Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences

The literature is full of claims regarding the consumption of polyphenol or polyamine-rich foods that offer some protection from developing cardiovascular disease(CVD). This is achieved by preventing cardiac hypertrophy and protecting blood vessels through improving the function of endothelium. However, do these interventions work in the aged human hearts? Cardiac aging is accompanied by an increase in left ventricular hypertrophy, along with diastolic and systolic dysfunction. It also confers significant cardiovascular risks for both sexes. The incidence and prevalence of CVD increase sharply at an earlier age in men than women. Furthermore, the patterns of heart failure differ between sexes, as do the lifetime risk factors. Do caloric restriction(CR)-mimetics, rich in polyphenol or polyamine, delay or reverse cardiac aging equally in both men and women? This review will discuss three areas:(1) mechanisms underlying age-related cardiac remodeling;(2) gender-related differences and potential mechanisms underlying diminished cardiac response in older men and women;(3) we select a few polyphenol or polyamine rich compounds as the CRmimetics, such as resveratrol, quercetin, curcumin, epigallocatechin gallate and spermidine, due to their capability to extend health-span and induce autophagy. We outline their abilities and issues on retarding aging in animal hearts and preventing CVD in humans. We discuss the confounding factors that should be considered for developing therapeutic strategies against cardiac aging in humans.

The effect of caloric restriction on genetical pathways

Energy restriction is defined as reducing nutrient intake without dragging the organism into malnutrition. Energy restriction is preferred because it is a non-genetic intervention that increases life expectancy. Nicotinamide adenine dinucleotide(NAD~+)and adenosine monophosphate(AMP)levels, which are the indicators of intracellular energy deficiency, increase with energy restriction. The increase in NAD~+ level stimulates sirtuin(SIRT)enzymes, and the increase in AMP level stimulates AMP-activated protein kinase(AMPK). Various mechanisms are regulated by stimulating these enzymes. By Forkhead box O(FoxO)transcription factors, the ability of resistance to oxidative stress increases, and antioxidant genes, DNA repair, and autophagy genes are stimulated. Apoptosis is induced by stimulation of the p53 protein, and tumor growth is suppressed by the disruption of aging cells. The suppression of phosphoinositide 3-kinase(PI3K)-/-Akt, and therefore mTOR signal stimulates autophagy and mitophagia, and cleanses damaged cells and organelles. Mitochondrial biogenesis is stimulated, antioxidant capacity increases, and inflammatory response decreases. Adipose tissue and lipid metabolism are regulated by the regulation of fatty acid synthesis and oxidation. As a consequence, the effects of caloric restriction on cellular metabolism are regulated through the genetic pathways.

Effects of ultrasound monitoring of gastric residual volume on feeding complications,caloric intake and prognosis of patients with severe mechanical ventilation

BACKGROUND Monitoring of gastric residual is an important approach for assessing gastric emptying in patients with mechanical ventilation.By monitoring gastric contents,the enteral nutrition scheme can be adjusted in time to ensure feeding safety.AIM To investigate the effects of ultrasound monitoring on the incidence of feeding complications,daily caloric intake and prognosis of patients with severe mechanical ventilation.To analyze the clinical significance of ultrasound monitoring of gastric residual volume(GRV)up to 250 mL to provide a theoretical basis for clinical practice.METHODS Patients admitted to the department of emergency medicine of the Affiliated Hospital of Nantong University from January 2018 to June 2022 who received invasive mechanical ventilation and continuous enteral nutrition support within 24-48 h after admission were enrolled in this study.Medical records for patients within 7 d of hospitalization were retrospectively analyzed to compare the incidence of feeding complications,daily caloric intake and clinical prognosis between patients with gastric residual≥250 mL and<250 mL,as monitored by ultrasound on the third day.RESULTS A total of 513 patients were enrolled in this study.Incidences of abdominal distension,diarrhea,and vomiting in the<250 mL and≥250 mL groups were:18.4%vs 21.0%,23.9%vs 32.3%and 4.0%vs 6.5%,respectively;mortality rates were 20.8%vs 22.65%;mechanical ventilation durations were 18.30 d vs 17.56 d while lengths of stay in the intensive care units(ICU)were 19.87 d vs 19.19±5.19 d.Differences in the above factors between groups were not significant.Gastric residual≥250 mL was not an independent risk factor for death and prolonged ICU stay.However,target feeding time of patients in the≥250 mL group was longer than that of patients in the≥250 mL group,and caloric intake(22.0,23.6,24.8,25.3 kcal/kg/d)for patients in the≥250 mL group from the 4^(th) day to the 7^(th) day of hospitalization was lower than that of patients in the≥250 mL group(23.2,24.8,25.7,25.8 kcal/kg/d).On the 4^(th) day(Z=4.324,P=0.013),on the 5^(th) day(Z=3.376,P=0.033),while on the 6^(th) day(Z=3.098,P=0.04),the differences were statistically significant.CONCLUSION The use of ultrasound to monitor GRV and undertaking clinical interventions when the monitoring value is≥250 mL has no significant effects on incidences of feeding complications and clinical prognostic outcomes,however,it significantly prolongs the time to reach target feeding,reduces the daily intake of calories during ICU hospitalization,and increases the risk of insufficient nutrition of patients.The accuracy and necessity of monitoring gastric remnants and monitoring frequencies should be investigated further.

Protective effects of estrogens and caloric restriction during aging on various rat testis parameters

Aim： To investigate the effects of 17β-estradiol （E2）, Peganum harmala extract （PHE） and caloric restriction （CR） on various testis parameters during aging. Methods： Twelve-month-old male rats were treated for 6 months with either E2 or PHE, or submitted to CR （40%）. Results： Our results show that estrogens and CR are able to protect the male gonad by preventing the decrease of testosterone and E2 levels as well as the decrease of aromatase and estrogen receptor gene expressions. Indeed, E2, PHE and CR treatments induced an increase in the superoxide dismutase activities and decreased the activity of testicular enzymes： gamma-glutamyl transferase, alkaline phosphatase, lactate deshydrogenase as well as the aspartate and lactate transaminases in aged animals. In addition, the testicular catalase and gluthatione peroxidase activities were enhanced in E2, PHE and CR-treated rats compared to untreated animals at 18 months of age. Moreover, the positive effects of estradiol, PHE and CR were further supported by a lower level of lipid peroxidation. Recovery of spermatogenesis was recorded in treated rats. Conclusion： Besides a low caloric diet which is beneficial for spermatogenesis, a protective antioxydant role of estrogens is suggested. Estrogens delay testicular cell damage, which leads to functional senescence and, therefore, estrogens are helpful in protecting the reproductive functions from the adverse effects exerted by reactive oxygen species （ROS） produced in large quanti- ties in the aged testis.

Age-related decrease in aromatase and estrogen receptor （ERα and ERβ） expression in rat testes： protective effect of low caloric diets

Aim： To examine the effects on rat aging of caloric restriction （CR1） and undernutrition （CR2） on the body and on testicular weights, on two enzymatic antioxidants （superoxide dismutase and catalase）, on lipid peroxidation and on the expression of testicular aromatase and estrogen receptors （ER）. Methods： CR was initiated in 1-month-old rats and carried on until the age of 18 months. Results： In control and CR2 rats an age-related decrease of the aromatase and of ER （α and β） gene expression was observed; in parallel a diminution of testicular weights, and of the total number and motility of epididymal spermatozo was recorded. In addition, aging in control and CR2 rats was accompartied by a significant decrease in testicular superoxide dismutase, catalase activities, and an increase in lipid peroxidation level （thiobarbituric acid reactive substance）, associated with alterations of spermatogenesis. Conversely, caloric restriction-treatment exerted a protective effect and all the parameters were less affected by aging. Conclusion： These results indicate that during aging, a low caloric diet （not undernutrition） is beneficial for spermatogenesis and likely improves the protection of the cells via an increase of the cellular antioxidant defense system in which aromatase/ ER could play a role. （Asian J Andro12008 Mar; 10： 177-187）

Autonomic laterality in caloric vestibular stimulation

BACKGROUND Caloric stimulation of the vestibular system is associated with autonomic response.The lateralization in the nervous system activities also involves the autonomic nervous system.AIM To compare the effect of the right and left ear caloric test on the cardiac sympathovagal tone in healthy persons.METHODS This self-control study was conducted on 12 healthy male volunteers.The minimal ice water caloric test was applied for vestibular stimulation.This was done by irrigating 1 milliliter of 4±2°C ice water into the external ear canal in 1 s.In each experiment,only one ear was stimulated.For each ear,the pessimum position was considered as sham control and the optimum position was set as caloric vestibular stimulation of horizontal semicircular channel.The order of right or left caloric vestibular stimulation and the sequence of optimum or pessimum head position in each set were random.The recovery time between each calorie test was 5 min.The short-term heart rate variability(HRV)was used for cardiac sympathovagal tone metrics.All variables were compared using the analysis of variance.RESULTS After caloric vestibular stimulation,the short-term time-domain and frequencydomain HRV indices as well as,the systolic and the diastolic arterial blood pressure,the respiratory rate and the respiratory amplitude,had no significant changes.These negative results were similar in the right and the left sides.Nystagmus duration of left caloric vestibular stimulations in the optimum and the pessimum positions had significant differences(e.g.,72.14±39.06 vs 45.35±35.65,P<0.01).Nystagmus duration of right caloric vestibular stimulations in the optimum and the pessimum positions had also significant differences(e.g.,86.42±67.20 vs 50.71±29.73,P<0.01).The time of the start of the nystagmus following caloric vestibular stimulation had no differences in both sides and both positions.CONCLUSION Minimal ice water caloric stimulation of the right and left vestibular system did not affect the cardiac sympathovagal balance according to HRV indices.

A possible objective test to detect benign paroxysmal positional vertigo. The role of the caloric and video-head impulse tests in the diagnosis

Background:Benign paroxysmal positional vertigo(BPPV)is characterized by vertigo lasting from seconds to minutes,induced by head movements.Objectives:Our study aimed to investigate the clinical significance of the caloric vestibular and video head-impulse tests(vHIT)diagnosing the disorder.Methods:68 patients suffering from posterior canal BPPV(25 male,43 females,mean age±SD,54.5±13.2 years)and 56 patients with a normal functioning vestibular system as control were investigated.Bithermal caloric test and vHIT was performed during the same medical check-up.Canal paresis(CP%),gain(GA)and asymmetry(GA%)parameters were calculated.Results:The Dix-Hallpike manoeuvre was only positive in 4%of this population.The CP%parameter was only pathologic in two patients,and there was no significant difference between control and BPPV patients(p=0.76).The GA value was never under 0.8 in this population,but GA%was abnormal in 63.2%.A significant difference comparing the GA%values to the control group was seen(p=0.034).There was no correlation detected between the CP%and GA%values in BPPV.Regarding the GA%value,61%sensitivity and 76%specificity was seen.Conclusion:The Dix-Hallpike manoeuvre was not often positive in the non-acute phase of BPPV;therefore,objective testing is essential.The caloric test does not have clinical significance in BPPV,but vHIT can be helpful based on the GA%parameter。

Inhibitory Effect of Estrogens,Phytoestrogens,and Caloric Restriction on Oxidative Stress and Hepato-toxicity in Aged Rats

Objective To investigate the protective effect of 17β-estradiol （E2）, peganum harmala extract （PHE） administration and calorie restriction （CR） treatment （60%） on oxidative stress and hepato-toxicity in aged rats. Methods Eighteen months old animals that were treated at the age of 12 months were divided into 4 groups： normal control group with free access to food, E2 treatment group, PHE treatment group and CR treatment group of the food given to control group. Six male rats at the age of 4 months were used as a reference group. Results Aging significantly decreased superoxide dismutase （SOD）, catalase （CAT） and glutathione peroxidase （GPX）, and increased lactate deshydrogenase （LDH）, gamma-glyiamyl transferase （GGT）, pbosphatase alkalines （PAL）, aspartate and lactate transaminase （AST and ALT） activities in the liver. Aging also induced an increased lipid peroxidation level, histological changes and a decreased E2 level. However, treatment with E2, PHE, and CR increased 17β-estradiol, and decreased hepatic dysfunction parameters and lipid peroxidation as well as histological changes in the liver of aged rats. Conclusion The antioxidant and hepatoprotective activity of PHE and CR is possibly attributed to its ability to increase E2 level, which as an antioxidant, acts as a scavenger of ROS. Further studies on the pharmaceutical functions of E2 in males may contribute to its clinical application.

Concerns about the misleading conclusions regarding estimation of the net energy value of soybean meal relative to corn using the caloric efficiency approach in pigs

Apart from energy balance trials such as calorimetry,growth trials could also be used to estimate the energy values of feed ingredients with caloric efficiency as an indicator.Recent work used such methods reported greater net energy(NE)value of soybean meal(SBM)relative to corn in nursery pigs.We theoretically compared the NE values of SBM and corn according to the definition of NE and properties of the major chemical compositions in each ingredient.Meanwhile,we thoroughly examined the diet formulations and related analysis used in this work and compared this study with some peer works.We found that this study may suffer from problems with experimental design,reference citation,and data interpretation.In summary,the conclusion from the recent work that the SBM NE value may be greater than the corn NE value is likely to be erroneous.

Influence of personal and lesson factors on caloric expenditure in physical education

Increasing caloric expenditure in physical education is considered an effective school-based approach to addressing the child obesity epidemic.This study was designed to determine synergistic influences of student characteristics and lesson factors o caloric expenditure in elementary and middle school physical education.Methods:The study used a multi-level design.Level-1 factors included personal characteristics:age,gender,and body mass index.Level-2 factors included lesson length,content,and school level.Based on the Center for Disease Control and Prevention age-gender adjusted growth chart,students in 87 classes from 14 elementary and 15 middle schools were pre-screened into "Overweight","Healthy weight",or “Thin” groups.One boy and one girl were randomly selected from each group in each class as data providers(264 elementary and 294 middle school students).Caloric expenditure was measured in 243 physical education lessons using accelerometers.Results:Analysis of variance revealed and hierarchical linear modeling confirmed separate age by body mass index,age by gender,and content by lesson-length interaction effects,suggesting that the personal and lesson factors influenced caloric expenditure independently.Older male and heavier students burned more calories in all lessons.Students burned more calories in 45-60 min sport skill or fitness lessons than in shorter (30 min)or longer(75-90 min)game or multi-activity lessons.Conclusions:The hypothesized cross-level interaction was not observed in the data.Caloric expenditure can be optimized in 45-60 min sport skill or fitness development lessons.It can be recommended that schools adopt 45-60 min lesson length and provide skill and fitness development tasks in physical education to maximize caloric expenditure.Copyright(c)2012,Shanghai University of Sport.Production and hosting by Elsevier B.V.All rights reserved.

Age predicts the absence of caloric-induced vertigo

Introduction: The absence of vertigo during the caloric test, despite a robust response, has been suggested to represent a central vestibular system phenomenon. The purpose of this investigation was to determine the prevalence of absent caloric-induced vertigo perception in an unselected group of patients and to assess possible predicting variables.Methods: Prospective investigation of 92 unselected patients who underwent caloric testing. Inclusion criteria were that each patient generate a maximum slow phase velocity(maxSPV) > 15 deg/sec and a caloric asymmetry of≤10%. Following the caloric, patients were asked, "Did you have any sensation of motion?"Results: Results showed 75% of patients reported motion with a mean age of 56.51 years compared to a mean age of 66.55 in the 25% of patients reporting an absence of motion. A logistic regression was performed and the overall model was statistically significant accounting for 29% of the variance in caloric perception. The significant predictor variables were patient age and maxSPV of the caloric response. The effect size for both variables was small with an odds ratio of.9 for maxSPV and 1.06 for age.Conclusions: The current investigation showed that both age and maxSPV of the caloric response were significant predictors of vertigo perception during the caloric exam. However, the association between age and caloric perception is not conclusive. Although there is evidence to suggest that these findings represent age-related changes in the central processing of vestibular system stimulation, there are additional unmeasured factors that influence the perception of caloric-induced vertigo.

APPLICATION OF THERMAL ANALYSIS TO THE QUICK DETERMINATION OF THE PROXIMATE ANALYSIS ITEMS AND CALORIC VALUE FOR COAL

A research on the application of a TG-DTA(thermal gravimetry aifferential thermal analysis)to the quick determination of moisture,organic volatile fixed carbon,ash and caloric value for coal is described.

Thermoelastoplastic Deformation Analysis of Electromechanical Equipments under Electrocaloric Shock

A coupled thermomechanical model is presented to investigate the thermoelastoplastic deformation mechanism of electromechanical equipments under the condition of electrocaloric shock. In the coupling model, differentiating from the previous analyzing viewpoint that looked upon deformation work as additional heat source, temperature-field equation is established by considering the weakening role of deformation work on the intensity of internal heat source; in the process of setting up displacement-field equation, G-derivative of nonlinear functional is introduced into the traditional theory of elastoplastic finite deformation to simplify the expression of structural stiffness; stress-field equation is constructed by using the least square method to improve the stress solution obtained by constitutive equation. The presented model is converted into finite element program to simulate deforming process of 3-D structures with temperature-dependent material properties. As an example, thermal deformation analysis of Shanghai metro cars’ brake resistor is performed and compared with experimental results for illustrating the validity of the presented model.

Lasertherapy as A Strategy for Treatment Healing under Caloric Restriction – Study in Rats

Complications in the healing process are challenging, especially in clinical situations of caloric restriction （CR）. The lasertherapy becomes an important strategy that aids the repair, especially in CR. Thus, it is important to investigate the InGaAlP-660 nm laser as an strategy to repair cutaneous wounds in rats submitted to 30% of CR and to understand the tissue repair in clinical situations of CR. Thirty-six male Wistar rats were used, of which half were fed with 30% less ration, and half with ad libitum diet, for 21 days. Then, punch lesions of 1.5 cm in diameter were made on the animals backs, which were divided into： NR （no-restricted）, R （restricted）-both before lesion; C （control）, RC （restricted-control）, L （laser）, RL （restricted-laser）-after lesion. Samples of the skin/lesion/scar were collected on the 2nd, 7th and 14th days post-injury for histological, biochemical and molecular analyses. The R group showed reduction of body mass, epidermal/dermal thickness, inflammation, angiogenesis, fibroplasia and collagenesis. The RL group showed control of inflammation, oxidative damage and increase of antioxidants than RC, which probably favored angiogenesis, collagenesis and reepithelialization, similar to C and L. Thus, 30% of CR impaired the skin （before lesion）. In the lesion, lasertherapy has shown to be effective in tissue repair mainly in CR status, being thus, the laser clinically important strategy to tissue repair in critical situations of caloric restriction.

Rat Hepatocyte Glucose Metabolism Is Affected by Caloric Restriction but not by Litter Size Reduction

This work aimed at investigating whether the liver glucose metabolism could have a role in any change of glucose homeostasis that might exist in the reduced-litter rat at the age of 60 days. Additionally, post-weaning caloric restriction and its hepatic effects were explored, as this intervention is reported as a useful measure against obesity and its related disturbances. The animals were raised in litters of nine （control, CG） or three pups during lactation. These small-litter pups were FG （fed freely） or subjected to 30% RG （caloric restriction） after weaning until 60 days of age. The increased adiposity induced by lactational overfeeding was not reversed by caloric restriction. Hepatocyte glucose metabolism and glucose tolerance test were not affected by litter size, but caloric restriction increased liver basal glucose release, diminished gluconeogenesis and retarded the glycemic decay during the insulin tolerance test. Liver glucose metabolism of young adult rats was not affected by lactational overfeeding. Up to this age, however, moderate caloric restriction had a potent influence that might compromise whole-body glucose homeostasis and prompt to insulin resistance.

Responses of the Adult Rat Glucose Metabolism to Early Life Feeding, Caloric Restriction and Refeeding

Early life overfeeding in the rat can be experimentally induced by reducing litter size. This investigation assessed the consequences of this manipulation on glucose metabolism in vivo and in isolated hepatocytes in 150-day old rats. Additionally, after body growth, the effects of caloric restriction and refeeding were tested. Adult rats from control （G9） and reduced litters （G3L） did not differ in body and fat weights, glucose tolerance or insulin resistance （insulin-induced hypoglycemia）, or hepatocyte glucose release under basal or gluconeogenic conditions. Caloric restriction （G3R） reduced body and fat weights, decreased glucose decay after insulin injection and decreased hepatocyte gluconeogenic glucose release. Refeeding after caloric restriction reversed these parameters to those of the freely-fed groups （G9 and G3L）. Taken together, these results suggest that the liver glucose metabolism is not programmed by lactational overfeeding, but rather is responsive to the current nutritional condition of the animal.

Caloric Restriction and Litter Size Do Not Compromise Renal Function of Male Wistar Rats

This work had the purpose of comparing some renal parameters of Wistar rats raised in small litters either freely-fed （G3L） or subjected to 30% caloric restriction （G3R） with those of rats from normal litters （Gg） at the age of 90 days. The results showed that the relative weight of the kidneys and urinary flow were not significantly different. All the groups had GFR （glomerular filtration rate） and proteinuria within normal values, despite group G3R having values statistically lower. However, group G3R had diminished glomerular area and increased numbers of renal corpuscles. Group G3L did not exhibit differences compared with controls （G9）. The effects of caloric restriction did not compromise kidney structure and function in 90-day-old rats.

Caloric restriction,Sirtuins,and cardiovascular diseases

Caloric restriction(CR)is a well-established dietary intervention known to extend healthy lifespan and exert positive effects on aging-related diseases,including cardiovascular conditions.Sirtuins,a family of nicotinamide adenine dinucleotide(NAD^(+))-dependent histone deacetylases,have emerged as key regulators of cellular metabolism,stress responses,and the aging process,serving as energy status sensors in response to CR.However,the mechanism through which CR regulates Sirtuin function to ameliorate cardiovascular disease remains unclear.This review not only provided an overview of recent research investigating the interplay between Sirtuins and CR,specifically focusing on their potential implications for cardiovascular health,but also provided a comprehensive summary of the benefits of CR for the cardiovascular system mediated directly via Sirtuins.CR has also been shown to have considerable impact on specific metabolic organs,leading to the production of small molecules that enter systemic circulation and subsequently regulate Sirtuin activity within the cardiovascular system.The direct and indirect effects of CR offer a potential mechanism for Sirtuin modulation and subsequent cardiovascular protection.Understanding the interplay between CR and Sirtuins will provide new insights for the development of interventions to prevent and treat cardiovascular diseases.

Phase transition regulation and caloric effect

Solid state refrigeration based on caloric effect is regarded as a potential candidate for replacing vapor-compression refrigeration.Numerous methods have been proposed to optimize the refrigeration properties of caloric materials,of which single field tuning as a relatively simple way has been systemically studied.However,single field tuning with few tunable parameters usually obtains an excellent performance in one specific aspect at the cost of worsening the performance in other aspects,like attaining a large caloric effect with narrowing the transition temperature range and introducing hysteresis.Because of the shortcomings of the caloric effect driven by a single field,multifield tuning on multicaloric materials that have a coupling between different ferro-orders came into view.This review mainly focuses on recent studies that apply this method to improve the cooling performance of materials,consisting of enlarging caloric effects,reducing hysteresis losses,adjusting transition temperatures,and widening transition temperature spans,which indicate that further progress can be made in the application of this method.Furthermore,research on the sign of lattice and spin contributions to the magnetocaloric effect found new phonon evolution mechanisms,calling for more attention on multicaloric effects.Other progress including improving cyclability of FeRh alloys by introducing second phases and realizing a large reversible barocaloric effect by hybridizing carbon chains and inorganic groups is described in brief.

Effects of caloric vestibular stimulation on serotoninergic system in the media vestibular nuclei of guinea pigs

Background Anatomic and electrophysiological studies have revealed that the neurons located in the media vestibular nuclei （MVN） receive most of the sensory vestibular input coming from the ipsilateral labyrinth and the responses of MVN neurons to caloric stimulation directly reflect changes in primary vestibular afferent activity. The aim of this study was to clarify the intrinsic characteristics of serotonin （5-hydroxytryptamine, 5-HT） release in the MVN during the period of vertigo induced by caloric stimulation. Methods We used an in vivo microdialysis technique to examine the effects of caloric stimulation on the serotoninergic system in MVN. Twenty four guinea pigs were randomly divided into the groups of irrigation of the ear canal with hot water （n=6）, ice water （n=6） and 37℃ water （n=4）, and the groups of irrigation of the auricle with hot water （n=-4） and ice water （n=4）, according to different caloric vestibular stimulation. We examined the animal＇s caloric nystagmus with a two-channel electronystagmographic recorder （ENG）, and meanwhile examine serotonin （5-hydroxytryptamine, 5-HT） level in the MVN with microdialysis technique after caloric stimulation. Results In the caloric test the hot water （44℃） irrigation of the right external auditory canal induced horizontal nystagmus towards the right side lasting about 60 seconds and the ice water irrigation of the right external auditory canal induced it towards the left side lasting for about 90 seconds. No nystagmus was induced by 37℃ water irrigation of the external ear canal. Therefore, it was used as a negative control stimulation to the middle ear. The MVN 5-HT levels significantly increased in the first 5-minute collecting interval and increased to 254% and 189% of the control group in the second collecting interval in response to caloric vestibular stimulation with ice water and hot water respectively. The serotonin release was not distinctly changed by the irrigation of the auricle with ice water or hot water. Conclusions Neither somato-sensory stimulation of the middle ear nor nonspecific cold or hot stress affects the serotonin release. The rise of 5-HT in MVN may be involved in the mechanism of vertigo induced by caloric stimulation.