Heart Weight Research Articles

Effect of Stanozolol and/or Cannabis Abuse on Hypertrophic Mechanism and Oxidative Stress of Male Albino Rat Cardiac Tissue in Relation to Exercise: A Sport Abuse Practice.

Adolescents commonly co-abuse many drugs including anabolic androgenic steroids either they are athletes or non-athletes. Stanozolol is the major anabolic used in recent years and was reported grouped with cannabis. The current study aimed at evaluating the biochemical and histopathological changes related to the hypertrophic effects of stanozolol and/or cannabis whether in condition of exercise practice or sedentary conditions. Adult male Wistar albino rats received either stanozolol (5mg/kg, s.c), cannabis (10mg/kg, i.p.), and a combination of both once daily for two months. Swimming exercise protocol was applied as a training model. Relative heart weight, oxidative stress biomarkers, cardiac tissue fibrotic markers were evaluated. Left ventricular morphometric analysis and collagen quantification was done. The combined treatment exhibited serious detrimental effects on the heart tissues. It increased heart tissue fibrotic markers (Masson's trichrome stain (p < 0.001), cardiac COL3 (p < 0.0001), and VEGF-A (p < 0.05)), lowered heart glutathione levels (p < 0.05) and dramatically elevated oxidative stress (increased malondialdehyde (p < 0.0001) and 8-OHDG (p < 0.0001)). Training was not ameliorating for the observed effects. Misuse of cannabis and stanozolol resulted in more hypertrophic consequences of the heart than either drug alone, which were at least largely assigned to oxidative stress, heart tissue fibrotic indicators, histological alterations, and morphometric changes.

Association of epicardial adipose tissue volume with heart weight in post-mortem cases.

Epicardial adipose tissue (EAT) deposition has been long associated with heart weight. However, recent research has failed to replicate this association. We aimed to determine the association of EAT volume with heart weight in post-mortem cases and identify potential confounding variables. EAT volume derived from post-mortem computed tomography (PMCT) and heart weight were measured in post-mortem cases (N = 87, age: 56 ± 16years, 28% female). Cases with hypertrophied heart weights (N = 44) were determined from reference tables. Univariable associations were tested using Spearman correlation and simple linear regression. Independence was determined with stepwise regression. In the total cohort, EAT volume (median 66 ± 45 cm3) was positively associated with heart weight (median 435 ± 132g) at the univariable level (r = 0.6, P < 0.0001) and after adjustment for age, female sex, and various body size metrics (R2 adjusted = 0.41-0.57). Median EAT volume was 1.9-fold greater in cases with hypertrophic hearts (P < 0.0001) but with considerably greater variability, especially in cases with extreme EAT volume or heart weight. As such, EAT volume was not associated with heart weight in hypertrophic cases, while a robust independent association was found in non-hypertrophic cases (R2 adjusted = 0.62-0.86). EAT mass estimated from EAT volume found that EAT comprised approximately 13% of overall heart mass in the total cases. This was significantly greater in cases with hypertrophy (median 15.5%; range, 3.6-36.6%) relative to non-hypertrophied cases (12.5%, 3.3-24.3%) (P = 0.04). EAT volume is independently and positively associated with heart weight in post-mortem cases. Excessive heart weight significantly confounded this association.

Withaferin A as a Potential Therapeutic Target for the Treatment of Angiotensin II-Induced Cardiac Cachexia.

In our previous studies, we showed that the generation of ovarian tumors in NSG mice (immune-compromised) resulted in the induction of muscle and cardiac cachexia, and treatment with withaferin A (WFA; a steroidal lactone) attenuated both muscle and cardiac cachexia. However, our studies could not address if these restorations by WFA were mediated by its anti-tumorigenic properties that might, in turn, reduce the tumor burden or WFA's direct, inherent anti-cachectic properties. To address this important issue, in our present study, we used a cachectic model induced by the continuous infusion of Ang II by implanting osmotic pumps in immunocompetent C57BL/6 mice. The continuous infusion of Ang II resulted in the loss of the normal functions of the left ventricle (LV) (both systolic and diastolic), including a significant reduction in fractional shortening, an increase in heart weight and LV wall thickness, and the development of cardiac hypertrophy. The infusion of Ang II also resulted in the development of cardiac fibrosis, and significant increases in the expression levels of genes (ANP, BNP, and MHCβ) associated with cardiac hypertrophy and the chemical staining of the collagen abundance as an indication of fibrosis. In addition, Ang II caused a significant increase in expression levels of inflammatory cytokines (IL-6, IL-17, MIP-2, and IFNγ), NLRP3 inflammasomes, AT1 receptor, and a decrease in AT2 receptor. Treatment with WFA rescued the LV functions and heart hypertrophy and fibrosis. Our results demonstrated, for the first time, that, while WFA has anti-tumorigenic properties, it also ameliorates the cardiac dysfunction induced by Ang II, suggesting that it could be an anticachectic agent that induces direct effects on cardiac muscles.

Rho kinase inhibitor Y-27632 downregulates IL-1β expression in mice with experimental autoimmune myocarditis

Autoimmune myocarditis is the limited or diffuse inflammation of the myocardium due to dysfunctional cellular and humoral immunity mechanisms. We constructed mouse models of experimental autoimmune myocarditis (EAM) using peptide MyHC-α614-629. On the day after secondary immunization, the mice were intraperitoneally injected with Rho kinase (ROCK) inhibitor Y-27632. On day 21, the cardiac tissues were harvested and weighed. The hearts of EAM mice were significantly enlarged and whitened. Furthermore, body weight (BW) slowly increased during the treatment period, the heart weight (HW) and the ratio of HW/eventual BW were increased, and inflammatory infiltration and fibrosis were aggravated in the myocardial tissue. Y-27632 treatment improved the aforementioned phenotypic and pathological features of EAM mice. Mechanistic analysis revealed a significant increase in Notch1, Hes1, Jag2, Dil1, Toll-like receptor (Tlr) 2, and interleukin (IL)-1β expression in the myocardial tissue of EAM mice. Notably, IL-1β expression was correlated with that of Notch1 and Tlr2. Following Y-27632 treatment, the expression of key target genes of the Notch signaling pathway (Notch1, Hes1, Dil1, and Jag2) and Tlr2 were obviously decreased. Y-27632 treatment also decreased the number of monocytes in the spleen of EAM mice. Thus, ROCK inhibitor Y-27632 exerted a protective effect in EAM mice by downregulating IL-1β expression. This study aimed to provide a reference point for the future treatment of myocarditis in clinical settings.

Genome-wide association analyses reveal genotype-by-environment interactions of growth and organ weights in gilthead seabream (Sparus aurata)

Gilthead seabream is one of the most important fish species for Mediterranean aquaculture. More than 80% of the genetically improved fingerlings of this species originate from a single country, Greece. A previous study revealed moderate genotype-by-environment (G x E) interactions for growth traits and organ weights between commercial production sites in Greece and Spain. The main objectives of this study were to identify QTLs and genes associated with growth traits and organ weights in gilthead seabream and to identify the biological processes and pathways controlling these traits under different temperature environments. For growth traits, we found fourteen genome-wide suggestive SNP effects in Spain. A strong peak between 1.97 Mb to 4.69 Mb on chromosome (chr) 22 was shared among three growth traits (harvest weight, fillet weight and thermal growth coefficient). Fourteen genome-wide suggestive SNP effects were also identified in Greece. However, none overlap with those found in Spain. Two SNPs on chr5 (chr5:5729959, chr5:2336903) and two SNPs on chr6 (chr6:1957732, chr6:3659811) were associated with all three growth traits. For organ weights, a total of 15 SNPs were associated above the suggestive threshold in Spain. Four SNPs (chr22:1966940, chr22:6094383, chr22:67838, chr15:16798259) are shared between viscera weight and liver weight, while one SNP (chr22:67838) is shared among viscera, liver and heart weight. Interestingly, three of these four SNPs (chr22:1966940, chr22:67838, and chr15:16798259) also overlap with significant SNPs associated with growth traits. None of the SNPs associated with viscera weight, liver weight and heart weight are shared with Greece. GO and KEGG functional enrichment analyses showed that light absorption and ECM-receptor interaction are significantly enriched with growth traits QTLs in Spain but not in Greece. For organ weights, response to stimulus is the most prominent process in Spain, while cell adhesion, and regulation of phosphorylation are more prominent in Greece. Genomic architectures for growth traits and organ weights differ between environments. These findings not only explain part of the G x E interactions, but also give insight into how genetics determines differences in how environmental conditions affect growth and organ weights.

Effects of Inclusion of Gongronema Latifolium Leaf Extract as a Supplementary Source of Vitamins and Minerals on the Growth Performance and Haematology of Broiler Finishers

The present study was conducted to determine the effects of Gongronema latifolium leaves extract (GLLE) as a supplementary source of vitamins and minerals on growth performance and haematology of broiler finishers. A total of 20 four (4) weeks old broilers were randomly selected and assigned to five treatment groups, namely water (control), water+ vitalyte, water+ 60ml GLLE, water+ 30ml GLLE and water+ 10mIGLLE. Results showed that there were significant (P&lt;0.05) differences in weight gain but there were no significant differences (P&gt;0.05) in Hb, PCV and RBC. The relative weights of gizzard, heart and liver of the broilers fed extract (except 30ml extract) were significantly (P&lt;0.05) reduced compared with the broilers fed vitalyte. The group fed 30ml extract had the highest weight in gizzard. 30ml GLLE enhanced the growth performance of broilers without any adverse effect on their blood. GLLE can serve as a substitute to the commercially synthetic vitamins and minerals premixes in feeding poultry.

Effects of Dietary Incorporation of Neem (Azadirachta indica), Moringa (Moringa oleifera), and Jute (Corchorus olitorius) Leaf Powder on Production Performance and Blood Indices of Broiler Chickens as a Substitute of Antibiotic

The study was planned to determine the effects of dietary incorporation of Neem (Azadirachta indica), Moringa (Moringa oleifera), and Jute (Corchorus olitorius) leaf powder on production performance, carcass traits, and blood indices of broiler chickens as a substitute for the antibiotic. A total of 200-day-old Cobb 500 broiler chicks were divided randomly into 5 experimental groups. Whereas groups T1, T2, T3, and T4 were offered basal feed supplemented with 2% Neem Leaf Powder (NLP), 2% Moringa Leaf Powder (MLP), 2% Jute Leaf Powder (JLP), and antibiotics, respectively. In this research, the total feed consumption of birds was significantly (P &lt; 0.05) lower in the T1 and T2 group than in the T3 and T4 group. Final live weight was significantly (P &lt; 0.05) higher in 2% MLP treated group T2 followed by T1, T3, and T0 group. Significantly (P &lt; 0.05) better feed conversion ratio (FCR) was found in the T2 group compared to T0, T3, and T4 groups. There found no significant (P &gt; 0.05) effect of treatments on the survivability percentage of birds. All the treatment groups showed an insignificant (P &gt; 0.05) effect on dressing percentage and organs (liver, heart, and gizzard) weight of broiler chicken. Weight of immune organs (spleen and bursa) and blood parameters (concentration of hemoglobin, glucose, and cholesterol) were not influenced (P &gt; 0.05) by dietary addition. Birds fed the lower amount of feed, higher body weight, and improved FCR were found in the 2% MLP treated group. In overall aspects, the effectiveness of 2% MLP addition was better than 2% NLP and 2% JLP as an antibiotic alternative.

Calorie restriction anti-hypertrophic effects are associated with improved mitochondrial content, blockage of Ca2+-induced mitochondrial damage, and lower reverse electron transport-mediated oxidative stress

Calorie restriction is a nutritional intervention that reproducibly protects against the maladaptive consequences of cardiovascular diseases. Pathological cardiac hypertrophy leads to cellular growth, dysfunction (with mitochondrial dysregulation), and oxidative stress. The mechanisms behind the cardiovascular protective effects of calorie restriction are still under investigation. In this study, we show that this dietetic intervention prevents cardiac protein elevation, avoids fetal gene reprogramming (atrial natriuretic peptide), and blocks the increase in heart weight per tibia length index (HW/TL) seen in isoproterenol-induced cardiac hypertrophy. Our findings suggest that calorie restriction inhibits cardiac pathological growth while also lowering mitochondrial reverse electron transport-induced hydrogen peroxide formation and improving mitochondrial content. Calorie restriction also attenuated the opening of the Ca2+-induced mitochondrial permeability transition pore. We also found that calorie restriction blocked the negative correlation of antioxidant enzymes (superoxide dimutase and glutatione peroxidase activity) and HW/TL, leading to the maintenance of protein sulphydryls and glutathione levels. Given the nature of isoproterenol-induced cardiac hypertrophy, we investigated whether calorie restriction could alter cardiac beta-adrenergic sensitivity. Using isolated rat hearts in a Langendorff system, we found that calorie restricted hearts have preserved beta-adrenergic signaling. In contrast, hypertrophic hearts (treated for seven days with isoproterenol) were insensitive to beta-adrenergic activation using isoproterenol (50 nM). Despite protecting against cardiac hypertrophy, calorie restriction did not alter the lack of responsiveness to isoproterenol in isolated hearts harvested from isoproterenol-treated rats. These results suggest (through a series of mitochondrial, oxidative stress, and cardiac hemodynamic studies) that calorie restriction possesses beneficial effects against hypertrophic cardiomyopathy.

Partial Resistance to Thyroid Hormone-Induced Tachycardia and Cardiac Hypertrophy in Mice Lacking Thyroid Hormone Receptor β.

Background: Thyroid hormones regulate cardiac functions mainly through direct actions in the heart and by binding to the thyroid hormone receptor (TR) isoforms α1 and β. While the role of the most abundantly expressed isoform, TRα1, is widely studied and well characterized, the role of TRβ in regulating heart functions is still poorly understood, primarily due to the accompanying elevation of circulating thyroid hormone in TRβ knockout mice (TRβ-KO). However, their hyperthyroidism is ameliorated at thermoneutrality, which allows studying the role of TRβ without this confounding factor. Methods: Here, we noninvasively monitored heart rate in TRβ-KO mice over several days using radiotelemetry at different housing temperatures (22°C and 30°C) and upon 3,3',5-triiodothyronine (T3) administration in comparison to wild-type animals. Results: TRβ-KO mice displayed normal average heart rate at both 22°C and 30°C with only minor changes in heart rate frequency distribution, which was confirmed by independent electrocardiogram recordings in freely-moving conscious mice. Parasympathetic nerve activity was, however, impaired in TRβ-KO mice at 22°C, and only partly rescued at 30°C. As expected, oral treatment with pharmacological doses of T3 at 30°C led to tachycardia in wild-types, accompanied by broader heart rate frequency distribution and increased heart weight. The TRβ-KO mice, in contrast, showed blunted tachycardia, as well as resistance to changes in heart rate frequency distribution and heart weight. At the molecular level, these observations were paralleled by a blunted cardiac mRNA induction of several important genes, including the pacemaker channels Hcn2 and Hcn4, as well as Kcna7. Conclusions: The phenotyping of TRβ-KO mice conducted at thermoneutrality allows novel insights on the role of TRβ in cardiac functions in the absence of the usual confounding hyperthyroidism. Even though TRβ is expressed at lower levels than TRα1 in the heart, our findings demonstrate an important role for this isoform in the cardiac response to thyroid hormones.

Nutritional reference values using the DRIS method and sample size for peach palm production

ABSTRACT One of the challenges in the peach palm production system is the interpretation of leaf analyses and the adaptation of fertilization recommendations. Tools that enhance fertilizer use efficiency are therefore needed. This study aimed to establish norms for evaluating the nutrient status of peach palms using the Diagnosis and Recommendation Integrated System (DRIS) and to determine the adequate number of palm heart samples necessary for a more accurate assessment of productivity. Production, leaf nutrient content, and soil fertility data were collected from 102 commercial stands of peach palm in the Ribeira Valley, state of São Paulo, Brazil, between 2015 and 2020. Adequate number of individual samples (palm hearts) to be collected per stand for productivity assessment was estimated. DRIS norms were established by dividing the database into high-yield (reference population) and low-yield subpopulations, using average productivity as a criterion. By assuming an acceptable error of 5 to 10 % for the assessment of peach palm productivity, taking into account total palm heart weight and/or the weight of cylinders, respectively, 16 plants per stand should be sampled. DRIS was not sensitive enough to diagnose differences in the probability of positive response to fertilization; however, the P, K, Ca, Mg, S, B, Fe, Cu, Mn and Zn contents were positively correlated with the respective nutrient indices.

Correction to: Prevalence of Abnormal Heart Weight After Sudden Death in People Younger than 40 Years of Age.

Correction to: Prevalence of Abnormal Heart Weight After Sudden Death in People Younger than 40 Years of Age.

The cardiothoracic ratio on postmortem CT as a screening tool for cardiomegaly in the Thai population.

IntroductionIn forensic radiology, the cardiothoracic ratio (CTR) calculated from postmortem computed tomography (PMCT) images can be used to detect cardiomegaly. In this study, a new measurement method is studied that involves measurement in the anteroposterior (AP) and transverse directions, with a reference level based on the Thai population. ObjectiveTo screen for cardiomegaly using the CTR calculated from PMCT images. Research methodA sample size of 116 deceased Thai individuals who underwent PMCT before autopsy was obtained. Individuals were divided into two groups: normal heart weight and overweight heart. Hearts heavier than the mean plus one standard deviation were categorized into the overweight group. The CTR was calculated in both the AP and transverse directions at six reference levels. Receiver operating characteristic curves (ROC) were calculated to determine the CTR cutoff point for the diagnosis of cardiomegaly. ResultsThe CTR cutoff values for diagnosing cardiomegaly were as follows: 1) CTR >0.5 in the transverse direction at the mid-vertebra of T7 (sensitivity, 75.6%; specificity, 70.6%; area under the ROC curve 0.81), 2) CTR >0.49 in the transverse direction at the mid-vertebra of T8 (sensitivity 71%, specificity 81.4%, area under the ROC curve 0.80). The selection of the cutoff values depended on the location of the heart. The area under the ROC curve in the AP direction was in the range 0.5-0.7, which is inferior compared to the transverse direction (0.7-0.9). ConclusionCalculating the CTR with a reference level on PMCT images can assist in the diagnosis of cardiomegaly.

β-Adrenergic signaling drives structural and functional maturation of mouse cardiomyocytes.

Cardiac maturation represents the last phase of heart development and is characterized by morphofunctional alterations that optimize the heart for efficient pumping. Its understanding provides important insights into cardiac regeneration therapies. Recent evidence implies that adrenergic signals are involved in the regulation of cardiac maturation, but the mechanistic underpinnings involved in this process are poorly understood. Herein, we explored the role of β-adrenergic receptor (β-AR) activation in determining structural and functional components of cardiomyocyte maturation. Temporal characterization of tyrosine hydroxylase and norepinephrine levels in the mouse heart revealed that sympathetic innervation develops during the first 3 wk of life, concurrent with the rise in β-AR expression. To assess the impact of adrenergic inhibition on maturation, we treated mice with propranolol, isolated cardiomyocytes, and evaluated morphofunctional parameters. Propranolol treatment reduced heart weight, cardiomyocyte size, and cellular shortening, while it increased the pool of mononucleated myocytes, resulting in impaired maturation. No changes in t-tubules were observed in cells from propranolol mice. To establish a causal link between β-AR signaling and cardiomyocyte maturation, mice were subjected to sympathectomy, followed or not by restoration with isoproterenol treatment. Cardiomyocytes from sympathectomyzed mice recapitulated the salient immaturity features of propranolol-treated mice, with the additional loss of t-tubules. Isoproterenol rescued the maturation deficits induced by sympathectomy, except for the t-tubule alterations. Our study identifies the β-AR stimuli as a maturation promoting signal and implies that this pathway can be modulated to improve cardiac regeneration therapies.NEW & NOTEWORTHY Maturation involves a series of morphofunctional alterations vital to heart development. Its regulatory mechanisms are only now being unveiled. Evidence implies that adrenergic signaling regulates cardiac maturation, but the mechanisms are poorly understood. To address this point, we blocked β-ARs or performed sympathectomy followed by rescue experiments with isoproterenol in neonatal mice. Our study identifies the β-AR stimuli as a maturation signal for cardiomyocytes and highlights the importance of this pathway in cardiac regeneration therapies.

In vivo tebuconazole administration impairs heart electrical function and facilitates the occurrence of dobutamine-induced arrhythmias: involvement of reactive oxygen species

Tebuconazole (TEB), a widely used pesticide in agriculture to combat fungal infections, is commonly detected in global food, potable water, groundwater, and human urine samples. Despite its known in vivo toxicity, its impact on heart function remains unclear. In a 28-day study on male Wistar rats (approximately 100 g), administering 10 mg/kg/day TEB or a vehicle (control) revealed no effect on body weight gain or heart weight, but an increase in the infarct area in TEB-treated animals. Notably, TEB induced time-dependent changes in in vivo electrocardiograms, particularly prolonging the QT interval after 28 days of administration. Isolated left ventricular cardiomyocytes exposed to TEB exhibited lengthened action potentials and reduced transient outward potassium current. TEB also increased reactive oxygen species (ROS) production in these cardiomyocytes, a phenomenon reversed by N-acetylcysteine (NAC). Furthermore, TEB-treated animals, when subjected to an in vivo dobutamine (Dob) and caffeine (Caf) challenge, displayed heightened susceptibility to severe arrhythmias, a phenotype prevented by NAC. In conclusion, TEB at the no observed adverse effect level (NOAEL) dose adversely affects heart electrical function, increases arrhythmic susceptibility, partially through ROS overproduction, and this phenotype is reversible by scavenging ROS with NAC.

Transcriptome and proteome analyses reveal that upregulation of GSTM2 by allisartan improves cardiac remodeling and dysfunction in hypertensive rats.

Long-term hypertension can lead to hypertensive heart disease, which ultimately progresses to heart failure. As an angiotensin receptor blocker antihypertensive drug, allisartan can control blood pressure, and improve cardiac remodeling and cardiac dysfunction caused by hypertension. The aim of the present study was to investigate the protective effects of allisartan on the heart of spontaneously hypertensive rats (SHRs) and the underlying mechanisms. SHRs were used as an animal model of hypertensive heart disease and were treated with allisartan orally at a dose of 25 mg/kg/day. The blood pressure levels of the rats were continuously monitored, their body and heart weights were measured, and their cardiac structure and function were evaluated using echocardiography. Wheat germ agglutinin staining and Masson trichrome staining were employed to assess the morphology of the myocardial tissue. In addition, transcriptome and proteome analyses were performed using the Solexa/Illumina sequencing platform and tandem mass tag technology, respectively. Immunofluorescence co-localization was conducted to analyze Nrf2 nuclear translocation, and TUNEL was performed to detect the levels of cell apoptosis. The protein expression levels of pro-collagen I, collagen III, phosphorylated (p)-AKT, AKT, p-PI3K and PI3K, and the mRNA expression levels of Col1a1 and Col3a1 were determined by western blotting and reverse transcription-quantitative PCR, respectively. Allisartan lowered blood pressure, attenuated cardiac remodeling and improved cardiac function in SHRs. In addition, allisartan alleviated cardiomyocyte hypertrophy and cardiac fibrosis. Allisartan also significantly affected the 'pentose phosphate pathway', 'fatty acid elongation', 'valine, leucine and isoleucine degradation', 'glutathione metabolism', and 'amino sugar and nucleotide sugar metabolism' pathways in the hearts of SHRs, and upregulated the expression levels of GSTM2. Furthermore, allisartan activated the PI3K-AKT-Nrf2 signaling pathway and inhibited cardiomyocyte apoptosis. In conclusion, the present study demonstrated that allisartan can effectively control blood pressure in SHRs, and improves cardiac remodeling and cardiac dysfunction. Allisartan may also upregulate the expression levels of GSTM2 in the hearts of SHRs and significantly affect glutathione metabolism, as determined by transcriptome and proteome analyses. The cardioprotective effect of allisartan may be mediated through activation of the PI3K-AKT-Nrf2 signaling pathway, upregulation of GSTM2 expression and reduction of cardiomyocyte apoptosis in SHRs.

The autonomic nerves around the vein of Marshall: apostmortem study with clinical implications.

This study aims to analyze the vein of Marshall (VOM) in human autopsy hearts and its correlation with clinical data to elucidate the morphological substrates of atrial fibrillation (AF) and other cardiac diseases. Twenty-three adult autopsy hearts were studied, assessing autonomic nerves by immunohistochemistry with tyrosine hydroxylase (sympathetic nerves), choline acetyltransferase (parasympathetic nerves), growth-associated protein 43 (neural growth), and S100 (general neural marker) antibodies. Interstitial fibrosis was assessed by Masson trichrome staining. Measurements were conducted via morphometric software. The results were correlated with clinical data. Sympathetic innervation was abundant in all VOM-adjacent regions. Subjects with a history of AF, cardiovascular cause of death, and histologically verified myocardial infarction had increased sympathetic innervation and neural growth around the VOM at the mitral isthmus. Interstitial fibrosis increased with age and heart weight was associated with AF and cardiovascular cause of death. This study increases our understanding of the cardiac autonomic innervation in the VOM area in various diseases, offering implications for the development of new therapeutic approaches targeting the autonomic nervous system.

HIGH DOSES OF KETAMINE INFLICT MYOCARDIAL INJURY AND CAUSE CHANGES IN THE RELATIVE BODY WEIGHT TO HEART OF ADULT ALBINO WISTAR RATS

Objective: Ketamine is widely used as an anesthetic agent in surgery and emergency medicine. It is also used for procedural sedation, treatment of depression, pain management, and sometimes as a recreational drug. These uses, however, have recommended doses to prevent myocardial injury. This study, therefore, was designed to investigate the level of injury on the myocardium following the administration of high doses of ketamine and to determine the relative body weight to heart weight of the experimental animals. Method: A total of 12 male albino Wistar rats were used and grouped into four including the control group. They were weighed daily and administered 100 mg, 150 mg, and 200 mg/kg/body weight of ketamine intraperitoneally for 2 weeks and weighed again. Experiment was terminated after 14 days and animals were sacrificed and the heart harvested for analysis. Results: Ketamine caused a significant myocardial injury with increase in the doses in different groups by causing inflammation, hypertrophy, vacuolar degenerative changes, atrophy, and extensive hemorrhage around the myocytes. Weight differentiation was noticed in all experimental groups with heart weight contributing to the total body weight by 1.63%, 1.7%, and 1.2% for the 100 mg, 150 mg, and 200 mg/kg/body weight of ketamine groups, respectively. Conclusion: Higher doses of ketamine cause significant myocardial injury as well as differential changes in body weight and heart weight in experimental animals.

Ostarine blunts the effect of endurance training on submaximal endurance in rats.

The purpose of this study is to study the effects of ostarine alone and in combination with endurance training in sexually mature, male Wistar rats. The rats were divided into a treadmill-trained group and a sedentary group. Half of each group received either ostarine or vehicle for 8weeks (n = 10 each, in total n = 40). We examined some functional, hormonal, and anthropometric parameters and the myogenic gene expression of myostatin, insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor-A (VEGF-A) in m. gastrocnemius. Ostarine decreased submaximal endurance and increased myogenic gene expression of myostatin but had no effect on maximal time to exhaustion and grip strength. Training increased submaximal endurance, maximal time to exhaustion, and grip strength. Our results indicate that both exercise and ostarine treatment had no significant effects on serum levels of luteinizing hormone, follicle-stimulating hormone, and testosterone, or on the myogenic gene expression of IGF-1 and VEGF-A. Neither ostarine nor the training had a significant effect on the testis, liver, and heart weights. In conclusion,ostarine had no effect on anthropometric and hormonal parameters but increased the myostatin gene expression in muscle. The SARM treatment decreased submaximal endurance without affecting maximal time to exhaustion, and training increased both metrics.

Sex-Linked Differences in Cardiac Atrophy After Mechanical Unloading Induced by Heterotopic Heart Transplantation.

No information is available about sex-related differences in unloading-induced cardiac atrophy. We aimed to compare the course of unloading-induced cardiac atrophy in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to obtain insight into the influence of sex hormones on this process. Heterotopic heart transplantation (HT((x)) was used as a model for heart unloading. Cardiac atrophy was assessed as the weight ratio of heterotopically transplanted heart weight (HW) to the native HW on days 7 and 14 after HTx in intact male and female rats. In separate experimental groups, gonadectomy was performed in male and female recipient animals 28 days before HT(x) and the course of cardiac atrophy was again evaluated on days 7 and 14 after HT(x). In intact male rats, HT(x) resulted in significantly greater decreases in whole HW when compared to intact female rats. The dynamics of the left ventricle (LV) and right ventricle (RV) atrophy after HT(x) was quite similar to that of whole hearts. Gonadectomy did not have any significant effect on the decreases in whole HW, LV, and RV weights, with similar results in male and female rats. Our results show that the development of unloading-induced cardiac atrophy is substantially reduced in female rats when compared to male rats. Since gonadectomy did not alter the course of cardiac atrophy after HTx, similarly in both male and female rats, we conclude that sex-linked differences in the development of unloading-induced cardiac atrophy are not caused by the activity of sex hormones.

Investigating the teratogenic potential of diclofenac sodium on chick embryos: A warning for pregnant women

Teratogenic and embryotoxic effect of diclofenac sodium (DS) on different developmental stages of the chick-embryos was investigated by examining different parameters such as its mortality rate, hatching, morphological measurements, weighing its internal organs and calculation of different indices. Experiment was divided into four trials with different dose (0.1 mL, 0.2 mL, 0.3 mL in groups A, B, and C, respectively and group D received 0.3 mL saline solution (0.9% NaCl) and group E remained un-injected) administration and observation. Results of first and second trial showed statistically (p<0.01) significant difference in bodyweight, body-length, forelimb and hindlimb length between experimental and control groups. In third trial, diclofenac sodium administration showed a statistically (p<0.01) significant difference in the bodyweight, body-length, forelimb, hindlimb length, liver weight, egg weight (EE ratio) and kidney somatic index (KSI). The beak-size, heart weight, kidney weight, cardiac somatic index (CSI) and hepato somatic index (HSI) were not significant (p>0.05) when compared with the control groups. In trial 4, forelimb, hindlimb length, heart weight, CSI and HSI were statistically (p<0.01) significant. Body-length and liver weight were significant (p<0.05). While bodyweight, beak size, kidney weight and KSI were non-significant (p>0.05). The mortality rate was increased with increase dose of DS and also affected the hatching. DS effect on chick embryos can be applied to humans because the early development of mammals and birds are closely related. So, it was concluded that DS should be used with caution during pregnancy especially during first trimester of pregnancy.