Floating thrombus arising from left sinus of Valsalva induced intermittent occlusion of left coronary artery and caused cardiogenic shock.
Explore the source record for details and available documents.
Aged↗
Biomedical subjects
Kazuhide Ogino
Publications and source records attributed to Kazuhide Ogino.
Catabolism of adenine nucleotides favors adenosine production following exercise in patients with chronic heart failure.
BACKGROUND: Adenosine 5'-triphosphate is catabolized to adenosine 5'-monophosphate (AMP), which is further degraded by 2 pathways: deamination to inosine 5'-monophosphate and ammonia by AMP deaminase, or dephosphorylation to adenosine and inorganic phosphate by 5'-nucleotidase. Because adenosine is believed to be cardioprotective and we have reported that ammonia production decreased after exercise in patients with chronic heart failure (CHF), we determined if plasma adenosine levels after exercise increases in patients with CHF. METHODS AND RESULTS: Maximal ergometer exercise tests with expired gas analysis were performed in 51 patients with CHF (age = 61 +/- 2 years, New York Heart Association [NYHA] class I/II/III = 19/18/14) and 20 age-matched normal controls. Serial changes in both plasma ammonia and adenosine levels were determined. The ratio for delta ammonia to peak work rate became smaller (control, NYHA I/II/III: 0.59 +/- 0.13/0.41 +/- 0.06/0.37 +/- 0.10/0.22 +/- 0.11 microg/dL x watts, respectively) and the ratio for delta adenosine to peak work rate was significantly higher in class III CHF (control, NYHA I/II/III: 0.93 +/- 0.21/0.86 +/- 0.14/1.11 +/- 0.27/2.92 +/- 0.67 nmol/L x watts, respectively). CONCLUSION: In patients with CHF after exercise, the plasma levels of adenosine increased along with the decrease in the plasma levels of ammonia. Considering the physiologic cardioprotective actions of adenosine, the enhanced adenosine production after exercise may be an important adaptive response in patients with CHF.
Adenine Nucleotides↗
Status of endothelial dependent vasodilation in patients with hyperuricemia.
Hyperuricemia has been associated with an increased risk for cardiovascular disease and increased mortality. However, the biologic mechanisms that link elevated serum uric acid to cardiovascular disease are uncertain. This study tested the hypothesis that elevated serum uric acid is associated with impaired endothelial function in hyperuricemic patients without any overt cardiovascular disease. Seventeen male patients with hyperuricemia (mean age 42+/-4 years) and 9 control subjects (mean age 45+/-5 years) were studied. All subjects were nonsmokers. All patients had never been treated for hyperuricemia, were on no medications, and were free of any other known diseases. Endothelial function was evaluated by flow-mediated dilation measured by ultrasound. Flow-mediated dilation was significantly impaired in patients with hyperuricemia (4.0+/-0.7%) compared with control subjects (6.4+/-0.8%) (p=0.044). Flow-mediated dilation correlated inversely with uric acid levels (r=-0.4, p=0.05). Nitrate-induced dilation was 12.3+/-1.0% in patients with hyperuricemia and 11.8+/-2.3% in control subjects (p=0.82). Impaired endothelial-dependent vasodilation is present in hyperuricemic patients even in the absence of any overt cardiovascular disease. The elevated serum uric acid, per se, may constitute a novel risk factor for endothelial dysfunction.
Adult↗
Effects of angiotensin II on the action potential durations of atrial myocytes in hypertensive rats.
Angiotensin II (Ang II) has been reported to indirectly influence atrial electrical activity and to play a critical role in atrial arrhythmias in hypertensive patients. However, it is unclear whether Ang II has direct effects on the electrophysiological activity of the atrium affected by hypertension. We examined the effects of Ang II on the action potentials of atrial myocytes enzymatically isolated from spontaneous hypertensive rats (SHRs). The action potentials were recorded by the perforated patch-clamp technique and the atrial expression of the receptors AT1a and AT2 was measured by radioimmunoassay. Ang II significantly shortened the action potential durations (APDs) of SHRs without changes in the resting membrane potentials (RMPs). Pretreatment with selective AT1a blockers abolished the Ang II-induced reduction of atrial APDs of SHRs; however, a selective AT2 blocker did not, which was consistent with the results of the receptor assay. Pretreatment with phosphatidylinositol 3 (PI3)-kinase inhibitor, phospholipase C inhibitor, or protein kinase C (PKC) inhibitor abolished the Ang II-induced shortening of atrial APDs, but pertussis toxin and protein kinase A (PKA) inhibitor did not. To study the effects of chronic AT1a inhibition on Ang II-induced shortening of atrial APD, SHRs were treated with AT1a blocker for 4 weeks. AT1a blocker abolished the Ang II-induced reduction of atrial APDs of SHRs and also significantly lowered their blood pressure. In conclusion, Ang II shortened atrial APDs of SHRs via AT1a coupled with the Gq-mediated inositol triphosphate (IP3)-PKC pathway. Our findings indicated that Ang II caused atrial arrhythmias in hypertensive patients by shortening the effective refractory period of the atrium.
Action Potentials↗
Protective effect of edaravone against hypoxia-reoxygenation injury in rabbit cardiomyocytes.
1 We examined whether edaravone (Eda), a clinically available radical scavenger, directly protects cardiomyocytes from ischemia/reperfusion (I/R) injury, and whether the timing of its application is critical for protection. 2 Cardioprotective effects of edaravone were tested in the modified cell-pelleting model of ischemia and under exogenous oxidative stress (hydrogen peroxide: H2O2) in isolated adult rabbit ventricular cells. Cell death and reactive oxygen species (ROS) generation were detected using propidium iodide (PI) and DCFH-DA, respectively. These parameters were evaluated objectively using flow cytometory. 3 Hypoxia and reoxygenation aggravated the proportion of dead cells from 32.2+/-1.8% (Baseline) to 51.3+/-2.7% (Control). When 15 microm edaravone was applied either throughout the entire experiment (Through) or only at reoxygenation (Reox), cell death was significantly reduced to 39.9+/-1.8% (P<0.01 vs Control) and 43.3+/-2.5% (P<0.05 vs Control), respectively. In contrast, when edaravone was applied 10 min after reoxygenation, its protective effect disappeared. Cardioprotection by edaravone was more remarkable than that afforded by other free radical scavengers, such as ascorbate and superoxide dismutase (SOD). There is a positive correlation between the cardioprotective effect of edaravone and the extent of ROS reduction. 4 Edaravone blunted the H2O2-induced changes in electrical properties, and significantly prolonged the time to contracture induced by H2O2 in single ventricular myocytes. 5 Taken together, edaravone directly protects cardiomyocytes from I/R injury by attenuating ROS production, even when applied at the time of reoxygenation, suggesting that edaravone could be a potent cardioprotective therapeutic agent against hypoxia-reoxygenation injury.
Action Potentials↗
Transient left ventricular apical ballooning in a patient with bicuspid aortic valve created a left ventricular thrombus leading to acute renal infarction.
A 44-year-old woman had tako-tsubo-like ventricular dysfunction with chest pain and ST segment elevation on the ECG. Echocardiography revealed a bicuspid aortic valve with moderate to severe aortic regurgitation. She developed mild heart failure during the clinical course, but the medication (furosemide, enalapril, and asprin) had to be stopped because of skin eruptions. Four weeks after ceasing the antiplatelet agent, she was re-admitted with acute renal infarction. Enhanced chest computed tomography revealed a filling defect in the left ventricle and echocardiography showed a high echogenic mass in the left ventricular apical wall. These findings strongly suggested that the renal infarction was caused by an embolism derived from a left ventricular thrombus that formed during the clinical course of the transient left ventricular apical ballooning. Anticoagulation therapy with urokinase and warfarin successfully lysed the thrombus. Left ventricular thrombus should be considered a complication of transient left ventricular apical ballooning, especially in patients with organic heart disease.
Acute Disease↗
Neurohumoral profiles in patients with hypertrophic cardiomyopathy: differences to hypertensive left ventricular hypertrophy.
BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) have increased concentrations of various neurohumoral factors. Thus, the aim of the present study was to evaluate the differences in the neurohumoral profiles of HCM and HHD. METHODS AND RESULTS: Plasma concentrations of epinephrine, norepinephrine, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), angiotensin II and endothelin-1 were measured in 40 patients with HCM, 35 with HHD, and 15 controls. Additionally, the concentrations of these neurohumoral factors in the coronary sinus and aortic root were measured in 12 HCM patients and 10 controls. Plasma concentrations of norepinephrine, ANP and BNP were significantly higher in HCM than HHD and controls. In HCM, there was no significant correlation between the left ventricular mass index and any neurohumoral factor. The plasma BNP concentration significantly correlated with left intraventricular pressure gradient in HCM. There were significant differences in the plasma concentrations of ANP and BNP between HCM with and without left ventricular diastolic dysfunction. Transcardiac production of BNP was significantly higher in patients with obstructive HCM than in those with non-obstructive HCM. CONCLUSIONS: The significant neurohumoral differences between HCM and HHD were the plasma concentrations of norepinephrine, ANP and BNP. In HCM patients, the plasma BNP concentration may reflect the intraventricular pressure gradient and left ventricular diastolic dysfunction whereas the plasma ANP concentration reflects only the left ventricular diastolic dysfunction.
Aged↗
Effects of angiotensin II type 1 receptor antagonist, losartan, on ventilatory response to exercise and neurohormonal profiles in patients with chronic heart failure.
Chronic heart failure (CHF) is associated with abnormal neurohormonal profiles and increased ventilatory response to exercise. This study determined if treatment with angiotensin II type 1 receptor antagonist, losartan, improves ventilatory efficiency and neurohormonal factors in patients with CHF. Symptom-limited cardiopulmonary exercise testing was performed after a 2-week placebo period (baseline) and after 16 weeks of treatment with losartan (40 +/- 4 mg/day) in 10 patients with CHF (age 57.7 +/- 3.7 years). Echocardiogram, daily physical activity (by the specific activity scale), and neurohormones were evaluated. Treatment with losartan increased left ventricular ejection fraction (baseline vs. losartan: 31 +/- 3 vs. 39 +/- 3%, p<0.01) and specific activity scale score (5.3 +/- 0.5 vs. 6.4 +/- 0.4 METS, p<0.05). Losartan decreased the ventilatory response to carbon dioxide production during exercise (VE/VCO2 slope: 34.6 +/- 2.4 vs. 32.0 +/- 2.2, p<0.05). Plasma brain natriuretic peptide concentrations were decreased after therapy (301 +/- 79 vs. 176 +/- 53 pg/ml, p<0.05). In summary, the results of this open-label, uncontrolled study suggest that chronic treatment with losartan may improve ventilatory efficiency and decrease plasma brain natriuretic peptide concentrations with the improvement of physical activity and left ventricular systolic function in patients with CHF.
Angiotensin II Type 1 Receptor Blockers↗
Coordinate induction of AMP deaminase in human atrium with mitochondrial DNA deletion.
Despite the heteroplasmic lower population of mitochondrial (mt) DNA deletion, mtDNA deletion is significantly related to the loss of atrial adenine nucleotides. To elucidate its mechanism, we examined the frequency of a 7.4-kb mtDNA deletion, the concentration of adenine nucleotides, and the activity of AMP catabolic enzymes in 10 human right atria obtained from cardiac surgery, using quantitative PCR, HPLC, and immunoprecipitations. The atrial concentrations of ATP, ADP, AMP, and the total adenine nucleotides were significantly lower in patients with deletion than those in patients without deletion, despite the lower frequency of their deletion. The activities of total AMP deaminase (AMPD), liver-type (AMPD 2), and heart-type isoform (AMPD 3) were significantly higher in patients with deletion than in patients without deletion, although there was no significant difference in the cytosolic 5(')-nucleotidase among them. In conclusion, mtDNA deletion coordinately induces AMP deaminase to contribute to the loss of atrial adenine nucleotides through degrading AMP excessively.
AMP Deaminase↗
Interleukin-6 and tumor necrosis factor-alpha levels increase in response to maximal exercise in patients with chronic heart failure.
Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. Strenuous exercise causes activation of both systems but the effect of acute bouts of exercise on cytokines is not known in patients with CHF. This study determined whether maximal exercise induces activation of cytokines in CHF. Plasma interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, epinephrine, norepinephrine, and atrial and brain natriuretic peptides (ANP and BNP) were determined before and after symptom-limited cardiopulmonary exercise testing in 80 patients with CHF (LVEF=38+/-1%, peak VO(2)=18.8+/-0.5 ml/min/kg) and age-matched 33 controls. Resting IL-6 (Controls vs. CHF: 1.3+/-0.2 vs. 2.5+/-0.3 pg/ml, P<0.001) and TNF-alpha (2.7+/-0.2 vs. 3.8+/-0.2 pg/ml, P<0.01) were elevated in CHF. LogIL-6 and logTNF-alpha were positively correlated (r=0.34 and r=0.35, respectively) with logplasma norepinephrine, and were negatively correlated (r=-0.39 and r=-0.32, respectively) with peak VO(2). Maximal exercise increased IL-6 and TNF-alpha both in controls and CHF (all P<0.01). Changes in IL-6 (DeltaIL-6) correlated with Deltaepinephrine (r=0.63, P<0.0001) and Deltanorepinephrine (r=0.57, P=0.0006) in controls, but not in CHF. DeltaTNF-alpha correlated with DeltaANP (r=0.28, P=0.01) only in CHF. In summary, cytokine activation at rest was associated with high plasma norepinephrine and exercise intolerance. Maximal exercise caused increases in IL-6 and TNF-alpha concentrations. Sympathetic activation seems to be important for the IL-6 increase during exercise in controls. In CHF, changes in ANP during exercise were associated with the exercise-induced increase in TNF-alpha, but still unknown mechanisms are involved for the cytokine activation during exercise.
Atrial Natriuretic Factor↗
Plasma endothelin-1 levels and clinical correlates in patients with chronic heart failure.
BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, and patients with chronic heart failure (CHF) are reported to have high plasma ET-1 levels. The aim of this study was to investigate the relation between plasma ET-1 levels and clinical correlates in patients with CHF. The effects of maximal exercise on plasma ET-1 levels were also investigated. METHODS: Plasma concentrations of ET-1, norepinephrine, and atrial and brain natriuretic peptide (ANP and BNP) both at rest and after maximal cardiopulmonary exercise test were determined in 100 patients with CHF (60 +/- 12 years, New York Heart Association [NYHA] class I-III, left ventricular ejection fraction [LVEF]=36 +/- 8%, peak oxygen uptake [VO2] = 18.2 +/- 5.0 mL/min/kg) and 27 controls. RESULTS: Patients with NYHA class II and III CHF had higher ET-1 levels (controls, NYHA class I, II, III: 2.1 +/- 0.6, 2.1 +/- 1.0, 2.6 +/- 0.9, 3.4 +/- 0.8 pg/mL, analysis of variance P <.0001). Maximal exercise did not alter ET-1 levels in controls or in each CHF subgroup. When all CHF patients were analyzed together, cardiothoracic ratio (P<.01), peak VO2 (P<.001), plasma norepinephrine (P<.01), plasma ANP (P<.01), and plasma BNP (P<.001) were significantly related with resting ET-1 levels on univariate analysis. Multivariate analysis revealed peak VO2 and plasma BNP levels showed an independent and significant relationship with the resting plasma ET-1 levels. CONCLUSIONS: Resting ET-1 levels were increased in symptomatic patients with CHF, and maximal exercise did not increase ET-1 levels. Peak VO2 and plasma BNP levels were independently associated with resting plasma ET-1 levels in patients with CHF.
Aged↗
Allopurinol improves cardiac dysfunction after ischemia-reperfusion via reduction of oxidative stress in isolated perfused rat hearts.
It has been reported that the xanthine oxidase inhibitor, allopurinol, has a protective effect on ischemia - reperfusion injury, but the precise mechanism of its action is still unclear. Therefore, in the present study the mechanisms of the myocardial protection of allopurinol were evaluated in isolated perfused rat hearts. Allopurinol significantly inhibited myocardial xanthine oxidase activity, and improved left ventricular dysfunction after ischemia - reperfusion. In addition, the lactate dehydrogenase content in the coronary effluent obtained after reperfusion was significantly decreased. ATP, ADP, AMP and IMP significantly decreased, whereas inosine, hypoxanthine and xanthine significantly increased after ischemia in both the control and allopurinol groups. The concentration of xanthine was significantly decreased after ischemia - reperfusion in the allopurinol group; however, allopurinol did not affect the other purine metabolites. To evaluate the accumulation of oxidative stress, thiobarbituric acid reactive substances (TBARS) production in myocardial tissue was measured and allopurinol significantly decreased TBARS formation after ischemia - reperfusion. Finally, myocardial hydroxyl radicals were directly measured by electron spin resonance spectroscopy with the nitroxide radical 4-hydroxy-2, 2,6,6-tetramethyl-piperidine-N-oxyl. Hydroxyl radicals significantly increased immediately after reperfusion, but were significantly decreased in the allopurinol group. In conclusion, allopurinol reduced myocardial injury after ischemia-reperfusion by suppressing oxidative stress, but not by salvage of ATP. These findings may lead to the development of new therapeutic strategies for myocardial ischemia - reperfusion injury.
Adenine Nucleotides↗
Current status of lipid management of hypertensive patients.
Hypertensives, in addition to requiring strict blood pressure control, need lipid management to prevent cardiovascular disease. To assess the current status of lipid management of hypertensives, we reviewed the profiles of 830 hypertensives. The quality of lipid management was assessed using the Japan Atherosclerosis Society (JAS) Guideline for Diagnosis and Treatment of Hyperlipidemia in Japanese Adults announced in 1997. Hyperlipidemia was diagnosed in 45.2% of hypertensives and in 56.6% of patients in category C (a group of patients with coronary heart disease). Lipid-lowering drugs were used in 63.5% of all hypercholesterolemic patients and in 78.1% of category C patients. Statins were administered to more than 80% of hypercholesterolemic patients. Only 39.4% of hypertensives achieved the target total cholesterol level and only a very small percentage (17.1%) of patients in category C reached the target levels. The elderly hypertensives were the single largest group (42.2% of all hypertensives) in this study population, and the target cholesterol level for this group has been elevated from 200 mg/dl to 220 mg/dl in the JAS Guidelines for Diagnosis and Treatment of Atherosclerotic Cardiovascular Diseases announced in 2002 (new guidelines). In conclusion, in hypertensives requiring lipid management, the lipid-lowering approach appeared insufficient, as the target achievement rate was relatively low despite a high treatment rate. This was most marked for patients in category C.
Aged↗
Neurohormonal determinants of peak oxygen uptake in patients with chronic heart failure.
Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. This study determined whether peak oxygen uptake (VO2) can be predicted by the degree of neurohormonal and cytokine activations in CHF. Plasma norepinephrine. epinephrine, renin-angiotensin system activity, ANP, BNP, and serum interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured in 84 CHF patients (age, 59 +/- 1 years, LVEF, 36 +/- 1%) and 34 controls. Maximal cardiopulmonary exercise testing was performed. Peak VO2 (Controls vs CHF: 27.8 +/- 1.3 vs 18.2 +/- 0.5 mL/min/kg, P < 0.0001) was lower in CHF. Patients with CHF had increased plasma norepinephrine (211 +/- 11 vs 315 +/- 24 pg/mL), renin activity (1.2 +/- 0.2 vs 6.2 +/- 1.1 ng/mL/hr), ANP (22 +/- 3 vs 72 +/- 7 pg/mL), and BNP levels (18 +/- 3 vs 200 +/- 25 pg/mL) (all P < 0.01). Serum IL-6 (1.1 0.1 vs 2.4 +/- 0.3 pg/mL) and TNF-alpha (2.7 +/- 0.2 vs 4.0 +/- 0.3 pg/mL) levels were higher in CHF (both P < 0.001). Univariate analysis revealed that age (P < 0.001), cardiothoracic ratio (P < 0.001), norepinephrine (P < 0.0001), ANP (P < 0.001), BNP (P < 0.01), and log IL-6 (P < 0.05) were significantly related with peak VO2. Stepwise regression analysis indicated that plasma norepinephrine and ANP emerged as significant determinants of peak VO2, independent of patient age (overall R = 0.61, P < 0.0001). In summary, patients with CHF exhibited activation of neurohormones and proinflammatory cytokines. Among the elevated hormonal and cytokine markers, plasma norepinephrine and ANP levels were independent predictors of exercise capacity.
Atrial Natriuretic Factor↗
Excessive purine degradation during semi-ischemic forearm test in patients with diabetes mellitus.
OBJECTIVE: The aim of this study was to investigate whether or not the purine degradation in the skeletal muscle during forearm exercise is augmented in patients with diabetes mellitus (DM). METHODS: We used the semi-ischemic forearm test to examine the release of lactate (deltaLAC), ammonia (deltaAmm) and hypoxanthine (deltaHX) before exercise, 0, 4, 10, and 60 minutes after exercise in eleven diabetic patients and seven normal controls. RESULTS: The sum of the increased HX (DM vs Controls: 26.1 +/- 21.2 vs 7.8 +/- 5.9 micromol/L, p < 0.05) was greater in diabetic patients. When patients were divided into the excessive response group (n = 7) and normal response group (n = 4), the maximum increments in deltaHX and deltaAmm in the excessive response group (16.8 +/- 3.2 micromol/l and 122 +/- 60 micromol/l) were greater (p < 0.05) than those in the control group (3.6 +/- 3.0 micromol/l and 32 +/- 34 micromol/l and the normal response group (2.9 +/- 2.9 micromol/l and 27.4 +/- 12.7 micromol/l). DeltaLAC both in the excessive response group (5.4 +/- 1.5 mmol/l) and the normal response group (3.6 +/- 1.0 mmol/l) were higher (p < 0.05) than that of the control group (1.7 +/- 0.5 mmol/l). The prevalence of diabetic retinopathy was higher in the excessive response group than in the normal response group (75% vs. 25%). CONCLUSION: These data suggest that patients with DM, especially with microangiopathy have augmented purine degradation during the semi-ischemic forearm test. Factors responsible for the augmented purine degradation in these patients remain to be determined.
Adolescent↗
[Anti hyperuricemic agents].
Explore the source record for details and available documents.
Allopurinol↗
[Drug-induced hypouricemia: pathophysiology and application to the hyperuricemia with life style related disease].
Explore the source record for details and available documents.
Angiotensin-Converting Enzyme Inhibitors↗
Relation between neurohormonal activation and enhanced ventilatory response to exercise in patients with chronic congestive heart failure.
Explore the source record for details and available documents.
Atrial Natriuretic Factor↗