Hidetoshi Yonemochi

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.

Circadian Variation of QT Interval Dispersion Correlation with Heart Rate Variability

The circadian variation of QT interval dispersion and its correlation with heart rate variability (HRV) was examined in 17 normal subjects by using 24-hour recordings of three-lead electrocardiograms. Measurements of HRV, R-R intervals, and QT intervals were made for the first 6 minutes of each hour over a 24-hour period. Spectral analysis of HRV yielded low-frequency power (LF) (0.04-0.15 Hz), high-frequency power (HF) (0.15-0.40 Hz), and the ratio of LF to HF (LF/HF). A rate-corrected QT interval (QTc) was calculated by Bazetts formula, and QT and QTc dispersion was defined as the difference between the maximum and minimum values in any two leads. High-frequency power and QT interval were greater at night than during the day: conversely, LF/HF and dispersion of QT and QTc were greater during the day. The QTc interval remained virtually unchanged throughout the 24-hour period. The dispersion of QTc showed a significant negative correlation with HF and a significant positive correlation with LF/HF. The results suggest that an increased sympathetic tone or a decreased vagal tone increases QT dispersion in healthy subjects.

Circadian rhythm of the signal averaged electrocardiogram and its relation to heart rate variability in healthy subjects

Objective To examine the circadian variation in the signal averaged electrocardiogram (saECG) and heart rate variability and investigate their relations in healthy subjects. Methods 24 hour ECGs were obtained with a three channel recorder using bipolar X, Y, and Z leads in 20 healthy subjects. The following variables were determined hourly: heart rate, filtered QRS (f-QRS) duration, low and high frequency components of heart rate variability (LF and HF), and the LF/HF ratio. Results Heart rate, f-QRS duration, HF, and the LF/HF ratio showed significant circadian rhythms, as determined by the single cosinor method. Heart rate and the LF/HF ratio increased during daytime, and f-QRS duration and HF increased at night. f-QRS duration was negatively correlated with heart rate (r = 0.95, p < 0.001) and the LF/HF ratio (r = 0.94, p < 0.001) and positively with HF (r = 0.93, p < 0.001). Conclusions f-QRS duration has a significant circadian rhythm in healthy subjects and is closely related to the circadian rhythm of autonomic tone.

Evaluation of Autonomic Influences on QT Dispersion Using the Head-Up Tilt Test in Healthy Subjects

Our objective was to examine the autonomic influence on QT interval dispersion using the head‐up tilt test in healthy subjects. RR and QT intervals, heart rate variability, and plasma norepinephrine concentration were measured in the supine position and tilting to 70± for 20 minutes using a footboard support in 15 healthy male volunteers (mean age ± SD: 28.0 ± 4.5 years). The rate‐corrected QT interval (QTc) was calculated using Bazetts formula, and QT and QTc dispersions were defined as the maximum minus minimum values for the QT and QTc, respectively, from the 12‐lead ECG. Spectral analysis of the heart rate variability generated values for the low‐ and high‐frequency powers (LF and HF) and their ratio (LF/HF). Compared with values obtained in the supine position, tilting significantly increased QT (P < 0.05) and QTc dispersion (P < 0.01), the LF/HF ratio (P < 0.0001), and plasma norepinephrine concentration (P < 0.0001), and significantly decreased HF (P < 0.0001). QTc dispersion was positively correlated with the LF/HF ratio and plasma norepinephrine concentration, and negatively correlated with HF. These results suggest that head‐up tilt testing increases QT dispersion by increasing sympathetic tone and/or decreasing vagal tone in healthy subjects.

Phosphatidylinositol 3-kinase-dependent activation of akt, an essential signal for hyperthermia-induced heat-shock protein 72, is attenuated in streptozotocin-induced diabetic heart

We tested the hypothesis that phosphatidylinositol 3-kinase (PI 3-kinase)-dependent activation of Akt is essential for the expression of cardiac heat-shock protein 72 (HSP72) and that this pathway is impaired in the streptozotocin (STZ)-induced diabetic heart. STZ-induced male diabetic rats were treated with insulin (STZ-insulin group, n = 26) or vehicle (STZ-vehicle group, n = 61) for 3 weeks. Whole-body hyperthermia (43°C for 20 min) was applied, and the heart was isolated 24 h later. Compared with control heart, hyperthermia-induced HSP72 expression and phosphorylation of Akt were attenuated in the STZ-vehicle heart. Pretreatment with wortmannin attenuated hyperthermia-induced HSP72 expression and phosphorylation of Akt. In isolated perfused heart experiments, the hyperthermia-treated STZ-vehicle heart showed poor left ventricular functional recovery during reperfusion after no-flow global ischemia compared with hyperthermia-treated control heart. Insulin treatment restored HSP72 expression and reperfusion-induced functional recovery. In cultured neonatal rat cardiomyocytes, hyperthermia-induced HSP72 expression was enhanced by insulin, together with tolerance against hypoxia-reoxygenation injury. Wortmannin and LY294002 inhibited hyperthermia-induced HSP72 expression and phosphorylation of Akt. Our results indicate that activation of Akt, in a PI 3-kinase–dependent manner, is essential for hyperthermia-induced HSP72 expression in association with cardioprotection, suggesting impairment of this signaling pathway in the STZ-induced diabetic heart, probably due to insulin deficiency.

Mechanism of β-Adrenergic Receptor Upregulation Induced by ACE Inhibition in Cultured Neonatal Rat Cardiac Myocytes Roles of Bradykinin and Protein Kinase C

Background—Although bradykinin is thought to contribute to the effects of ACE inhibitors on the cardiovascular system, its precise role remains to be elucidated. Evidence suggests that bradykinin might be important in the upregulation of β-adrenergic receptors (β-ARs) induced by ACE inhibitors, and the role of bradykinin in this effect has now been investigated with cultured neonatal rat cardiac myocytes. Methods and Results—The density of β-ARs on the myocyte surface was determined with a binding assay with [3H]CGP-12177. Incubation of cultured myocytes for 24 hours with the ACE inhibitor captopril (1 μmol/L) increased β-AR density by 35% and enhanced the response of cells to isoproterenol but not to forskolin. Neither an angiotensin-II type 1 (AT1) receptor antagonist, CV-11974, nor angiotensin-I affected β-AR density. However, the bradykinin B2 receptor antagonist Hoe 140 abolished the effect of captopril on β-AR upregulation in a dose-dependent manner. The protein kinase C inhibitor staurosporine (20 ...

Gender differences in ventricular repolarization: Terminal T wave interval was shorter in women than in men

NAKAGAWA, M., et al. : Gender Difference in Ventricular Repolarization: Terminal T Wave Interval was Shorter in Woman than in Men. The incidence of sudden death is lower in women than in men, although women have a longer QT interval and are more prone to develop torsades de points than men. It has been recently proposed that the time interval between the apex and end of the T wave (Ta‐e) represents the transmural dispersion of ventricular repolarization. Gender and age differences in Ta‐e interval have not been fully assessed previously. Standard surface 12‐lead ECGs recorded in 760 healthy subjects (382 women, 0–88 years of age) were studied. The intervals from j‐point to the apex of the T wave (JaT) and to the end of the T wave (JeT) were measured in lead V5 in each ECG and corrected by preceding RR intervals using the formula of Bazett (JaTc and JeTc). The Ta‐e and Ta‐e/JeT ratio were also evaluated. Both JaTc and JeTc intervals were significantly longer in women aged > 20 years than in men of the same age(P < 0.0001). The difference was due to shortening of these intervals after puberty in men. However, the Ta‐e interval was significantly shorter in women than in men(P < 0.05)and subsequently the Ta‐e/JeT ratio was significantly smaller in women than in men (P < 0.0001). The results showed gender differences in the Ta‐e interval and JaTc and JeTc intervals in healthy adults, and suggest that the small transmural dispersion of repolarization in women, in spite of the long JaTc and JeTc intervals, might be a beneficial antiarrhythmic property. (PACE 2003; 26[Pt. I]:59–64)

Pioglitazone shift circadian rhythm of blood pressure from non‐dipper to dipper type in type 2 diabetes mellitus

Background  Insulin resistance significantly correlated with a non‐dipper type of essential hypertension. Thiazolidinediones (TZD), oral hypoglycaemic agents that act as insulin sensitizers, have been demonstrated in multiple in vivo and in vitro studies to possess antihypertensive properties. This study examined the efficacy of TZD therapy with pioglitazone at transforming the circadian rhythms of blood pressure from a non‐dipper to a dipper type.

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 · kg−1 · day−1) or glibenclamide (5 mg · kg−1 · day−1) for 4 weeks. Thereafter, hyperthermia (43°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.

Smoking is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients

Background  Smoking and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetic patients. This study tested the hypothesis that smoking is associated with insulin resistance/hyperinsulinaemia and cardiovascular autonomic dysfunction in type 2 diabetic patients who are not treated with insulin.