Differential Effect of Three Macrolide Antibiotics on Cardiac Pathology and Electrophysiology in a Myocardial Infarction Rat Model: Influence on Sodium Nav1.5 Channel Expression

Macrolides were reported to have cardiotoxic effects presented mainly by electrocardiogram (ECG) changes with increased risk in cardiac patients. We aimed to determine the impact of three macrolides, azithromycin, clarithromycin and erythromycin, on cardiac electrophysiology, cardiac enzyme activities, histopathological changes, and sodium voltage-gated alpha subunit 5 (Nav1.5) channel expression. We used eight experimental groups of male albino rats: vehicle, azithromycin (100 mg/kg), clarithromycin (100 mg/kg), erythromycin (100 mg/kg), MI + vehicle, MI + azithromycin (100 mg/kg), MI + clarithromycin (100 mg/kg) and MI + erythromycin (100 mg/kg); each group received chronic oral doses of the vehicle/drugs for seven weeks. ECG abnormalities and elevated serum cardiac enzymes were observed particularly in rats with AMI compared to healthy rats. Microscopic examination revealed elevated pathology scores for rats treated with clarithromycin in both experiments following treatment with erythromycin in healthy rats. Although rats with MI did not show further elevations in fibrosis score on treatment with macrolides, they produced significant fibrosis in healthy rats. Downregulation of cardiac Nav1.5 transcript was observed following macrolides treatment in both groups (healthy rats and rats with MI). In conclusion, the current findings suggested the potential cardiotoxic effects of chronic doses of macrolide antibiotics in rats with MI as manifested by abnormal ECG changes and pathological findings in addition to downregulation of Nav1.5 channels. Furthermore, in the current dose ranges, azithromycin produced the least toxicity compared to clarithromycin and erythromycin.

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Protective effect of febuxostat in sepsis-induced liver and kidney injuries after cecal ligation and puncture with the impact of xanthine oxidase, interleukin 1β, and c-Jun N-terminal kinases

Human & Experimental Toxicology ◽

10.1177/0960327120905957 ◽

2020 ◽

Vol 39 (7) ◽

pp. 906-919 ◽

Cited By ~ 1

Author(s):

YF Ibrahim ◽

RR Fadl ◽

SAE Ibrahim ◽

MF Gayyed ◽

AMA Bayoumi ◽

...

Keyword(s):

Protective Effect ◽

Xanthine Oxidase ◽

Tissue Injury ◽

Cecal Ligation ◽

Elevated Serum ◽

Albino Rats ◽

Cecal Ligation And Puncture ◽

Necrosis Factor Alpha ◽

Liver And Kidney ◽

The Impact

Sepsis is one of the most common causes of death among hospitalized patients. Activity of xanthine oxidase (XO), a reactive oxygen species-producing enzyme, is known to be elevated in septic patients. Our aim was to investigate the possible protective role of XO inhibitor, febuxostat (FEB), in a rat model of sepsis-induced liver and kidney injures. Adult male albino rats were divided into four groups ( n = 12 each): sham control, sham + FEB, cecal ligation and puncture (CLP), and CLP + FEB groups. FEB (10 mg/kg per os (p.o.)) was given once daily for 2 days and 30 min prior to laparotomy with CLP. CLP was associated with a high mortality rate accompanied by significant liver and kidney injuries indicated by elevated serum alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels and confirmed by histopathological tissue injury. Moreover, there was an increase in neutrophil gelatinase-associated lipocalin, uric acid, malondialdehyde, and nitric oxide levels and with decreased superoxide dismutase activity and total antioxidant capacity. In addition, CLP caused increased expression of the inflammatory markers tumor necrosis factor alpha, interleukin 1beta protein levels, and nuclear factor kappa B immunoexpression. Finally, CLP operated rats exhibited an upregulation in the apoptotic mediators, caspase 3, and P-C-Jun N-terminal kinases (JNK) proteins. FEB treatment of CLP rats caused a significant improvement and normalization in all measured parameters. Moreover, FEB amerliorates degenerative histopathological changes and improves the overall survival rate. In conclusion, FEB exhibited a protective effect in sepsis-induced liver and kidney injuries most probably through its anti-inflammatory, antioxidant, and antiapoptotic properties and attenuating JNK signaling pathway secondary to its XO enzyme inhibitory activity.

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Non Concurrent Multimodal Stress Decreases Sperm Quality and Motor Activity in Male Wister Albino Rats

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1781 ◽

2019 ◽

Vol 12 (3) ◽

pp. 1505-1517 ◽

Cited By ~ 1

Author(s):

Jyothi Ashok Kumar ◽

Thotakura Balaji ◽

C. Swathi Priyadarshini ◽

Manickam Subramanian ◽

Indumathi Sundaramurthi

Keyword(s):

Body Weight ◽

Muscle Strength ◽

Motor Activity ◽

Sperm Quality ◽

Elevated Serum ◽

Male Reproduction ◽

Male Rats ◽

Albino Rats ◽

Serum Corticosterone ◽

The Impact

Every human being is exposed to the stress in one or the other form in the day to day life. Most of the existing studies on the impact of stress on the male reproduction were assessed by using single stressor, which may lead habituation to that stressor. The present study intends to estimate the consequence of stress on motor activity, sperm quality and histopathology of the testis in stress-induced male rats using multimodal stress one per day. Four weeks old Wister albino rats were randomly split into 4 groups and induced multimodal stress at different ages of life span. After induction of stress serum corticosterone levels, muscle strength and coordination, quality of sperm and histopathology of testes were estimated. Elevated serum corticosterone levels and body weight, reduced muscle strength, coordination. Sperm concentration and motility was significantly reduced and increased morphologically abnormal sperm in stress induced animals but sperm viability was not altered much. Histopathology of testes in stress received animals showed decreased tubular diameter and increased intertubular space. Multimodal stress caused elevated serum corticosterone and body weight, decreased motor activity, sperm quality and degenerative changes in the testis

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Prolonged antimicrobial prophylaxis following cardiac device procedures increases preventable harm: insights from the VA CART program

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2018.170 ◽

2018 ◽

Vol 39 (9) ◽

pp. 1030-1036 ◽

Cited By ~ 8

Author(s):

Archana Asundi ◽

Maggie Stanislawski ◽

Payal Mehta ◽

Anna E. Barón ◽

Howard Gold ◽

...

Keyword(s):

Antimicrobial Therapy ◽

Cardiac Electrophysiology ◽

Electronic Device ◽

Antimicrobial Prophylaxis ◽

Secondary Outcome ◽

Antimicrobial Use ◽

Cardiac Device ◽

Increased Risk ◽

Preventable Harm ◽

The Impact

AbstractBackgroundThe rate of cardiovascular implantable electronic device (CIED) infection is increasing coincident with an increase in the number of device procedures. Preprocedural antimicrobial prophylaxis reduces CIED infections; however, there is no evidence that prolonged postprocedural antimicrobials additionally reduce risk. Thus, we sought to quantify the harms associated with this approach.ObjectiveTo measure the association between Clostridium difficile infection (CDI), acute kidney injury (AKI) and receipt of prolonged postprocedural antimicrobials.MethodsCIED procedures entered into the VA Clinical Assessment Reporting and Tracking Electrophysiology (CART-EP) database during fiscal years 2008–2016 were included. The primary outcome was 90-day incidence of CDI and the secondary outcome was the 7-day incidence of AKI. The primary exposure measure was duration of postprocedural antimicrobial therapy. Associations were measured using Cox-proportional hazards and binomial regression.ResultsProlonged postprocedural antimicrobial therapy was identified following 3,331 of 6,497 CIED procedures (51.3%), and the median duration of prophylaxis was 5 days. Prolonged postprocedural antimicrobial use was associated with increased risk of CDI (hazard ratio [HR], 2.90; 95% confidence interval [CI], 1.54–5.46). Of the 27 patients who developed CDI, 11 subsequently died. Postprocedural antimicrobial use with ≥2 antimicrobials was associated with an increased risk of AKI (OR, 4.16; 95% CI, 2.50–6.90). The impact was particularly significant when one of the dual agents prescribed was vancomycin (adjusted OR, 8.41; 95% CI, 5.53–12.79).ConclusionsProlonged antimicrobial prophylaxis following CIED procedures increases preventable harm; this practice should be discouraged in procedural settings such as the cardiac electrophysiology laboratory.

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The Impact of Everolimus and Radiation Therapy on Pulmonary Fibrosis

Medicina ◽

10.3390/medicina56070348 ◽

2020 ◽

Vol 56 (7) ◽

pp. 348

Author(s):

Mehmet Fuat Eren ◽

Ayfer Ay Eren ◽

Mutlay Sayan ◽

Birsen Yücel ◽

Şahende Elagöz ◽

...

Keyword(s):

Radiation Therapy ◽

Pulmonary Fibrosis ◽

Synergistic Effects ◽

Control Group ◽

Albino Rats ◽

Fibrosis Score ◽

Group 4 ◽

Increased Risk ◽

Pulmonary Damage ◽

The Impact

Background and objectives: Everolimus (EVE) is a mammalian target of the rapamycin (mTOR) inhibitor that is widely used in cancer patients. Pulmonary toxicity, usually manifesting as interstitial pneumonitis, is a serious adverse effect of this drug. Radiation therapy, which is often administered in conjunction with chemotherapy for synergistic effects, also causes pulmonary fibrosis. In view of pulmonary damage development in these two forms of cancer treatment, we have examined the effect of EVE administration individually, in combination with radiation given in varying sequences, and its relation to the extent of pulmonary damage. Materials and Methods: We performed an experimental study in albino rats, which were randomized into five groups: (1) control group, (2) EVE alone, (3) EVE 22 h after radiation, (4) EVE 2 h after irradiation, and (5) only radiation. Sixteen weeks after thoracic irradiation, rat lung tissue samples were examined under light microscopy, and the extent of pulmonary damage was estimated. After this, we calculated median fibrosis scores in each group. Results: The highest fibrosis score was noted in Group 4. Among the five groups, the control group had a significantly lower median fibrosis score compared to the others. When the median fibrosis score of the group that received concurrent EVE with radiation therapy (RT) (Group 4) was compared with that of the control group, the difference was statistically significant (p = 0.0022). However, no significant differences were achieved among the study groups that received EVE only or RT only, whether concurrently or sequentially (p > 0.05). Conclusion: EVE is an effective treatment option for the management of several malignancies and is often combined with other therapies, such as radiation, for a more efficient response. However, an increased risk of pulmonary fibrosis should also be anticipated when these two modalities are combined, as they both can cause pulmonary damage, especially when administered concurrently.

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Clinical assessment of the athlete’s heart: normal and abnormal ECGs in athletes

ESC CardioMed ◽

10.1093/med/9780198784906.003.0706 ◽

2018 ◽

pp. 2916-2920

Author(s):

Alessandro Zorzi ◽

Domenico Corrado

Keyword(s):

Cardiovascular Disease ◽

Athlete’S Heart ◽

Physiological Adaptation ◽

Ecg Changes ◽

Increased Risk ◽

Electrocardiogram Ecg ◽

Ecg Abnormalities ◽

Work Up ◽

And Training ◽

Athlete's Heart

The electrocardiogram (ECG) of trained athletes may show changes that represent the consequence of the heart’s adaptation to physical exercise (‘athlete’s heart’) such as enlarged cardiac chamber size and increased vagal tone. Physiological ECG changes must be differentiated from the ECG abnormalities secondary to an underlying cardiovascular disease that may be responsible for sudden cardiac death during exercise. The ECG changes of athletes are classified according to their prevalence, relation to exercise training, association with an increased risk of cardiovascular disease, and the need for further investigations: common ECG changes should be considered as a benign sign of physiological adaptation to exercise and do not require additional evaluation; on the other hand, in case of uncommon and training-unrelated abnormalities, which may be associated with an underlying cardiovascular disease, further work-up should be performed. This chapter reviews the abnormalities that may be found in an athlete’s ECG and proposes criteria for interpretation of such changes as normal or abnormal findings.

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Hormones and sex differences: changes in cardiac electrophysiology with pregnancy

Clinical Science ◽

10.1042/cs20150710 ◽

2016 ◽

Vol 130 (10) ◽

pp. 747-759 ◽

Cited By ~ 13

Author(s):

Glenna C.L. Bett

Keyword(s):

Postpartum Period ◽

Cardiac Electrophysiology ◽

Delayed Rectifier ◽

Hormonal Changes ◽

Large Variability ◽

Early Symptom ◽

Cardiac Electrical Activity ◽

Channel Expression ◽

Electrocardiogram Ecg ◽

Ionic Basis

Disruption of cardiac electrical activity resulting in palpitations and syncope is often an early symptom of pregnancy. Pregnancy is a time of dramatic and dynamic physiological and hormonal changes during which numerous demands are placed on the heart. These changes result in electrical remodelling which can be detected as changes in the electrocardiogram (ECG). This gestational remodelling is a very under-researched area. There are no systematic large studies powered to determine changes in the ECG from pre-pregnancy, through gestation, and into the postpartum period. The large variability between patients and the dynamic nature of pregnancy hampers interpretation of smaller studies, but some facts are consistent. Gestational cardiac hypertrophy and a physical shift of the heart contribute to changes in the ECG. There are also electrical changes such as an increased heart rate and lengthening of the QT interval. There is an increased susceptibility to arrhythmias during pregnancy and the postpartum period. Some changes in the ECG are clearly the result of changes in ion channel expression and behaviour, but little is known about the ionic basis for this electrical remodelling. Most information comes from animal models, and implicates changes in the delayed-rectifier channels. However, it is likely that there are additional roles for sodium channels as well as changes in calcium homoeostasis. The changes in the electrical profile of the heart during pregnancy and the postpartum period have clear implications for the safety of pregnant women, but the field remains relatively undeveloped.

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Association between elevated serum triglycerides and asthma in patients with obesity: An explorative study

Allergy and Asthma Proceedings ◽

10.2500/aap.2021.42.210020 ◽

2021 ◽

Vol 42 (3) ◽

pp. e71-e76

Author(s):

Cathelijne M. van Zelst ◽

Geertje M. de Boer ◽

Yasemin Türk ◽

Astrid van Huisstede ◽

Johannes C. C. M. In't Veen ◽

...

Keyword(s):

Inhaled Corticosteroids ◽

Clinical Symptoms ◽

Elevated Serum ◽

High Body Mass Index ◽

Forced Expiratory Volume ◽

Lipid Levels ◽

Serum Triglycerides ◽

Increased Risk ◽

Blood Eosinophils ◽

The Impact

Background: Adults with a high body mass index (BMI) have an increased risk of developing asthma. To explore the impact of increased lipids on the presence of asthma, this study investigated the relationship between lipid levels and inflammatory markers in patients with asthma and controls with obesity. Objective: We hypothesized that higher lipid levels are more prevalent in patients with obesity and asthma. Methods: In this explorative cohort study, 96 patients with asthma and 45 controls were included. All the patients participated in one of three asthma studies; two of these studies included only patients with obesity. An asthma diagnosis was defined by the presence of typical clinical symptoms, reversible airway obstruction (+12% improvement in forced expiratory volume in the first second of expiration after bronchodilator), or bronchial hyperreactivity (Histamine PC20 < 8 mg/mL), or a fractional exhaled nitric oxide of > 50 ppb. We compared lipid levels and neutrophils and eosinophils in patients with asthma and the controls with a wide BMI range (17.8‐63.8 kg/m2). Multivariable logistic regression was used to analyze the data. Results: Serum triglycerides were statistically significantly higher in patients with obesity and asthma adjusted for BMI, blood eosinophils, and statin use (odds ratio [OR] 2.56 [95% confidence interval, 1.34‐4.88]; p = 0.004). Inclusion or exclusion of those who used long-acting β2-agonists and inhaled corticosteroids led to comparable adjusted ORs for blood triglyceride and blood eosinophils levels. Conclusion: Elevated serum triglycerides were associated with the presence of asthma in patients with obesity. This indicated that elevated triglycerides might be a yet unrecognized trait that contributed to the development of asthma. The precise cause and effect of these high triglyceride levels in the patients with asthma and with obesity were not determined in this study.Clinical trial Trial registration NCT03278561, <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>; NL4262, NL3056, trialregister.nl

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Development and optimization of an in vivo electrocardiogram recording method and analysis program for adult zebrafish

Disease Models & Mechanisms ◽

10.1242/dmm.048827 ◽

2021 ◽

Author(s):

ThuyVy Duong ◽

Rebecca Rose ◽

Adriana Blazeski ◽

Noah Fine ◽

Courtney E Woods ◽

...

Keyword(s):

Cardiac Electrophysiology ◽

Data Interpretation ◽

Model Systems ◽

Adult Zebrafish ◽

High Quality ◽

Qt Intervals ◽

Flecainide Acetate ◽

Electrocardiogram Ecg ◽

The Impact

Clinically pertinent electrocardiogram (ECG) data from model systems, such as zebrafish, are crucial for illuminating factors contributing to human cardiac electrophysiology abnormalities and disease. Current zebrafish ECG collection strategies have not adequately addressed the consistent acquisition of high-quality traces or sources of phenotypic variation that could obscure data interpretation. Thus, we developed a novel platform to ensure high-quality recording of in vivo subdermal adult zebrafish ECGs and zERG (Zebrafish ECG Reading GUI), a program to acquire measurements from traces commercial software cannot examine due to erroneous peak calling. We evaluate normal ECG trait variation, revealing the intervals are highly reproducible while wave amplitude variation appears largely driven by recording artifacts, and identify sex and body size as potential confounders to PR, QRS, and QT intervals. With this framework, we characterize the effect of the class I anti-arrhythmic drug flecainide acetate on adults, provide support for the impact of a Long QT syndrome model, and establish power calculations for this and other studies. These results highlight our pipeline as a robust approach to evaluate zebrafish models of human cardiac electrophysiologic phenotypes.

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Zinc Depletion Increases Readmission in Older Patients: An Example of Interactions Between Nutrition and Disease

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000275 ◽

2017 ◽

Vol 87 (1-2) ◽

pp. 10-16 ◽

Cited By ~ 1

Author(s):

Salah Gariballa ◽

Awad Alessa

Keyword(s):

Nutritional Status ◽

Inductively Coupled Plasma ◽

Older Patients ◽

Controlled Trial ◽

Prognostic Indicators ◽

Hospitalised Patients ◽

Increased Risk ◽

Co Morbidity ◽

The Impact ◽

Poor Nutrition

Abstract. Background: ill health may lead to poor nutrition and poor nutrition to ill health, so identifying priorities for management still remains a challenge. The aim of this report is to present data on the impact of plasma zinc (Zn) depletion on important health outcomes after adjusting for other poor prognostic indicators in hospitalised patients. Methods: Hospitalised acutely ill older patients who were part of a large randomised controlled trial had their nutritional status assessed using anthropometric, hematological and biochemical data. Plasma Zn concentrations were measured at baseline, 6 weeks and at 6 months using inductively- coupled plasma spectroscopy method. Other clinical outcome measures of health were also measured. Results: A total of 345 patients assessed at baseline, 133 at 6 weeks and 163 at 6 months. At baseline 254 (74%) patients had a plasma Zn concentration below 10.71 μmol/L indicating biochemical depletion. The figures at 6 weeks and 6 months were 86 (65%) and 114 (70%) patients respectively. After adjusting for age, co-morbidity, nutritional status and tissue inflammation measured using CRP, only muscle mass and serum albumin showed significant and independent effects on plasma Zn concentrations. The risk of non-elective readmission in the 6-months follow up period was significantly lower in patients with normal Zn concentrations compared with those diagnosed with Zn depletion (adjusted hazard ratio 0.62 (95% CI: 0.38 to 0.99), p = 0.047. Conclusions: Zn depletion is common and associated with increased risk of readmission in acutely-ill older patients, however, the influence of underlying comorbidity on these results can not excluded.

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Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽

10.1024/0301-1526/a000447 ◽

2015 ◽

Vol 44 (4) ◽

pp. 313-323 ◽

Cited By ~ 6

Author(s):

Lea Weingarz ◽

Marc Schindewolf ◽

Jan Schwonberg ◽

Carola Hecking ◽

Zsuzsanna Wolf ◽

...

Keyword(s):

Factor V Leiden ◽

Cox Proportional Hazards ◽

First Episode ◽

Factor V ◽

Factor V Leiden Mutation ◽

Younger Patients ◽

Risk Of Recurrence ◽

G20210a Mutation ◽

Increased Risk ◽

The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

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