Donor Heart Preservation: Current Knowledge and the New Era of Machine Perfusion.

Heart transplantation remains the conventional treatment in end-stage heart failure, with static cold storage (SCS) being the standard technique used for donor preservation. Nevertheless, prolonged cold ischemic storage is associated with the increased risk of early graft dysfunction attributed to residual ischemia, reperfusion, and rewarming damage. In addition, the demand for the use of marginal grafts requires the development of new methods for organ preservation and repair. In this review, we focus on current knowledge and novel methods of donor preservation in heart transplantation. Hypothermic or normothermic machine perfusion may be a promising novel method of donor preservation based on the administration of cardioprotective agents. Machine perfusion seems to be comparable to cold cardioplegia regarding donor preservation and allows potential repair treatments to be employed and the assessment of graft function before implantation. It is also a promising platform for using marginal organs and increasing donor pool. New pharmacological cardiac repair treatments, as well as cardioprotective interventions have emerged and could allow for the optimization of this modality, making it more practical and cost-effective for the real world of transplantation. Recently, the use of triiodothyronine during normothermic perfusion has shown a favorable profile on cardiac function and microvascular dysfunction, likely by suppressing pro-apoptotic signaling and increasing the expression of cardioprotective molecules.

Endothelin Modulates Rhythm Disturbances and Autonomic Responses to Acute Emotional Stress in Rats.

The ubiquitous peptide endothelin is currently under investigation as a modulatory factor of autonomic responses to acute emotional stress. Baseline plasma levels of endothelin alter blood pressure responses, but it remains unclear whether autonomic activity and arrhythmogenesis (i.e., brady- or tachyarrhythmias) are affected. We recorded sympathetic and vagal indices (derived from heart rate variability analysis), rhythm disturbances, voluntary motion, and systolic blood pressure after acute emotional stress in conscious rats with implanted telemetry devices. Two strains were compared, namely wild-type and ETB-deficient rats, the latter displaying elevated plasma endothelin. No differences in heart rate or blood pressure were evident, but sympathetic responses were blunted in ETB-deficient rats, contrasting prompt activation in wild-type rats. Vagal withdrawal was observed in both strains at the onset of stress, but vagal activity was subsequently restored in ETB-deficient rats, accompanied by low voluntary motion during recovery. Reflecting such distinct autonomic patterns, frequent premature ventricular contractions were recorded in wild-type rats, as opposed to sinus pauses in ETB-deficient rats. Thus, chronically elevated plasma endothelin levels blunt autonomic responses to acute emotional stress, resulting in vagal dominance and bradyarrhythmias. Our study provides further insights into the pathophysiology of stress-induced tachyarrhythmias and syncope.

Thyroid Hormone and Heart Failure: Charting Known Pathways for Cardiac Repair/Regeneration.

Heart failure affects more than 64 million people worldwide, having a serious impact on their survival and quality of life. Exploring its pathophysiology and molecular bases is an urgent need in order to develop new therapeutic approaches. Thyroid hormone signaling, evolutionarily conserved, controls fundamental biological processes and has a crucial role in development and metabolism. Its active form is L-triiodothyronine, which not only regulates important gene expression by binding to its nuclear receptors, but also has nongenomic actions, controlling crucial intracellular signalings. Stressful stimuli, such as acute myocardial infarction, lead to changes in thyroid hormone signaling, and especially in the relation of the thyroid hormone and its nuclear receptor, which are associated with the reactivation of fetal development programmes, with structural remodeling and phenotypical changes in the cardiomyocytes. The recapitulation of fetal-like features of the signaling may be partially an incomplete effort of the myocardium to recapitulate its developmental program and enable cardiomyocytes to proliferate and finally to regenerate. In this review, we will discuss the experimental and clinical evidence about the role of the thyroid hormone in the recovery of the myocardium in the setting of heart failure with reduced and preserved ejection fraction and its future therapeutic implications.

Effects of T3 Administration on Ex Vivo Rat Hearts Subjected to Normothermic Perfusion: Therapeutic Implications in Donor Heart Preservation and Repair.

The present study investigated the effects of triiodothyronine (T3) administration in ex vivo model of rat heart normothermic perfusion. T3 is cardioprotective and has the potential to repair the injured myocardium. Isolated hearts were subjected to normothermic perfusion (NP) with Krebs-Henseleit for 4 h with vehicle (NP) or 60 nM T3 in the perfusate (NP + T3). Left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), perfusion pressure (PP) and percentage of change of these parameters from the baseline values were measured. Activation of stress induced kinase signaling was assessed in tissue samples. Baseline parameters were similar between groups. LVEDP was increased from the baseline by 13% (70) for NP + T3 vs. 139% (160) for NP group, p = 0.048. LVDP was reduced by 18.2% (5) for NP + T3 vs. 25.3% (19) for NP group, p = 0.01. PP was increased by 41% (19) for NP + T3 vs.91% (56) for NP group, p = 0.024. T3 increased activation of pro-survival Akt by 1.85 fold (p = 0.047) and AMPK by 2.25 fold (p = 0.01) and reduced activation of pro-apoptotic p38 MAPK by 3fold (p = 0.04) and p54 JNK by 4.0 fold (p = 0.04). Administration of T3 in normothermic perfusion had favorable effects on cardiac function and perfusion pressure and switched death to pro-survival kinase signaling.

Catheter-Associated Urinary Tract Infections, Bacteremia, and Infection Control Interventions in a Hospital: A Six-Year Time-Series Study.

Catheter-associated urinary tract infections (CAUTIs) are among the most common healthcare-associated infections. Urine catheters are often reservoirs of multidrug-resistant (MDR) bacteria and sources of pathogens transmission to other patients. The current study was conducted to investigate the correlation between CAUTIs, MDR bacteremia, and infection control interventions, in a tertiary-care hospital in Athens, from 2013 to 2018. The following data were analyzed per month: 1. CAUTI incidence; 2. consumption of hand hygiene disinfectants; 3. incidence of isolation of MDR carrier patients, and 4.incidence of bacteremia/1000 patient-days [total resistant a.Gram-negative: carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae; b.Gram-positive: vancomycin-resistant Enterococci and methicillin-resistant Staphylococcus aureus]. The use of scrub disinfectant solutions was associated with decreased CAUTI rate in Total Hospital Clinics (OR: 0.97, 95% CI: 0.96−0.98, p-value: <0.001) and in Adults ICU (OR: 0.79, 95% CI: 0.65−0.96, p-value:0.018) while no correlation was found with isolation rate of MDR-carrier pathogens. Interestingly, an increase in total bacteremia (OR: 0.81, 95% CI: 0.75−0.87, p-value:<0.001) or carbapenem-resistant bacteremia correlated with decreased incidence of CAUTIs (OR: 0.96, 95% CI: 0.94−0.99, p-value: 0.008). Hand hygiene measures had a robust and constant effect on infection control, reducing the incidence of CAUTIs.

Mathieu Joseph Bonaventure Orfila (1787-1853): The Founder of Modern Toxicology.

Mateu Joseph Bonaventura Orfila i Rotger was a prominent Spanish chemist and scholar of the 19th century whose experimental work has enormously contributed to the progress of toxicology. Being a pioneer with his research on the effects of toxins and antidotes on live animals, he established basic principles of modern medicine and pharmacology. Orfila improved the accuracy of several chemical techniques such as the Marsh test. He served as an expert and well-known scientific investigator in important legal trials involving alleged poisonings with arsenic and other chemical substances. In 1840, he was asked to investigate the notorious case of Charles Lafarge's death, whose wife had been accused with murder by poisoning his food with arsenic. After four failed chemical analyses, Orfila was finally able to detect arsenic in the victim's body, leading the court to convict Madame Lafarge. Due to his overall contribution to the field, Orfila is considered the father of modern toxicology.

The Potential of Thyroid Hormone Therapy in Severe COVID-19: Rationale and Preliminary Evidence.

Tissue hypoxia is one of the main pathophysiologic mechanisms in sepsis and particularly in COVID-19. Microvascular dysfunction, endothelialitis and alterations in red blood cell hemorheology are all implicated in severe COVID-19 hypoxia and multiorgan dysfunction. Tissue hypoxia results in tissue injury and remodeling with re-emergence of fetal programming via hypoxia-inducible factor-1α (HIF-1a)-dependent and -independent pathways. In this context, thyroid hormone (TH), a critical regulator of organ maturation, may be of relevance in preventing fetal-like hypoxia-induced remodeling in COVID-19 sepsis. Acute triiodothyronine (T3) treatment can prevent cardiac remodeling and improve recovery of function in clinical settings of hypoxic injury as acute myocardial infarction and by-pass cardiac surgery. Furthermore, T3 administration prevents tissue hypoxia in experimental sepsis. On the basis of this evidence, the use of T3 treatment was proposed for ICU (Intensive Care Unit) COVID-19 patients (Thy-Support, NCT04348513). The rationale for T3 therapy in severe COVID-19 and preliminary experimental and clinical evidence are discussed in this review.

Low concentrations of bisphenol A promote the activation of the mitochondrial apoptotic pathway on Beta-TC-6 cells via the generation of intracellular reactive oxygen species and mitochondrial superoxide.

Τhe natural history of type 2 diabetes mellitus is characterized by a progressive loss of pancreatic beta cell function and insulin resistance. Bisphenol A (BPA) is an endocrine-disrupting chemical that is used widely in industry; people are exposed to BPA and its products daily. Studies have delineated that BPA alters the function of pancreatic beta cells. Herein, we examined the effect of low doses of BPA on pancreatic beta cell viability and apoptosis and we tried to elucidate the mechanisms involved in these processes. Beta-TC-6 (ATCC® CRL-11506™) cells were cultured with a medium containing the following dilutions of BPA: 0.002, 0.02, 0.1, 0.2, 2 µΜ up to 72 h. We examined the viability and adenosine triphosphate (ATP) levels of cells. Then, we measured apoptosis, cell cycle, and insulin levels. We quantified the levels of proteins implicated in the mitochondrial pathway of apoptosis; and finally, we quantified the intracellular reactive oxygen species and mitochondrial superoxide. We found that the exposure of Beta-TC-6 cells to BPA results in a decrease in cell viability, ATP levels, and an increase in insulin levels. We found an increase in apoptosis levels and a decrease in cell cycle levels. In addition, we provide evidence of the levels of apoptotic proteins. Finally, we found an increase in the cellular reactive oxygen species and mitochondrial superoxide production. Exposure to low concentrations of BPA triggers the mitochondrial pathway of apoptosis via the generation of intracellular reactive oxygen species and mitochondrial superoxide on Beta-TC-6 cells in a dose-dependent way.

Assessment of frailty and related outcomes in older patients with heart failure: A cohort study.

OBJECTIVE: Heart failure (HF) is a common cause of morbidity and mortality in older patients. Frailty is prevalent and complicates the course of HF. We sought to investigate the impact of frailty on HF outcomes. METHODS: Patients over 65 years old hospitalized with acute decompensated HF and mildly reduced or preserved EF, between September 2017 and September 2019 were enrolled in the study. Before hospital discharge at euvolemic state, patients underwent six-minute walk test (6MWT) and frailty assessment using FRIED and modified SOF scores. Predictors of death, readmissions, and increase in diuretic dose were analyzed by multivariable logistic regression models. RESULTS: We enrolled 193 consecutive patients (mean age 78.6 ± 8.4 years, 29.5% males, 59.6% with HF and preserved EF). All patients had at least one comorbidity (40.9% coronary artery disease, 71% diabetes, and 86% hypertension). The mean 6MWT distance was 316.2 meters. According to FRIED score, 4.7% were normal and 17.6% were categorized as pre-frail and 77.7% as frail, while according to SOF index 9.8% were normal, 15% were categorized as pre-frail and 75.1% as frail. Frail patients according to both indices had a higher risk of 90-day readmissions, uptitration of diuretics within 90 days (p < 0.001 for both) and numerically but not significantly higher risk of death. Frailty status was independently associated with higher risk of 90-day readmissions, uptitration of diuretics, and higher BNP at 90 days. CONCLUSIONS: Frailty in older patients with HF is common and associated with worse prognosis. Pre-discharge frailty assessment may aid in identification of patients at high-risk for short-term complications.

Effects of Acute Triiodothyronine Treatment in Patients with Anterior Myocardial Infarction Undergoing Primary Angioplasty: Evidence from a Pilot Randomized Clinical Trial (ThyRepair Study).

Background: Thyroid hormone has a differential action on healthy and ischemic heart. Triiodothyronine (T3) administration improved postischemic cardiac function while it limited apoptosis in experimentally induced ischemia. Thus, the present study investigated the potential effects of acute liothyronine (LT3) treatment in patients with anterior myocardial infarction. Methods: This study is a pilot, randomized, double-blind, placebo-controlled trial (ThyRepair study). We randomized 52 patients and analyzed data from 37 patients (n = 16 placebo and n = 21 LT3), per prespecified per protocol analysis. We excluded three patients who had died of cardiovascular causes (one in placebo and two in LT3 arm), four with small infarct size below a pre-specified threshold (in the placebo arm), and the rest, who lacked follow-up data. LT3 treatment started after stenting as an intravenous (i.v.) bolus injection of 0.8 µg/kg of LT3 followed by a constant infusion of 0.113 µg/kg/h i.v. for 48 hours. All patients had cardiac magnetic resonance (CMR) at hospital discharge and 6 months follow-up. The primary end point was CMR left ventricular (LV) ejection fraction (LVEF) and secondary endpoints were LV volumes, infarct volume (IV), and safety. Results: The CMR LVEF% at 6 months was 53.6 ± 9.5 for the LT3-treated group and 48.6 ± 11 for placebo, p = 0.15. Acute LT3 treatment resulted in a significantly lower LV end-diastolic volume index (92.2 ± 16.8 mL/m2 vs. 107.5 ± 22.2, p = 0.022) and LV systolic volume index (47.5 ± 13.9 mL/m2 vs. 61.3 ± 21.7, p = 0.024) at hospital discharge, but not at 6 months. There was no statistically significant difference in CMR IV at hospital discharge between the groups (p = 0.24). CMR IV tended to be lower in the LT3-treated group at 6 months (18.7 ± 9.5 vs. 25.9 ± 11.7, in placebo, p = 0.05). Serious, life-threatening events related to LT3 treatment were not observed. A tendency for an increased incidence of atrial fibrillation (AF) was found in the LT3 group during the first 48 hours (19% for T3 group vs. 5% for placebo, p = 0.13). Conclusion: This pilot randomized, placebo-controlled trial study suggests potential favorable effects (acute cardiac dilatation and 6-month IV) as well as potential concerns regarding a higher risk of AF after LT3 administration early after myocardial infarction, which should be tested in a larger scale study.

Machine learning based analysis of stroke lesions on mouse tissue sections.

An unbiased, automated and reliable method for analysis of brain lesions in tissue after ischemic stroke is missing. Manual infarct volumetry or by threshold-based semi-automated approaches is laborious, and biased to human error or biased by many false -positive and -negative data, respectively. Thereby, we developed a novel machine learning, atlas-based method for fully automated stroke analysis in mouse brain slices stained with 2% Triphenyltetrazolium-chloride (2% TTC), named "StrokeAnalyst", which runs on a user-friendly graphical interface. StrokeAnalyst registers subject images on a common spatial domain (a novel mouse TTC- brain atlas of 80 average mathematical images), calculates pixel-based, tissue-intensity statistics (z-scores), applies outlier-detection and machine learning (Random-Forest) models to increase accuracy of lesion detection, and produces volumetry data and detailed neuroanatomical information per lesion. We validated StrokeAnalyst in two separate experimental sets using the filament stroke model. StrokeAnalyst detects stroke lesions in a rater-independent and reproducible way, correctly detects hemispheric volumes even in presence of post-stroke edema and significantly minimizes false-positive errors compared to threshold-based approaches (false-positive rate 1.2-2.3%, p < 0.05). It can process scanner-acquired, and even smartphone-captured or pdf-retrieved images. Overall, StrokeAnalyst surpasses all previous TTC-volumetry approaches and increases quality, reproducibility and reliability of stroke detection in relevant preclinical models.

Association between consumption of antibiotics, infection control interventions and Clostridioides difficile infections: Analysis of six-year time-series data in a tertiary-care hospital in Greece.

BACKGROUND: To investigate the association between Clostridioides difficile infection (CDI), antibiotic use, and infection control interventions, during an antibiotic stewardship program (ASP) implemented in a tertiary-care hospital in Greece from 2013 to 2018. METHODS: Analysis was applied for the following monthly indices: 1. consumption of antibiotics; 2. use of hand hygiene disinfectant solutions; 3. percentage of isolations of patients either with multidrug-resistant (MDR) bacteria, or CDI, or admitted from another hospital; and 4. percentage of patients with CDI divided into two groups: community-acquired CDI (CACDI) and hospital-associated CDI (HACDI) (onset ≤72 h and >72 h after admission, respectively). RESULTS: During the study, a significant reduction in CACDI rate from 0.3%/admissions [95% CI 0.1-0.6] to 0.1%/admissions [95% CI 0.0-0.3] (p-value = 0.035) was observed in adults ICU, while CDI rates were stable in the rest of the hospital. Antibiotic consumption showed a significant reduction in total hospital, from 91.7 DDDs [95% CI 89.7-93.7] to 80.1 DDDs [95% CI 79.1-81.1] (p-value<0.001), except adults ICU. Non-advanced antibiotics correlated with decreased CDI rates in Adults Clinic Departments and ICU. Isolation of patients one and two months earlier correlated with decreased CACDI rates per 20% [95% CI 0.64-1.00, p-value = 0.046] and HACDI per 23% [95% CI 0.60-1.00, p-value = 0.050] in Adults Clinic Departments. Consumption of disinfectant solutions current month correlated with decreased rate for CACDI per 33% [95% CI 0.49-0.91, p-value = 0.011] and HACDI per 38% [95% CI 0.40-0.98, p-value = 0.040] in total Hospital Clinics. CONCLUSION: Rational antibiotic prescribing during ASP along with multipronged intervention strategy focusing on hand hygiene and patient isolation measures prevent and control CDI outbreaks in the hospital setting.

Changes in Thyroid Hormone Signaling Mediate Cardiac Dysfunction in the Tg197 Mouse Model of Arthritis: Potential Therapeutic Implications.

Background Rheumatoid Arthritis (RA) patients show a higher risk of heart failure. The present study investigated possible causes of cardiac dysfunction related to thyroid hormone (TH) signaling in a RA mouse model. Methods A TNF-driven mouse model of RA[TghuTNF (Tg197)] was used. Cardiac function was evaluated by echocardiography. SERCA2a and phospholamban protein levels in left ventricle (LV) tissue, thyroid hormone levels in serum, TH receptors in LV and TH-related kinase signaling pathways were measured. T3 hormone was administered in female Tg197 mice. Results We show LV and atrial dilatation with systolic dysfunction in Tg197 animals, accompanied by downregulated SERCA2a. We suggest an interaction of pro-inflammatory and thyroid hormone signaling indicated by increased p38 MAPK and downregulation of TRß1 receptor in Tg197 hearts. Interestingly, female Tg197 mice showed a worse cardiac phenotype related to reduced T3 levels and Akt activation. T3 supplementation increased Akt activation, restored SERCA2a expression and improved cardiac function in female Tg197 mice. Conclusions TNF overexpression of Tg197 mice results in cardiac dysfunction via p38 MAPK activation and downregulation of TRß1. Gender-specific reduction in T3 levels could cause the worse cardiac phenotype observed in female mice, while T3 administration improves cardiac function and calcium handling via modified Akt activation.

Effects of Thyroid Hormone on Tissue Hypoxia: Relevance to Sepsis Therapy.

Tissue hypoxia occurs in various conditions such as myocardial or brain ischemia and infarction, sepsis, and trauma, and induces cellular damage and tissue remodeling with recapitulation of fetal-like reprogramming, which eventually results in organ failure. Analogies seem to exist between the damaged hypoxic and developing organs, indicating that a regulatory network which drives embryonic organ development may control aspects of heart (or tissue) repair. In this context, thyroid hormone (TH), which is a critical regulator of organ maturation, physiologic angiogenesis, and mitochondrial biogenesis during fetal development, may be of important physiological relevance upon stress (hypoxia)-induced fetal reprogramming. TH signaling has been implicated in hypoxic tissue remodeling after myocardial infarction and T3 prevents remodeling of the postinfarcted heart. Similarly, preliminary experimental evidence suggests that T3 can prevent early tissue hypoxia during sepsis with important physiological consequences. Thus, based on common pathways between different paradigms, we propose a possible role of TH in tissue hypoxia after sepsis with the potential to reduce secondary organ failure.

Acute triiodothyronine treatment and red blood cell sedimentation rate (ESR) in critically ill COVID-19 patients: A novel association?

Sepsis and septic shock result in impaired microcirculation and red blood cell rheology which lead to tissue hypoxia and multi-organ failure. Early administration of triiodothyronine prevents tissue hypoxia in experimental sepsis. In this context, a clinical trial was initiated to test the efficacy of acute triiodothyronine administration to combat tissue hypoxia in critically ill COVID19 patients. Here, we provide preliminary data from interim analysis of this study showing a novel acute effect of triiodothyronine on erythrocyte sedimentation rate which may have an important therapeutic impact on red blood cell rheology and tissue hypoxia in sepsis and particular in COVID19 critical illness.Trial registration: ClinicalTrials.gov, NCT04348513. Registered 16 April 2020, https://clinicaltrials.gov/ct2/show/NCT04348513.

Translational Block in Stroke: A Constructive and "Out-of-the-Box" Reappraisal.

Why can we still not translate preclinical research to clinical treatments for acute strokes? Despite > 1000 successful preclinical studies, drugs, and concepts for acute stroke, only two have reached clinical translation. This is the translational block. Yet, we continue to routinely model strokes using almost the same concepts we have used for over 30 years. Methodological improvements and criteria from the last decade have shed some light but have not solved the problem. In this conceptual analysis, we review the current status and reappraise it by thinking "out-of-the-box" and over the edges. As such, we query why other scientific fields have also faced the same translational failures, to find common denominators. In parallel, we query how migraine, multiple sclerosis, and hypothermia in hypoxic encephalopathy have achieved significant translation successes. Should we view ischemic stroke as a "chronic, relapsing, vascular" disease, then secondary prevention strategies are also a successful translation. Finally, based on the lessons learned, we propose how stroke should be modeled, and how preclinical and clinical scientists, editors, grant reviewers, and industry should reconsider their routine way of conducting research. Translational success for stroke treatments may eventually require a bold change with solutions that are outside of the box.

Theophrastus Bombastus Von Hohenheim: Theological Reformer, Philosopher and Physician.

Theophrastus Bombastus Von Hohenheim (1493-1541), known as Paracelsus, was a German-Swiss Renaissance man. His interests included alchemy and medicine. During the early 1500s, he worked as a physician, introducing mineral-based therapies to treat ailments. He is credited with developing the first recipe for laudanum, a powerful opium-based pain medication. He had radical beliefs, claiming that supreme knowledge could be reached by observing nature, not by reading books. He expressed rebellious opinions on religious topics and, though devoted Christian, criticized the Catholic Church, preaching that the spirit of Christianity dwells in the human soul and not within the church walls. Paracelsus' efforts to "renovate" the expression of the Christian faith by limiting the ritual and augmenting the spirituality among believers are presented.

The Use of L-Glucose in Cancer Diagnosis: Results from In Vitro and In Vivo Studies.

BACKGROUND: Cancer cells are characterized by metabolic heterogeneity. Although many research groups make efforts to analyze this heterogeneity, little attention has been paid to cancer cells utilizing otherwise unusable substrates as fuel for tumor development. Of the two stereoisomers of glucose, D-glucose but not L-glucose, the mirror image isomer of D-glucose is abundantly found in nature. D-glucose is the human body's key source of energy through aerobic respiration. However, data from in vitro and in vivo studies examining the ability of cancer cells to take up L-glucose are scarce. OBJECTIVES: The present mini-review aims to present current literature data on the role of L-glucose in cancer diagnosis based on in vitro and in vivo studies. METHODS: The MEDLINE, EMBASE, and the Cochrane Library with restrictions to articles in English language databases were searched to retrieve available data. RESULTS: There are limited data in the literature regarding in vitro and in vivo studies that examined the ability of cancer cells to take up L-glucose. Research work so far has shown that that the binding of a fluorescent detector to an L-glucose molecule produced a fluorescent probe that was specifically taken up by malignant cancer cells, thus providing a unique method for their detection. CONCLUSION: Given that L-glucose is taken up by cancer cells, L-glucose fluorescent probes can be a useful tool for visualization and characterization of cancer cells. More research on the potential biologic effects of L-glucose in cancer is necessary.

Sympathetic and Vagal Responses Elicited by Acute Stress in Rats.

Introduction Acute emotional stress triggers autonomic responses that affect sympathovagal balance. However, the temporal pattern of changes in each autonomic arm during stress and recovery remains unclear. Therefore, we analyzed separately sympathetic and vagal activity, elicited by acute unpredictable stress in a rat model. Methods Continuous electrocardiographic recording was performed during (32 minutes) and after (two hours) successive use of restraint and air-jet stress in 10 rats, whereas five rats served as controls. Sympathetic and vagal indices were calculated non-invasively after heart rate variability analysis. Voluntary motion was quantified during recovery, as an index of continuing anxiety. Results The sympathetic nervous system index increased during stress and remained elevated during the initial stage of recovery. The parasympathetic nervous system index decreased immediately after the onset of stress and remained low throughout the observational period. During recovery, voluntary activity was more pronounced in the stress group than in the controls. Conclusion Successive restraint and air-jet stress in rats increased sympathetic activity and decreased vagal activity. These changes displayed only partial recovery post-stress and were accompanied by enhanced voluntary motion. Our findings may be important in the evaluation of the cardiac electrophysiologic implications of autonomic changes elicited by acute emotional stress.