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Biomedical subjects

Akira Kitabatake

Publications and source records attributed to Akira Kitabatake.

102 records · Page 6Linked to original sources

In vivo echocardiographic detection of cardiovascular lesions in apolipoprotein E-knockout mice using a novel high-frequency high-speed echocardiography technique.

Apolipoprotein E-knockout (apoE-KO) mice have been used for studying atherogenesis, but the in vivo features including cardiovascular function have not yet been reported. This study aimed to noninvasively evaluate cardiovascular lesions in 6 apoE-KO mice and 6 control (C57BL/6) mice using transthoracic echocardiography performed using an originally developed linear scanner that permits a high-speed scan with wideband high-frequency ultrasound. Two independent observers evaluated and scored the degree of atherosclerotic changes in the aortic root from 2-dimensional long-axis and short-axis images. M-mode measurements included left ventricular end-diastolic dimension (LVDd), posterior wall thickness (LVPWT), fractional shortening, aortic root dimension and rate of systolic expansion of the aorta (%SEAo). The wall thickness of the aortic root was measured from the serial histological sections. Significant differences between apoE-KO and C57BL/6 mice were found in the atherosclerotic score, %SEAo, LVDd and LVPWT. The atherosclerotic score and %SEAo were significantly correlated with the aortic wall thickness. Transthoracic echocardiography with a high-frequency ultrasound system can detect atherosclerotic lesions and the decreased distensibility of the ascending aorta, as well as secondary changes in left ventricular geometry, in apoE-KO mice.

Animals↗

Coronary disease morphology and distribution determined by quantitative angiography and intravascular ultrasound--re-evaluation in a cooperative multicenter intravascular ultrasound study (COMIUS).

Although previous studies have demonstrated that even quantitative coronary angiography (QCA) can not provide accurate disease morphology, there has not been a systematic comparison of disease morphology determined by QCA and intravascular ultrasound (IVUS), particularly in Japanese patients. Therefore, the present study prospectively examined patients in a multicenter cooperative study. A total of 491 coronary sites from 562 patients (446 men, 116 women; mean age, 64+/-11 years) who underwent coronary interventions were enrolled. The target lesions (>50% diameter stenosis) were evaluated pre-operatively by both QCA and IVUS operating at 30-40 MHz and the percent area stenosis, eccentricity index (EI) and lesion length were determined. The minimal (min) and maximal (max) distances from the center of the stenotic lesion to the outline of the vessel wall were measured, and the EI was calculated by the formula: [(max - min)/max]. By QCA, lesion length was determined by measuring the distance between the proximal and distal shoulders of the lesion. When the lesions were observed by IVUS with a motorized pull-back system, the length was calculated by multiplying the time for observation of the disease and 0.5 or 1 mm/s. Although the severity of the stenosis determined by QCA (86+/-10%, mean +/- SD) did not differ from that by IVUS (83+/-13%), there was no correlation between them (r=0.32, y=0.25x+65) and the correlation did not improve when lesions with remodeling, enlargement (n=176) or shrinkage (n=79) were omitted from the calculation. The EIs by QCA and IVUS were 0.51+/-0.26 and 0.52+/-0.22, respectively (NS), and there was no correlation between them (r=0.30, y=0.36x+33). However, when the lesions with remodeling were excluded, the correlation greatly improved (r=0.80, y=0.84x+10.6, p<0.05). Lesion length determined by QCA (12.4+/-6.1 mm) was significantly shorter than that by IVUS (16.3+/-8.9 mm, p<0.01). These results demonstrate that coronary angiography significantly misinterprets disease morphology in terms of severity, eccentricity and length, in part because of vessel remodeling that can be accurately determined only by IVUS.

Aged↗

Association of cardiovascular risk factors and endothelial dysfunction in japanese hypertensive patients: implications for early atherosclerosis.

Although hypertension, hyperlipidemia, diabetes and smoking are known risk factors of atherosclerosis in Caucasians, their relative contributions to early atherosclerosis among Japanese are unknown. Decrease in flow-mediated dilation (FMD) of the brachial artery is a useful marker of endothelial dysfunction and early atherosclerosis. To evaluate the relative contribution of hypertension to early atherogenesis, we determined FMD, as well as plasma levels of tissue-type plasminogen activator (t-PA; a sensitive index of endothelial damage) and tumor necrosis factor (TNF)-a and interleukin (IL)-6 (established markers of inflammation) in normotensive and hypertensive patients under treatment. FMD was significantly reduced as the number of risk factors increased, suggesting that accumulations of risk factors were related to endothelial dysfunction. FMD was reduced in hypertensives (9.9 +/- 5.8 (SD) %) compared to normotensives (14.6 +/- 7.6, p<0.01) despite good blood pressure control (139 +/- 20/80 +/- 14 mmHg in hypertensives). Nitroglycerine-induced endothelium-independent vasodilation was not altered in hypertensives (16.0 +/- 6.3%) as compared to normotensives (16.7 +/- 5.8). Plasma t-PA, TNF-alpha, and IL-6 levels were increased in hypertensives despite good blood pressure control. Thus, hypertension alone is a high risk for early atherosclerosis. Persistent endothelial damage and moderate inflammation may increase the risk of early atherosclerosis synergistically under the presence of hypertension in Japanese.

Adult↗

Prevalence and predictors of renal artery stenosis in patients undergoing cardiac catheterization.

Renal artery stenosis (RAS) is recognized as a major co-morbid condition for patients with cardiovascular disease. Although the prevalence of RAS in Western countries has been reported as 13.5-18% in patients with suspected coronary artery disease (CAD) undergoing coronary angiography, there is little information available about the prevalence of RAS in Asian populations, which are less susceptible to atherosclerosis. To evaluate the prevalence of RAS in Japanese patients suspected of cardiovascular disease and the relationships among RAS and vascular risk factors, especially hypertension, renal artery angiography was performed in a total of 289 consecutive patients receiving diagnostic cardiac catheterization. RAS with a stenosis diameter greater than 50% was considered significant. The prevalence of RAS was 21/289 (7%) including 18 (6%) cases of unilateral stenosis and 3 (1%) of bilateral stenosis. RAS accompanied 14/220 (6%) cases of CAD, 4/34 (12%) cases of valvular heart disease and 1/14 (7%) cases of cardiomyopathy. In the subgroups of CAD, the prevalence of RAS was 5%, 10%, 9%, and 19% in cases of 0, 1, 2 and 3-vessel disease, respectively. Hypertension was more frequent among patients with than among those without RAS (86% vs. 45%, p=0.0003). The prevalence of RAS was 13% in hypertensives and 2% in normotensives (p = 0.004). Thus RAS was frequent in patients with established CAD, and particularly in those with 3-vessel disease. Together, the results showed that hypertension was closely associated with RAS, appearing as both a risk factor and a possible clinical manifestation of the disease. We conclude that more attention should be paid to RAS in Japanese patients with hypertension and cardiovascular disease.

Aged↗

Relationships between brachial artery flow mediated dilation and carotid artery intima-media thickness in patients with suspected coronary artery disease.

The correlation of peripheral endothelial dysfunction and intima-media thickness (IMT) in patients with suspected coronary artery disease (CAD) has been unclear. Inflammation and thrombosis may play a role at early stages of atherosclerosis. Thus, early atherosclerosis was noninvasively examined morphologically by IMT of carotid arteries, and functionally by flow mediated dilation (FMD) of brachial arteries in patients who were suspected of CAD and had undergone coronary angiography. Plasma antigen levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, representative atherogenic cytokines, tissue factor (TF) and tissue factor pathway inhibitor (TFPI), markers of coagulation, and plasma activity level of plasminogen activator inhibitor type-1 (PAI-1), a marker of defective fibrinolysis, were measured. Patients with coronary atherosclerosis in one or more vessels with lesion > or = 50% had significantly reduced FMD compared with those with angiographically normal coronary arteries. Carotid artery IMT increased significantly only in patients with advanced coronary atherosclerosis in one or more vessels with lesion > or = 90%. Plasma antigen levels of IL-6 were significantly increased in patients with reduced FMD (< 5%) compared to those in patients with FMD between 10 and 15%. Plasma antigen levels of TF, total and free TFPI, and PAI-1 activity tended to increase with a reduction in FMD. Thus, (1) FMD was reduced at early stages of CAD while IMT was increased in advanced CAD, and (2) inflammation and thrombosis may play a role in the early stages of the atherosclerotic process.

Aged↗

Iodine-123-metaiodobenzylguanidine scintigraphy of total cardiac adrenergic denervation in Brugada syndrome.

A 22-year-old Japanese man with Brugada syndrome was resuscitated from cardiopulmonary arrest. In addition to the electrocardiographic evidence of the syndrome and the absence of apparent structural heart disease, no accumulation of iodine-123-metaiodobenzylguanidine (MIBG) was found anywhere throughout the heart. Thallium-201 (Tl) single photon emission computed tomography (SPECT) distribution showed no significant decrease in its uptake. To our knowledge, this is the first report that has demonstrated a homogeneous absence of cardiac accumulation of MIBG in Brugada syndrome.

3-Iodobenzylguanidine↗

A case of accordion phenomenon accompanied by severe transmural myocardial ischemia.

Percutaneous coronary intervention was performed in a severely tortuous right coronary artery (RCA). Immediately after straightening its tortuousity by using two guidewires, angiographic slow flow, ischemic electrocardiographic changes, and anginal pain developed. This is a rare case who had severe myocardial ischemia caused by the accordion phenomenon.

Angina Pectoris↗

Long-term combined therapy with an angiotensin type I receptor blocker and an angiotensin converting enzyme inhibitor prolongs survival in dilated cardiomyopathy.

The efficacy of ACE inhibitors (ACEIs) in the treatment of chronic heart failures is well documented. However, ACEIs may provide incomplete blockade of the renin-angiotensin system (RAS) because of the alternative pathways for angiotensin II (All) production. We hypothesized that more complete blockade of RAS by adding an AT1 receptor blocker (ARB) may have greater potential to decrease mortality associated with heart failure and improve cardiac function than monotherapy with ACEIs. The objective of this study was to evaluate the effect of combined therapy on cardiac functions and survival in cardiomyopathic hamsters. Male cardiomyopathic hamsters (BIO TO2) were administered either placebo (group C), enalapril (30 mg/kg/day) (group E), or enalapril (30 mg/kg/day) + valsartan (500 mg/ kg/day) (group EV), starting at the age of 6 weeks. Kaplan-Meier analysis was performed to assess the differences in survival. Cardiac functions were evaluated by echocardiogram and cardiac catheterization. Group EV showed significant increases in fractional shortening, LV dP/dTmax, and deceleration time, and showed significant decreases in left ventricular diastolic dimension, LV dP/dTmin, and early diastolic mitral velocity/atrial systolic velocity. Treatment with enalapril resulted in longer survival compared with placebo. Moreover, life expectancy (median probability of survival: 433 days) increased significantly in group EV compared with group E (P<0.05) as well as group C (P<0.001). It is concluded that combined therapy improved cardiac function and survival compared to placebo or enalapril monotherapy.

Angiotensin I↗

[Hormone replacement therapy (HRT) for hyperlipidemia after menopause].

Women are about 10 years older than men to suffer from ischemic heart disease(IHD) and they often experience a sudden rise in cholesterol after menopause. These phenomena are thought to be caused by the production of estrogen in women during normal menstruation cycle and its loss after menopause. Hormone replacement therapy(HRT) has been shown to reduce IHD by nearly 50 per cent. This is caused in part by effects of estrogen on lipid metabolism; it reduces LDL and Lp(a), and increases HDL. Although the first large prospective trial of HRT for secondary prevention of IHD failed to demonstrate estrogen's protective effects, HRT was effective in women with high Lp(a). Thus, selection of patients and HRT regimen seems important.

Estrogen Replacement Therapy↗

[The trend of anti-arrhythmic drug development].

New anti-arrhythmic drugs have been developed by the progress of molecular-biological and physiological research on an ion channel and the elucidation of pharmacological effects of traditional anti-arrhythmic drugs. After CAST study, K+ channel blockers instead of Na+ channel blockers were developed and used in anti-arrhythmic treatment. In Sicilian Gambit, it was advocated that the anti-arrhythmic drug selection was based on both pharmacological action of drugs and mechanism of arrhythmias, including electrical remodeling which was mainly studied on atrial fibrillation and structural remodeling such as myocardial fibrosis. Furthermore, the target of anti-arrhythmic treatment will be not only the arrhythmic control with drugs but changing many factors related to the arrhythmic substrates, modulators and triggers of arrhythmias.

Anti-Arrhythmia Agents↗

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: a study using oxygen 15-labeled water PET.

BACKGROUND: Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD. METHODS AND RESULTS: Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg. kg(-1). min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P <.05), in group C (2.92 +/- 1.21, P <.01), and in normal segments (3.86 +/- 1.24, P <.001). CFR in group B was lower than in group C (P <.02) and in normal segments (P <.001). CFR in group C was lower than in normal segments (P <.02). CONCLUSIONS: Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.

Aged↗

Cardioprotective effect of perfluorochemical emulsion for cardiac preservation after six-hour cold storage.

Perfluoro-octyl bromide (PFOB) emulsion is capable of transferring oxygen to tissues even at 4 degrees C, suggesting an application in myocardial preservation. We evaluated the cardioprotective effect of PFOB emulsion added to the storage solution. Guinea pig hearts were isolated (n = 24) and perfused with Krebs-Henseleit solution (KHS) and then cooled and perfused with St. Thomas Hospital II solution (STS). The hearts were stored in three different solutions: STS (STS group), oxygenated (O2) STS (O2 STS group), and O2 STS with PFOB emulsion (30%) (O2 STS + PFOB group) for 6 hours at 4 degrees C. After storage, rewarming was performed, followed by reperfusion with KHS. Left ventricular developed pressure of O2 STS + PFOB group was significantly higher than that of the other groups during reperfusion (p < 0.01). There was no difference among the three groups in O2 extraction and cardiac efficiency; however, cardiac oxygen consumption in the O2 STS + PFOB group significantly improved during reperfusion. In the O2 STS + PFOB group, creatinine kinase, lactate dehydrogenase, and myocardial water content were significantly decreased (p < 0.01). This study suggests that PFOB emulsion is beneficial for the cardioprotection of donor hearts, allowing a prolonged cardiac storage time.

Animals↗