circadian clock function, cardiac ion channel expression, slows heart rate, and prolongs the QT-interval at slow heart rates. This study determined how inducing the deletion of Bmal1 in adult cardiomyocytes impacted the in vivo electrophysiological phenotype of a knock-in mouse model for the arrhythmogenic long QT syndrome (Scn5a+/ΔKPQ). Electrocardiographic telemetry showed inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation increased the QT-interval at RR-intervals that were ≥130 ms. Inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation also increased the day/night rhythm-adjusted mean in the RR-interval, but it did not change the period, phase or amplitude. Compared to mice without the ΔKPQ-Scn5a mutation, mice with the ΔKPQ-Scn5a mutation had reduced heart rate variability (HRV) during the peak of the day/night rhythm in the RR-interval. Inducing the deletion of Bmal1 in cardiomyocytes did not affect HRV in mice without the ΔKPQ-Scn5a mutation, but it did increase HRV in mice with the ΔKPQ-Scn5a mutation. The data demonstrate that deleting Bmal1 in cardiomyocytes exacerbates QT- and RR-interval prolongation in mice with the ΔKPQ-Scn5a mutation.

Heartbeat evoked potentials (HEP) capture brain activity affecting subsequent heartbeat

Beat-to-beat heart rate variability is known to be associated with neural activity not only in areas regulating reflexes but also in higher brain areas; however, temporal aspects of involvement of higher brain functions are not clear. The temporal dynamics of brain activity in relation to heart activity can be captured by heartbeat evoked potentials (HEP). The aim of this study is to investigate whether HEP amplitudes across the cardiac cycle could reflect brain activity which contribute to the regulation of the heart rate. We present a new method to analyse the human brain–heart interactions by contrasting EEG activity with respect to relative duration of EKG R-R intervals. Healthy participants were asked to sit still and fixate their gaze on the computer screen while EEG and EKG were recorded. EKG R peaks were identified and used for splitting EEG data into epochs. All epochs were classified into two groups depending on the difference between adjacent R-R intervals (RRI), i.e., whether the epoch-related RRI was longer (shorter) than the subsequent RRI. HEPs associated with prolongation vs. shortening of RRI were compared by the permutation test. HEP amplitudes in the middle of diastole were more positive at centro-parietal scalp sites before prolongation of RRI (i.e., before deceleration of the heart rate) compared to amplitudes before shortening of RRI (i.e., before acceleration of the heart rate). We show that the method of contrasting HEPs allows capturing brain activity, which contributes to the postponement of the subsequent heartbeat.

In vivo Dominant-Negative Effect of an SCN5A Brugada Syndrome Variant.

Loss-of-function mutations in the cardiac Na+ channel α-subunit Nav1.5, encoded by SCN5A, cause Brugada syndrome (BrS), a hereditary disease characterized by sudden cardiac death due to ventricular fibrillation. We previously evidenced in vitro the dominant-negative effect of the BrS Nav1.5-R104W variant, inducing retention of wild-type (WT) channels and leading to a drastic reduction of the resulting Na+ current (INa). To explore this dominant-negative effect in vivo, we created a murine model using adeno-associated viruses (AAVs).MethodsDue to the large size of SCN5A, a dual AAV vector strategy was used combining viral DNA recombination and trans-splicing. Mice were injected with two AAV serotypes capsid 9: one packaging the cardiac specific troponin-T promoter, the 5′ half of hSCN5A cDNA, a splicing donor site and a recombinogenic sequence; and another packaging the complementary recombinogenic sequence, a splicing acceptor site, the 3′ half of hSCN5A cDNA fused to the gfp gene sequence, and the SV40 polyA signal. Eight weeks after AAV systemic injection in wild-type (WT) mice, echocardiography and ECG were recorded and mice were sacrificed. The full-length hSCN5A-gfp expression was assessed by western blot and immunohistochemistry in transduced heart tissues and the Na+ current was recorded by the patch-clamp technique in isolated adult GFP-expressing heart cells.ResultsAlmost 75% of the cardiomyocytes were transduced in hearts of mice injected with hNav1.5 and ∼30% in hNav1.5-R104W overexpressing tissues. In ventricular mice cardiomyocytes expressing R104W mutant channels, the endogenous INa was significantly decreased. Moreover, overexpression of R104W channels in normal hearts led to a decrease of total Nav1.5 expression. The R104W mutant also induced a slight dilatation of mice left ventricles and a prolongation of RR interval and P-wave duration in transduced mice. Altogether, our results demonstrated an in vivo dominant-negative effect of defective R104W channels on endogenous ones.ConclusionUsing a trans-splicing and viral DNA recombination strategy to overexpress the Na+ channel in mouse hearts allowed us to demonstrate in vivo the dominant-negative effect of a BrS variant identified in the N-terminus of Nav1.5.

Tamarindus indica. Linn leaves ameliorates experimental induced heart failure in Wistar rats

Cardiovascular diseases (CVDs) are highly prevalent in various countries, and heart failure accounts for the majority of deaths. The present study focuses on determining the protective effect of ethanol extract of leaves of Tamarindus indica (TIEE) by in vitro and in vivo methods. In vitro cardiotonic activity was determined using Langendorff's heart perfusion assembly. In vivo studies were performed using Doxorubicin (1.5mg/kg, i.p for sevendays) induced cardiotoxicity in rats. These animals were simultaneously treated with the TIEE at a low dose (200mg/kg, p.o), high dose (400mg/kg, p.o) and standard drug Digoxin (100μg/kg, p.o) for sevendays. At the end of the study, various parameters like electrocardiogram (ECG) recording, serum levels of serum glutamic pyruvic transaminase (SGPT), lactate dehydrogenase (LDH), creatinine phosphokinase (CPK), and presence of cardiac troponin (cTnI) were determined. Isolated hearts were subjected to histopathological studies. The TIEE at a concentration of 60μg/mL showed a significant cardiotonic effect in vitro that was evident by increased force of contraction, heart rate, and cardiac output. In vivo studies revealed that the TIEE decreased the prolongation of QT and RR interval of ECG, lowered the serum enzyme levels like LDH, CPK indicating cardiac protection, and the same was established by the absence of cTnI in blood. Histopathological examinations of heart tissue sections showed improved architecture in the treatment groups when compared with diseased groups. The study revealed the cardioprotective activity of T.indica leaf extract by both in vitro and in vivo methods.

Menthol exposure induces reversible cardiac depression and reduces lipid peroxidation in the heart tissue of tambaqui Colossoma macropomum

Exposure to menthol is expected to alleviate physiological and oxidative stress in fish. Yet, its effects as an anesthetic-like compound on the heart function and associated physiological and biochemical changes still need further clarification. This study aimed to analyze the effects of menthol on the cardiac function and oxidative stress responses of Colossoma macropomum exposed to short-term baths. Fish were divided into three groups: control, menthol-exposed fish (40, 60 and 80 mg L−1) and fish in recovery. The electrocardiogram (ECG) tracing patterns, wave intervals (RR; QT), complex duration (QRS) and heart rate were assessed after 5 min recordings throughout exposure and recovery. Total antioxidant capacity against peroxyl radicals (ACAP), glutathione S-transferase (GST) activity and lipoperoxidation (LPO) levels were also evaluated in the heart tissue. All concentrations of menthol depressed the heart rate and prolonged RR and QT intervals in a concentration-dependent fashion. QRS complex duration was only reduced at the highest dose of menthol. During recovery, heart rate and mean amplitude were still reduced at 60 or 80 mg L−1 menthol, whereas wave intervals were still longer at these concentrations. Notwithstanding, QRS complex resumed its normal duration during recovery. GST activity and ACAP were unchanged in fish exposed to menthol. However, LPO reduced in fish exposed to 40 and 60 mg L−1 menthol. In conclusion, all concentrations of menthol induced anesthesia in C. macropomum without causing mortality, albeit provoking transient cardiac alterations. Menthol at 40 and 60 mg L−1 could be considered suitable concentrations to immobilize fish as they not only did not compromise cardiac function but reduced LPO in the heart. Yet, menthol at 80 mg L−1 or higher doses should be avoided as there is a potential for the emergence of a life-threatening cardiac depression and oxidative stress.

Changes in Heart Rate Variability and Baroreflex Sensitivity During Daytime Naps.

Background and ObjectivesChanges in autonomic cardiac activity during night sleep are well documented. However, there is limited information regarding changes in the autonomic cardiac profile during daytime naps. Heart rate variability (HRV) and baroreflex sensitivity (BRS) are reliable measures of autonomic cardiac activity. The purpose of this study was to determine the changes in HRV and BRS during daytime naps in healthy men.MethodsThis was a cross-sectional study of 25 healthy men. Polysomnographic recording with electrocardiogram monitoring was conducted for all volunteers during a 50–80 min nap between 3.30 pm and 5.30 pm. Five-minute segments during pre-nap wakefulness, non-rapid eye movement (NREM) sleep stages (N1, N2, and N3), rapid eye movement (REM) sleep stage, and post-nap wakefulness were used to measure changes in the variation in HRV parameters, including inter-beat interval (RR-interval), total spectral power (TP), high-frequency power (HF), low-frequency power (LF), and low frequency/high-frequency ratio (LF/HF). BRS was also measured for 10 min during pre- and post-nap wakefulness using finger arterial pressure measurement (Finometer Pro ®).ResultsHRV increased significantly during NREM sleep compared with that during pre-nap wakefulness (p < 0.05), as reflected by RR-interval prolongation, higher HF, and increased HFnu (normalized units). Furthermore, there was a parallel reduction in TP, LF, and LF/HF ratio during NREM sleep, indicating parasympathetic predominance over cardiac autonomic activity. HF and HFnu were significantly reduced during REM sleep compared with that during NREM sleep (p < 0.05). BRS did not show significant differences between pre- and post-nap wakefulness.ConclusionWe observed a progressive increase in parasympathetic activity during daytime sleep as NREM sleep deepened compared with that during wakefulness and REM sleep. Daytime nap may have a favorable cardiovascular impact.

Cardioprotective effect of thymol against adrenaline-induced myocardial injury in rats

Cardiovascular disease represents a vital global disease burden. This study aims to assess the possible cardioprotective effect of thymol against adrenaline-induced myocardial injury (MI) in rats. Furthermore the effect of thymol on cardiac function biomarkers, electrocardiogram (ECG) alterations, oxidative stress, inflammation, apoptosis and histopathological changes was assessed. MI was induced by adrenaline (2 mg/kg, s.c.) injected as a single dose for 2 consecutive days (24 h apart). Normal and control groups received the vehicle for 21 consecutive days. The other 3 groups were orally administered thymol (15, 30, 60 mg/kg) for 21 consecutive days and on day 22, adrenaline was injected as a single dose for 2 consecutive days. Then ECG examination, biochemical, histopathological, immunohistochemical analyses were carried out. Thymol reversed adrenaline-induced reduction of heart rate, prolongation of RR interval and elevation of ST interval. Thymol pretreatment significantly reduced serum aspartate dehydrogenase (AST), lactate dehydrogenase (LDH), and creatine kinase (CK) levels in MI rats. Oral pretreatment with thymol increased reduced glutathione (GSH), reduced malondialdehyde (MDA), nuclear factor-kappa B (NF-κB), and interleukin-1β (IL-1β) cardiac contents in MI rats. Additionally, thymol administration significantly decreased protein expression of caspase-3, increased Bcl-2 protein expression in cardiac tissue and ameliorated histopathological changes. This study reveals that thymol exerted cardioprotective effect against adrenaline-induced MI in rats evidenced by improving cardiac function, attenuating ECG and histopathological changes which may be partly mediated through its anti-oxidant, anti-inflammatory and anti-apoptotic effect.

Protective effects of Gαq‐RGS2 signalling inhibitor in aminophylline induced cardiac arrhythmia

An over activation of GPCR mediated Gαq dependent signalling pathway is widely associated with the development of cardiovascular abnormalities. The objective of study was to evaluate the effects of (1-(5-chloro-2-hydroxyphenyl)-3-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol-5(4H)-one) Gαq-RGS2 signalling inhibitor on aminophylline induced cardiac arrhythmia in rats. Rats were divided into four groups; normal rats, disease control (DC, aminophylline treated 100mg/kg/d, i.p., 7days), Gαq-RGS2 signalling inhibitor (1 and 10mg/kg/d, p.o., 7days) treated arrhythmic rats. Gαq-RGS2 signalling inhibitor was administered 1hour prior to the administration of aminophylline from 1st day. At the end of study, heart rate (HR), QRS complex, QT and RR interval were measured by electrocardiogram (ECG) of anesthetized rats. Systolic and diastolic blood pressure (SBP, DBP) by invasive method, cardiac damage markers (CK-MB, LDH) in the serum, antioxidant enzymes (SOD, catalase, glutathione) and cAMP level were measured. The treatment of Gαq-RGS2 signalling inhibitor (10mg/kg) significantly abolished the aminophylline induced increase of heart rate, prolongation of RR and QT interval as compared to DC rats. Gαq-RGS2 signalling inhibitor (1 and 10mg/kg) significantly attenuated the prolongation in QRS complex, increase of SBP, DBP and cardiac damage markers as compared to DC. Gαq-RGS2 signalling inhibitor treatment (10mg/kg) significantly reduced the cAMP level and increased the antioxidant enzyme level as compared to DC. Gαq-RGS2 signalling inhibitor (10mg/kg) showed the protective effect against the aminophylline induced cardiac arrhythmia and it might be due to improvement in cAMP level and antioxidant enzymes.

Amiodarone Treatment in the Early Phase of Acute Myocardial Infarction Protects Against Ventricular Fibrillation in a Porcine Model

Ventricular fibrillation (VF) occurring in the first minutes to hours of acute myocardial infarction (AMI) is a frequent cause of death and treatment options are limited. The aim was to test whether early infusion of amiodarone 10 min after onset of AMI reduced the incidence of VF in a porcine model. Eighteen female Danish landrace pigs were randomized to a control and an amiodarone group. AMI was induced by ligation of the mid-left anterior descending artery for 120 min followed by 60 min of reperfusion. VF occurred in 0/8 pigs treated with amiodarone compared to 7/10 controls (P < 0.01). Amiodarone treatment prolonged RR intervals, reduced dispersion of action potential duration in the infarcted area and mean number of ectopic beats. No negative effects on cardiac output and blood pressure were observed with amiodarone. Amiodarone qualifies as a potential drug candidate to prevent VF in the first minutes to hours of AMI.