Chronic Diclofenac Exposure Increases Mitochondrial Oxidative Stress, Inflammatory Mediators, and Cardiac Dysfunction

Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) are among one of the most commonly prescribed medications for pain and inflammation. Diclofenac (DIC) is a commonly prescribed NSAID that is known to increase the risk of cardiovascular diseases. However, the mechanisms underlying its cardiotoxic effects remain largely unknown. In this study, we tested the hypothesis that chronic exposure to DIC increases oxidative stress, which ultimately impairs cardiovascular function. Methods and Results Mice were treated with DIC for 4 weeks and subsequently subjected to in vivo and in vitro functional assessments. Chronic DIC exposure resulted in not only systolic but also diastolic dysfunction. DIC treatment, however, did not alter blood pressure or electrocardiographic recordings. Importantly, treatment with DIC significantly increased inflammatory cytokines and chemokines as well as cardiac fibroblast activation and proliferation. There was increased reactive oxygen species (ROS) production in cardiomyocytes from DIC-treated mice, which may contribute to the more depolarized mitochondrial membrane potential and reduced energy production, leading to a significant decrease in sarcoplasmic reticulum (SR) Ca2+ load, Ca2+ transients, and sarcomere shortening. Using unbiased metabolomic analyses, we demonstrated significant alterations in oxylipin profiles towards inflammatory features in chronic DIC treatment. Conclusions Together, chronic treatment with DIC resulted in severe cardiotoxicity, which was mediated, in part, by an increase in mitochondrial oxidative stress.

Electrocardiographic Interpretations of Cardiac Disorders in Dogs

Background: Cardiac disorders are the second most common disorders after cancer in dogs. Cardiac disorders are often fatal and/or silent killers in canines. In our country, in the majority of cardiovascular disorders, there is a frequent omission by clinician and client due to lack of awareness. However, any cardiac abnormality requires to be dealt with top priority to avoid morbidity and mortality in the dog population. The present study was aimed to know the electrocardiographic interpretations of cardiac disorders in dogs. Methods: For this purpose, a total of 5110 dogs presented at Veterinary Clinical Complex, College of Veterinary Science and Animal Husbandry, Nanaji Deshmukh Veterinary Science University, Jabalpur, Madhya Pradesh, from November 2019 to June 2020 were screened. Among them, 137 dogs had clinical signs about cardiac disorders were subjected to thorough electrocardiographic recordings for interpretations of various cardiac conduction anomalies. Result: Electrocardiography revealed various types of supraventricular and ventricular abnormalities. Among supraventricular disorders maximally wandering pacemaker (30.60%) was recorded followed by atrial fibrillation (22.58%), left atrial enlargement (8.06%) and sinus arrest (4.84%) in dogs. Among ventricular abnormalities; left ventricular enlargement, right ventricular enlargement and biventricular enlargement (i.e. 41.67%, 37.49% and 8.33%, respectively) were commonly diagnosed.

Hyperinsulinaemic hypoglycaemia in non-anaesthetized Göttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes

The potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8–1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.

Internal Macroscopic Anatomy and Electrical Evaluation of the Bradypus variegatus Heart

Background: The Bradypus variegatus species presents peculiar anatomophysiological properties and many aspects of its organic systems still need to be clarified, especially regarding the cardiovascular system, given its participation in vital activities. Disorderly anthropic action has had drastic consequences in sloth populations and the need to treat sick and injured animals is increasingly common. To this end, the importance of knowing its characteristics is emphasized. Therefore, this study proposed to describe the internal macroscopic structures of the sloth's heart, as well as to measure the ventricular walls and indicate the electrical activity of the organ.Materials, Methods and Results: For the dissections, 15 Bradypus variegatus cadavers were used (1 young female, 9 adults females and 5 adult males) belonging to the Área de Anatomia of the Departamento de Morfologia e Fisiologia Animal (DMFA), Universidade Federal Rural de Pernambuco (UFRPE), Recide, PE, Brazil. After they were fixed and preserved, the specimens received a midsagittal incision in the chest, followed by soft tissue folding and removal of ribs to access the heart. The organ was derived from the cavity and sectioned sagittal medially to identify its internal anatomy. Ventricular walls and interventricular septum were measured with a steel caliper (150 mm / 0.02 mm). An electrocardiogram was performed to determine the electrical profile on 5 healthy B. variegatus sloths, living under semi-livestock conditions at the Recife Zoo, PE, Brazil. The electrodes were taken from the regions, scapular and glutes of the animals that were called hugging a keeper during the procedure, carried out in the Zoo itself, using a portable device. Based on the data obtained, sloths have cardiac chambers separated by septa, however between atria and ventricles, in both antimeres, there are atrioventricular ostia, where valves are found, consisting of 3 valves on the right and 2 on the left. The atria are practically smooth inside and have their cavity enlarged by the atria, the right being larger than the left, these having a greater amount of pectineal muscles in relation to the atria. The ventricles have trabeculae and papillary muscles, 3 on the right and 2 on the left. These muscles hold the tendinous chords that connect the valves. The existence of trabeculae marginal septum was not evidenced. The thickness of the wall of the left ventricle, as well as that of the interventricular septum, proved to be greater than the thickness of the wall of the right ventricle, regardless of the age or sex of the animals. Based on the electrocardiographic recordings, the sloths presented sinus rhythm, with a heart rate between 67 and 100 bpm. The electrical axis ranged from -60º to -90º. The P wave is smoother than the QRS complex. While the S-T segment was classified as isoelectric. The T wave was shown to be + and predominantly > or = at 25% of the S wave, which characterized an rS type QRS deflection in both females and males.Discussion: The general characteristics of the cardiac chambers in sloths are similar to those observed in other domestic and wild mammals. However, the presence of pectineal muscles associated with the atria and auricles differs from that observed in mammals such as the paca and raccoon and in birds such as the ostrich, which have trabecular structures in these cavities. The number of valves in sloths is equal to the anteater. However, it has a marginal trabeculae septum, not seen in Bradypus variegatus. According to the electrocardiographic findings, the rhythm was sinus, but much lower than that observed in the capuchin monkey, which also maintains arboreal habits. Keywords: Xenarthra, common sloth, internal anatomy, heart, electrocardiogram.Descritores: Xenarthra, preguiça-comum, anatomia interna, coração, eletrocardiograma.

A Pilot Study of the Reliability and Agreement of Heart Rate, Respiratory Rate and Short-Term Heart Rate Variability in Elite Modern Pentathlon Athletes

Research on reliability of heart rate variability (HRV) parameters in athletes has received increasing attention. The aims of this study were to examine the inter-day reliability of short-term (5 min) and ultra-short-term (1 min) heart rate (HR), respiratory rate (RespRate) and HRV parameters, agreement between short-term and ultra-short-term parameters, and association between differences in HR, RespRate and HRV parameters in elite modern pentathletes. Electrocardiographic recordings were performed in stable measurement conditions with a week interval between tests. Relative reliability was evaluated by intra-class correlation coefficients, absolute reliability was evaluated by within-subject coefficient of variation, and agreement was evaluated using Bland–Altman (BA) plot with limits of agreement and defined a priori maximum acceptable difference. Short-term HR, RespRate, log transformed (ln) root mean square of successive normal-to-normal interval differences (lnRMSSD), ln high frequency (lnHF) and SD2/SD1 HRV indices and ultra-short-term HR, RespRate and lnRMSSD presented acceptable, satisfactory inter-day reliability. Although there were no significant differences between short-term and ultra-short-term HR, RespRate and lnRMSSD, no parameter showed acceptable differences with BA plots. Differences in time-domain and non-linear HRV parameters were more correlated with differences in HR than with differences in RespRate. Inverse results were observed for frequency-domain parameters. Short-term HR, RespRate, lnRMSSD, lnHF, and SD2/SD1 and ultra-short-term HR, RespRate and lnRMSSD could be used as reliable parameters in endurance athletes. However, practitioners should interpret changes in HRV parameters with regard to concomitant differences in HR and RespRate and caution should be taken before considering 5 min and 1 min parameters as interchangeable.

Rhythm dynamics of the aging heart: an experimental study using conscious, restrained mice

We have investigated age-associated alterations of heart rate properties in mice using conscious electrocardiographic recordings. Our findings support the notion that aging is coupled with altered sympathovagal balance with consequences on heart rate variability. Moreover, by using a genetically engineered mouse line, we provide evidence that sodium channels modulate heart rate and its age-related adaptations.

Electrocardiographic abnormalities with quinine and artesunate combinations in comparison to quinine or artesunate alone in severe falciparum malaria

Background: In Multi drug resistant falciparum malaria anti-malarial combinations are frequently used i.e. Quinine and IV Artesunate. Quinine is associated with electrocardiographic disturbances. Artesunate in high dose produce QTC prolongation in animal models, so the electrocardiogram (ECG) is thoroughly studied.Methods: Severe falciparum malaria cases 15 to 60 years were randomly allocated into 3 treatment regimens i.e. Artesunate, Quinine alone and their combination. Electrocardiographic recordings were taken periodically in 3 groups and compared statistically.Results: The mean QTC interval is significantly prolonged in combination treatment group from 0.40+0.02 to 0.49+0.09 (P<0.05) ECG disturbance (44%). QTC prolongation was commonest (i.e. 27%) with electrolyte imbalance could produce life threatening cardiac arrhythmia (Polymorphic VT with Sr K+ 2.9). Artesunate alone was list prone (i.e. only 6%) Quinine though has comparatively more (i.e. 25%) but there is no life-threatening cardiac arrhythmia in artesunate and Quinine.

The effects of breed, age, sex, and body weight on electrocardiographic parameters in military working dogs

Aim: This study aimed to investigate the effects of breed, sex, age, and body weight on different electrocardiographic parameters in military working dogs (Labrador Retriever and German Shepherd). Materials and Methods: Electrocardiographic recordings (paper speed = 25 mm/s and calibration = 10 mm/mV) were performed to obtain all the standard bipolar limb leads (leads I, II, and III) and unipolar augmented limb leads (leads aVR, aVL, and aVF). A total of 16 Labrador Retrievers and 14 German Shepherds were restrained manually in the right lateral recumbency without any tranquilizer or anesthetic drug. Amplitude and duration of P, QRS, and T wave, PR and QT interval, mean electrical axis, and heart rate were measured in each recording. Results: There was no significant difference in electrocardiographic parameters across breed and sex. However, QRS duration tended to alter by breed (p<0.1) in Labrador Retrievers (0.04±0.005 s), which is lower than German Shepherds (0.05±0.005 s). PR interval was influenced by sex (p<0.1). PR interval was higher in females (0.13±0.005 s) than males (0.11±0.008 s). In addition, electrocardiographic values were not significantly affected by age and body weight, except that the amplitude of R wave was statistically affected by age (p<0.05). A correlation was found between the decrease in R wave amplitude and increase in age of dogs. Conclusion: Different electrocardiographic parameters were within the normal range. A significant effect of age was seen on amplitude of R wave. However, the effect of breed, sex, and body weight was not significant on different electrocardiographic parameters in Labrador Retriever and German Shepherd dogs.