Biomedical subjects

Shota Sasaki

Publications and source records attributed to Shota Sasaki.

12 recordsLinked to original sources

PubMed2006

Plain computed tomography for assessment of early coronary microcirculatory damage after revascularization therapy in acute myocardial infarction.

BACKGROUND: Coronary microcirculatory damage is an important factor for the prognosis for acute myocardial infarction (MI) after revascularization. The myocardial enhancement area with contrast media infused during coronary revascularization therapy, detected by computed tomography (CT) just after revascularization, has been reported to correspond to the area of hemorrhagic infarction. The relationship between myocardial contrast enhancement and coronary microcirculatory damage was investigated in the present study. METHODS AND RESULTS: Thirteen patients with acute anterior MI underwent successful coronary revascularization within 6 h of symptom onset were enrolled. The coronary flow velocity pattern was measured using a Doppler guidewire and chest CT assessments were performed immediately after coronary revascularization. The ratio of mean CT number of the highest-enhanced myocardial area and the lumen of the left ventricle was defined as a relative CT number. The relative CT number significantly correlated with coronary diastolic deceleration time (r=-0.78, p<0.002) and coronary diastolic deceleration rate (r=0.74, p<0.04). It also correlated with peak myocardial enzyme release in plasma. CONCLUSION: Myocardial contrast enhancement detected using plain CT just after coronary reperfusion therapy implies coronary microcirculatory damage in acute MI. The relative CT number is useful in evaluating the impaired coronary microcirculatory state.

Acute Disease↗

PubMed2005

Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production.

Deficiency of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, decreases NO production and increases reactive oxygen species. The purpose of this study was to elucidate the effects of aging on endothelial function and to determine whether the degree of BH4 deficiency is related to aging and oxidative stress. We evaluated forearm blood flow (FBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, before and after co-infusion of BH4 (500 mg/min) in 37 healthy men (mean age, 41+/-18 yr; range, 19-81 yr). FBF was measured using strain-gauge plethysmograph. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) were measured as indices of oxidative stress. Both ACh and ISDN increased the FBF in a dose-dependent manner in all subjects. Co-infusion of BH4 resulted in a significant increase in ACh-induced vasodilation (from 22.3+/-6.7 to 30.1+/-7.5 mL/min/100 mL tissue, P<0.05). Aging was found to be significantly correlated with ACh-induced vasodilation (r=-0.47, P=0.006), urinary 8-OHdG (r=0.38, P=0.02), serum MDA-LDL (r=0.36, P=0.02), and the change in ACh-induced vasodilation after co-infusion of BH4 (r=0.45, P=0.007). The FBF response to ISDN did not correlate with any parameters. Infusion of N(G)-monomethyl-L-arginine, an NO synthase inhibitor, abolished the BH4-induced enhancement of forearm vasorelaxation evoked by ACh. The increase in FBF after ISDN was not altered by BH4. These findings suggest that a deficiency of BH4 may be involved in the pathogenesis of disturbances in endothelium-dependent vasodilation related to aging through decrease in NO production and increase in oxidative stress.

Acetylcholine↗

PubMed2005

Determination of the optimal atrioventricular interval in sick sinus syndrome during DDD pacing.

BACKGROUND: Although the AAI pacing mode has been shown to be electromechanically superior to the DDD pacing mode in sick sinus syndrome (SSS), there is evidence suggesting that during AAI pacing the presence of natural ventricular activation pattern is not enough for hemodynamic benefit to occur. Myocardial performance index (MPI) is a simply measurable Doppler-derived index of combined systolic and diastolic myocardial performance. The aim of this study was to investigate whether AAI pacing mode is electromechanically superior to the DDD mode in patients with SSS by using Doppler-derived MPI. METHODS: Thirty-nine SSS patients with dual-chamber pacing devices were evaluated by using Doppler echocardiography in AAI mode and DDD mode. The optimal atrioventricular (AV) interval in DDD mode was determined and atrial stimulus-R interval was measured in AAI mode. The ratio of the atrial stimulus-R interval to the optimal AV interval was defined as relative AV interval (rAVI) and the ratio of MPI in AAI mode to that in DDD mode was defined as relative MPI (rMPI). RESULTS: The rMPI was significantly correlated with atrial stimulus-R interval and rAVI (r = 0.57, P = 0.0002, and r = 0.67, P < 0.0001, respectively). A cutoff point of 1.73 for rAVI provided optimum sensitivity and specificity for rMPI >1 based on the receiver operator curves. CONCLUSIONS: Even though the intrinsic AV conduction is moderately prolonged, some SSS patients with dual-chamber pacing devices benefit from the ventricular pacing with optimal AV interval. MPI is useful to determine the optimal pacing mode in acute experiment.

Aged↗

PubMed2004

Production and role of extracellular guanosine cyclic 3', 5' monophosphate in sodium uptake in human proximal tubule cells.

The present study was designed to determine the capability of human renal proximal tubule (RPT) to generate and export guanosine cyclic 3', 5' monophosphate (cGMP) in response to direct stimulation of soluble guanylyl cyclase by nitric oxide (NO) donors. In addition, we investigated whether cGMP extrusion from human RPT cells is required for inhibition of cellular sodium uptake. RPT cells were cultured from fresh human kidneys (normotensive subjects, n=4, mean age 65+/-4.7 years, 3 men, 1 woman; hypertensive patients, n=6, mean age 64+/-6.1 years, 4 men, 2 women) after unilateral nephrectomy. The fluorescence dye Sodium Green was employed to determine cytoplasmic Na+ concentration. In the presence of the Na+/K+ ATPase inhibitor ouabain, fluorescence was monitored at the appropriate wavelength (excitation 485 nm, emission 535 nm). Nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP, 10(-4) M), increased both intracellular and extracellular cGMP (from 1.26+/-0.21 to 88.7+/-12.6 pmol/mg protein and from 0.58+/-0.10 to 9.24+/-1.9 pmol/mL, respectively, P<0.01) and decreased cellular Na+ uptake by 37.4+/-6.8% (P<0.05) compared with control. The effects of SNAP on cGMP production were similar in normotensive and hypertensive subjects. The increases in intracellular and extracellular cGMP concentration because of SNAP were blocked completely by soluble guanylyl cyclase inhibitor ODQ (1-H-[1,2,4] oxadiazolo [4,2-alpha] quinoxalin-1-one). Probenecid, an organic anion transport inhibitor, augmented the SNAP (10(-6) M)-induced increase in intracellular cGMP accumulation (from 4.9+/-0.9 to 9.8+/-1.5 pmol/mg protein, P<0.05), abrogated the SNAP-induced increase in extracellular cGMP extrusion (from 1.07+/-0.4 to 0.37+/-0.1 pmol/L, P<0.05) and blocked the SNAP-induced reduction in cellular Na+ uptake. Neither intracellular nor extracellular cGMP were influenced by l-arginine, the metabolic precursor of NO, or N(G)-nitro-L-arginine methyl ester, an inhibitor of NO synthase. After exogenous administration of cGMP (10(-5) M) or its membrane-permeable analogue 8-Br-cGMP (10(-5) M), only 8-Br-cGMP crossed the cell membrane to increase intracellular cGMP (from 1.36+/-0.19 to 289.7+/-29.4 pmol/mg protein, P<0.01). However, both cGMP and 8-Br-cGMP were effective in decreasing cellular Na+ uptake. In conclusion, human RPT cells contain soluble guanylyl cyclase and are able to generate and export cGMP in response to NO. Because human RPT cells do not themselves contain constitutive NO synthase, the NO-generating cGMP must be derived from sources outside the human RPT. The cGMP cellular export system is critical in the regulation of RPT cellular Na+ absorption in humans.

Arginine↗

PubMed2004

Intracoronary verapamil rapidly terminates reperfusion tachyarrhythmias in acute myocardial infarction.

BACKGROUND: The restoration of coronary flow after transient ischemia immediately induces life-threatening ventricular tachyarrhythmias. Although most of these arrhythmias disappear spontaneously, some of them induce serious hemodynamic changes. This retrospective study investigates the efficacy of therapy with intracoronary verapamil to terminate reperfusion-induced ventricular tachyarrhythmias in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Between February 1992 and February 2003, 390 patients with a diagnosis of AMI were enrolled into the study. All patients received mechanical revascularization therapy within 6 h of onset of symptoms, and 109 patients experienced reperfusion-induced tachyarrhythmias. A subset of these patients was treated with intracoronary verapamil (0.25 to 1.0 mg) to terminate the reperfusion-induced tachyarrhythmia. They were evaluated for immediate termination of the tachyarrhythmias, hemodynamic changes, resumption rates, and major complications. Thirty-one patients (28%) were treated with intracoronary verapamil for the immediate termination of reperfusion-induced ventricular tachyarrhythmias. These tachyarrhythmias included 6 premature ventricular contractions, 19 accelerated idioventricular rhythms, 3 ventricular tachycardias, 2 ventricular fibrillations (VFs), and 1 torsades de pointes. Intracoronary verapamil was effective in rapidly terminating all reperfusion-induced arrhythmias except for VFs. The side effects of treatment included temporary hypotension (two patients) and bradycardia (one patient), although all patients recovered spontaneously. No major complications were induced by the intracoronary use of verapamil, and no resumptions of arrhythmias were documented. CONCLUSION: Intracoronary administration of verapamil can safely terminate reperfusion-induced ventricular tachyarrhythmias in a rapid manner. However, this effect was not seen for reperfusion-induced VF.

Adult↗

PubMed2003

Low body mass index is a risk factor for impaired endothelium-dependent vasodilation in humans: role of nitric oxide and oxidative stress.

OBJECTIVES: The purpose of this study was to evaluate the relationship between body mass index (BMI), including low BMIs, and endothelial function. BACKGROUND: Epidemiologic study has demonstrated that not only obesity but also a low BMI may be a risk factor for cardiovascular disease. METHODS: The forearm blood flow (FBF) response to acetylcholine (ACh) and isosorbide dinitrate (ISDN) was measured in 87 healthy young men (15 low BMI, 51 normal, 14 obese, and 7 extremely obese). RESULTS: Plasma concentrations of 8-hydroxy-2'-deoxyguanosine and serum concentrations of malondialdehyde-modified low-density lipoprotein were higher in low BMI, obese, and extremely obese subjects than in normal subjects and were similar among the low BMI, obese, and extremely obese groups. The FBF response to ACh was greater in the normal group than in the other groups (p < 0.001), and was lower in the extremely obese group as compared with the other groups (p < 0.001). The ACh-stimulated vasodilation was similar between the low BMI group and the obese group. The ISDN-stimulated vasodilation was similar in all four groups. There were no significant differences in ACh-stimulated vasodilation between the four groups after the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine infusion. Co-infusion of vitamin C augmented the FBF response to ACh in low BMI, obese, and extremely obese groups--but not in normal BMI group. CONCLUSIONS: These findings suggest that not only obesity but also a low BMI may be a risk factor for impaired endothelium-dependent vasodilation through the increased oxidative stress, leading to the reduced bioavailability of NO.

Acetylcholine↗

PubMed2002

Endothelial function and oxidative stress in renovascular hypertension.

BACKGROUND: It has been reported that renovascular hypertension activates the renin-angiotensin system, leading to an increase in oxidative stress. We sought to determine whether renal-artery angioplasty improves endothelial dysfunction in patients with renovascular hypertension through a reduction in oxidative stress. METHODS: We evaluated the response of forearm blood flow to acetylcholine, an endothelium-dependent vasodilator, and isosorbide dinitrate, an endothelium-independent vasodilator, before and after renal-artery angioplasty in 15 subjects with renovascular hypertension and 15 controls without hypertension who were matched for age and sex. Forearm blood flow was measured with the use of a mercury-filled Silastic strain-gauge plethysmograph. RESULTS: The forearm blood flow in response to acetylcholine was less in subjects with renovascular hypertension than in controls, although the forearm blood flow in response to isosorbide dinitrate was similar in the two groups. Angioplasty decreased systolic and diastolic blood pressures, forearm vascular resistance, and urinary excretion of 8-hydroxy-2'-deoxyguanosine and serum malondialdehyde-modified low-density lipoprotein (LDL), indexes of oxidative stress. After angioplasty, the mean (+/-SD) forearm blood flow in response to acetylcholine was increased in the patients with renovascular hypertension (19.3+/-6.8 vs. 29.6+/-7.1 ml per minute per 100 ml, P=0.002). The increase in the maximal forearm blood flow in response to acetylcholine correlated significantly with the decrease in urinary excretion of 8-hydroxy-2'-deoxyguanosine (r=-0.51, P=0.004) and serum malondialdehyde-modified LDL (r=-0.39, P=0.02). Coinfusion of ascorbic acid (vitamin C) augmented the response of forearm blood flow to acetylcholine before angioplasty (P<0.001) but not after angioplasty. CONCLUSIONS: These findings suggest that excessive oxidative stress is involved, at least in part, in impaired endothelium-dependent vasodilatation in patients with renovascular hypertension.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2002

Tetrahydrobiopterin enhances forearm vascular response to acetylcholine in both normotensive and hypertensive individuals.

BACKGROUND: A deficiency of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide (NO) synthase, decreases NO synthesis and increases superoxide production. Supplementation of BH4 has been postulated to improve endothelial function in atherosclerotic patients. The purpose of this study was to determine whether BH4 restores endothelium-dependent vasodilation in patients with essential hypertension. METHODS: We evaluated the effects of BH4 on forearm vascular responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, both in patients with essential hypertension and in age- and sex-matched normal control subjects. Forearm blood flow (FBF) was measured using strain gauge plethysmography. RESULTS: The response of FBF to ACh was less in hypertensive patients (n = 8) than in normal control subjects (n = 8). There was no significant difference in FBF response to ISDN in the two groups. During coinfusion of BH4 (500 mg/min), the FBF response to ACh in hypertensive patients increased significantly (14.8 +/- 4.6 to 25.6 +/- 7.3 mL/min/100 mL tissue, P < .05) to the level of normal control subjects. In the control subjects, also, BH4 augmented the FBF response to ACh (27.8 +/- 8.7 to 36.1 +/- 9.6 mL/min/100 mL tissue, P < .05). The increase in FBF after ISDN was not altered by BH4 in either group (each group, n = 6). CONCLUSION: Supplementation of BH4 augments endothelium-dependent vasodilation in both normotensive and hypertensive individuals.

Acetylcholine↗

PubMed2002

A low-calorie diet improves endothelium-dependent vasodilation in obese patients with essential hypertension.

BACKGROUND: Both obesity and hypertension are associated with endothelial dysfunction. The purpose of this study was to investigate the effects of a low-calorie diet on endothelial function in obese patients with essential hypertension. METHODS: We measured forearm blood flow (FBF) during intra-arterial infusion of acetylcholine (ACh; 7.5, 15, 30 microg/min), an index of endothelium-dependent vasodilation, and isosorbide dinitrate (ISDN; 0.75, 1.5, 3.0 microg/min), an index of endothelium-independent vasodilation, in obese patients with essential hypertension before and after 2 weeks on a low-calorie diet (800 kcal/d). The study included 11 obese hypertensive Japanese patients (mean body mass index, 30.8 +/- 3.6 kg/m2). Fifteen healthy Japanese normotensive individuals were recruited as a control group. RESULTS: In obese patients with hypertension, the response of FBF to ACh was attenuated compared to healthy individuals (P < .001). Caloric restriction reduced body weight from 77.5 +/- 15.0 to 73.2 +/- 13.5 kg (P < .01), the mean blood pressure from 118.4 +/- 8.7 to 105.7 +/- 8.5 mm Hg (P < .01), fasting plasma insulin from 85.8 +/- 22.8 to 64.8 +/- 27.0 pmol/L (P < .05), serum total cholesterol from 5.30 +/- 0.76 to 4.67 +/- 0.58 mmol/L (P < .05), and low density lipoprotein cholesterol from 3.80 +/- 0.48 to 3.29 +/- 0.44 mmol/L (P < .05). Basal FBF was similar before and after weight reduction. Caloric restriction enhanced the response of FBF to ACh (P < .05), but did not alter the response to ISDN. The intra-arterial infusion of NG-monomethyl-L-arginine (8 micromol/min), a nitric oxide synthase inhibitor, decreased the enhanced ACh-induced blood flow response induced by caloric restriction. CONCLUSIONS: The present findings suggest that the caloric restriction improves endothelial-dependent vasodilation through an increased release of nitric oxide in obese hypertensive patients.

Acetylcholine↗

PubMed2002

Severity of hypertension affects improved resistance artery endothelial function by angiotensin-converting enzyme inhibition.

The purpose of this study was to determine whether there are differences in the restoration of endothelial function by angiotensin-converting enzyme inhibition based on the severity of hypertension. Forearm blood flow (FBF) was measured in 69 patients with essential hypertension (mild, n = 23; moderate, n = 29; and severe, n = 17 randomly assigned to treatment with either imidapril or amlodipine for 24 weeks in a double-blind fashion during reactive hyperemia and after sublingual administration of nitroglycerin. Imidapril augmented the FBF response to reactive hyperemia after 24 weeks of treatment in the mild and moderate hypertensive groups, but not in the severe hypertensive group. The augmentation of the FBF response to reactive hyperemia induced by imidapril was significantly greater in the moderate hypertensive group than in the mild hypertensive group. Amlodipine did not alter the FBF response to reactive hyperemia. The increase in FBF after the sublingually administered nitroglycerin was similar in all groups. The infusion of NG-monomethyl-l-arginine, a nitric oxide synthase inhibitor, abolished the enhancement of reactive hyperemia in the mild and moderate hypertensive groups treated with imidapril. These findings suggest that the effects of imidapril on endothelial function are affected by the severity of hypertension and that angiotensin-converting enzyme inhibitor-induced augmentation of reactive hyperemia may be due to increased nitric oxide production.

Adult↗

PubMed2002

Excess norepinephrine impairs both endothelium-dependent and -independent vasodilation in patients with pheochromocytoma.

There is little information concerning the interaction of nitric oxide and norepinephrine (NE) on endothelial function in humans. The purpose of this study was to determine whether endothelial function is impaired by NE secreted from patients with pheochromocytoma (pheo) and whether surgical resection of the tumor improves endothelial function in these patients. We evaluated the forearm blood flow (FBF) response to acetylcholine (ACh), an endothelium-dependent vasodilator, and isosorbide dinitrate (ISDN), an endothelium-independent vasodilator, before and after adrenalectomy in 8 pheo patients, 20 normotensive subjects, and 20 patients with essential hypertension. FBF was measured using a mercury-filled silastic strain-gauge plethysmograph. The FBF response to ACh was the greatest in normotensive subjects and the least in pheo patients. The FBF response to ISDN was significantly less in pheo patients than in the other 2 groups, which had similar responses to ISDN. Adrenalectomy significantly decreased plasma and urinary NE, systolic and diastolic blood pressures, heart rate, and forearm vascular resistance. After adrenalectomy, FBF responses to both ACh and ISDN were enhanced in all pheo patients. The ratio of maximal ACh-stimulated FBF to maximal ISDN-stimulated FBF was significantly higher after adrenalectomy than before adrenalectomy (2.1 +/- 0.4 versus 1.1 +/- 0.1; P<0.05). The increase in maximal FBF response to ACh correlated significantly with the decrease in urinary excretion of NE (r=-0.62, P<0.01). These findings suggest that excess NE from pheo may predominantly impair endothelium-dependent vasodilation in humans.

Adrenalectomy↗

PubMed2002

Leptin causes vasodilation in humans.

Leptin, a product of the ob gene, plays an important role in the regulation of body fat and has been suggested to cause vasodilation in rats. The purpose of this study was to evaluate whether leptin also has a vasodilating effect in humans. Using a strain-gauge plethysmography, we evaluated forearm blood flow (FBF) during intra-arterial infusion of leptin (1, 10 or 100 ng/kg/min for 5 min) in the absence and presence of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 8 micromol/min for 5 min) in ten healthy men (mean age, 23.0+/-1.2 years). Leptin infusion significantly increased the FBF (8.5+/-3.8, 20.3+/-7.0 and 17.7+/-5.4% at 1, 10 and 100 ng/kg/min of leptin, respectively; p<0.05) and the forearm vascular resistance (FVR; -6.9+/-3.1, -14.6+/-4.3 and -13.4+/-3.9% at 1, 10 and 100 ng/kg/min of leptin, respectively; p<0.05). No significant changes in blood pressure or heart rate were detected during infusion of leptin. The intra-arterial infusion of L-NMMA did not alter the FBF response (6.6+/-4.9, 22.1+/-7.5, 13.3+/-3.2% at 1, 10 and 100 ng/kg/min of leptin, respectively) or the FVR response (-4.3+/-4.6, -15.2+/-5.4, -11.1+/-2.5% at 1, 10 and 100 ng/kg/min of leptin, respectively) to leptin. These findings suggest that leptin per se directly causes vasodilation and that leptin-induced vasodilatation is nitric oxide-independent in healthy men.

Adult↗