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Hiroko Miyazaki,
Mikiko Nakagawa,
Yukie Shin,
Osamu Wakisaka,
Tetsuji Shinohara,
Kaori Ezaki,
Yasushi Teshima, Kunio Yufu,
Naohiko Takahashi,
Masahide Hara,
Tetsunori Saikawa
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ABSTRACT: Background: Although J-waves are seen in both patients with idiopathic ventricular fibrillation (IVF) and the general population, their genesis remains unclear. To assess the relationship between J-waves and autonomic tone we investigated the circadian variation of J-waves in individuals with and without IVF. Methods and Results: In study 1, we obtained resting 12-lead ECG and Holter ECG recordings in 258 individuals undergoing screening for heart disease. In 60 of these subjects (23.3%), we detected J-waves on Holter ECGs; 40 of them (66.7%) had shown no J-waves on 12-lead ECGs. In study 2, we measured the J-wave amplitude, heart rate (HR), and HR variability [high frequency (HF) and the ratio of low- to high-frequency (LF/HF)] on Holter ECGs recorded in 5 patients with IVF and 20 control subjects who had manifested J-waves. The J-wave amplitude increased at night and decreased during the day in both groups; it was significantly higher in the IVF patients (P<0.0001). In both groups, the J-wave amplitude showed a significant negative correlation with HR and LF/HF and a significant positive correlation with HF. The slope of the J/HR and J/(LF/HF) relationship was significantly steeper in the IVF patients. Conclusions: The J-wave amplitude was more significantly influenced by the autonomic balance in IVF patients than in the controls. Autonomic J-wave modulation may yield important information on the genesis of J-waves.
Circulation Journal 10/2012; · 3.77 Impact Factor
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ABSTRACT: Background: We previously reported that baroreflex sensitivity (BRS) or cardiac iodine 123 metaiodobenzylguanidine ((123)I-MIBG) scintigraphic findings can predict cardiovascular prognosis in type 2 diabetic patients. We therefore tested the hypothesis that the combination of BRS and (123)I-MIBG scintigraphic findings could strengthen the predictive power for major adverse cerebral and cardiovascular events (MACCE). Methods and Results: From 1998, we have evaluated both BRS and (123)I-MIBG scintigraphy in 165 type 2 diabetic patients (77 females, 88 males, mean age 59±12 years). Based on the ROC curves, depressed BRS was defined as <5.63mmHg/s, and enhanced washout ratio (WR) was defined as ≥41.4%. Each patient was divided into 3 groups based on the "BRS-MIBG combination score" as follows: 0, patients having both preserved BRS and preserved WR; 1, patients having either depressed BRS or enhanced WR; 2, patients having both depressed BRS and enhanced WR. During the mean of 4.7±2.7 years of follow-up, 19 patients developed MACCE. The MACCE-free ratio was significantly higher in the lower BRS-MIBG combination score group (log-rank 16.41, P=0.0003). Cox proportional hazards regression analysis revealed that BRS-MIBG combination score was independently associated with the incidence of MACCE (hazard ratio 4.06, P=0.0237). Conclusions: Our results suggest that combined assessment of the BRS and (123)I-MIBG scintigraphic findings is more useful for identifying the type 2 diabetic patients at high risk for MACCE.
Circulation Journal 09/2012; · 3.77 Impact Factor
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ABSTRACT: Reactive oxygen species (ROS) are important intracellular signaling molecules and are implicated in cardioprotective pathways
including ischemic preconditioning. Statins have been shown to have cardioprotective effects against ischemia/reperfusion
injury, however, the precise mechanisms remain to be elucidated. We hypothesized that ROS-mediated signaling cascade may be
involved in pravastatin-induced cardioprotection. Cultured rat cardiomyocytes were exposed to H2O2 for 30min to induce cell injury. Pravastatin significantly suppressed H2O2-induced cell death evaluated by propidium iodide staining and the MTT assay. Incubation with pravastatin activated catalase,
and prevented a ROS burst induced by H2O2, which preserved mitochondrial membrane potential. Protective effects were induced very rapidly within 10min, which was
concordant with the up-regulation of phosphorylated ERK1/2. L-NAME, 5HD, N-acetylcysteine (NAC) and staurosporine inhibited ERK1/2 phosphorylation and also reduced pravastatin-induced cardioprotection,
suggesting NO, mitochondrial KATP (mitoKATP) channels, ROS and PKC should be involved in the cardioprotective signaling. We also demonstrated that pravastatin moderately
up-regulated ROS generation in a 5HD-inhibitable manner. In isolated perfused rat heart experiments, pravastatin administered
10min prior to no-flow global ischemia significantly improved left ventricular functional recovery, and also reduced infarct
size, which were attenuated by the treatment with NAC, 5HD, L-NAME or staurosporine. Administration of pravastatin from the
beginning of reperfusion also conferred cardioprotection. Pravastatin protected the cardiomyocytes against oxidative stress
by preventing the ROS burst and preserving mitochondrial function. Moderately up-regulated ROS production by mitoKATP channels opening is involved in the pro-survival signaling cascade activated by pravastatin.
KeywordsReactive oxygen species-Statin-Mitochondria-Catalase-ERK1/2
APOPTOSIS 04/2012; 15(6):669-678. · 4.79 Impact Factor
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ABSTRACT: The false tendons (FTs) are fibromuscular bands that transverse the left ventricular cavity and often contain conduction tissue, suggesting that FTs may contribute to the occurrence of ventricular arrhythmias. The presence of J waves is associated with vulnerability to ventricular arrhythmias; however, the mechanisms underlying the manifestation of J waves remain to be elucidated.
To investigate the electrocardiographic characteristics, including the presence of J waves, in patients with FTs.
We studied 44 patients with distinct FTs detected by echocardiography (FT group) and 88 age- and sex-matched healthy subjects without FTs (control group). The PQ, QRS, JT, QT, corrected JT, and corrected QT intervals were automatically measured on surface 12-lead electrocardiograms, and the presence or absence of J waves was also determined. J waves were defined as terminal QRS notching or slurring. FTs were classified according to their points of attachment as type 1 (longitudinal, 52%), type 2 (diagonal, 25%), type 3 (transverse, 16%), and type 4 (weblike, 7%).
QRS and corrected QT intervals were significantly longer in the FT group than in the control group (P <.005 and P <.05, respectively). The incidence of J waves was significantly higher in the FT group (64%) than in the control group (19%) (P <.0001). J waves were more prevalent in type 1 (78%) and type 2 (73%) than in type 3 (14%) and 4 FTs (33%) (P <0.05) and in patients with thick FTs (≥ 2 mm) than with thinner FTs (<2 mm) (71% vs 33%; P <.05). The J-wave location differed according to the FT type.
Our results suggest that FTs may carry a certain role to the genesis of J waves.
Heart rhythm: the official journal of the Heart Rhythm Society 12/2011; 9(5):782-8. · 4.56 Impact Factor
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ABSTRACT: Cardiac iodine-123 metaiodobenzylguanidine ((123)I-MIBG) scintigraphy is an established method of assessment of cardiovascular sympathetic function. The aim of the present study was to investigate the long-term cardiovascular predictive value of cardiac (123)I-MIBG scintigraphy parameters in Japanese type 2 diabetic patients without structural heart disease.
Cardiac (123)I-MIBG scintigraphy in 108 patients with type 2 diabetes who did not have structural heart disease, was evaluated. The washout rate (WR) was considered enhanced if it was ≥40%. Accurate follow-up information for 4.6 years was obtained in 54 enhanced WR patients (27 male; mean age, 61 ± 11 years) and in 54 sex- and age-matched preserved WR patients (27 male; mean age, 61 ± 10 years). Major adverse cardiac and cerebrovascular events (MACCE) were investigated. During follow-up, 10 enhanced WR patients developed MACCE including cardiac death, coronary revascularization, stroke, and congestive heart failure, while MACCE occurred in only 3 male patients. The Kaplan-Meier curves indicated that enhanced WR patients had higher incidence of MACCE than those with preserved WR (P<0.05). Cox proportional hazards regression analysis showed that age and enhanced WR were independently associated with the incidence of MACCE (hazard ratio, 4.06; 95% confidence interval: 1.194-18.76, P = 0.0237).
Abnormal WR of cardiac (123)I-MIBG scintigraphy at baseline has long-term cardiovascular predictive value in Japanese patients with type 2 diabetes without structural heart disease.
Circulation Journal 11/2011; 76(2):399-404. · 3.77 Impact Factor
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Yayoi Taniguchi,
Naohiko Takahashi,
Akira Fukui,
Yasuko Nagano-Torigoe,
Luong Cong Thuc,
Yasushi Teshima,
Tetsuji Shinohara,
Osamu Wakisaka,
Tatsuhiko Ooie,
Yukichi Murozono, Kunio Yufu,
Mikiko Nakagawa,
Masahide Hara,
Hironobu Yoshimatsu,
Tetsunori Saikawa
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ABSTRACT: We tested the hypothesis that candesartan, an angiotensin II (AII) type 1 receptor antagonist, would restore the depressed phosphatidylinositol 3 (PI3) kinase-dependent Akt phosphorylation, an essential signal to induce heat-shock protein 72 (Hsp72) in response to hyperthermia, in Otsuka Long-Evans Tokushima fatty (OLETF) rats.
At 14 weeks of age, male OLETF rats and Long-Evans Tokushima Otsuka (LETO) rats were treated with candesartan (0.25 mg/kg/day) for 2 weeks. Thereafter, hyperthermia (43°C for 20 min) was applied. We observed the following: (i) Candesartan did not improve insulin sensitivity in OLETF rats. (ii) Candesartan restored depressed PI3 kinase-dependent Akt phosphorylation and Hsp72 expression in OLETF rat hearts. (iii) Cardiac ventricular tissue contents of AII were greater in OLETF rats, which were suppressed by candesartan. (iv) Cardiac levels of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) phosphorylation were greater in OLETF rats, which were suppressed by candesartan. In cultured cardiomyocytes, application of AII induced PTEN phosphorylation, which was suppressed by candesartan. (v) In high-fat diet insulin-resistant rats, similar results were observed with respect to Hsp72 expression, Akt phosphorylation and PTEN phosphorylation. (vi) In isolated, perfused heart experiments, reperfusion-induced cardiac functional recovery was suppressed in OLETF rat hearts, which was improved by candesartan.
Our results suggest that the depression of PI3 kinase-dependent Akt activation in response to hyperthermia in OLETF rats can be restored by candesartan. Substantial activation of the renin-angiotensin system, represented by increased myocardial AII content and subsequent PTEN phosphorylation, may underlie the pathogenesis which is ameliorated by candesartan.
Cardiovascular research 09/2011; 92(3):439-48. · 5.80 Impact Factor
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Luong Cong Thuc,
Yasushi Teshima,
Naohiko Takahashi,
Satoru Nishio,
Akira Fukui,
Osamu Kume,
Kaori Ezaki,
Hiroko Miyazaki, Kunio Yufu,
Masahide Hara,
Mikiko Nakagawa,
Tetsunori Saikawa
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ABSTRACT: Statins are reported to reduce mortality in patients with coronary artery disease and that mortality benefit might be related to the drugs' antiarrhythmic properties.
Male rats were fed with or without pravastatin (0.1 mg·kg⁻¹·day⁻¹) for 7 days, and thereafter subjected to 10 min of ischemia by coronary artery ligation followed by 20 min reperfusion. Treatment with pravastatin reduced the frequency and duration of ventricular tachycardia and fibrillation (VT/VF) and improved the arrhythmia score after reperfusion. To investigate the rapid effects of pravastatin, isolated perfused rat hearts were subjected to 20 min of global ischemia followed by 30 or 60 min of reperfusion. Treatment with pravastatin (10 nmol/L) from 10 min before ischemia shortened the total duration of reperfusion-induced VT/VF. Interestingly, pravastatin administered from the beginning of reperfusion also exerted antiarrhythmic effects. These results indicate that pravastatin exerts antiarrhythmic effects not only with daily oral intake but also when administered just before ischemia or even after ischemia. Intracellular calcium ([Ca²⁺](i)) overload and collapse of mitochondrial inner membrane potential (Δψ(m)) are associated with the arrhythmogenesis during ischemia-reperfusion. In cultured cardiomyocytes, pretreatment with pravastatin (10 nmol/L) suppressed [Ca²⁺](i) overload and prevented Δψ(m) loss induced by H₂O₂.
Pravastatin attenuated reperfusion-induced lethal ventricular arrhythmias. Inhibition of [Ca²⁺](i) overload and preserving Δψ(m) may be the mechanisms of the observed antiarrhythmic effects of pravastatin.
Circulation Journal 06/2011; 75(7):1601-8. · 3.77 Impact Factor
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ABSTRACT: Cardiac autonomic dysfunction is associated with a poor prognosis in patients with heart failure (HF). Systemic inflammation is elevated in patients with HF. We hypothesized that cardiac resynchronization therapy (CRT) improves cardiac sympathetic nervous dysfunction and systemic inflammation. To test our hypothesis, we evaluated cardiac sympathetic activity and serum levels of high sensitive C-reactive protein (hs-CRP) before and after CRT.
Twenty-seven patients with chronic HF (19 men, eight women; mean age 67 ± 10 years) with nonischemic cardiomyopathy who underwent CRT were evaluated. Each patient was evaluated before and 6 months after CRT. Responders were defined as patients showing ≥15% absolute decrease in left ventricular end-systolic volume. Cardiac sympathetic activity was estimated with cardiac (123) I-metaiodobenzylguanidine (MIBG) scintigrams.
Patients were categorized as responders (n = 19) and nonresponders (n = 8) according to echocardiographic findings. In responders, the mean heart-to-mediastinum (H/M) ratio at the delayed phase in cardiac (123) I-MIBG scintigraphic findings was significantly increased (P<0.05) and serum levels of hs-CRP were decreased (P <0.01). Such improvements were not observed in nonresponders. Stepwise multiple regression analysis showed that the reduction in hs-CRP level was independently associated with the increase in the H/M ratio at delayed phase.
Our results demonstrated that cardiac sympathetic nervous dysfunction and systemic inflammation were improved in responder HF patients to CRT. Furthermore, the reduction in systemic inflammation was associated with the improvement in cardiac sympathetic nervous dysfunction.
Pacing and Clinical Electrophysiology 06/2011; 34(10):1225-30. · 1.35 Impact Factor
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ABSTRACT: Cardiovascular autonomic neuropathy is a major complication in patients with diabetes mellitus (DM), and baroreflex sensitivity (BRS) reportedly can predict cardiovascular prognosis in type 2 DM patients. The hypothesis that cardiovascular events are associated with gender differences in BRS was tested in the present study.
From 1998, we have evaluated BRS by phenylephrine methods in 185 consecutive type 2 DM patients. The long-term prognostic value of BRS was compared between 91 female (5812 years) and 94 male patients (5811 years). There was no significant difference in age or severity and duration of DM between the 2 groups. When compared to male, the BRS value in female patients was significantly lower (9.266.0 vs. 5.975.0 ms/mmHg, P < 0.0001). During a mean of 62.7 months of follow-up, 16 female patients developed cardiovascular events (17.6%) including stroke, acute myocardial infarction, angina pectoris requiring percutaneous coronary intervention or coronary artery bypass grafting and congestive heart failure requiring admission, while only 4 male patients developed events (4.3%, P < 0.005). In females, the Kaplan-Meier curves revealed that those with depressed BRS (< 6 ms/mmHg) had a higher incidence of cardiovascular events than those with preserved BRS (P < 0.05), but this relationship was not observed in male patients.
Although the reason why females had a more depressed BRS remains unclear, our findings demonstrated that a depressed BRS value can accurately predict cardiovascular events, especially in female patients with type 2 DM.
Circulation Journal 05/2011; 75(6):1418-23. · 3.77 Impact Factor
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Kaori Ezaki,
Mikiko Nakagawa,
Yayoi Taniguchi,
Yasuko Nagano,
Yasushi Teshima, Kunio Yufu,
Naohiko Takahashi,
Takeo Nomura,
Fuminori Satoh,
Hiromitsu Mimata,
Tetsunori Saikawa
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ABSTRACT: ST-segment elevation in a structurally normal heart is observed in Brugada- and early repolarization syndrome. The incidence of both syndromes is much higher in males than females. Clinical and basic studies suggest that testosterone plays an important role in ventricular repolarization.
Standard surface 12-lead electrocardiograms recorded in 640 healthy subjects were studied (310 males, 330 females ranging in age from 5 to 89 years) (Study 1). The 3 ST levels (ST-J, -M, and -E) were measured in leads V(2) and V(5), which are representative of the right and left ventricles, respectively. The effect of androgen-deprivation therapy on the ST segment was also evaluated in 21 prostate cancer patients (Study 2). In both leads, the 3 ST levels were significantly higher in adult males than females (P<0.0001) due to a marked increase after puberty in males. As their age increased, males manifested a gradual reduction in the ST level in both leads; in females, there was a reduction in lead V(5) only. In both sexes, all 3 ST levels were significantly higher in lead V(2) than V(5) (P<0.0001). Androgen-deprivation therapy significantly decreased all 3 ST segments in both leads.
Significant age- and gender differences in the ST segment in healthy adults were found, suggesting that testosterone modulates the early phase of ventricular repolarization.
Circulation Journal 11/2010; 74(11):2448-54. · 3.77 Impact Factor
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ABSTRACT: Inflammatory processes are involved in the pathogenesis of atrial fibrillation (AF).
The purpose of this study was to test the hypothesis that atrial fibrosis and enhanced vulnerability to AF evoked by pressure overload can be attenuated by pioglitazone, a peroxisome proliferator-activated receptor-γ agonist, via suppression of inflammatory profibrotic signals.
Male Sprague-Dawley rats were subjected to abdominal aortic constriction (AAC). Pioglitazone 3 mg/kg/day or vehicle was orally administered for 4 weeks.
Western blot analysis revealed that AAC enhanced expression of monocyte chemoattractant protein (MCP)-1, transforming growth factor-β1 and α-smooth muscle actin in the left atrium (LA), which was suppressed by pioglitazone. Messenger RNA expression of collagen type 1 and atrial natriuretic peptide in the LA was increased by AAC, which was suppressed by pioglitazone. Gelatin zymography demonstrated that activity of matrix metalloproteinase-9 was increased by AAC, which was suppressed by pioglitazone. Pioglitazone attenuated AAC-induced LA fibrosis. In isolated-perfused heart experiments, AAC did not alter the refractory period of the LA or the right atrium (RA), but it did prolong the interatrial conduction time. Programmed extrastimuli from the RA induced AF in all of the AAC-treated rats (8/8 [100%]). This was suppressed by pioglitazone (2/8 [25%], P <.05) with normalization to interatrial conduction time.
The results of this study suggest that inflammatory profibrotic mechanisms are involved in this pressure-overloaded AF model. The results also suggest that pioglitazone is effective at attenuating atrial fibrosis, possibly via suppression of MCP-1-mediated inflammatory profibrotic processes.
Heart rhythm: the official journal of the Heart Rhythm Society 10/2010; 8(2):278-85. · 4.56 Impact Factor
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Yasushi Teshima,
Naohiko Takahashi,
Luong Cong Thuc,
Satoru Nishio,
Yasuko Nagano-Torigoe,
Hiroko Miyazaki,
Kaori Ezaki, Kunio Yufu,
Masahide Hara,
Mikiko Nakagawa,
Tetsunori Saikawa
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ABSTRACT: Mechanical stress induces cardiomyocyte injury and contributes to the progression of heart failure in patients with hypertension. In this study, we investigated whether insulin exerts cardioprotective effects against mechanical stretching-induced cell injury, and whether the protective effect is influenced by high-glucose condition.
Cultured neonatal rat cardiomyocytes were plated on silicone chambers, and the cells were mechanically stretched by 15% to induce cell injury.
Mechanical stretching increased reactive oxygen species (ROS) and decreased mitochondrial inner membrane potential (DeltaPsi(m)), eventually leading to cell death by apoptosis and necrosis. Insulin activated the phosphoinositide 3 (PI3) kinase/Akt pathway and reduced apoptosis and necrosis by suppressing ROS increase and preserving DeltaPsi(m). However, high-glucose condition attenuated the insulin-induced Akt phosphorylation and cardioprotection. To investigate the mechanisms that attenuated the effects of insulin in high-glucose condition, we examined the expression of tensin homologue deleted on chromosome 10 (PTEN), which is a negative regulator of the PI3 kinase/Akt pathway. The expressions of PTEN and phosphorylated PTEN were significantly decreased by insulin, and those effects were attenuated in high-glucose condition.
The present results suggest that insulin prevents mechanical stress-induced cell injury which otherwise lead to heart failure. Furthermore, we found that high-glucose condition prevented the decrease in PTEN expression and the cardioprotective effects induced by insulin.
Life sciences 07/2010; 87(5-6):154-61. · 2.56 Impact Factor
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Norihiro Okada,
Naohiko Takahashi, Kunio Yufu,
Yukichi Murozono,
Osamu Wakisaka,
Tetsuji Shinohara,
Futoshi Anan,
Mikiko Nakagawa,
Masahide Hara,
Tetsunori Saikawa,
Hironobu Yoshimatsu
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ABSTRACT: Cardiovascular autonomic neuropathy is a major complication in patients with diabetes mellitus (DM). However, the relationship between cardiovascular autonomic neuropathy and the incidence of cardiovascular events has been poorly investigated in type 2 DM. The present study aimed to assess the long-term cardiovascular predictive value of baroreflex sensitivity (BRS) in Japanese patients with type 2 DM without structural heart disease.
BRS was evaluated using the phenylephrine method in 210 patients with type 2 DM who did not have structural heart disease or other severe complications. BRS was considered depressed if <6 ms/mmHg. Accurate follow-up information for 3-10 years (mean 4.7 years) was obtained in 184 patients (90 females, 94 males; mean age 58+/-12 years). The initial onset of a major adverse cardiovascular event (MACE) was investigated. During follow-up, 19 patients presented with a MACE (4 cardiovascular deaths, 3 nonfatal myocardial infarctions, 4 coronary revascularizations, 5 strokes, 2 congestive heart failures). Cox proportional hazards regression analysis revealed that depressed BRS was independently associated with the incidence of MACE (hazard ratio 1.93, 95% confidence interval 1.09-3.82, P=0.0236).
Depressed BRS at baseline has long-term cardiovascular predictive value in Japanese patients with type 2 DM without structural heart disease.
Circulation Journal 04/2010; 74(7):1379-83. · 3.77 Impact Factor
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ABSTRACT: Reactive oxygen species (ROS) are important intracellular signaling molecules and are implicated in cardioprotective pathways including ischemic preconditioning. Statins have been shown to have cardioprotective effects against ischemia/reperfusion injury, however, the precise mechanisms remain to be elucidated. We hypothesized that ROS-mediated signaling cascade may be involved in pravastatin-induced cardioprotection. Cultured rat cardiomyocytes were exposed to H(2)O(2) for 30 min to induce cell injury. Pravastatin significantly suppressed H(2)O(2)-induced cell death evaluated by propidium iodide staining and the MTT assay. Incubation with pravastatin activated catalase, and prevented a ROS burst induced by H(2)O(2), which preserved mitochondrial membrane potential. Protective effects were induced very rapidly within 10 min, which was concordant with the up-regulation of phosphorylated ERK1/2. L-NAME, 5HD, N-acetylcysteine (NAC) and staurosporine inhibited ERK1/2 phosphorylation and also reduced pravastatin-induced cardioprotection, suggesting NO, mitochondrial K(ATP) (mitoK(ATP)) channels, ROS and PKC should be involved in the cardioprotective signaling. We also demonstrated that pravastatin moderately up-regulated ROS generation in a 5HD-inhibitable manner. In isolated perfused rat heart experiments, pravastatin administered 10 min prior to no-flow global ischemia significantly improved left ventricular functional recovery, and also reduced infarct size, which were attenuated by the treatment with NAC, 5HD, L-NAME or staurosporine. Administration of pravastatin from the beginning of reperfusion also conferred cardioprotection. Pravastatin protected the cardiomyocytes against oxidative stress by preventing the ROS burst and preserving mitochondrial function. Moderately up-regulated ROS production by mitoK(ATP) channels opening is involved in the pro-survival signaling cascade activated by pravastatin.
Apoptosis 02/2010; 15(6):669-78. · 4.07 Impact Factor
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ABSTRACT: White matter lesions (WMLs) and cardiovascular autonomic dysfunction are associated with high mortality in type 2 diabetes mellitus patients. This preliminary study was therefore designed to test the hypothesis that WML is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetes mellitus patients without insulin treatment. Based on brain magnetic resonance imaging findings, 55 type 2 diabetes mellitus patients were divided into 2 groups: a WML-positive group (59 +/- 5 years [mean +/- SD], n = 21) and a WML-negative group (58 +/- 6 years, n = 34). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy. Baroreflex sensitivity was lower in the WML-positive group than in the WML-negative group (P < .01). Early and delayed (123)I-MIBG myocardial uptake values were lower (P < .005 and P < .001, respectively) and the percentage washout rate (WR) of (123)I-MIBG was higher (P < .0001) in the WML-positive group than in the WML-negative group. The fasting plasma glucose (P < .005) and insulin concentrations (P < .0001) and the homeostasis model assessment (HOMA) index values (P < .0001) were higher in the WML-positive group than in the WML-negative group. Multiple logistic regression analysis revealed that HOMA index and percentage WR of (123)I-MIBG were associated with WML patients. Our results suggested that WML was associated with depressed cardiovascular autonomic function and insulin resistance and that HOMA index and the percentage WR of (123)I-MIBG were independent associations for WML in Japanese patients with type 2 diabetes mellitus.
Metabolism: clinical and experimental 05/2009; 58(5):696-703. · 2.59 Impact Factor
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ABSTRACT: 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.
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).
Initiation of atorvastatin in the early phase of an AMI has beneficial effects on cardiac function, probably by improving left ventricular remodeling.
Journal of Cardiology 02/2009; 53(1):58-64. · 1.28 Impact Factor
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ABSTRACT: Flow-mediated dilatation (FMD) of the brachial artery represents systemic endothelial function, so the relationship between FMD and blood pressure (BP) profile, in relation to the effects of cigarette smoking, was investigated in young healthy subjects.
The 62 healthy subjects (14 females, 48 males; mean 29.7+/-5.5 years old), were divided into a smoking group (n=30) and non-smoking group (n=32). FMD was induced by reactive hyperemia. It was lower in the smoking group than in the non-smoking group (P<0.05). In the non-smoking group, there was an inverse correlation (r=-0.59, P<0.0005) between FMD and systolic BP (SBP), which was not recognized in the smoking group. Multiple stepwise regression analysis revealed that FMD was predicted by either the SBP or the brachial artery diameter in the non-smoking group, whereas it was predicted by the brachial artery diameter in the smoking group. Subdivision by cut-off value of SBP =120 mmHg demonstrated that although FMD with SBP <120 mmHg was preserved in subjects in the non-smoking group, it was depressed to a level comparable with SBP >or=120 mmHg in the smoking group.
Highly-preserved FMD in subjects with SBP <120 mmHg appears to be impaired by cigarette smoking, resulting in a loss of association between FMD and SBP.
Circulation Journal 12/2008; 73(1):174-8. · 3.77 Impact Factor
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ABSTRACT: Increased serum interleukin-6 (IL-6) levels are associated with an increased risk of cardiovascular disease, and cardiovascular autonomic dysfunction is associated with high mortality in type 2 diabetic patients. However, the relationship between IL-6 levels and cardiovascular autonomic dysfunction has not been fully elucidated. The aim of this study was to determine whether serum IL-6 levels are associated with cardiovascular autonomic dysfunction in type 2 diabetic patients.
Eighty type 2 diabetic patients who did not have organic heart disease were categorized into a high IL-6 group (>2.5 pg/ml, n = 40, age 59 +/- 12 years) or a non-high IL-6 group (<2.5 pg/ml, n = 40, 61 +/- 12 years). Cardiac autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations and (123)I-metaiodobenzylguanidine (MIBG) scintigraphy.
The body mass index values (BMI), fasting insulin levels and homeostasis model assessment index values were higher in the high IL-6 group than in the non-high IL-6 group (p < 0.01). Early and delayed (123)I-MIBG myocardial uptake values were lower (p < 0.01), and the percent washout rate of (123)I-MIBG was higher (p < 0.05) in the high IL-6 group than in the non-high IL-6 group. Furthermore, multiple regression analysis revealed that the IL-6 level was independently predicted by the BMI and the myocardial uptake of (123)I-MIBG during the delayed phase.
The results indicate that elevated IL-6 levels are associated with depressed cardiovascular autonomic function and obesity in type 2 diabetic patients.
European journal of nuclear medicine and molecular imaging 05/2008; 35(9):1616-23. · 4.99 Impact Factor
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ABSTRACT: The brachial-ankle pulse wave velocity (PWV) is a quick test which adequately estimates arterial stiffness. Because flow-mediated dilatation (FMD) of the brachial artery assesses an essential endothelial function, we tested the hypothesis that the brachial-ankle PWV could reflect the early stages of endothelial dysfunction caused by smoking in young, healthy subjects. Fifty-seven healthy subjects (13 females and 44 males; mean 29.9+/-5.6 years) were enrolled. Twenty-six of the subjects (30.4+/-5.7 years) were active smokers, with a mean cumulative nicotine consumption of 10.0+/-8.6 pack/years, and thus were assigned to the smoking group. Thirty-one subjects without a history of smoking (29.5+/-5.5 years) were assigned to the non-smoking group. The brachial-ankle PWV and arterial blood pressure were simultaneously measured using a recently established, non-invasive automatic device (model BP-203RPE; Nihon Colin, Tokyo, Japan). Endothelium-dependent FMD was induced by reactive hyperemia, while endothelium-independent vasodilation of the brachial artery was induced by administration of sublingual nitroglycerin spray. The FMD was lower in the smoking group than in the non-smoking group (p<0.05). There was no significant difference between the two groups with respect to the brachial-ankle PWV. In the non-smoking group, multiple stepwise regression analysis revealed that FMD was predicted by the systolic blood pressure (F=16.351). In the smoking group, statistical analysis revealed that FMD was independently predicted by either the brachial-ankle PWV (F=8.108) or the subject's age (F=4.381). Our results suggest that a reduction in FMD is closely associated with the early stages of endothelial dysfunction caused by cigarette smoking in young, healthy subjects, which is at least partly reflected by the PWV value.
Hypertension Research 07/2007; 30(7):607-12. · 2.58 Impact Factor
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Naohiko Takahashi,
Futoshi Anan,
Mikiko Nakagawa, Kunio Yufu,
Tetsuji Shinohara,
Tetsuo Tsubone,
Koro Goto,
Takayuki Masaki,
Isao Katsuragi,
Katsuhiro Tanaka,
Testsuya Kakuma,
Masahide Hara,
Tetsunori Saikawa,
Hironobu Yoshimatsu
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ABSTRACT: Hypoadiponectinemia is associated with insulin resistance. However, there is very limited information about the relationship between plasma adiponectin and cardiac autonomic nervous function. We tested the hypothesis that hypoadiponectinemia is associated with cardiac sympathetic overactivity in patients with type 2 diabetes mellitus. Thirty-three male type 2 diabetic patients not on insulin treatment were classified into a hypoadiponectinemia group (plasma adiponectin concentration, <4.0 microg/mL; age, 58.6 +/- 8.6 years [mean +/- SD]; n = 14) and an age-matched normoadiponectinemia group (serum adiponectin concentration, >/=4.0 microg/mL; age, 58.2 +/- 8.1 years; n = 19). In each patient, baroreflex sensitivity, heart rate variability, plasma norepinephrine concentration, and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings were assessed. Compared with the normoadiponectinemia group, the hypoadiponectinemia group had a higher body mass index (P < .01), higher plasma concentrations of glucose and insulin (P < .05 and P < .01, respectively), higher homeostasis model assessment of insulin resistance (HOMA-IR) values (P < .005), higher plasma triglyceride levels (P < .05), and lower plasma high-density lipoprotein cholesterol levels (P < .05). In the hypoadiponectinemia group, the autonomic function measurements included a lower baroreflex sensitivity (P< .05) and a lower delayed myocardial uptake of (123)I-MIBG (P < .01) with a higher washout rate (P < .05). Multiple regression analysis revealed that the plasma adiponectin level was independently associated with HOMA-IR (F = 9.916) and the percent washout rate of (123)I-MIBG (F = 5.985). Our results suggest that in middle-aged men with type 2 diabetes mellitus, hypoadiponectinemia is associated with cardiac sympathetic overactivity as determined by (123)I-MIBG scintigraphy.
Metabolism 07/2007; 56(7):919-24. · 2.66 Impact Factor
