Gender differences in the effect of auditory stimuli on ventricular repolarization in healthy subjects.

INTRODUCTION: Gender differences in the incidence of ventricular arrhythmias have been reported and torsade de pointes associated with long-QT syndrome (LQTS) is more common in women than men. Although auditory stimulation has been recognized as an important trigger of torsade de pointes in LQT2 patients, the normal response and gender differences in ventricular repolarization induced by auditory stimuli remained to be evaluated systematically. METHODS: Holter ECGs were recorded in 30 healthy volunteers (14 men aged 25 +/- 4 years and 16 women aged 23 +/- 2 years). They were awakened by an alarm clock at 5:00 am. The RR and QT (QTc) intervals and the T-wave amplitude were measured before and after alarm ringing. RESULTS: The morphology of the T-wave changed dynamically and transiently during awakening. The RR interval significantly decreased just after sounding of the alarm in both sexes (P < 0.0001). The QT interval changed little after the alarm ringing and was significantly longer in women than men (P < 0.0001). The QTc intervals were significantly prolonged just after alarm ringing in both sexes (P < 0.0001); QTc prolongation was significantly longer and more sustained in women than men (P < 0.0001). The T-wave amplitude decreased after the alarm and was significantly lower in women than men (P = 0.0001). CONCLUSION: Auditory stimulation abruptly and abnormally modulated the dynamics of ventricular repolarization in healthy subjects; the effect was more pronounced in women than men. This gender difference may partially account for the increased susceptibility of women with electrically unstable hearts to arrhythmogenesis.

Early atorvastatin therapy improves cardiac function in patients with acute myocardial infarction.

BACKGROUND: A number of experimental and clinical studies have demonstrated a cardioprotective effect of statins; however, the effect of atorvastatin on cardiac function in patients with an acute myocardial infarction (AMI) has not been established. METHODS AND RESULTS: Thirty consecutive patients with an AMI (16 males and 14 females) were enrolled. All the patients underwent successful percutaneous coronary intervention in the early phase after the onset of an AMI. Patients with a total cholesterol level > 200mg/dL on admission (n = 14) were assigned to the atorvastatin group. They began taking 10 mg of atorvastatin daily within 48 h after the onset of the AMI, while the other patients (n = 16) did not receive atorvastatin and served as the control group. Echocardiography and blood sampling to measure brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) levels were repeated on the 2nd day (2D), 3 weeks (3W), 12 weeks (12W), and 24 weeks (24W) after the onset of the AMI. The percentage of patients with a high BNP level (BNP > 20 pg/mL) was significantly decreased from 2D to 24W in the atorvastatin group, but not in the control group (100 to 57% in the atorvastatin group, p < 0.05; 100 to 80% in the control group, n.s.). Similar results also occurred with respect to the ANP level (ANP > 40 pg/mL) (62 to 21% in the atorvastatin group, p < 0.05; 57 to 40% in the control group, n.s.). The left ventricular ejection fraction was significantly higher in the atorvastatin group than the control group at 3W (66.0 ± 7.8% vs. 56.5 ± 11.8%, p < 0.05) and 24W (67.5 ± 9.2% vs. 59.7 ± 9.8%, p < 0.05). In the atorvastatin group, the left ventricular systolic diameter was significantly decreased at 24W compared with that at 2D (37.1 ± 8.0 mm to 31.4 ± 6.5 mm, p < 0.05). CONCLUSIONS: Initiation of atorvastatin in the early phase of an AMI has beneficial effects on cardiac function, probably by improving left ventricular remodeling.

Hepatocyte growth factor levels are associated with the results of 123I-metaiodobenzylguanidine myocardial scintigraphy in patients with type 2 diabetes mellitus.

Elevated hepatocyte growth factor (HGF) levels and cardiovascular autonomic dysfunction are associated with a high mortality rate in patients with type 2 diabetes mellitus. We tested the hypothesis that elevated HGF is associated with insulin resistance and cardiovascular autonomic dysfunction in patients with type 2 diabetes mellitus not receiving insulin treatment. The study group consisted of 21 type 2 diabetes mellitus patients with high HGF levels (>0.26 ng/mL, 58 +/- 5 years old, high-HGF group). The control group consisted of 25 type 2 diabetes mellitus patients with normal HGF levels (

Correlations of visceral fat accumulation and atherosclerosis in Japanese patients with type 2 diabetes mellitus.

We tested the hypothesis that increased abdominal visceral fat accumulation (VFA) is associated with insulin resistance and aortic stiffness in patients with type 2 diabetes mellitus not receiving insulin treatment. The study consisted of 22 Japanese patients with type 2 diabetes mellitus and high VFA (> or =100 cm(2); age, 61 +/- 7 years; high VFA group) and a control group of 18 age-matched patients with normal VFA (<100 cm(2); age, 60 +/- 8 years; normal VFA group). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method. The BaPWV was used as an index of atherosclerosis. The body mass index values (P < .05), waist circumferences (P < .0005), and waist-to-hip ratios (P < .05) were larger in the high VFA group than in the normal VFA group. The BaPWV was higher in the high VFA group than in the normal VFA group (P < .0001). Fasting plasma glucose (P < .05), insulin concentrations (P < .0001), and the homeostasis model assessment (HOMA) index (P < .001) were higher in the high VFA group than in the normal VFA group. Multiple regression analysis showed that the VFA level was independently predicted by BaPWV and the HOMA index. Our results indicate that the elevation of VFA in Japanese patients with type 2 diabetes mellitus is characterized by increased aortic stiffness and insulin resistance and that BaPWV and the HOMA index are independent predictors of VFA.

High-sensitivity C-reactive protein level is a significant risk factor for silent cerebral infarction in patients on hemodialysis.

In patients with chronic renal failure on hemodialysis (HD), silent cerebral infarctions (SCIs) are associated with high mortality. The levels of high-sensitivity C-reactive protein (HSCRP), a marker of inflammation and atherosclerosis, elevate with increasing renal dysfunction. We tested the hypothesis that increased HSCRP levels correlate with the occurrence of SCI in HD patients. By brain magnetic resonance imaging findings, we divided 54 patients undergoing HD into a with-SCI group (61 +/- 8 years, n = 30) and a without-SCI group (60 +/- 7 years, n = 24). We compared sex, body mass index, metabolic profiles, HSCRP levels, and smoking habits in Japanese patients on HD with and without SCI. We made the following observations: (1) The number of patients with diabetes or hypertension did not differ between the 2 groups. (2) The levels of HSCRP were higher in the with-SCI group in comparison with the without-SCI group (P < .0001). (3) The proportion of smokers was higher in the with-SCI group than in the without-SCI group (P < .05). (4) Plasma levels of high-density lipoprotein cholesterol were lower, whereas uric acid was higher, in the with-SCI group than in the without-SCI group (P < .05 and P < .0001, respectively). (5) Multivariate logistic analysis identified HSCRP levels as being significantly associated with the presence of SCI (odds ratio, 1.61; 95% confidence interval, 1.17-2.85; P < .001). This study indicates that patients in chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI and that HSCRP is significantly associated with the presence of SCI in HD patients.

Correlations between homocysteine levels and atherosclerosis in Japanese type 2 diabetic patients.

Elevated total plasma homocysteine (tHcy) level and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that tHcy correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 40 Japanese patients with type 2 diabetes mellitus and high tHcy levels (mean age +/- SD, 57 +/- 7 years) and a control group of 45 age-matched patients with normal tHcy levels (mean age +/- SD, 57 +/- 6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by an automatic oscillometric method. Brachial-ankle pulse wave velocity was used as an index of atherosclerosis. Body mass index values (P < .05), waist circumferences (P < .05), and the waist-to-hip ratios (P < .05) were larger in the high-tHcy group than in the normal-tHcy group. The BaPWV was higher in the high-tHcy group than in the normal-tHcy group (P < .0001). Fasting plasma glucose (P < .005) and insulin concentrations (P < .0001), and the homeostasis model assessment (HOMA) index (P < .0001) were higher in the high-tHcy group than in the normal-tHcy group. Multiple regression analysis showed that tHcy levels were independently predicted by BaPWV and the HOMA index. In conclusion, our results indicate that the elevated level of tHcy in Japanese patients with type 2 diabetes mellitus is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and the HOMA index are independent predictors of tHcy.

Hyperthermia treatment prevents angiotensin II-mediated atrial fibrosis and fibrillation via induction of heat-shock protein 72.

We tested the hypothesis that atrial fibrosis and atrial fibrillation (AF) evoked by angiotensin II (AII) could be prevented by the induction of heat-shock protein 72 (HSP72) by hyperthermia (HT). In cultured atrial fibroblasts isolated from male Sprague-Dawley rats, HT (42 degrees C) was applied for 30 min. AII (100 nmol/L) was added to the medium 8 h later. HT induced the expression of HSP72, which was associated with the attenuation of AII-induced extracellular signal-regulated kinase (ERK1/ERK2) phosphorylation, alpha-smooth muscle actin (alpha-SMA) expression, transforming growth factor-beta(1) secretion, collagen synthesis, and expression of collagen type I and tissue inhibitor of metalloproteinases-1. A small interfering RNA targeting HSP72 abolished these anti-fibrotic effects of HT. In male Sprague-Dawley rats in vivo, an osmotic mini-pump was subcutaneously implanted for continuous infusion of AII (400 ng/kg/min). Whole-body HT (43 degrees C, 20 min) was applied 24 h before and 7, 14, and 21 days after the start of the AII infusion. Repeated HT led to the induction of HSP72 expression, which resulted in an attenuation of AII-induced left atrial fibrosis. In an electrophysiological study using isolated perfused heart, continuous AII caused slowing of interatrial conduction without affecting atrial refractoriness. In AII-treated hearts, extrastimuli from the right atrial appendage resulted in a high incidence of repetitive atrial responses, which were suppressed by treatment with HT. Our results suggest that HT treatment is effective in suppressing AII-mediated atrial fibrosis and AF via induction of HSP72 at least in parts, and is thus expected to be a novel strategy for prevention of AF.

Correlations of high-sensitivity C-reactive protein and atherosclerosis in Japanese type 2 diabetic patients.

BACKGROUND: The elevated level of high-sensitivity C-reactive protein (HSCRP) and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the HSCRP correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. MATERIAL AND METHODS: The study consisted of 46 Japanese patients with type 2 diabetes and high HSCRP group (0.3-1.0 mg/dl, age: 57+/-5 years, mean+/-s.d.) and a control group of 55 age-matched patients with low HSCRP group (<0.3 mg/dl, 57+/-6 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method and was used as an index of atherosclerosis. RESULTS: The body mass index (BMI) values (P<0.05) and waist circumferences (P<0.0005) and the waist-to-hip ratios (P<0.05) were higher in the high HSCRP group than in the low HSCRP group. The BaPWV was higher in the high HSCRP group than in the low HSCRP group (P<0.0001). Fasting plasma glucose (FPG; P<0.005) and insulin concentrations (P<0.0001), and the homeostasis model assessment (HOMA) index (P<0.0001), were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis showed that HSCRP levels were independently predicted by BaPWV and HOMA index. CONCLUSIONS: Our results indicate that the elevated level of HSCRP in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV and HOMA index are independent predictors of HSCRP.

Predictors for silent cerebral infarction in patients with chronic renal failure undergoing hemodialysis.

In patients with chronic renal failure undergoing hemodialysis (HD), silent cerebral infarctions (SCIs) are associated with high mortality. Levels of hepatocyte growth factor (HGF) increase with renal dysfunction and may be a novel predictor of cerebrovascular events. We examined if HGF is a predictor of SCI in HD patients. Brain magnetic resonance imaging findings were used to divide 50 patients undergoing HD into 2 groups, a group with SCI (age, 61 +/- 8 years, mean +/- SD; n = 27) and a group without SCI (age, 60 +/- 7 years; n = 23). These patients received 24-hour ambulatory blood pressure monitoring. The number of patients with diabetes or hypertension was not different between the 2 groups. We made the following observations: (1) The percentage of smokers was higher in the group with SCI than in the group without SCI (P < .05). (2) Plasma levels of high-density lipoprotein cholesterol were lower and HGF levels were higher in the group with SCI compared with the group without SCI (P < .05 and P < .005, respectively). (3) Systolic ambulatory blood pressure and mean heart rate at night were higher in the group with SCI than in the group without SCI (P < .05). Multiple logistic regression analysis identified HGF as a significant risk factor for SCI (odds ratio, 1.89; 95% confidence interval, 1.57-3.38; P < .005). Our findings indicate that HGF may be a novel useful predictor of SCI in patients with chronic renal failure undergoing HD.

Abdominal visceral fat accumulation is associated with the results of (123)I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients.

PURPOSE: We tested the hypothesis that increased abdominal visceral accumulation (VFA) is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. METHODS: The fat distribution was evaluated by measuring the VFA by abdominal computed tomography at the umbilical level. The study group consisted of 24 type 2 diabetic patients with high VFA (> or =100 cm(2), age 60 +/- 8 years, high VFA group). The control group consisted of 19 age-matched type 2 diabetic patients with normal VFA (<100 cm(2), age 60 +/- 7 years, normal VFA group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy. RESULTS: Early and delayed (123)I-MIBG myocardial uptake values were lower (p < 0.005 and p < 0.0001, respectively) and the percent washout rate of (123)I-MIBG was higher (p < 0.0005) in the high VFA group than in the normal VFA group. The fasting plasma insulin concentrations (p < 0.005) and the homeostasis model assessment (HOMA) index values (p < 0.0005) were higher in the high VFA group than in normal VFA group. Multiple regression analysis revealed that the level of VFA was independently predicted by the HOMA index values and the myocardial uptake of (123)I-MIBG during the delayed phase. CONCLUSION: Our results demonstrate that the level of VFA is associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus.

High-density lipoprotein cholesterol and insulin resistance are independent and additive markers of left ventricular hypertrophy in essential hypertension.

We examined whether plasma high-density lipoprotein-cholesterol (HDL-C) levels and glucose metabolism parameters are independent or additive predictors of left ventricular hypertrophy (LVH) in patients with untreated essential hypertension. The study group consisted of 41 Japanese patients with untreated essential hypertension and LVH (left ventricular mass index [LVMI] >125 g/m2; age 58+/-6 years, mean+/-SD), and the control group consisted of 39 age-matched patients with untreated essential hypertension without LVH (LVMI

Receptor-mediated suppression of cardiac heat-shock protein 72 expression by testosterone in male rat heart.

The impact of testosterone on cardiac expression of heat-shock protein 72 (HSP72) remains to be elucidated. Male Sprague Dawley rats 10 wk of age (adult) were castrated. Four weeks later, testosterone (10 mg/kg, ip) was administered as a single dose, followed by the application of hyperthermia (HT) (43 C) at 6 h after testosterone administration. Twenty-four hours later, each heart was isolated. Cardiomyocytes were prepared from 3- to 5-d-old Wistar rats and male Sprague Dawley rats 10 wk of age. Testosterone (0.1-10 microM) was added to the medium, followed by the application of HT (42 C). Twenty-four hours later, cells were collected. We observed the following: 1) Exogenous testosterone suppressed HT-induced HSP72 expression, but castration alone had no influence. 2) HT resulted in better reperfusion-induced cardiac performance in castrated rats comparable with sham-operated rats, which was inhibited by testosterone. The number of apoptotic cells after ischemia/reperfusion was also increased by testosterone. 3) HT-induced HSP72 expression in cultured cardiomyocytes was suppressed by testosterone. 4) HT resulted in less damage to cells, including apoptosis, in response to hypoxia/reoxygenation, which was inhibited by testosterone. 5) Flutamide, a testosterone receptor blocker, cancelled the suppressive effects of testosterone on HSP72 expression. 6) The HT-induced increase in heat-shock factor 1 activity to bind to heat-shock element DNA was suppressed by testosterone, and this was reversed by flutamide. Our results indicate that testosterone potentially has inhibitory effects on cardiac HSP72 expression by modulating transcription, through testosterone receptor-mediated genomic mechanisms.

Correlations of urinary albumin excretion and atherosclerosis in Japanese type 2 diabetic patients.

Microalbuminuria and aortic stiffness are associated with high mortality in type 2 diabetic patients. We tested the hypothesis that the presence of microalbuminuria correlates with aortic stiffness and insulin resistance in type 2 diabetic patients. The study consisted of 36 Japanese patients with type 2 diabetes and microalbuminuria (age: 56+/-9 years, mean+/-S.D.) and a control group of 44 age-matched patients with normoalbuminuria (56+/-7 years). Brachial-ankle pulse wave velocity (BaPWV) was measured by automatic oscillometric method. BaPWV was used as an index of atherosclerosis. The BaPWV was higher in the microalbuminuria group than in the normoalbuminuria group (p<0.005). Fasting plasma glucose (p<0.05) and insulin concentrations (p<0.005), and the homeostasis model assessment (HOMA) index (p<0.0005), were higher in the microalbuminuria group than in the normoalbuminuria group. Multiple regression analysis showed that urinary albumin excretion was independently predicted by BaPWV and HOMA index. Our results indicate that the presence of microalbuminuria in Japanese patients with type 2 diabetes is characterized by increased aortic stiffness and insulin resistance, and that the BaPWV, HOMA index are independent predictors of urine albumin excretion.

Smoking is associated with urinary albumin excretion: an evaluation of premenopausal patients with type 2 diabetes mellitus.

Cigarette smoking and an increase in urinary albumin excretion are associated with high mortality in patients with type 2 diabetes mellitus. We tested the hypothesis that the presence of a smoking habit correlates with increased urinary albumin excretion in premenopausal Japanese women with type 2 diabetes mellitus. The study consisted of 20 premenopausal Japanese patients with type 2 diabetes mellitus in the current-smokers group (age, 45 +/- 4 years, mean +/- SD). The control group consisted of 35 age-matched never-smoker patients (age, 45 +/- 5 years). Serum triglyceride levels were higher and high-density lipoprotein cholesterol levels were lower in the current-smokers group than in the never-smokers group (P < .05 and P < .01, respectively). Furthermore, fasting plasma insulin concentrations and the homeostasis model assessment index were higher in the current-smokers group than in the never-smokers group (P < .005 and P < .001, respectively). Urinary albumin excretion also was higher in the current-smokers group than in the never-smokers group (P < .0001). Multivariate logistic analysis revealed that urinary albumin excretion is independently associated with current smoking in Japanese premenopausal with type 2 diabetes mellitus (odds ratio, 1.79; 95% confidence interval, 1.08-3.87; P < .01). The results of this study show that current smoking is associated with an increased level of urinary albumin excretion, suggesting that smoking was a risk factor in the development of increased urinary albumin excretion in these patients.

Homocysteine levels are associated with the results of 123I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients.

PURPOSE: Elevated total plasma homocysteine (tHcy) levels and cardiovascular autonomic dysfunction are associated with a high mortality in type 2 diabetic patients. We tested the hypothesis that hyperhomocysteinemia is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. METHODS: The study group consisted of 17 type 2 diabetic patients with high tHcy levels (>15 mmol/l, age 58+/-5 years, high tHcy group). The control group consisted of 23 age-matched type 2 diabetic patients with normal tHcy levels (

[Evaluation of autonomic function using posture change].

There are several examinations to evaluate cardiac autonomic function. Autonomic neuropathy is a common complication of diabetes mellitus and is associated with increased mortality. Baroreflex sensitivity (BRS) is a marker for the ability to augment vagal activity. Several studies have shown that BRS is impaired in diabetes with autonomic neuropathy. The head-up tilt test is the most useful tool to diagnose the neurally mediated syncope. We have developed a new non-invasive method to evaluate the baroreflex using downward tilting (DT-BRS). In our previous study conducted in healthy volunteers and diabetic patients, we demonstrated a strong correlation between systolic blood pressure increase and corresponding RR interval lengthening during downward tilting, which yielded DT-BRS values that correlated well with the BRS value obtained by the phenylephrine method (Phe-BRS). Heart rate responses observed after both squatting and standing (squatting test) are assumed to be a simple and useful tool to assess autonomic activity. We reported that indices of the squatting test showed a significant correlation with BRS assessed by Phe-BRS in diabetes. DT-BRS and the squatting test may provide promising information for the assessment of reflex vagal activity in diabetes.

Pioglitazone but not glibenclamide improves cardiac expression of heat shock protein 72 and tolerance against ischemia/reperfusion injury in the heredity insulin-resistant rat.

We tested the hypothesis that pioglitazone could restore expression of heat shock protein (HSP)72 in insulin-resistant rat heart. At 12 weeks of age, male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control (LETO) rats were treated with pioglitazone (10 mg x kg(-1) x day(-1)) or glibenclamide (5 mg x kg(-1) x day(-1)) for 4 weeks. Thereafter, hyperthermia (43 degrees C for 20 min) was applied. In response to hyperthermia, the activation of serine/threonine kinase Akt depending on phosphatidylinositol 3 (PI3) kinase was necessary for cardiac expression of HSP72. Hyperthermia-induced activation of Akt and HSP72 expression were depressed in OLETF rat hearts. Pioglitazone but not glibenclamide improved insulin sensitivity in OLETF rats, which was associated with the restoration of Akt activation and HSP72 expression. In experiments with isolated perfused heart, reperfusion-induced cardiac functional recovery was suppressed in OLETF rat hearts, which was improved by pioglitazone but not glibenclamide. Our results suggest that PI3 kinase-dependent Akt activation, an essential signal for HSP72 expression, is depressed in the heart in insulin-resistant OLETF rats, and the results suggest also that the restoration of HSP72 expression and tolerance against ischemia/reperfusion injury by treatment with pioglitazone might be due to an improvement of insulin resistance, leading to restoration of impaired PI3 kinase-dependent Akt activation in response to hyperthermia.

Diazoxide-induced cardioprotection via DeltaPsim loss depending on timing of application.

Although the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in cardioprotection is widely accepted, it remains unclear when their opening is critical for protection. We tested the hypothesis that the mitoKATP channel acts as a trigger or mediator of protection against apoptosis through loss of mitochondrial inner membrane potential (DeltaPsim). Exposure of neonatal rat cardiomyocytes to H2O2 (0.5 mmol/L) resulted in apoptosis associated with severe DeltaPsim loss. Pretreatment with diazoxide (20 to 100 micromol/L) prevented H2O2-induced apoptosis and DeltaPsim loss at 2 but not 18 h after exposure, while the latter was prevented by cotreatment with diazoxide. Lack of protection by pretreatment with diazoxide was observed in cardiomyocytes cultured in a medium containing H2O2 for 2 h and then not containing for 16 h. The slopes of the regression lines of the relationship between the proportion of apoptotic cells and DeltaPsim loss (y = -0.89 vs. -0.42) and the proportion of cells with high side scatter signal differed between cardiomyocytes exposed H2O2 for 2 and 18 h. Diazoxide per se caused a transient DeltaPsim loss (within 30 min) with a recovery followed by persistent DeltaPsim loss (after 6 h). Inhibition of the former by 5-hydroxydecanoate (5-HD, 0.5 mmol/L) abolished protection of pretreatment with diazoxide (trigger phase), while that of the latter prevented the protection of cotreatment with diazoxide (mediator phase). Our results suggest that mitoKATP channels act as a trigger and mediator of cardioprotection through a transient or persistent DeltaPsim loss depending on phenotypic consequence in response to oxidants.

Influence of menstrual cycle on QT interval dynamics.

OBJECTIVES: The aim of this study was to investigate the effects of the menstrual cycle on QT interval dynamics and the autonomic tone in healthy women. METHODS: Holter ECGs were recorded in 11 healthy women aged 18-32 years during the follicular and luteal phases of their regular menstrual cycle. The interval from QRS onset to the apex (QaT) and to the end of the T-wave (QeT), the interval between the apex and the end of the T-wave (Ta-e), and RR intervals were measured automatically in the course of 24 hours by Holter ECGs. The QeT/RR, QaT/RR, and Ta-e/RR relationships were evaluated in each subject. The autonomic tone was assessed by the serum catecholamine level at rest and heart rate variability was measured by Holter ECGs. RESULTS: (1) The follicular and luteal phases did not differ significantly with respect to the slopes of the QeT/RR, QaT/RR, and Ta-e/RR relationships. However, QeT and QaT intervals were significantly shorter for all RR intervals in the luteal than in the follicular phase (P < 0.0001). (2) The serum progesterone concentration was significantly higher in the luteal than in the follicular phase (P < 0.001). (3) Noradrenaline was significantly higher in the luteal than in the follicular phase (P < 0.05). There was no significant difference in the follicular and luteal phases with respect to heart rate variability measurements. CONCLUSIONS: Our results suggest that the menstrual cycle affects the QT intervals. The observed shorter QT interval during the luteal than the follicular phase may be attributable to the increase in serum progesterone and sympathetic tone.

Hyperhomocysteinemia is a significant risk factor for silent cerebral infarction in patients with chronic renal failure undergoing hemodialysis.

In patients with chronic renal failure undergoing hemodialysis (HD), the presence of silent cerebral infarction (SCI) is associated with high mortality. Plasma total homocysteine (tHcy), which increases with renal dysfunction, has been flagged as a novel predictor for cerebrovascular events. We tested the hypothesis that the presence of SCI correlates with tHcy in HD patients. Based on brain magnetic resonance imaging findings, 44 patients undergoing HD were divided into a with-SCI group (61+/-9 years [mean+/-SD]; n=24) and a without-SCI group (60+/-8 years, n=20), in whom 24-hour ambulatory blood pressure monitoring was performed. The number of patients with diabetes or hypertension was not different between the 2 groups. We made the following observations: (1) the percentage of smokers was higher in the with-SCI group than in the without-SCI group (P<.05); (2) plasma levels of high-density lipoprotein cholesterol were lower and tHcy was higher in the with-SCI group than in the without-SCI group (P<.05 and P<.0001, respectively); (3) and systolic ambulatory blood pressure and mean heart rate during nighttime were higher in the with-SCI group than in the without-SCI group (P<.05). Multivariate logistic analysis identified hyperhomocysteinemia as an independent and significant risk factor for SCI (odds ratio, 1.22; 95% CI, 1.10-1.36; P<.01). Our findings indicate that plasma tHcy may be a novel useful predictor for SCI in patients with chronic renal failure undergoing HD.