Superior mechanical resistance in the exoskeleton of the coconut crab, Birgus latro.

The hierarchical tissue structure that can balance the lightweight and strength of organisms gives hints on the development of biologically inspired materials. The exoskeleton of the coconut crab, Birgus latro, which is the largest terrestrial crustacean, was systematically analyzed using a materials science approach. The tissue structures, chemical compositions, and mechanical properties of the claw, walking legs, cephalothorax, and abdomen were compared. The local mechanical properties, hardness(H) and stiffness(E), were examined by nanoindentation testing. The stacking height, Sh, of the twisted plywood structure observed only in the exocuticle, the exoskeleton thickness, and the thickness and compositions at each layer differed significantly by body part. The exocuticle is strongly mineralized regardless of body parts. The claw and walking legs were thicker than the cephalothorax and abdomen, and their endocuticle was mineralized as compared to the endocuticle in the cephalothorax and abdomen. The H and Sh had a correlation in the exocuticle layer, and the H increased with decreasing the Sh. On the H-E map for abrasion resistance of materials, the results showed that the exocuticle layer of the coconut crab was superior to that of other arthropods and all engineering polymers and competitive with the hardest metallic alloys.

Simultaneous assessment of coronary flow reserve and left ventricular function during vasodilator stress evaluated by 13N-ammonia hybrid PET/MRI.

AIM: To explore changes in left ventricular (LV) function and the relationship of these changes with myocardial blood flow (MBF) evaluated by 13N-ammonia hybrid positron-emission tomography (PET)/magnetic resonance imaging (MRI) during vasodilator stress in patients with suspected coronary artery disease (CAD). MATERIALS AND METHODS: Fifty-two consecutive patients with suspected CAD, who underwent 13N-ammonia PET/MRI, were enrolled. Vasodilator stress was induced by intravenous injection of adenosine. MBF and coronary flow reserve (CFR) were calculated from dynamic acquisition of 13N-ammonia PET. LV function was evaluated by MRI both at rest and during vasodilator stress. An abnormal perfusion on myocardial images was defined as a summed difference score of ≥4. RESULTS: MRI showed that the LV end-diastolic volume, LV end-systolic volume, and LV ejection fraction (LVEF) remained unchanged during vasodilator stress in all patients (n=52) as well as in the patients with CFR of <2 (n=27), stress MBF of <1.3 ml/g/min (n=28), abnormal myocardial perfusion (n=30), and more than one diseased vessel (n=46). In only four patients, the LVEF measured by MRI decreased by >5% during vasodilator stress. In these four patients, CFR was lower (1.57 ± 0.12 versus 2.18 ± 0.86, p<0.01) and the number of diseased vessels was higher (2.75 ± 0.50 versus 1.48 ± 0.92, p<0.01) than in patients without post-stress LV dysfunction. CONCLUSION: The LV volume and systolic function evaluated by cardiac MRI remained unchanged during vasodilator stress; however, LV dysfunction during vasodilator stress may occur in patients with severe CAD.

Fermented milk retains beneficial effects on skeletal muscle protein anabolism after processing by centrifugation and supernatant removal.

Lactobacillus-fermented milk can stimulate anabolic effects in skeletal muscle. Fermented milk containing Lactobacillus produces aqueous molecules, such as free AA and lactate. This study aimed to investigate how processing fermented milk by centrifugation and removal of supernatant affects AA absorption and postprandial skeletal muscle protein synthesis (MPS) when mice are fed fermented milk. We gavaged male Sprague-Dawley rats with skim milk (S), fermented milk (F), or processed fermented milk (P), and examined the total AA content in portal vein blood (reflecting AA absorption) and plantaris muscle MPS at 30, 60, and 90 min following administration. Relative to fasted rats, at 30 min the total AA concentration in portal vein blood from rats in the P groups was significantly higher, followed by F and S, respectively. The MPS rates were higher for the F or P groups compared with the S group. Phosphorylation levels of p70S6 kinase in the P and F groups were significantly higher than those for the S group 30 min after administration, although the level of Akt phosphorylation was similar among the groups. These results suggested that fermentation improves AA absorption that in turn enhances postprandial MPS via Akt-independent mechanisms, and that processed fermented milk retains these favorable effects on MPS.

The Association Between MCT1 T1470A Polymorphism and Power-Oriented Athletic Performance.

The purpose of this study was to investigate the effects of the MCT1 T1470A polymorphism (rs1049434) on power-oriented performance and lactate concentration during or after cycling sprints in Japanese wrestlers. Participants (199 wrestlers and 649 controls) were genotyped for the MCT1 T1470A genotype (rs1049434) using the TaqMan® Assay. All wrestlers were international (n=77) or national (n=122) level athletes. Among them, 46 wrestlers performed 2 anaerobic performance tests, a 30-s Wingate Anaerobic test (WAnT) and a series of 10 maximal effort 10-s sprints on a cycle ergometer. Blood lactate levels were measured before, during, and after the tests. In the A-allele recessive model (AA vs. TA+TT), the frequency of the AA genotype was significantly higher in all wrestlers than in controls (p=0.037). Wrestlers with AA genotype had lower blood lactate concentrations than those with TA+TT genotype at 10 min after the WAnT and following the 5th and the final set of repeated cycling sprints (p<0.05). The AA genotype of the MCT1 T1470A polymorphism is over-represented in wrestlers compared with controls and is associated with lower blood lactate concentrations after 30-s WAnT and during intermittent sprint tests in Japanese wrestlers.

The Relation between Hamstring Strain Injury and Physical Characteristics of Japanese Collegiate Sepak Takraw Players.

The aim of this study was to investigate the injuries in Japanese collegiate sepak takraw players. We primarily focused on hamstring strain injury (HSI), and investigated the associated physical characteristics. The study included 77 Japanese collegiate sepak takraw players who were interviewed; data were collected regarding injuries sustained by them during the game within the past year. The hip range of motion (ROM) was measured. The total number of injuries was 48 in a year. The rate of HSI was the highest (31.3%) among all the injuries. All HSIs occurred in the dominant leg because of the sunback spike. Using the Mann-Whitney U test, significant differences in age and sport-related experience were observed between the injured group and uninjured group. Upon using logistic regression analysis, the presence of a HSI was found to be associated with the sport-related experience (adjusted odds ratio [OR], 0.30; 95% confidence interval [CI], 0.12-0.77) and the hip extension ROM (adjusted OR, 0.81; 95% CI, 0.66-0.99) after adjusting for sex, sport-related experience, and the hip ROM. HSI is the most common injury in Japanese collegiate sepak takraw players. Short sport-related experience and small hip extension ROM are related with the occurrence of HSI.

Muscle plasticity related to changes in tubulin and αB-crystallin levels induced by eccentric contraction in rat skeletal muscles.

We used the model of eccentric contraction of the hindlimb muscle by Ochi et al. to examine the role of eccentric contraction in muscle plasticity. This model aims to focus on stimulated skeletal muscle responses by measuring tissue weights and tracing the quantities of αB-crystallin and tubulin. The medial gastrocnemius muscle (GCM) responded to electrically induced eccentric contraction (EIEC) with significant increases in tissue weight (p < 0.01) and the ratio of tissue weight to body weight (p < 0.05); however, there was a decrease in soleus muscle weight after EIEC. EIEC in the GCM caused contractile-induced sustenance of the traced proteins, but the soleus muscle exhibited a remarkable decrease in α-tubulin and a 19% decrease in αB-crystallin. EIEC caused fast-to-slow myosin heavy chain (MHC) isoform type-oriented shift within both the GCM and soleus muscle. These results have shown that different MHC isoform type-expressing slow and fast muscles commonly undergo fast-to-slow type MHC isoform transformation. This suggests that different levels of EIEC affected each of the slow and fast muscles to induce different quantitative changes in the expression of αB-crystallin and α-tubulin.

Radiological abnormalities and low back pain in gymnasts.

Several studies have shown a higher prevalence of radiological abnormalities among gymnasts. However, the types of radiological abnormalities associated with low back pain (LBP) have not been clarified. The hypothesis was that significant relationships between radiological abnormalities and LBP may be revealed by discriminating between the types of MRI abnormalities while considering confounding factors. The subjects were 104 Japanese collegiate gymnasts (men, 70; women, 34). The presence of LBP was evaluated using the questionnaire developed by Osaka City University (OCU Test). Magnetic resonance imaging (MRI) abnormalities were evaluated using T1- and T2-weighted MRI. The prevalence of more than 1 MRI abnormality in gymnasts was 47.1% (49/104). The chi-square test showed that the incidence of lumbar disc degeneration (LDDG) and limbus vertebra was significantly greater in gymnasts with LBP than in gymnasts without LBP. By using logistic regression analysis to analyze the concomitant environmental variables, only LDDG (odds ratio, 2.70; 95% confidence interval, 1.10-6.66) was selected as a statistically significant variable accounting for LBP. In conclusion, LDDG is a predictor for LBP in Japanese collegiate gymnasts.

Vitamin C administration attenuates overload-induced skeletal muscle hypertrophy in rats.

AIM: This study aimed to investigate the effects of vitamin C administration on skeletal muscle hypertrophy induced by mechanical overload in rats. METHODS: Male Wistar rats were randomly assigned to three groups: (i) sham-operated group (n = 8), (ii) placebo-administered group (n = 8) and (iii) vitamin C-administered group (n = 8). In the placebo-administered and vitamin C-administered groups, the gastrocnemius and soleus muscles of the right hindlimb were surgically removed to overload the plantaris muscle. Vitamin C (500 mg kg(-1)) was orally administered to the vitamin C-administered group once a day for 14 days. RESULTS: Synergist muscle ablation caused significant increases in wet weight and protein concentration of the plantaris muscle in both the placebo-administered (P < 0.01) and vitamin C-administered groups (P < 0.01) compared with the sham-operated group (SHA). However, the magnitude of plantaris muscle hypertrophy (expressed as a percentage of the contralateral plantaris muscle) was significantly smaller (P < 0.01) in the vitamin C-administered group (141%) than in the placebo-administered group (PLA) (152%). Compared with the SHA, only the PLA showed higher expressions of phosphorylated p70s6k and Erk1/2 (positive regulators of muscle protein synthesis) and a lower expression of atrogin-1 (a muscle atrophy marker). Concentrations of vitamin C and oxidative stress markers in the overloaded muscle were similar between the placebo-administered and vitamin C-administered groups. CONCLUSION: Oral vitamin C administration can attenuate overload-induced skeletal muscle hypertrophy, which may have implications for antioxidant supplementation during exercise training.

Genetic strain-dependent protein metabolism and muscle hypertrophy under chronic isometric training in rat gastrocnemius muscle.

Genetic strain-dependent reactivity to mechanical stimuli in rat skeletal muscle has not been examined. This study aimed to examine whether genetic strain-dependency is associated with reactivity in protein metabolism and the resultant muscle hypertrophy after isometric resistance training (RT). The right triceps of Sprague-Dawley (SD) and Wistar rats underwent 12 sessions of RT. After RT, a transition from the IIb to the IIx myosin heavy-chain isoform was observed in both strains. In SD rats, the lateral gastrocnemius muscle (LG) mass of the trained legs (TRN) was significantly higher than that of the control legs (CON) (7.8 %, P<0.05). Meanwhile, in Wistar rats, the LG mass was unchanged. In SD rats, the levels of 70-kDa ribosomal protein S6 kinase (p70S6k) and forkhead box 3a (FOXO3a) phosphorylation in the TRN were significantly greater than those of the CON (2.2- and 1.9-fold, respectively; P<0.05). The expression of muscle ring finger-1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin-1) in the TRN were significantly lower than those of the CON (0.6- and 0.7-fold, respectively; P<0.05). However, in Wistar rats, there was no significant difference. These results suggest a genetic strain difference in protein metabolism. This phenomenon may be useful for studying individual differences in response to RT.

COL11A1 gene is associated with limbus vertebra in gymnasts.

Several studies have shown higher frequencies of radiological abnormalities among gymnasts. Recently, the gene encoding the α1 chain of type XI collagen, (COL11A1) (rs 1676486), was associated with lumbar disc herniation in the Japanese population. We hypothesized that there was a significant relationship between abnormal magnetic resonance imaging (MRI) findings of the lumbar spine and the COL11A1 4603C/T gene polymorphism in collegiate gymnasts. Our study participants included 103 Japanese collegiate gymnasts (70 men and 33 women). Radiological abnormalities were evaluated using T1- and T2-weighted MRI. Genotyping for COL11A1 was performed for all the participants. By using logistic regression analysis, we observed significant associations between limbus vertebra and age (adjusted odds ratio=0.51, 95% confidence interval: 0.27-0.96), sporting experience (adjusted odds ratio=1.49, 95% confidence interval: 1.14-1.94), and a TT genotype (adjusted odds ratio=7.83, 95% confidence interval: 1.33-46.03). We conclude that a TT genotype of COL11A1 polymorphism may be a significant risk factor for limbus vertebra in Japanese collegiate gymnasts.

Blood flow-restricted training does not improve jump performance in untrained young men.

The purpose of this study was to investigate the effect of blood flow-restricted training (BFRT) on jump performance in relation to changes in muscle strength. Seventeen untrained young men were assigned into either BFRT or normal training (NORT) groups and performed low-intensity [30-40% of one-repetition maximum (1RM)] resistance exercise (horizontal squat, 3-4 sets × 15-30 repetitions) twice a week for 10 weeks. The BFRT performed the exercise with their proximal thighs compressed by air-pressure cuffs for the purpose of blood flow restriction. Squat 1RM, muscle cross-sectional area (CSA) of quadriceps femoris, and countermovement jump (CMJ) height were measured before and after the 10-wk training period. Squat 1RM increased greater in BFRT than in NORT (19.3% vs. 9.7%, P < 0.01). Although the CSA increase was independent of groups, it tended to be larger in BFRT than in NORT (8.3% vs. 2.9%, P = 0.094). On the other hand, CMJ height did not change after the training (P = 0.51). In conclusion, the present study showed that BFRT induced muscle hypertrophy and strength increase, whereas it did not increase CMJ height in previously untrained young men. It is suggested that BFRT is ineffective in improving jump performance.

The cartilage intermediate layer protein gene is associated with lumbar disc degeneration in collegiate judokas.

Lumbar disc degeneration is frequently seen in athletes. Lumbar disc diseases include a spectrum of diseases and/or symptoms, including lumbar disc degeneration. Some reports suggest an association between lumbar disc diseases and a functional single-nucleotide polymorphism (SNP;1184T/C, rs 2073711) of the cartilage intermediate layer protein ( CILP) gene. We hypothesized that lumbar disc degeneration occurrence may be significantly associated with SNP variants at the CILP gene in Japanese collegiate judo athletes. Eighty-nine Japanese judo athletes participated in this study. T2-weighted magnetic resonance imaging was used to define lumbar disc degeneration. Genotyping of the CILP gene (1184T/C) was performed using DNA sequencing. By using logistic regression analysis, significant associations of lumbar disc degeneration with the CILP C allele (odds ratio=4.1, 95% confidence interval: 1.57-10.71) and body weight (odds ratio=1.06, 95% confidence interval: 1.02-1.09) were observed. We conclude that the CILP gene 1184T/C polymorphism is a significant risk factor for lumbar disc degeneration occurrence in Japanese collegiate judo athletes.

Intracellular changes of metal elements by fucoidan extracted from brown seaweed (Cladosiphon okamuranus).

This study was undertaken to elucidate the intracellular changes of metal elements after the administration of fucoidan extracted from Cladosiphon okamuranus. TRL1215 cells (normal rat liver cell line) were treated with 0, 0.1, or 1.0 mg/ml fucoidan and incubated in 5% CO2 at 37 degrees C. The cellular levels of Mg, Al, Fe, and Zn were significantly increased in the 1.0 mg/ml fucoidan-treated cells compared to those of the 0.1 mg/ml fucoidan-treated cells and the control. Next, TRL1215 cells were cultured on Mylar film overnight. At 24 h after 5-bromo-2'-deoxyuridine dosing, 0, 0.1, or 1.0 mg/ml fucoidan was treated for 9 h. The cellular distribution of elements was analyzed using in-air micro-micro-particle induced X-ray emission. The X-ray spectra showed that yields of Al, Mg, and Zn were high in order of the 1.0 mg/ml fucoidan-treated sample, the 0.1 mg/ml fucoidan-treated sample, and the control. Fe yield was mildly increased by fucoidan administration. In fucoidan-treated cells, the focal accumulation of Br was correlated spatially with phosphorous-rich region, suggesting that Br was localized within the nucleus. Al distribution provided a spatial association with Br map. These data suggest that fucoidan increases the accumulations of Al, Mg, Fe, and Zn in normal rat hepatocytes, and fucoidan-binding Al is postulated to be transferred into the nucleus.

Analysis of tissue cadmium distribution in chronic cadmium-exposed mice using in-air micro-PIXE.

This study undertook the analysis of tissue cadmium (Cd) distribution using in-air micro-particle-induced X-ray emission (PIXE) and the examination of the involvement of metal ions in parenteral Cd toxicity. A mouse was injected intraperitoneally with 3 mg/kg body weight of CdCl2 thrice weekly. After 27 wk, the liver and kidney were excised and fixed in 10% formalin solution for 4 h and then embedded in paraffin. Thin paraffin sections were used to analyze trace elements with in-air micro-PIXE and to examine metallothionein protein and histological changes. Cd distribution was determined by micro-PIXE in the liver and renal cortex of the Cd-exposed mouse, and the net Cd count was higher in the liver than in the renal cortex. The net iron (Fe) count was higher in the liver of the Cd-exposed mouse compared to the control, and an opposite tendency was observed in the renal cortex. Wide cellular Cd distribution was demonstrated in the liver and renal cortex of the chronic Cd-exposed mouse compared to the control. Metallothionein staining was increased by chronic exposure to Cd both in the liver and kidney, and nephrotoxicity was more apparent than hepatotoxicity. The modification of tissue Fe and calcium distribution by an intraperitoneal injection of Cd might be involved in Cd-induced toxicity.

Increased plasminogen activator inhibitor-1 and apolipoprotein (a) in coronary atherectomy specimens in acute coronary syndromes.

BACKGROUND: Although increased tissue factor expression is known in vulnerable plaques, there is no reported study to compare plaque fibrinolysis in stable and unstable plaques. This study investigates the extent of plasminogen activator inhibitor-1 (PAI-1) and apolipoprotein (a) [apo(a)] in the plaques of different types of coronary artery disease as well as the correlation between these molecules and infiltration of macrophages to plaques. METHODS: Using immunohistochemical staining, we examined PAI-1 expression and apo(a) deposition in coronary atherosclerotic specimens obtained by directional coronary atherectomy from 19 patients with acute myocardial infarction (AMI), 12 with unstable angina pectoris (UAP), and 13 with stable angina pectoris (SAP). The percentages of the total areas of specimens stained with PAI-1 or apo(a) were estimated by an NIH image program. The proportion of macrophages as a percentage of all cells in plaques was calculated as the macrophage density. RESULTS: We found significantly higher percentages of total areas of specimens stained with PAI-1 in AMI (25.5 +/- 8.6%, P < 0.001) and UAP (22.2 +/- 10.4%, P < 0.005) than in SAP (9.5 +/- 5.0%), as well as with apo(a) (AMI; 11.7 +/- 7.1%, P < 0.005, UAP; 11.1 +/- 5.5%, P < 0.01 versus SAP; 3.9 +/- 1.5%). Linear regression analysis of all the samples showed a correlation between PAI-1 or apo(a) and macrophage density (PAI-1: r = 0.75, P < 0.001 and apo(a): r = 0.56, P < 0.001). CONCLUSIONS: Our results suggest a possible contribution of increased PAI-1 and apo(a) in plaques to the pathogenesis of acute coronary syndromes including impaired fibrinolysis.

Comparison of the isometric cervical extension strength and a cross-sectional area of neck extensor muscles in college wrestlers and judo athletes.

Increasing neck muscle strength can play an important role in preventing neck injuries in contact sports. The purpose of this study was to examine the actual conditions of the isometric cervical extension strength (ICES) and the cross-sectional area (CSA) of neck extensor muscles in male athletes participating in college wrestling and judo. The subjects comprised 18 wrestlers and 37 judo athletes from Nippon Sports Science University in Japan. The ICES was measured at eight angles (126 degrees, 108 degrees, 90 degrees, 72 degrees, 54 degrees, 36 degrees, 18 degrees, 0 degrees ). Transverse slices of 10 mm thickness were obtained at the position of each intervertebral disc between C2 and C3, C3 and C4, C4 and C5 and C5 and C6 using magnetic resonance imaging. The ICES of the wrestlers were significantly higher than those of the judo athletes. The ICES curve against the angle in wrestlers tended to differ from that of judo athletes. The CSA of neck extensor muscles in the wrestlers was significantly larger at all intervertebral levels examined than those of the judo athletes. A significant difference was observed in the CSA of the deepest area of neck extensor muscles between the groups although the difference was not significant in the superficial area. In this study, the ICES and the CSA in wrestlers were shown to be significantly higher and larger respectively than in the judo athletes, indicating a significant difference between these two sports.

Effects of blockade of the renin-angiotensin system on tissue factor and plasminogen activator inhibitor-1 synthesis in human cultured monocytes.

OBJECTIVES: To clarify the pathophysiological significance of the renin-angiotensin system (RAS) in monocytes, we examined the effect of its blockade on tissue factor and plasminogen activator inhibitor-1 (PAI-1) synthesis in human cultured monocytes. METHODS: Monocytes were isolated from healthy volunteers and cultured. Tissue factor and PAI-1 antigens in culture medium and cells were measured by enzyme-linked immunosorbent assay and Western blotting, and mRNA levels were assessed by reverse-transcriptase polymerase chain reaction. RESULTS: We show that the RAS is present in isolated human peripheral blood monocytes. Exogenous angiotensin II increased the levels of tissue factor antigen and mRNA in cultured monocytes, but not of PAI-1 synthesis. An angiotensin converting enzyme (ACE) inhibitor (captopril) and an angiotensin II type 1 (AT1) receptor antagonist (candesartan) decreased the levels of tissue factor protein and mRNA in cultured monocytes. These alterations were accompanied by a reduction in the levels of tumour necrosis factor-alpha protein and mRNA. The levels of PAI-1 protein were reduced by captopril, but not by candesartan. A bradykinin B2 receptor antagonist abolished the suppressive effect of captopril on PAI-1 antigen. CONCLUSIONS: An ACE inhibitor and an AT1 receptor antagonist reduced tissue factor synthesis in these cells. We show different actions of these agents on PAI-1 synthesis. ACE inhibition decreased PAI-1 synthesis mediated by bradykinin production, but AT1 receptor inhibition had no effect.

Expression of very low density lipoprotein receptor mRNA in circulating human monocytes: its up-regulation by hypoxia.

Although very low density lipoprotein (VLDL) receptor expression by macrophages has been shown in the vascular wall, it is not clear whether or not circulating monocytes express the VLDL receptor. We investigated the expression of VLDL receptor mRNA in human peripheral blood monocytes and monocyte-derived macrophages by reverse transcriptase polymerase chain reaction (RT-PCR) and nucleotide sequencing after subcloning of PCR product. VLDL receptor mRNA was detected both in peripheral blood monocytes and monocyte-derived macrophages. Expression of VLDL receptor mRNA was upregulated by hypoxia in monocytes, whereas treatment with oxidized LDL, interleukin-1beta or monocyte chemoattractant protein-1 did not affect the levels of VLDL receptor mRNA in monocytes and macrophages. The present study shows a novel response of VLDL receptor mRNA to hypoxia, suggesting a role for VLDL receptor in the metabolism of lipoproteins in the vascular wall and the development of atherosclerosis.

ST segment elevation in the right precordial leads following administration of class Ic antiarrhythmic drugs.

Electrocardiographic changes were evaluated retrospectively in five patients without previous episodes of syncope or ventricular fibrillation who developed abnormal ST segment elevation mimicking the Brugada syndrome in leads V1-V3 after the administration of class Ic antiarrhythmic drugs. Pilsicainide (four patients) or flecainide (one patient) were administered orally for the treatment of symptomatic paroxysmal atrial fibrillation or premature atrial contractions. The QRS duration, QTc, and JT intervals on 12 lead surface ECG before administration of these drugs were all within normal range. After administration of the drugs, coved-type ST segment elevation in the right precordial leads was observed with mild QRS prolongation, but there were no apparent changes in JT intervals. No serious arrhythmias were observed during the follow up periods. Since ST segment elevation with mild QRS prolongation was observed with both pilsicainide and flecainide, strong sodium channel blocking effects in the depolarisation may have been the main factors responsible for the ECG changes. As the relation between ST segment elevation and the incidence of serious arrhythmias has not yet been sufficiently clarified, electrocardiographic changes should be closely monitored whenever class Ic drugs are given.

Circadian variation of vasovagal syncope.

INTRODUCTION: Circadian patterns have been demonstrated for several cardiovascular catastrophes. Chronobiologic factors play a role in the emergence of vasovagal syncope (VVS); however, diurnal variation of syncopal episodes in VVS has not been reported previously. METHODS AND RESULTS: We assessed daily distribution of the time of syncopal episodes in VVS. Time of syncope could be determined in 80 episodes in 54 patients (32 men and 22 women; mean age 37 years, range 12 to 67). Patients who were prescribed beta blockers or vasodilators, and who had syncopes related to alcohol intake, were excluded from the study. Head-up tilt testing was performed in 53 patients. The distribution of the episodes of VVS in 3-hour intervals differed significantly from uniform occurrence (P < 0.0001), with a peak frequency between 6 A.M. and noon (67.5% of total episodes). In patients who had experienced the initial syncope in the morning, most (78%) of the next syncopal episodes also occurred in the morning. There was no significant correlation between the time of last syncopes and tilt testing results. CONCLUSION: We demonstrated a prominent circadian variation in the frequency of VVS, with a peak in the morning. Recognition of the daily distribution of VVS is useful for patient education and therapeutic strategy.