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This paper proposes a new product development of yogurt project based on industry academia collaboration between Teikyo University and Tohoku Kyodo Milk Industry and discusses the possible economic impact of this project on the Tohoku region as well as the Tama area in Tokyo. We also introduce a preliminary survey to partially clarify the consumption patterns for yogurt among students at Teikyo University. The survey reveals that most of our respondents consume yogurt regularly. The stated reason for yogurt consumption is to enjoy yogurt as a dessert rather than as a health food. We also find that the most significant determinant factors for purchasing yogurt are taste, price, and quantity. Based on the data, respondents are willing to pay between 100 JPY and 145 JPY for yogurt. In response to these findings, we discuss some additional surveys that need to be conducted in the future.

Objective: The association of high-density lipoprotein particle (HDL-P) with atherosclerosis may be stronger than that of HDL-cholesterol (HDL-C) and independent of conventional cardiovascular risk factors. Whether associations persist in populations at low risk of coronary heart disease (CHD) remains unclear. This study examines the associations of HDL-P and HDL-C with carotid intima-media thickness (cIMT) and plaque counts among Japanese men, who characteristically have higher HDL-C levels and a lower CHD burden than those in men of Western populations., Methods: We cross-sectionally examined a community-based sample of 870 Japanese men aged 40-79 years, free of known clinical cardiovascular disease (CVD) and not on lipid-lowering medication. Participants were randomly selected among Japanese living in Kusatsu City in Shiga, Japan., Results: Both HDL-P and HDL-C were inversely and independently associated with cIMT in models adjusted for conventional CHD risk factors, including low-density lipoprotein cholesterol (LDL-C) and diabetes. HDL-P maintained an association with cIMT after further adjustment for HDL-C (P < 0.01), whereas the association of HDL-C with cIMT was noticeably absent after inclusion of HDL-P in the model. In plaque counts of the carotid arteries, HDL-P was significantly associated with a reduction in plaque count, whereas HDL-C was not., Conclusion: HDL-P, in comparison to HDL-C, is more strongly associated with measures of carotid atherosclerosis in a cross-sectional study of Japanese men. Findings demonstrate that, HDL-P is a strong correlate of subclinical atherosclerosis even in a population at low risk for CHD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate clinical usefulness of a novel program "Heart Function View (HFV)" for evaluating left ventricular (LV) function from myocardial perfusion SPECT (MPS), we compared LV functional parameters (F(x)) calculated by HFV with those obtained by the other similar programs QGS and cardioGRAF or by ultrasound echocardiography (UCG) and examined their correlations with clinical markers of heart failure: plasma BNP concentrations (BNPs) and exercise capacity., Methods: Studied patients (n = 60) underwent technetium-99m tetrofosmin quantitative gated MPS including treadmill exercise for examining heart disease. Myocardial stress images were acquired 30 min after the first tracer injection during maximal exercise. Three hours later, the second tracer was injected, and resting images were acquired. LV systolic F(x) [ejection fraction (EF), peak ejection rate (PER)] and diastolic F(x) [first third filling fraction (1/3FF), first third filling rate (1/3FR), peak filling rate (PFR), time to PFR (TPF)] were analyzed, and phase standard deviation (SD) and histogram bandwidth were obtained by phase analysis., Results: LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF obtained from HFV were well correlated with those from QGS, cardioGRAF and UCG. A diastolic parameter Doppler E/e' from UCG was significantly with PFR from HFV. There were good correlations between LVEDV, LVESV, LVEF, PER, PFR, 1/3FR, TPF and 1/3FF from HFV and those from cardioGRAF. LVEF, PER, 1/3FR, and PFR were significantly correlated with plasma BNP concentrations. In patients with non-ischemic heart disease (n = 42), phase SD and histogram bandwidth were correlated negatively with exercise capacity or PFR., Conclusions: HFV-derived LVF(x) are correlated with LVF(x) from the other programs or UCG, or with the clinical markers of heart failure and are thus useful in the functional assessment for patients with heart disease.

Objective: Decreased heart iodine-123 metaiodobenzylguanidine ((123)I-MIBG) uptake [heart-to-mediastinum count ratio (H/M)] is reported in heart disease (HD) or Lewy body disease (LBD). When LBD is merged, therefore, information regarding HD severity may be ambiguous. We aimed to examine whether lung (123)I-MIBG uptake [lung-to-mediastinum count ratio (L/M)] assessment might be useful for differentiating two clinical conditions of HD and LBD, and to investigate whether L/M could reflect the grade of left ventricular (LV) dysfunction., Methods: Three groups were examined: LBD (patient group with Parkinson's disease or dementia with Lewy bodies, n = 33), PS (group with other Parkinsonian syndromes, n = 20) and HD (group with heart disease). HD consisted of 4 subgroups: HD(I) [H/M(<2.30)-matched group with LBD, n = 34), HD(II) [H/M(≥2.30)-matched group with PS, n = 33], HD(III) [group for functional analysis, LV ejection fraction, first-third and peak filling rates (1/3FR and PFR) and time to PFR were calculated using gated SPECT, n = 35] and HD(IV) (group for examining cardiac prognosis, follow-up period of 1283 ± 506 days, n = 54). Using Doppler echocardiography, a diastolic parameter E/e' and pulmonary artery pressure (ePAP) were estimated., Results: H/Ms did not differ between HD(I) and LBD, or between PS and HD(II). However, L/Ms were increased in the order of LBD, PS, HD(II) and HD(I) groups. In combined LBD, PS, HD(I) and HD(II), L/Ms correlated positively with a diastolic parameter E/e'. L/Ms correlated with ePAP, while H/Ms did not. H/Ms correlated with a systolic parameter EF (r = 0.56) and diastolic parameters 1/3FR (r = 0.51) and PFR (r = 0.51), and L/Ms correlated with diastolic parameters 1/3FR (r = -0.36) and PFR (r = -0.36) but not with EF in HD(III). Kaplan-Meier analysis showed earlier cardiac death in patients with decreased H/Ms, but not in patients with increased L/Ms in HD(IV)., Conclusions: Our study suggest that increased lung (123)I-MIBG uptake is useful as a reference marker for differentiating two clinical conditions of HD and LBD, and can reflect the degree of LV diastolic dysfunction. Elevated ePAP caused by LV diastolic dysfunction may be involved in the mechanism(s) of increased lung uptake.

Objective: The serum level of LOX-1 ligand containing ApoB (LAB) may reflect atherogenicity better than LDL cholesterol (LDLC), total LDL particles and usual measurement of oxidized LDL. The association between LAB and intima-media thickness (IMT) of carotid artery was investigated by ultrasound in US and Japan men., Methods: Participants were 297 US Caucasian and 310 Japanese men, aged 40-49 years without past history of cardiovascular disease. Serum LAB levels were measured by ELISAs with recombinant LOX-1 and monoclonal anti-apolipoprotein B antibody., Results: Serum LAB levels [median (interquartile range), μg/L] were 1321 (936, 1730) in US Caucasians and 940 (688, 1259) in Japanese. For Caucasian men, average IMT was higher in higher LAB quartile, which was 0.653, 0.667, 0.688, and 0.702 mm, respectively (p for trend = 0.02). Linear regression analysis showed serum LAB was significantly associated with IMT after adjustment for LDLC or total LDL particles in addition to other traditional or novel risk factors for atherosclerosis such as C-reactive protein. However, there was no significant relationship between LAB and IMT in Japanese men., Conclusion: Serum LAB, a new candidate biomarker for residual risk, was associated with an increased carotid IMT in US Caucasian men independently of various risk factors; however, ethnic difference should be clarified in the future., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

This case report describes agranulocytosis immediately after oral administration of cibenzoline and dabigatran in a 70-year-old woman with paroxysmal atrial fibrillation (AF). No blasts were found in peripheral blood and bone marrow, and the white blood cell count increased abruptly by intravenous administration of granulocyte colony-stimulation factor, suggesting an allergic response caused by cibenzoline or dabigatran, or both. Though antiarrhythmic drugs with anticoagulation therapy are commonly used to treat paroxysmal AF, caution has to be paid to drug-induced agranulocytosis.

Background and Purpose: Recent studies reported the differential effect of docosahexaenoic (DHA) and eicosapentaenoic acids (EPA). We examined the differential association of DHA and EPA with carotid intima-media thickness (IMT) in Japanese individuals in Japan and in U.S. white individuals and explored whether DHA or EPA contributes to the difference in IMT between the two groups., Methods: A population-based cross-sectional study in 608 Japanese and U.S. white men aged 40 to 49 was conducted to assess IMT, serum DHA, EPA, and other cardiovascular risk factors., Results: Japanese compared to U.S. whites had significantly lower IMT (mean±SD, 618±81 and 672±94 μm for Japanese and whites, respectively; P<0.001) and had >2-fold higher levels of DHA and EPA. DHA, but not EPA, had an inverse association with IMT in both Japanese and U.S. whites. The inverse association remained only in Japanese men after adjusting for risk and other factors. The significant difference in multivariable-adjusted IMT became nonsignificant after further adjusting for DHA (mean difference, 17 μm; 95% CI, -8 to 43; P=0.177) but not EPA. In this multivariable-adjusted model, DHA but not EPA was a significant predictor of IMT (P=-0.032 versus 0.863, respectively)., Conclusions: These data suggest that DHA may have a more potent antiatherogenic effect than EPA, especially in levels observed in the Japanese, independent of risk factors.

1. Coronary endothelial function and brachial-ankle pulse wave velocity (baPWV) are independent predictors of cardiovascular events. Thus, in the present study we examined the relationship between baPWV and endothelium-dependent and -independent coronary vasodilatory functions. 2. Sixty-five patients (12 diabetic and 53 non-diabetic) with no significant stenosis of the coronary artery were studied and baPWV determined. After cardiac catheterization, graded doses of bradykinin (BK; 0.2, 0.6 and 2.0 μg/min), nitroglycerin (NTG; 250 μg) and papaverine (Pa; 12 mg) were administered into the left anterior descending coronary artery. Coronary blood flow (CBF) was measured using a Doppler flow wire. 3. In the 65 patients, an inverse correlation was found between baPWV and the percentage change in epicardial coronary artery diameter (Δ%CoD), as well as the percentage change in CBF (Δ%CBF), following administration of BK (endothelium-dependent vasodilator). Moreover, inverse correlations were found between baPWV and Δ%CoD following administration of NTG (endothelium-independent vasodilator) and Δ%CBF following administration of Pa (endothelium-independent vasodilator). 4. Multivariate analysis revealed diabetes to be independently and significantly associated with baPWV, BK-induced Δ%CBF and Δ%CoD and Pa-induced Δ%CBF. 5. In conclusion, the results of the present study suggest that increased baPWV is associated with endothelium-dependent and -independent coronary vasodilatory dysfunction. Non-invasive and straightforward baPWV measurement may be useful for the assessment of coronary risk factors, particularly in diabetic patients., (© 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd.)

Background: Myocardial lipid overstorage may produce cardiomyopathy, leading to dysfunction, but advanced heart failure may cause lipolysis via sympathetic nerve activation. In the failing heart, the creatine kinase system may also be impaired. The aims of this study were to assess myocardial triglyceride (TG) and creatine (CR) in different types of cardiomyopathy and to investigate whether they are related to the severity of cardiac dysfunction., Methods and Results: In patients with hypertrophic cardiomyopathy (HCM, n = 8), dilated cardiomyopathy (DCM, n = 12) or ischemic cardiomyopathy (ICM, n = 10), and normal subjects (NML, n = 22), myocardial TG and CR were evaluated using proton magnetic resonance spectroscopy. To assess cardiac sympathetic nerve activity, myocardial MIBG (a radioactive guanethidine analog) uptake was measured in DCM. Myocardial TG was significantly lower in hypertrophic cardiomyopathy (HCM) (1.92 ± 0.99 μmol/g), but higher in ICM (7.59 ± 4.36 μmol/g) than in NML hearts (4.05 ± 1.94 μmol/g). There was no significant difference in TG between DCM (4.84 ± 6.45 μmol/g) and NML. Myocardial CR in HCM (20.4 ± 8.4 μmol/g), DCM (14.8 ± 4.8 μmol/g), and ICM (19.4 ± 6.3 μmol/g) was significantly lower than that in NML hearts (27.1 ± 4.3 μmol/g). Overall, myocardial CR correlated positively with the severity of heart failure estimated by ejection fraction or myocardial BMIPP (a radioactive fatty acid analog) uptake, but TG did not. In DCM, myocardial TG correlated with body mass index, but not with MIBG uptake., Conclusions: Myocardial TG may be related to the specific cause of disease rather than the severity of cardiac dysfunction. In contrast, myocardial CR reflects the severity of heart failure despite different pathoetiologic mechanisms of dysfunction. In DCM, myocardial TG may be affected by an overweight state rather than cardiac sympathetic nerve dysfunction. Thus, myocardial CR has a closer relationship to heart failure severity than does myocardial TG., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: Echocardiographic studies have suggested an association between diastolic dysfunction and exercise intolerance. The aim of this study was to examine the relationship between exercise capacity and left ventricular (LV) function during stress myocardial scintigraphy, and to investigate whether or not this relationship is caused by ischemia during exercise., Methods: The studied patients underwent technetium-99m sestamibi quantitative gated SPECT, including treadmill exercise. Myocardial stress images were acquired 30 min after the first tracer injection (370 MBq) during maximal exercise. Three hours later, the second tracer (740 MBq) was injected, and resting images were acquired 30 min after this injection. The presence of ischemia was determined by tracer accumulation. From the same data source, LV diastolic parameters [first third filling fraction (1/3FF), first third filling rate (1/3FR), peak filling rate (PFR) and time to PFR (TPF)], and systolic parameters [ejection fraction (EF), peak ejection rate (PER), time to PER (TPE) and first third ejection fraction (1/3EF)] were analyzed., Results: Subjects with exercise inability (<6 METs) were excluded. In 45 patients, diastolic parameters 1/3FF, 1/3FR, PFR and TPF correlated significantly with exercise duration (r = 0.32*, 0.37*, 0.37* and -0.40(#), respectively; *p < 0.05, (#) p < 0.01), but systolic parameters EF, PER, TPE and 1/3EF did not. At rest, 1/3FF, PFR and PER were significantly increased, suggesting functional deterioration during exercise. Even after 3 h, 1/3FR, PFR and TPF still correlated significantly with exercise duration (r = 0.29*, 0.36* and -0.30*, respectively; *p < 0.05). Such findings were observed even when the 10 patients who exhibited ischemia during exercise were excluded (1/3FR: r = 0.34*; PFR: r = 0.37*; TPF: r = -0.36*; *p < 0.05, n = 35)., Conclusions: Our findings suggested that LV diastolic dysfunction, not systolic dysfunction, is associated with limited exercise capacity independent of the occurrence of ischemia.

The aim of this study was to determine the impact of pitavastatin on low-density lipoprotein cholesterol (LDL-C) and lectin-like oxidized LDL receptor-1 (LOX-1) in patients with hypercholesterolemia. Twenty-five hypercholesterolemic patients (8 male, 17 female; age 66 +/- 13, 21-80 years) who had not received anti-dyslipidemic agents and had LDL-C levels of more than 160 mg/dL were examined. Biochemical factors were measured at baseline and after treatment with pitavastatin (2 mg/day) for 6 months. Serum levels of LOX-1 with apolipoprotein B-100 particle ligand and a soluble form of LOX-1 (sLOX-1) were measured by ELISA. All subjects completed the study with no adverse side effects. Total-C (268 +/- 26 vs. 176 +/- 17 mg/dL), LDL-C (182 +/- 21 vs. 96 +/- 14 mg/dL), and LOX-1 ligand (867 +/- 452 vs. 435 +/- 262 ng/mL) were reduced with pitavastatin treatment (P < 0.0001 for each). Significant decreases in triacylglycerols were noted (P < 0.0001), but there were no changes in high-density lipoprotein cholesterol. After 6 months, there were no significant changes in high-sensitivity CRP or soluble LOX-1. At baseline, there were no significant correlations between LOX-1 ligand and either LDL-C or sLOX-1. The decrease in LOX-1 ligand was not correlated with the decrease in LDL-C, but was correlated with the decrease in sLOX-1 (r = 0.47, P < 0.05). In conclusion, pitavastatin therapy had beneficial effects on markers of oxidative stress in hypercholesterolemic subjects. Serum levels of LOX-1 ligand may be a useful biomarker of the pleiotropic effects of statins.

The relation between cholesteryl ester transfer protein (CETP) levels and atherosclerosis is controversial. We examined whether the serum CETP levels were associated with subclinical atherosclerosis, independent of its most common gene variant, in a sample of Japanese men. A population-based cross-sectional study of 250 Japanese men aged 40 to 49 years was conducted to assess the intima-media thickness of the carotid artery, coronary artery calcium, serum CETP levels, and the CETP D442G gene variant. Compared with the lowest CETP quartile, the multivariate adjusted odds ratio for coronary artery calcium was 0.77 (95% confidence interval 0.18 to 3.36), 0.96 (95% confidence interval 0.27 to 3.40), and 3.49 (95% confidence interval 1.05 to 11.6) with increasing CETP quartiles. The serum CETP quartiles were also positively associated with the intima-media thickness of the carotid artery (adjusted mean 602, 616, 615, and 646 mum for the lowest to top quartile, respectively). The findings remained unchanged after additional adjustment for the CETP D442G gene variant. No significant difference was found in the prevalence of coronary artery calcium or in the mean intima-media thickness of the carotid artery between participants with and without the CETP D442G gene variant.

Objective: Studies have suggested that ischemia-induced diastolic dysfunction persists longer than systolic dysfunction. We examined whether global left ventricular (LV) diastolic function during stress testing assessed by 16-frame gated myocardial perfusion single-photon emission computed tomography (SPECT) is useful as an indicator of myocardial ischemia., Methods: Thirty-nine patients underwent 16-frame technetium-99m (Tc-99m) quantitative gated SPECT (QGS), including treadmill exercise testing for suspected ischemic heart disease. Diastolic parameters of the first-third filling fraction (1/3FF), and the peak filling rate (PFR) were calculated by a time-volume curve from the QGS data., Results: The patients were divided into four groups, namely, IS, NL, DN, and DD, on the basis of tracer accumulation and the LV ejection fraction (LVEF) at rest. In the IS group (reversible tracer uptake reduction suggesting ischemia; n=11), LVEF, 1/3FF, and PFR after stress were significantly lower than those at rest, whereas in the NL group (normal perfusion; n=10) and DN group (fixed tracer uptake reduction with normal systolic function; EF>or=60% at rest; n=10), LVEF, 1/3FF, and PFR after stress did not differ from those at rest. However, in the DD group (fixed tracer uptake reduction with cardiac dysfunction; EF<60%, average 47.1%; n=8), LVEF, 1/3FF, and PFR were significantly altered after stress., Conclusions: Altered global LV diastolic function during stress assessed by 16-frame gated myocardial perfusion SPECT is useful for the detection of myocardial ischemia. However, similar findings are observed in patients with cardiac dysfunction but without detectable ischemia. Our findings do suggest that tests should be performed with caution to determine whether ischemia exists on the basis of altered global LV function after stress in patients with cardiac dysfunction.

Objectives: We sought to examine whether marine-derived n-3 fatty acids are associated with less atherosclerosis in Japanese versus white populations in the U.S., Background: Marine-derived n-3 fatty acids at low levels are cardioprotective through their antiarrhythmic effect., Methods: A population-based cross-sectional study in 281 Japanese (defined as born and living in Japan), 306 white (defined as white men born and living in the U.S.), and 281 Japanese-American men (defined as Japanese men born and living in the U.S.) ages 40 to 49 years was conducted to assess intima-media thickness (IMT) of the carotid artery, coronary artery calcification (CAC), and serum fatty acids., Results: Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar levels. Japanese had 2-fold higher levels of marine-derived n-3 fatty acids than whites and Japanese Americans in the U.S. Japanese had significant and nonsignificant inverse associations of marine-derived n-3 fatty acids with IMT and CAC prevalence, respectively. The significant inverse association with IMT remained after adjusting for traditional cardiovascular risk factors. Neither whites nor Japanese Americans had such associations. Significant differences between Japanese and whites in multivariable-adjusted IMT (mean difference 39 mum, 95% confidence interval [CI]: 21 to 57mum, p < 0.001) and CAC prevalence (mean difference 10.7%, 95% CI: 2.9% to 18.4%, p = 0.007) became nonsignificant after we adjusted further for marine-derived n-3 fatty acids (22 mum, 95% CI: -1 to 46 mum, p = 0.065 and 5.0%, 95% CI: -5.3% to 15.4%, p = 0.341, respectively)., Conclusions: Very high levels of marine-derived n-3 fatty acids have antiatherogenic properties that are independent of traditional cardiovascular risk factors and may contribute to lower the burden of atherosclerosis in Japanese, a lower burden that is unlikely the result of genetic factors.

The authors examine the clinical significance of radial augmentation index (rAI) and brachial-ankle pulse wave velocity (baPWV). In 78 hypertensive patients, rAI correlates inversely with pulse rate (PR; r = -0.57, P < .001), but baPWV does not. A weak correlation between rAI and systolic blood pressure (SBP) is observed (r = 0.28, P < .05). rAI has no significant correlation with diastolic blood pressure (DBP). In contrast, baPWV correlates positively with both SBP (r = 0.54, P < .001) and DBP (r = 0.43, P < .001). In 56 of these patients, baPWV correlates with the diastolic parameters-the mitral E/A ratio (r = -0.35, P < .01), pulmonary vein S/D ratio (r = 0.41, P < .01), and deceleration time (r = 0.28, P < .05)--by echocardiography, but AI.P75 (rAI corrected for PR 75 bpm because of PR dependence) does not. Therefore, for detection of diastolic dysfunction, baPWV may be more sensitive than rAI.

Objective: We examined the cardiac function of patients who underwent Tc-99m sestamibi quantitative gated myocardial single photon emission computed tomography with 16-framing data acquisition between January 1, 2004 and March 31, 2006 for an evaluation of suspected or known heart disease in our hospital., Methods: In 192 patients aged >or=40 years, the left ventricular (LV) systolic function [parameter: ejection fraction (EF)] and diastolic function [first third filling fraction (1/3FF), peak filling rate (PFR), and time-to-peak filling (TPF)] were estimated by volume curve analysis. In 51 (age >or=60 years) of 192 patients, brachial-ankle pulse wave velocity (baPWV) was also measured., Results: The correlation between diastolic parameters PFR and 1/3FF was mild (r = 0.28, P < 0.001). On the basis of EF and PFR, 192 patients were divided into four groups: P (preserved LV function), Q (isolated systolic dysfunction, EF < 50%), R (isolated diastolic dysfunction, PFR < 1.8 EDV/s), and S (both dysfunctions). The numbers of patients in P, Q, R, and S groups were 94 (49.0%), 7 (3.6%), 31 (16.1%), and 60 (31.3%), respectively. The 1/3FF correlated weakly but significantly with age (r = -0.16, P < 0.05). The TPF also correlated weakly with age (r = 0.25, P < 0.01), but EF did not. The baPWV, an indicator of cardiovascular stiffness, correlated inversely with 1/3FF (r = -0.59, P < 0.001) or correlated positively with TPF (r = 0.45, P < 0.001), but not with EF., Conclusions: Our study suggests that cardiovascular stiffness associated with increased baPWV may contribute to the occurrence of diastolic dysfunction in elderly patients.

Background: In the heart, the creatine kinase system plays an important role in energy reserves, and myocardial energy production essentially depends upon fatty acid metabolism., Purpose: To examine myocardial creatine (CR) concentration and altered cardiac fatty acid metabolism in various forms of heart disease., Material and Methods: Myocardial CR concentration of the septum was measured by gated 1H magnetic resonance spectroscopy (MRS), applying a point-resolved spectroscopy (PRESS) sequence in 34 patients with heart disease. Of these patients, 14 underwent 123I BMIPP (radioactive fatty acid analogue) myocardial scintigraphy to evaluate myocardial fatty acid metabolism. Cardiac 123I BMIPP uptake was calculated as the heart-to-mediastinum count ratio., Results: Myocardial CR concentration correlated positively with the left ventricular ejection fraction (LVEF) by echocardiography (R = 0.61, P<0.001, n = 34), suggesting that the degree of reduced CR is related to the severity of contractile dysfunction. Cardiac 123I BMIPP uptake also correlated positively with LVEF (initial image, R = 0.60, P<0.05; delayed image, R = 0.63, P<0.05; n = 14). There was a significant correlation between myocardial CR and cardiac 123I BMIPP uptake (initial image, R = 0.77, P<0.01; delayed image, R = 0.82, P<0.001; n = 14)., Conclusion: Our study suggests an association between CR depletion and impaired fatty acid metabolism in various forms of heart diseases.

Purpose: To investigate whether cardiac parameters obtained by I-123 15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP, a radioactive fatty acid analogue) myocardial scintigraphy are useful as indicators of disease severity and predictors of cardiac events in congestive heart failure (CHF)., Material and Methods: Thirty-two CHF patients (functional class: 17 in NYHA II and 15 in NYHA III at the time of this study) were compared with 18 normal control subjects. Myocardial scintigraphy was performed 15 min and 3 hours after I-123 BMIPP injection. The heart-to-mediastinum count ratio of I-123 BMIPP on the initial (H/Mi) and delayed (H/Md) images and the washout rate (WR) were calculated., Results: Both H/Mi and H/Md were lower in CHF than in controls (H/Mi 1.96+/-0.18 vs. 2.30+/-0.29; H/Md 1.72+/-0.15 vs. 1.97+/-0.21; both P<0.001), but WR was higher in CHF than in controls (WR (%) 23.7+/-5.7 vs. 18.2+/-6.0, P<0.01). Both H/Mi (R = 0.42, P<0.05) and H/Md (R = 0.45, P<0.05) correlated positively with the left ventricular (LV) ejection fraction (EF), estimated by echocardiography. The WR correlated positively with the plasma B-type natriuretic peptide (BNP) level (R = 0.47, P<0.01). Kaplan-Meier analysis showed an earlier CHF progression for patients with a lower H/Mi (<1.94)., Conclusion: Myocardial metabolic abnormality evaluated by I-123 BMIPP scintigraphy is related to the severity of CHF. Furthermore, it may be useful as a predictor for cardiac events.

Epidemiologic studies have investigated the relation between alcohol intake and coronary calcification, with controversial results. Furthermore, the influence of heavy drinking has not been well elucidated. In the present study, a random sample of community-based Japanese men aged 40 to 49 years without a history of cardiovascular disease (n=245) were examined for coronary artery calcium (CAC) determined by electron-beam computed tomography and drinking status. There was a J-shaped association between alcohol intake and CAC. There was an increase of CAC in heavy drinkers (>or=46 g/day), and participants who were drinking>or=69 g/day showed a significant increase in CAC compared with never drinkers after adjusting for other cardiovascular risk factors.

Objective: The aim of this study was to evaluate the left ventricular (LV) functional parameters calculated using quantitative electrocardiography (ECG)-gated myocardial perfusion single photon emission computed tomography (QGS). In addition to LV systolic parameters, diastolic parameters were compared with those by ultrasound echocardiography (UCG) and also with plasma B-type natriuretic peptide (BNP) concentrations., Methods: We examined 46 patients with various forms of heart disease. By the QGS data with 16 framing data acquisition using technetium (Tc)-99m methoxyisobutylisonitrile (MIBI) perfusion, we calculated the following parameters: LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), peak filling rate (PFR), filling rate during the first third of the filling time (1/3FR) and first third filling fraction (1/3FF). By UCG, we measured mitral early to atrial (E/A) wave velocity ratio and pulmonary venous inflow systolic/diastolic (S/D) ratio as diastolic functional parameters. Plasma BNP concentrations were also measured., Results: There was a significant correlation between LVEDV, ESV and EF measured by QGS and UCG (EDV, r = 0.71, p < 0.001; ESV, r = 0.82, p < 0.001; EF, r = 0.75, p < 0.001). The PFR, 1/3FR and 1/3FF obtained by QGS correlated positively with E/A ratio (PFR, r = 0.54, p < 0.001; 1/3FR, r = 0.61, p < 0.001; 1/3FF, r = 0.42, p < 0.01) and negatively with S/D ratio (PFR, r = -0.40, p < 0.01; 1/3FR, r = -0.38, p < 0.05; 1/3FF, r = -0.39, p < 0.01) obtained by UCG. Plasma BNP concentrations in EF < 50% patients were greater than those in EF > or = 50% patients (335.2 +/- 60.2 vs. 101.2 +/- 41.3 pg/ml, p < 0.01, both n = 17). Plasma BNP levels were also compared between higher and lower 1/3FF patients matched for LVEF. Plasma BNP concentrations in 1/3FF < 35% patients were significantly greater than those in 1/3FF > or = 35% patients (312.9 +/- 62.5 vs. 120.5 +/- 32.8 pg/ml, p < 0.05, both n = 14)., Conclusions: The degree of LV systolic and diastolic dysfunctions evaluated by QGS correlated with that by UCG or BNP. The QGS functional parameters offer useful information regarding cardiac failure.

Background: Previous (31)P magnetic resonance spectroscopy (MRS) studies demonstrated that the myocardial phosphocreatine-to-ATP ratio offered important information concerning the degree of dysfunction and prognosis in patients with cardiomyopathy. In the present study, we investigated total creatine (CR) levels in various diseased hearts using 1H MRS., Methods and Results: Fourteen patients with the following conditions were examined: cardiac amyloidosis (n = 2); hypertensive heart disease (4); valvular disease (2); hypertrophic cardiomyopathy (2); dilated cardiomyopathy (2); restrictive cardiomyopathy (1); and post-operative atrial septal defect (1). Myocardial CR was measured using 1H MRS with point-resolved spectroscopy localization. Overall, myocardial CR levels in diseased hearts were significantly lower than those in the control group [16.5+/-6.0 (n = 14) vs 27.1+/-3.2 micromol/g (n = 10), p < 0.001]. There was a positive correlation between myocardial CR and left ventricular ejection fraction (42.9+/-13.8%, range 19.5-69.1%) despite the different mechanisms of cardiac dysfunction (r = 0.60, p < 0.05). Myocardial CR levels in patients who were hospitalized due to heart failure within 1 year were significantly lower than those in other patients [11.3+/-1.0 (n = 4) vs 18.6+/-5.9 micromol/g (n = 10), p < 0.05]., Conclusions: Noninvasive measurement of myocardial CR using 1H MRS may be valuable in the assessment of disease severity and prediction of clinical course in various forms of heart disease.

Previous studies suggested that alteration of systemic skeletal muscle metabolism is a major determinant of exercise tolerance in patients with chronic heart failure (CHF). The authors examined calf muscle metabolism during continuous exercise of the foot in patients with CHF compared with normal subjects using (31)P magnetic resonance spectroscopy. The subjects were patients with New York Heart Association class II CHF who had previously suffered New York Heart Association class IV heart failure. Plantarflexion of the foot was repeated for 8 min 40 s at a rate of one contraction per second against a 2 kg load inside the magnet. At rest, during exercise (divided into the first one-half [EX1] and the latter one-half [EX2]) and at recovery, (31)P magnetic resonance spectroscopy data sets were acquired every 4 min 20 s. At rest, the phosphocreatine to hexamethylphosphoric triamide (PCr:HMPT) and the inorganic phosphate (Pi) to PCr ratios in the CHF group were not different from those in the normal group. During EX1 in the normal group, PCr levels decreased and Pi levels increased. Although exercise continued, these changes improved during EX2, suggesting there was an adaptation to exercise. The degree of change in the PCr:HMPT ratio during EX1 in the CHF group was not significantly different from that during EX1 in the normal group; however, the improvement during EX2 in the CHF group was impaired. The Pi:PCr ratio of EX1 to EX2 in the CHF group was significantly greater than that in the normal group (0.74+/-0.22 versus 0.19+/-0.05, respectively, P<0.005). Thus, in CHF, adaptation to continuous exercise may be impaired by alteration of skeletal muscle metabolism and this alteration may worsen exercise capacity.

Background: Since World War II (WWII), exposures to westernized lifestyle have occurred in many non-Western countries, including Japan. National surveys showed that risk factor profiles for atherosclerosis around 1990 were similar in men in the post WWII birth cohorts in the US and Japan. We compared the degree of coronary calcium and other factors in men in the post WWII birth cohort: men aged 40-49 in the US and Japan., Methods: We conducted a cross-sectional study examining randomly selected 100 men from Kusatsu, Japan, and 100 men from Allegheny County, US. Coronary calcium was assessed using electron-beam computed tomography., Results: Systolic blood pressure, total cholesterol, low density lipoprotein (LDL)-cholesterol, and smoking rates were higher among the Japanese (122.6 +/- 14.1 versus 113.7 +/- 9.6 mmHg, P < 0.01; 5.72 +/- 0.90 versus 4.99 +/- 0.81 mmol/l (220.9 +/- 34.6 versus 192.8 +/- 31.3 mg/dl), P < 0.01; 3.52 +/- 1.01 versus 3.10 +/- 0.78 mmol/l (136.0 +/- 39.0 versus 119.7 +/- 30.0 mg/dl), P < 0.01; and 48 versus 15%, P < 0.01, respectively). Triglycerides and fibrinogen were similar. High density lipoprotein (HDL)-cholesterol was higher among the Japanese. Body mass index, fasting insulin, and C-reactive protein were higher among the Americans. Prevalence of coronary artery calcium score >0 was strikingly lower among the Japanese than the Americans (13% versus 47%, P < 0.01)., Conclusions: Much lower prevalence of coronary calcium despite a less favourable profile of many major independent risk factors in the Japanese might imply that there are strong protective factors against atherosclerosis in the Japanese. Further investigation is of critical importance.

Objective: To clarify whether stiffness and impaired blood flow in lower-leg arteries are associated with severity of coronary artery calcification among asymptomatic diabetic patients., Research Design and Methods: We enrolled 102 asymptomatic type 2 diabetic patients with no history of cardiovascular complications consecutively admitted to our hospital. Agatston coronary artery calcium (CAC) score, as a marker of coronary artery calcification, was obtained using electron-beam computed tomography. Total flow volume and resistive index, as an index of vascular resistance, at the popliteal artery were evaluated using gated two-dimensional cine-mode phase-contrast magnetic resonance imaging. Brachial-ankle pulse-wave velocity (PWV), as an index of distensibility in the lower-extremity arteries, was also measured using an automatic device., Results: When the patients were grouped according to CAC scores of 0-10 (n = 54), 11-100 (n = 25), and > 100 (n = 23), those with the highest scores, which is considered to show possible coronary artery disease, showed the highest brachial-ankle PWV (P < 0.001) and resistive index (P < 0.001) and the lowest total flow volume (P < 0.001) among the groups. Simple linear regression analyses showed that both brachial-ankle PWV (r = 0.508, P < 0.001) and resistive index (r = 0.500, P < 0.001) were positively correlated and total flow volume (r = -0.528, P < 0.001) was negatively correlated with the log-transformed CAC score. Receiver operator characteristic curve analyses indicated that 1,800 cm/s for brachial-ankle PWV, 1.03 for resistive index, and 70 ml/min for total flow volume were diagnostic values for identifying patients with the highest scores., Conclusions: Quantitatively assessed stiffness and impaired blood flow in lower-leg arteries may help identify diabetic patients with possible coronary artery disease., (Copyright 2004 American Diabetes Association)

Creatine depletion in the non-viable infarcted human heart was previously demonstrated with proton magnetic resonance (MR) spectroscopy (1H MRS). In the present study, we assessed total creatine (CR) in human hearts with non-ischemic dysfunctions such as cardiomyopathy. Using cardiac-gated 1H MRS with MR image-guided PRESS localization, we measured septal CR in healthy and diseased human hearts. Fifteen patients with chronic heart failure (CHF, left ventricular ejection fraction < 45%) and 14 age-matched normal subjects were examined. Myocardial CR was significantly (p < 0.001) lower in failing hearts (15.1+/-SD 5.0 micromol/g wet weight, range 8.0-22.9) than in normal hearts (27.6+/-4.1 micromol/g wet weight, range 20.8-36.2). Myocardial CR concentrations in six heart failure patients with plasma B-type natriuretic peptide (BNP) levels of > 200 pg/ml (11.5+/-0.9 micromol/g wet weight, range 9.9-12.3) were significantly lower than those in four heart failure patients with plasma BNP levels of < 200 pg/ml (19.8+/-2.5 micromol/g wet weight, range 17.7-22.9, p < 0.001). Thus, our study showed that myocardial CR was decreased in non-ischemic dysfunctional hearts. Noninvasive measurements of myocardial CR by 1H MRS may be useful in the assessment of the severity of heart failure.

To assess quantitatively phosphocreatine (PCr), adenosine triphosphate (ATP) and total creatine (CR) in asynergic regions of ischemic human myocardium using phosphorus (31P) and proton magnetic resonance spectroscopy (1H MRS). Patients were divided into two groups: 31P MRS and 1H MRS. In each group, patients were subdivided into three groups using echocardiography: a normokinetic [WN(P) (n = 6) in 31P MRS, WN(H) (n = 10) in 1H MRS], a hypokinetic [WH(P) (n = 13), WH(H) (n = 7)], and a- or dyskinetic wall motion groups [WA(P) (n = 14), WA(H) (n =6)]. They were compared with normal subjects of each group [CNP (n = 10), CN(H) (n = 10)]. 31P MRS spectra were obtained from the anterior and apical regions of the left ventricle by slice-selected 1D CSI. 1H MRS spectra were obtained from the 2 x 2 x 2-cm voxel set in the left ventricular wall by the PRESS method. In the 31P MRS group, myocardial PCr was significantly lower in the WH(P) and WA(P) groups than in the CN(P) group, but myocardial PCr in the WN(P) group did not differ from that in CN(P). A difference in ATP could not be detected among the four groups. In the 1H MRS group, myocardial CR was significantly lower in the WH(H) and WA(H) groups than in the CN(H) group. Myocardial CR in the WNH group did not differ from that in the CN(H). The noninvasive 31P and 1H MRS approach is useful in the assessment of metabolite reduction associated with wall motion abnormality.

Objectives: This study noninvasively examined total creatine (CR) of the myocardium in dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) using proton magnetic resonance spectroscopy ((1)H-MRS)., Background: Abnormalities in CR metabolism in failing hearts have been reported. A biochemical study suggested that myocardial metabolic changes are very similar in DCM and HCM despite the different heart failure (HF) mechanisms., Methods: Using cardiac-gated (1)H-MRS with magnetic resonance image (MRI)-guided point-resolved spectroscopy (PRESS) localization, we quantitatively measured septal CR. Patients with either DCM (n = 11) or HCM (n = 7) and age-matched normal subjects (n = 14) were examined., Results: Myocardial CR was significantly lower in DCM patients (16.1 +/- 4.5 micromol/g wet weight [range 10.2 to 22.9], p < 0.05) than that in subjects with normal hearts (27.6 +/- 4.1 micromol/g [range 21.4 to 36.2]). Myocardial CR in HCM patients (22.6 +/- 8.1 micromol/g [range 12.2 to 34.5]) was significantly lower than that in subjects with normal hearts (p < 0.05) but was significantly higher than that in DCM patients (p < 0.05). In 18 patients with either DCM or HCM, myocardial CR correlated positively with left ventricular ejection fraction (LVEF) (y = 0.22x + 9.8, r = 0.73, p = 0.0006) but correlated negatively with plasma B-type natriuretic peptide (BNP) levels (y = -0.012x + 22.4, r = -0.54, p = 0.022)., Conclusions: This study showed that (1)H-MRS can noninvasively detect CR depletion associated with the severity of HF in cardiomyopathy.

Despite similar traditional risk factors, morbidity and mortality rates from coronary heart disease in western and non-western cohorts remain substantially different. Careful study of such cohorts may help identify novel risk factors for CHD, and contribute to the formulation of new preventive strategies

1. The roles of ATP-sensitive K+ channels (KATP channels) in ischaemic or pharmacological preconditioning in the rabbit heart remain unclear. Infarct limitation by ischaemic preconditioning was abolished by the KATP channel blocker glibenclamide under ketamine/xylazine anaesthesia, but not under anaesthesia induced by pentobarbital. Infarct limitation by the KATP channel opener pinacidil was detected under ketamine/xylazine anaesthesia, but not under pentobarbital anaesthesia. Thus, these effects appear to be anaesthetic dependent. 2. In the present study, we examined whether nicorandil (a KATP channel opener nitrate) exhibits cardioprotective actions under halothane anaesthesia, another commonly used volatile anaesthetic. Control animals were subjected to 40 min coronary occlusion and 120 min reperfusion. Before 40 min ischaemia, the nicorandil group received nicorandil (100 microg/kg per min, i.v., for 10 min), the 5' preconditioning (PC) group received 5 min ischaemia/20 min reperfusion, the 2.5'PC group received 2.5 min preconditioning ischaemia/20 min reperfusion, the nicorandil +2.5'PC group received both nicorandil and 2.5 min ischaemia/20 min reperfusion, the nicorandil +2.5'PC + 5-hydroxydecanoate (5HD) group received both nicorandil and 2.5 min ischaemia/20 min reperfusion in the presence of 5-hydroxydecanoate (5HD; a KATP blocker) and the 5HD group received 5 mg/kg, i.v., 5HD alone. Myocardial infarct size in control (n = 7), nicorandil (n = 5), 5'PC (n = 8), 2.5'PC (n = 5), nicorandil + 2.5'PC (n = 5), nicorandil + 2.5'PC + 5HD (n = 5) and 5HD (n = 4) groups averaged 44.4 +/- 3.6, 41.7 +/- 5.7, 17.8 +/- 3.2,* 34.1 +/- 4.8, 21.3 +/- 4.2,* 39.1 +/- 5.6 and 38.9 +/- 5.0% of the area at risk, respectively (*P <0.05 vs control). 3. Thus, nicorandil alone did not have an infarct size-limiting effect in halothane-anaesthetized rabbits. However, the results suggest that even when nicorandil alone does not demonstrate a direct cardioprotective effect, it may enhance ischaemic preconditioning via KATP channels. Key words: ATP-sensitive K+ (KATP) channel, ischaemic preconditioning, myocardial infarction, nicorandil, rabbit.

We investigated the cardiovascular profile of nicorandil, an antianginal agent, in humans. Pharmacologically, nicorandil acts as both an adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channel opener and a nitrate. We examined which of these mechanistic components has a predominant vasodilatory effect at clinical doses. Fourteen patients underwent cardiac catheterization. The effects of the continuous intravenous infusion of nicorandil (12 mg/45 min) were examined in angiographically normal coronary arteries. Coronary vascular resistance was calculated from coronary artery diameter and coronary blood flow velocity measured using an intravascular Doppler catheter. We compared the hemodynamic responses to nicorandil with those to the intracoronary injection of nitroglycerin (250 microg) and papaverine (12 mg). The epicardial coronary arteries responded to nicorandil at the lowest plasma concentration examined (dilation of +14.0 +/- 3.3% at approximately 170 ng/ml), whereas dilation of the coronary resistance arteries (i.e., a decrease in coronary vascular resistance) took place only at higher concentrations (>200 ng/ml). Nitroglycerin caused no further changes in coronary artery diameter or coronary vascular resistance. Papaverine caused no further increase in coronary artery diameter, but markedly decreased coronary vascular resistance (1.6 +/- 0.3 to 0.4 +/- 0.1 mm Hg/ml/min; p < 0.05). Nicorandil significantly decreased pulmonary capillary wedge pressure (i.e., reduced cardiac preload) at a plasma level of >200 ng/ml, but did not change either systemic or pulmonary vascular resistance. Thus nicorandil preferentially dilated epicardial coronary arteries rather than coronary resistance arteries, and had a stronger effect on preload than on afterload. These changes in human coronary hemodynamics suggest that the nitrate actions of nicorandil as a coronary vasodilator predominate over those as a K(ATP) opener.

Objectives: This study examined the changes in myocardial energy metabolism during myocardial ischemia after "remote preconditioning" and investigated the involvement of adenosine receptors in the mechanisms of this effect., Background: Recent studies have indicated that a brief period of ischemia and reperfusion (ischemic preconditioning, PC) in a remote organ reduces myocardial infarct size (IS) protecting against subsequent sustained myocardial ischemia. However, the mechanisms of "remote PC" remain unclear. We assessed myocardial energy metabolism during sustained myocardial ischemia and reperfusion after renal PC (RPC), in comparison with that after myocardial PC (MPC) in open-chest rabbits. It has been established that adenosine receptors are involved in the mechanisms of MPC., Methods: Rabbits that had been anesthetized with halothane were divided into six groups. The control (CNT) group underwent 40-min coronary occlusion followed by 120 min reperfusion. Before the procedure, the MPC group underwent an additional protocol of 5 min coronary artery occlusion and 20 min reperfusion, and the RPC group received a 10 min episode of renal artery occlusion and 20 min reperfusion. In additional experimental groups, 8 sulfophenyl-theophylline (SPT, 10 mg/kg), an adenosine receptor inhibitor, was intravenously injected before the 40 min myocardial ischemia (SPT, MPC + SPT and RPC + SPT groups, respectively). Myocardial levels of phosphocreatine (PCr), ATP and intracellular pH (pHi) were measured by 31P-NMR spectroscopy., Results: RPC and MPC delayed the decreases in ATP levels, preserved pHi during 40-min myocardial ischemia and resulted in better recovery of ATP and PCr during 120 min reperfusion compared with the controls. SPT abolished the improvement in myocardial energy metabolism and the reduction in myocardial IS caused by MPC or RPC. Myocardial IS in the CNT (n = 8), MPC (n = 9), RPC (n = 9), SPT (n = 6), MPC + SPT (n = 8) and RPC + SPT (n = 8) groups averaged 42.8+/-3.5%, 18.2+/-1.8%*, 19.6+/-1.3%*, 44.9+/-5.0%, 35.6+/-2.7% and 34.8+/-3.6% of the area at risk (*p < 0.05 vs. CNT), respectively., Conclusions: PC in a remote organ, similar to MPC, improved myocardial energy metabolism during ischemia and reperfusion and reduced IS in vivo by an adenosine-dependent mechanism in rabbits.

Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients with essential hypertension. Ten patients (four men and six women) with essential hypertension received candesartan cilexetil 2-8 mg/day orally for 8-12 weeks. After drug administration, systolic blood pressure (BP) decreased from 178.9 +/- 17.2 mmHg (mean +/- SD) to 150.2 +/- 14.3 mmHg (P < 0.0001) and diastolic BP from 101.4 +/- 6.5 mmHg to 87.8 +/- 11.9 mmHg (P = 0.0021). Both MRI and echocardiography revealed a significant decrease in LV mass index (LVMI) after candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 +/- 31.3 g/m2 to 102.6 +/- 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from 123.9 +/- 31.1 g/m2 to 115.8 +/- 31.4 g/m2 (P = 0.0316). Total systemic vascular resistance decreased significantly during treatment with candesartan cilexetil in both MRI and echocardiography assessment, from 1847.2 +/- 636.3 dynes.s.cm-5 to 1540.4 +/- 432.0 dynes.s.cm-5 (P = 0.0034) on MRI and from 1820.4 +/- 318.8 dynes.s.cm-5 to 1659.0 +/- 317.7 dynes.s.cm-5 (P = 0.0060) on echocardiography. These findings suggest that candesartan cilexetil 2-8 mg/day orally for 8-12 weeks is beneficial in the regression of cardiac hypertrophy in patients with essential hypertension.

Unlabelled: This study assessed the utility of myocardial fatty acid imaging using 123I-labeled 15-(beta-methyl-p-iodophenyl-pentadecanic acid (BMIPP) to evaluate improvement after percutaneous transluminal coronary angioplasty in patients with chronic coronary artery disease., Methods: Thirty-eight patients (18 old myocardial infarction and 20 angina pectoris patients) with chronic coronary artery stenosis and 8 control subjects were enrolled in this study. All patients underwent successful angioplasty, and BMIPP SPECT was performed before and after angioplasty. SPECT images were divided into 13 segments and scored visually from 0 (normal uptake) to 4 (defect). The defect score was calculated as the summation of the total scores in each patient. The regional washout rate was calculated in both the reperfused areas and normal uptake areas using a bull's-eye map., Results: In nonrestenosis patients, BMIPP defect scores before and after angioplasty did not change on the initial image (9.6 +/- 9.3 compared to 9.0 +/- 9.2, nonsignificant p value), whereas they improved significantly on the delayed image (9.9 +/- 8.8 compared to 8.2 +/- 8.7, p < 0.05). In nonrestenosis patients, BMIPP washout rate in reperfused areas after angioplasty was significantly lower than that before angioplasty and the washout rate in control subjects (22.9% +/- 8.4% compared to 31.5% +/- 10.6% and 29.5% +/- 8.0%, p < 0.01 and p < 0.05, respectively). In restenosis patients, BMIPP washout rate in both reperfused areas and normal uptake areas did not change after angioplasty., Conclusion: These data suggest that decreased BMIPP washout rate after angioplasty indicates improved fatty acid utilization in patients with chronic coronary artery disease.

To evaluate the prognostic value of the simultaneous assessment of perfusion and left ventricular wall motion, exercise non-gated/rest electrocardiogram (ECG)-gated 99mTc methoxy-isobutyl isonitrile (MIBI) single-photon emission computed tomography (SPECT) was performed in 182 patients suspected of having coronary artery disease. After injection of 250 MBq of 99mTc-MIBI at peak exercise, stress perfusion images were classified into 3 groups: normal, equivocal, and abnormal. Normal subjects completed the 1-day protocol but not the resting study, whereas patients with abnormal or equivocal perfusion images underwent ECG-gated SPECT study with injection of 750 MBq of 99mTc-MIBI 3 h later. Patients with normal perfusion during this protocol had a benign prognosis. Only 4 soft events occurred in the normal group (4.8%). In contrast, patients with both myocardial infarction and abnormal wall motion at rest experienced more cardiac events (7 cardiac events including 1 cardiac death among a total of 45 patients; 15.6%, p<0.05 compared with normal subjects). In addition, ischemic patients also experienced more cardiac events (7 events including 2 cardiac deaths among a total of 25 subjects; 28.0%, p<0.01 compared with normal patients). Our data suggest that the simultaneous assessment of perfusion and wall motion by stress/rest ECG-gated 99mTc-MIBI SPECT is a reliable indicator of prognosis in patients suspected of having coronary artery disease.

Although both aging and hypertrophy are extremely important factors for cardiac performance, their influence on cardiac metabolism, especially that of high-energy phosphates, has not been fully elucidated as yet. Quantitative measurements of high-energy phosphates were attempted by comparing myocardial 31P NMR spectra with an external reference using depth-resolved surface-coil spectroscopy. The voxel size of the region of interest (ROI) was disk-shaped with 15-cm diameter and 25-mm thickness, but the left ventricular weight actually involved in the ROI was estimated to be between 22 and 66 g using MRI. Myocardial phosphocreatine (PCr) content and adenosine triphosphate (ATP) content for the 30 normal volunteers showed significant age dependence since both decreased in relation to increasing age. Myocardial PCr content and ATP content in patients with hypertension did not differ significantly from the age-matched control group. PCr content (6.1 +/- 2.2 micromol/g wet tissue, n = 10) and ATP content (4.1 +/- 1.3 micromol/g wet tissue) in patients with hypertrophic cardiomyopathy were less than the age-matched control group (n = 15; PCr: 9.7 +/- 2.5 micromol/g wet tissue, P < 0.01; ATP: 6.4 +/- 1.8 micromol/g wet tissue, P < 0.05), respectively. These results indicate that quantitative 31P MRS may be valuable in the assessment of changes in high-energy phosphate metabolism caused by aging or hypertrophy.

Reversible thallium-201 (201Tl) abnormalities during exercise stress have been used as markers of myocardial ischemia in hypertrophic cardiomyopathy (HCM) and are most likely to identify relatively underperfused myocardium. Although metabolic abnormalities in HCM were reported, the relationship between impaired energy metabolism and exercise-induced ischemia has not been fully elucidated as yet. To assess the relationship between myocardial perfusion abnormalities and fatty acid metabolic abnormalities, 28 patients with HCM underwent exercise 201Tl and rest 123I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (BMIPP) scintigraphy. Perfusion abnormalities were observed by exercise 201Tl in 19/28 patients with HCM. 123I-BMIPP uptake was decreased compared with delayed 201Tl in 106/364 (29%) of the total myocardial segments (p<0.01, McNemar symmetry test). Such disparity between 123I-BMIPP and 201Tl was observed more often in the 49/75 (65%) segments with reversible exercise 201Tl defects (p<0.001). Our results indicate that exercise-induced myocardial ischemia exists in HCM, resulting in metabolic abnormalities. The combination of 123I BMIPP and 201Tl suggests that myocardial ischemia may play an important role in metabolic abnormalities in HCM.

S-Nitrosocaptopril (S-NO-Cap), a nitrate and an angiotensin-converting enzyme (ACE) inhibitor, may be produced after coadministration of nitroglycerin (NTG) and captopril (CAP). We synthesized S-NO-Cap and investigated its in vivo tolerance. In open-chest dogs, S-NO-Cap [300 microg; intracoronary (i.c.)] and NTG (50 microg, i.c.) increased coronary blood flow (CBF) similarly (8.0 vs. 9.0 ml/min; p = NS; n = 5). After a 2-h i.c. NTG infusion at high dose (1.32 micromol/min), NTG (50 microg, i.c.) had no significant effect on CBF, whereas S-NO-Cap (300 microg, i.c.) still produced an attenuated increase in CBF (4.9 ml/min; p < 0.05 vs. control). On the other hand, after a 2-h i.c. infusion of S-NO-Cap (1.32 micromol/min), the CBF response to S-NO-Cap (300 microg) showed no attenuation, whereas that to NTG (50 microg) was potentiated (8.8 vs. 12.6 ml/min; p < 0.05; n = 6). Under basal conditions, S-NO-Cap (30-300 microg, i.c.) increased CBF dose dependently, whereas CAP (30-300 microg, i.c.) had no effect on CBF, suggesting that S-NO-Cap dilates coronary vessels by a nitrate action but not by an ACE-inhibitory action. In nonsurgical dogs, 2-h intravenous (i.v.) infusion of S-NO-Cap (1.32 micromol/min) had a stable hypotensive effect, whereas that of NTG (1.32 micromol/min) gradually attenuated the effect. Plasma NO3-, an oxidative product of nitric oxide (NO), increased after both infusions, suggesting that S-NO-Cap may act partially as an NO donor, similarly to NTG. Plasma ACE activity was reduced after an S-NO-Cap infusion (5.84 vs. 4.10 IU/L; p < 0.01; n = 5), and plasma aldosterone was markedly increased after NTG infusion relative to that after S-NO-Cap infusion (243.0 vs. 38.6 pg/ml; p < 0.05). Plasma norepinephrine increased after both infusions (393.6 vs. 289.0 pg/ml; p = NS). As judged by the increase in CBF, whereas S-NO-Cap showed partial tolerance with NTG, no tolerance was found with S-NO-Cap itself. The in vivo coronary vascular response to S-NO-Cap may, therefore, be partially reduced by activation of the adrenergic or renin-angiotensin-aldosterone systems or both induced by NTG, because S-NO-Cap showed no cross-tolerance with NTG in our earlier in vitro study.

Unlabelled: Septal hypoperfusion is often observed in patients with complete left bundle branch block (LBBB) in myocardial perfusion imaging. Abnormal wall motion in the septal region may potentially cause artifactual perfusion abnormalities. To assess the effect of abnormal wall thickening on myocardial perfusion images, ECG-gated sestamibi SPECT was performed on 12 patients with LBBB and 10 normal subjects used as controls., Methods: After administration of 740 MBq 99mTc-sestamibi injection at rest, ECG-gated SPECT was obtained 60 min later with division of the cardiac cycle into eight frames., Results: Septal hypoperfusion was noted in 10 patients on nongated images and 11 patients on end-systolic (ES) images, whereas only two patients showed abnormalities on end-diastolic (ED) images. The septal to lateral wall count ratio in the LBBB group was lower (0.72 +/- 0.09) than in the control group (0.84 +/- 0.09) (p < 0.01) at nongated images, while it was similar at ED images (0.84 +/- 0.11 versus 0.86 +/- 0.12; ns). In addition, the count increase from ED to ES during a cardiac cycle in the septal region was smaller compared with the lateral region in the LBBB patients (25% +/- 19% in the septal region, versus 48% +/- 14% in the lateral region; p < 0.01), indicating less wall thickening in the septal region., Conclusion: Smaller count increase due to reduced wall thickening in the septal region may mimic hypoperfusion in patients with LBBB. This artifact can be eliminated with ECG-gated 99mTc-sestamibi SPECT, particularly with ED images.

Background: 31P metabolite measurements in the human heart by magnetic resonance spectroscopy (MRS) have been reported previously. By use of a method in which metabolite content was quantified with reference to a standard located outside the chest, it has become possible to measure the content of phosphocreatine (PCr) and ATP in vivo in the human heart. In this study, PCr and ATP contents were measured by 31P MRS and compared in human myocardium with reversible ischemia or scar diagnosed by exercise thallium scintigraphy., Methods and Results: Forty-one subjects with stenosis of the left anterior descending coronary artery (> 50%) and 11 healthy control subjects (C) composed the present study group. Patients were divided into two groups on the basis of exercise 201Tl scintigraphy: a reversible 201Tl defect group (RD[+], n = 29) who demonstrated redistribution at late image and a fixed 201Tl defect group (RD[-], n = 12). While the subjects lay supine within the magnet, 31P MR spectra were obtained from the anterior and apical regions of the left ventricle by slice-selected one-dimensional chemical shift imaging. For metabolite quantification, a standard was placed at the center of the surface coil. ANOVA revealed significant differences among the three groups with respect to the mean (+/- SD) PCr at rest (C, 12.14 +/- 4.25 > RD[+], 7.64 +/- 3.00 > RD[-], 3.94 +/- 2.21 mumol/g wet heart tissue, P < .05) as well as a significant decrease in ATP in the RD(-) group (C, 7.72 +/- 2.97; RD[+], 6.35 +/- 3.17 > RD[-], 4.35 +/- 1.52 mumol/g wet heart tissue, P < .05)., Conclusions: Compared with healthy control subjects, PCr content decreased significantly in patients with both reversible and fixed 201Tl defects, and ATP content decreased significantly in subjects with fixed thallium defects. These results suggest that the measurement of ATP content in the human heart by 31P MRS is a clinically important method for the evaluation of myocardial viability.

Background: The metabolic changes of myocardial ischemia in patients with coronary artery disease assessed by 31P magnetic resonance spectroscopy (MRS) have been reported previously. A significant decrease in the ratio of phosphocreatine (PCr) to ATP during handgrip exercise in a group of patients with severe coronary artery disease has been demonstrated. However, there are no reports at present that directly compare cardiac 31P MRS data with exercise 201Tl myocardial scintigraphy, now established as one of the most important clinical methods to assess myocardial ischemia. The purpose of this study was to investigate whether 31P MRS with handgrip exercise testing is able to detect myocardial ischemia, demonstrated by exercise 201Tl scintigraphy., Methods and Results: Twenty-seven patients with severe stenosis of the left anterior descending coronary artery (> or = 75%) and 11 normal control subjects composed the present study. Patients were divided into two groups on the basis of exercise 201Tl scintigraphy: a reversible 201Tl defect group (RD[+]) who demonstrated redistribution at the late image and a fixed 201Tl defect group (RD[-]). While lying supine within the magnet, subjects performed handgrip exercise at 30% of maximal force once in every two cardiac cycles. 31P MR spectra were collected before and during handgrip exercise. Data were corrected for the saturation factor. ANOVA revealed significant differences among the three groups with respect to the mean +/- SD PCr/ATP ratio at rest (control, 1.85 +/- 0.28 > RD(+), 1.60 +/- 0.19 > RD(-), 1.24 +/- 0.30; P < .05). The PCr/ATP ratio decreased significantly from 1.60 +/- 0.19 at rest to 0.96 +/- 0.28 during exercise (P < .001) in the RD(+) group (n = 15). However, in the RD(-) group (n = 12), the ratio did not change significantly during handgrip exercise (1.24 +/- 0.30 at rest versus 1.19 +/- 0.28 during exercise). Similarly, the ratio did not change in the control group (n = 11) (1.85 +/- 0.28 at rest versus 1.90 +/- 0.23 during exercise)., Conclusions: Contrary to normal subjects or patients with fixed thallium defects, the PCr/ATP ratio was significantly altered by exercise in patients with reversible thallium defects. These results suggest that 31P MRS with handgrip exercise testing is a sensitive method for detecting myocardial ischemia.

We measured and compared left ventricular mass in 20 patients by ultrafast computed tomography (UFCT), magnetic resonance imaging (MRI), and contrast left ventriculography (LVG). Left ventricular mass was calculated by UFCT and MRI in two ways: (1) excluding papillary muscles and trabeculae (LV mass), and (2) including papillary muscles and trabeculae (LV mass + PM&T) by Simpson's method. Left ventricular mass excluding papillary muscles and trabeculae (LV mass) in LVG was calculated by Rackley's method by biplane angiocardiography. LV mass was significantly larger in LVG than in MRI and UFCT (p < 0.01). Although LV mass was significantly larger in MRI than in UFCT (p < 0.01), there was no significant difference in LV mass + PM&T between UFCT and MRI. Interobserver and intraobserver variability showed good correlation of coefficient in both UFCT and MRI. We therefore conclude that left ventricular mass is best measured by including papillary muscles and trabeculae by Simpson's method in UFCT or MRI.

High dose-dobutamine (DOB) has been previously used as a pharmacological stress test to evaluate wall motion abnormalities. As a result, recent stress echocardiography with low-dose DOB has been reported to be valuable for investigating stunned myocardium after thrombolysis. However, echocardiography requires an operator's skill and experience to evaluate wall motion abnormalities which are subjectively determined by the observer. In contrast, ultrafast computed tomography (UFCT) does not necessarily require extreme technical skill and experience. To evaluate the feasibility of stress UFCT with low-dose DOB, we scanned 10 normal subjects along the short-axis by 8-slice-multicine mode. After scanning at rest for baseline, we scanned during the administration of 4 and 8 micrograms/kg/min of DOB, respectively, for 5 min. Ejection fraction, contraction, and thickening were higher during 8 micrograms/kg/min of DOB than during 4 micrograms/kg/min of DOB and baseline, while the above values were higher during 4 micrograms/kg/min of DOB than during baseline (p < 0.01). It was possible to detect changes of cardiac function and wall motion due to low-dose DOB by UFCT. We therefore conclude that UFCT is a reliable modality for evaluating cardiac function and wall motion for low-dose DOB stress test because of its excellent spatial and contrast resolution.

To assess the usefulness of in vivo 31P nuclear magnetic resonance (NMR) spectroscopy, we investigated spectra from the myocardium in 6 patients with old Q-wave infarction (QMI), 6 with old non-Q-wave infarction (NQMI) and 9 controls by ECG-gated depth-resolved surface-coil spectroscopy. External hexamethylphosphoric triamide (HMPT) was used to quantify the signal intensities. Left ventricular weight in the region of interest (LVW) was estimated from 1H magnetic resonance images. The extent score by 201Tl scintigraphy was determined in 3 QMI and 4 NQMI patients. No significant differences were found among the 3 groups in peak area ratios of 31P NMR spectra to phosphocreatine (PCr) or adenosine triphosphate (ATP). Compared with controls, significant reductions were observed in values for the peak areas of PCr normalized by the standard HMPT (PCr/HMPT) or by both HMPT and LVW (PCr/HMPT/LVW) for QMI patients (p less than 0.05), and in ATP/HMPT and ATP/HMPT/LVW for QMI and NQMI patients (p less than 0.01). There was a significant negative correlation between ATP/HMPT and the 201Tl scintigraphy extent score (p less than 0.05). These findings suggest that in vivo 31P NMR spectroscopy can detect high-energy phosphate reduction in the infarcted myocardium and may be useful in evaluating myocardial viability.

We determined the effect of the calcium antagonistic agent, diltiazem hydrochloride upon ischemia-reperfusion injury in the dog. Ischemia was produced by occluding the left anterior descending artery for 40 min. Subsequent reperfusion was accomplished for 120 min by virtue of removal of the occlusion. Sixteen of the dogs studied were randomly assigned to diltiazem (D)-treated group (n = 8) and saline (S)-treated group (n = 8). D in saline was intravenously infused at a concentration of 3 mcq/kg/min starting 15 min after the occlusion. Myocardial blood flow (MBF) was measured using hydrogen gas clearance method. Infarct size was quantified as percent myocardium at risk by triphenyltetrazolium chloride staining. D administration caused a slight decline in mean aortic pressure, heart rate, and heart rate X systolic blood pressure throughout the periods of occlusion and reperfusion. However, there was no significant difference observed in both groups of dogs. MBF to ischemic myocardium was not significantly enhanced by D during ischemia. After 5 min of reperfusion subepicardial MBF was increased in group S, indicating a tendency towards reactive hyperemia. After 120 min of reperfusion there was a significant reduction in subendocardial MBF in group S and the transmural blood flow ratio was 1.23 +/- 0.59 in group D as compared with 0.53 +/- 0.39 in group S (p less than 0.05). The infarcted area as a percentage of the risk area was considerably smaller in group D than in group S (27.5 +/- 3.0 vs 47.0 +/- 6.5%, p less than 0.05). D markedly reduced the elevation of tissue calcium especially in the subendocardium. These findings suggest that D reduces the ultimate infarct size through the beneficial effect on ischemia-reperfusion injury.

Nicorandil therapy was compared with placebo therapy in 11 patients with chronic stable angina pectoris. A computer-assisted treadmill exercise test was performed after administration of either 10 or 30 mg of nicorandil. Analysis of variance showed a significant difference among placebo and nicorandil treatments (p less than 0.01). Ten milligrams of nicorandil prolonged time to onset of ischemia 36% (p less than 0.05) but increased the exercise duration only 15%. Thirty milligrams of nicorandil prolonged time to onset of ischemia 82% (p less than 0.01) and exercise duration 45% (p less than 0.01). Both time to onset of ischemia and exercise duration increased progressively from the 10-mg to the 30-mg dose (p less than 0.05). Heart rate at rest was significantly higher and systolic pressure at rest significantly lower with 30 mg of nicorandil than with placebo. After administration of 30 mg of nicorandil there was a significant reduction in ST depression associated with a slight decrease in the double product at the end of Bruce stage 2 exercise. The peak double product was greater after administration of 30 mg of nicorandil than after placebo, indicating an increased myocardial oxygen supply to the ischemic area. The plasma concentration of nicorandil averaged 78 +/- 83 ng/ml with the 10 mg and 313 +/- 142 ng/ml with 30 mg. There was an increase in exercise duration of more than 1 minute in 8 of 9 patients who had plasma nicorandil concentrations greater than 100 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Using the histo- and cytochemical technique we assessed the Ca2+-transporting function of mitochondria (Mit) and sarcoplasmic reticulum (SR), and the ATP producing function of Mit in the ischemic myocardial cell of a dog's heart. In comparing ultrastructural ischemic changes, cytochrome oxidase (CO) and Ca2+-ATPase were cytochemically and histochemically measured when the myocardium was subjected to the ischemia of left anterior descending coronary artery occlusion for 15 min, and 60 min. After 15 min of occlusion the ischemic alterations consisted of a wide I band, decreased glycogen (G) and Mit swelling with a slight reduction of matrix density. Although CO activity was not reduced, Ca2+-ATPase had decreased mainly in Mit. Sixty min of ischemia resulted in loss of G, intermyofibrillar edema, marked Mit swelling with loss of matrix density and partial disruption of cristae, and dilatation of SR. Ca2+-ATPase activity was significantly reduced in Mit, SR and myofibrils. Although there was Mit swelling with partial disruption of cristae after 60 min of ischemia, CO activity was found to still exist in the remaining cristae. These findings suggest that intracellular organelle dysfunction progresses in the ischemic myocardial cell at different rates, and that disruption of intracellular Ca2+-homeostasis may occur early in the ischemic state.

Deflection area vectors of QRS (Aqrs) and T (At) and ventricular gradient (G) calculated from vectorcardiographic leads were compared in single vessel coronary artery diseases divided into subgroups of normokinetic, hypokinetic and akinetic by left ventriculography. In the LAD group, Aqrs shifted posteriorly, At were smaller and shifted to the right and G were smaller and shifted posteriorly or to the right. In the RCA group, Aqrs were smaller and shifted upwards, At shifted upwards and G were smaller and shifted upwards. In the LCx group, Aqrs shifted upwards, At shifted anteriorly and upwards and G were smaller and shifted upwards. Decreased magnitude and directional change of G reflect the severity and location of myocardial damage.

In animal experiments, a new inotropic agent, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenetyl)amino] ethanol, designated TA-064 was found to possess a more positive inotropic than chronotropic action. Its effectiveness and lack of significant toxicity make it beneficial for clinical use as a cardiotonic in human heart failure. The effects of TA-064 were investigated in patients with various types of heart disease (n = 29). Cardiac output increased, left ventricular end-systolic dimension decreased, and left ventricular fractional shortening increased for 15 minutes after a single intravenous dose (1 mg). The plasma level of TA-064 at the cessation of infusion was 61.1 +/- 49.6 ng/ml and thereafter declined biexponentially. After a single oral dose (10 mg), TA-064 appeared in the plasma at 30 minutes and reached its peak levels of 13.7 +/- 5.6 ng/ml at 60 minutes. Seven hours later, the plasma level was 5.9 +/- 3.1 ng/ml which was considered to be within the effective range according to the results after intravenous administration. In conclusion, minimal effective plasma levels of TA-064 are obtained by oral administration of 10 mg three times a day.