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Biomedical subjects

Tetsunori Saikawa

Publications and source records attributed to Tetsunori Saikawa.

At least 19 recordsLinked to original sources
PubMed2007

Smoking is associated with urinary albumin excretion: an evaluation of premenopausal patients with type 2 diabetes mellitus.

Cigarette smoking and an increase in urinary albumin excretion are associated with high mortality in patients with type 2 diabetes mellitus. We tested the hypothesis that the presence of a smoking habit correlates with increased urinary albumin excretion in premenopausal Japanese women with type 2 diabetes mellitus. The study consisted of 20 premenopausal Japanese patients with type 2 diabetes mellitus in the current-smokers group (age, 45 +/- 4 years, mean +/- SD). The control group consisted of 35 age-matched never-smoker patients (age, 45 +/- 5 years). Serum triglyceride levels were higher and high-density lipoprotein cholesterol levels were lower in the current-smokers group than in the never-smokers group (P < .05 and P < .01, respectively). Furthermore, fasting plasma insulin concentrations and the homeostasis model assessment index were higher in the current-smokers group than in the never-smokers group (P < .005 and P < .001, respectively). Urinary albumin excretion also was higher in the current-smokers group than in the never-smokers group (P < .0001). Multivariate logistic analysis revealed that urinary albumin excretion is independently associated with current smoking in Japanese premenopausal with type 2 diabetes mellitus (odds ratio, 1.79; 95% confidence interval, 1.08-3.87; P < .01). The results of this study show that current smoking is associated with an increased level of urinary albumin excretion, suggesting that smoking was a risk factor in the development of increased urinary albumin excretion in these patients.

Adult↗
PubMed2006

Homocysteine levels are associated with the results of 123I-metaiodobenzylguanidine myocardial scintigraphy in type 2 diabetic patients.

PURPOSE: Elevated total plasma homocysteine (tHcy) levels and cardiovascular autonomic dysfunction are associated with a high mortality in type 2 diabetic patients. We tested the hypothesis that hyperhomocysteinemia is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients not receiving insulin treatment. METHODS: The study group consisted of 17 type 2 diabetic patients with high tHcy levels (>15 mmol/l, age 58+/-5 years, high tHcy group). The control group consisted of 23 age-matched type 2 diabetic patients with normal tHcy levels (<or=15 mmol/l, age 58+/-9 years, normal tHcy group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentrations, and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy. RESULTS: Early and delayed (123)I-MIBG myocardial uptake values were lower (p<0.005 and p<0.01, respectively) and the percent washout rate of (123)I-MIBG was higher (p<0.001) in the high tHcy group than in the normal tHcy group. The fasting plasma insulin concentrations (p<0.0001) and the homeostasis model assessment (HOMA) index values (p<0.0001) were higher in the high tHcy group than in the normal tHcy group. Multiple regression analysis revealed that the level of tHcy was independently predicted by the HOMA index values and the myocardial uptake of (123)I-MIBG at the delayed phase. CONCLUSION: Our results demonstrate that high levels of tHcy are associated with depressed cardiovascular autonomic function and insulin resistance in patients with type 2 diabetes mellitus.

3-Iodobenzylguanidine↗
PubMed2006

Diazoxide-induced cardioprotection via DeltaPsim loss depending on timing of application.

Although the role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in cardioprotection is widely accepted, it remains unclear when their opening is critical for protection. We tested the hypothesis that the mitoKATP channel acts as a trigger or mediator of protection against apoptosis through loss of mitochondrial inner membrane potential (DeltaPsim). Exposure of neonatal rat cardiomyocytes to H2O2 (0.5 mmol/L) resulted in apoptosis associated with severe DeltaPsim loss. Pretreatment with diazoxide (20 to 100 micromol/L) prevented H2O2-induced apoptosis and DeltaPsim loss at 2 but not 18 h after exposure, while the latter was prevented by cotreatment with diazoxide. Lack of protection by pretreatment with diazoxide was observed in cardiomyocytes cultured in a medium containing H2O2 for 2 h and then not containing for 16 h. The slopes of the regression lines of the relationship between the proportion of apoptotic cells and DeltaPsim loss (y = -0.89 vs. -0.42) and the proportion of cells with high side scatter signal differed between cardiomyocytes exposed H2O2 for 2 and 18 h. Diazoxide per se caused a transient DeltaPsim loss (within 30 min) with a recovery followed by persistent DeltaPsim loss (after 6 h). Inhibition of the former by 5-hydroxydecanoate (5-HD, 0.5 mmol/L) abolished protection of pretreatment with diazoxide (trigger phase), while that of the latter prevented the protection of cotreatment with diazoxide (mediator phase). Our results suggest that mitoKATP channels act as a trigger and mediator of cardioprotection through a transient or persistent DeltaPsim loss depending on phenotypic consequence in response to oxidants.

Animals↗
PubMed2006

Hyperhomocysteinemia is a significant risk factor for silent cerebral infarction in patients with chronic renal failure undergoing hemodialysis.

In patients with chronic renal failure undergoing hemodialysis (HD), the presence of silent cerebral infarction (SCI) is associated with high mortality. Plasma total homocysteine (tHcy), which increases with renal dysfunction, has been flagged as a novel predictor for cerebrovascular events. We tested the hypothesis that the presence of SCI correlates with tHcy in HD patients. Based on brain magnetic resonance imaging findings, 44 patients undergoing HD were divided into a with-SCI group (61+/-9 years [mean+/-SD]; n=24) and a without-SCI group (60+/-8 years, n=20), in whom 24-hour ambulatory blood pressure monitoring was performed. The number of patients with diabetes or hypertension was not different between the 2 groups. We made the following observations: (1) the percentage of smokers was higher in the with-SCI group than in the without-SCI group (P<.05); (2) plasma levels of high-density lipoprotein cholesterol were lower and tHcy was higher in the with-SCI group than in the without-SCI group (P<.05 and P<.0001, respectively); (3) and systolic ambulatory blood pressure and mean heart rate during nighttime were higher in the with-SCI group than in the without-SCI group (P<.05). Multivariate logistic analysis identified hyperhomocysteinemia as an independent and significant risk factor for SCI (odds ratio, 1.22; 95% CI, 1.10-1.36; P<.01). Our findings indicate that plasma tHcy may be a novel useful predictor for SCI in patients with chronic renal failure undergoing HD.

Blood Pressure Monitoring, Ambulatory↗
PubMed2006

Influence of menstrual cycle on QT interval dynamics.

OBJECTIVES: The aim of this study was to investigate the effects of the menstrual cycle on QT interval dynamics and the autonomic tone in healthy women. METHODS: Holter ECGs were recorded in 11 healthy women aged 18-32 years during the follicular and luteal phases of their regular menstrual cycle. The interval from QRS onset to the apex (QaT) and to the end of the T-wave (QeT), the interval between the apex and the end of the T-wave (Ta-e), and RR intervals were measured automatically in the course of 24 hours by Holter ECGs. The QeT/RR, QaT/RR, and Ta-e/RR relationships were evaluated in each subject. The autonomic tone was assessed by the serum catecholamine level at rest and heart rate variability was measured by Holter ECGs. RESULTS: (1) The follicular and luteal phases did not differ significantly with respect to the slopes of the QeT/RR, QaT/RR, and Ta-e/RR relationships. However, QeT and QaT intervals were significantly shorter for all RR intervals in the luteal than in the follicular phase (P < 0.0001). (2) The serum progesterone concentration was significantly higher in the luteal than in the follicular phase (P < 0.001). (3) Noradrenaline was significantly higher in the luteal than in the follicular phase (P < 0.05). There was no significant difference in the follicular and luteal phases with respect to heart rate variability measurements. CONCLUSIONS: Our results suggest that the menstrual cycle affects the QT intervals. The observed shorter QT interval during the luteal than the follicular phase may be attributable to the increase in serum progesterone and sympathetic tone.

Adolescent↗
PubMed2006

Randomized study of angiotensin II type 1 receptor blocker vs dihydropiridine calcium antagonist for the treatment of paroxysmal atrial fibrillation in patients with hypertension.

BACKGROUND: Mega trials of rhythm vs rate control could not demonstrate the usefulness of available antiarrhythmic drugs, so a more effective and safer therapy for atrial fibrillation (AF) is now required. One candidate is the so-called "upstream therapy", which refers to the blockade of upstream modifying elements (renin - angiotensin system, cathecholamines, oxidative stress etc) that contribute to the arrhythmogenic substrate. METHODS AND RESULTS: The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is a randomized comparative evaluation of an angiotensin II type 1 blocker (candesartan) and a dihydropiridine calcium blocker (amlodipine), both combined with antithrombotic therapy, as an antiarrhythmic therapy for the treatment of paroxysmal AF (PAF) associated with hypertension. To test the usefulness of this therapy, this study will reveal the recurrence rate of asymptomatic as well as symptomatic PAF during 1-year of treatment with candesartan or amlodipine, using daily transtelephonic monitoring. CONCLUSIONS: The J-RHYTHM II study will follow 400 patients with PAF and hypertension who were treated at approximately 50 sites throughout Japan, and will provide clinically important information.

Amlodipine↗
PubMed2006

Phosphatidylinositol 3-kinase-dependent activation of akt, an essential signal for hyperthermia-induced heat-shock protein 72, is attenuated in streptozotocin-induced diabetic heart.

We tested the hypothesis that phosphatidylinositol 3-kinase (PI 3-kinase)-dependent activation of Akt is essential for the expression of cardiac heat-shock protein 72 (HSP72) and that this pathway is impaired in the streptozotocin (STZ)-induced diabetic heart. STZ-induced male diabetic rats were treated with insulin (STZ-insulin group, n = 26) or vehicle (STZ-vehicle group, n = 61) for 3 weeks. Whole-body hyperthermia (43 degrees C for 20 min) was applied, and the heart was isolated 24 h later. Compared with control heart, hyperthermia-induced HSP72 expression and phosphorylation of Akt were attenuated in the STZ-vehicle heart. Pretreatment with wortmannin attenuated hyperthermia-induced HSP72 expression and phosphorylation of Akt. In isolated perfused heart experiments, the hyperthermia-treated STZ-vehicle heart showed poor left ventricular functional recovery during reperfusion after no-flow global ischemia compared with hyperthermia-treated control heart. Insulin treatment restored HSP72 expression and reperfusion-induced functional recovery. In cultured neonatal rat cardiomyocytes, hyperthermia-induced HSP72 expression was enhanced by insulin, together with tolerance against hypoxia-reoxygenation injury. Wortmannin and LY294002 inhibited hyperthermia-induced HSP72 expression and phosphorylation of Akt. Our results indicate that activation of Akt, in a PI 3-kinase-dependent manner, is essential for hyperthermia-induced HSP72 expression in association with cardioprotection, suggesting impairment of this signaling pathway in the STZ-induced diabetic heart, probably due to insulin deficiency.

Androstadienes↗
PubMed2006

Pioglitazone but not glibenclamide improves cardiac expression of heat shock protein 72 and tolerance against ischemia/reperfusion injury in the heredity insulin-resistant rat.

We tested the hypothesis that pioglitazone could restore expression of heat shock protein (HSP)72 in insulin-resistant rat heart. At 12 weeks of age, male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control (LETO) rats were treated with pioglitazone (10 mg x kg(-1) x day(-1)) or glibenclamide (5 mg x kg(-1) x day(-1)) for 4 weeks. Thereafter, hyperthermia (43 degrees C for 20 min) was applied. In response to hyperthermia, the activation of serine/threonine kinase Akt depending on phosphatidylinositol 3 (PI3) kinase was necessary for cardiac expression of HSP72. Hyperthermia-induced activation of Akt and HSP72 expression were depressed in OLETF rat hearts. Pioglitazone but not glibenclamide improved insulin sensitivity in OLETF rats, which was associated with the restoration of Akt activation and HSP72 expression. In experiments with isolated perfused heart, reperfusion-induced cardiac functional recovery was suppressed in OLETF rat hearts, which was improved by pioglitazone but not glibenclamide. Our results suggest that PI3 kinase-dependent Akt activation, an essential signal for HSP72 expression, is depressed in the heart in insulin-resistant OLETF rats, and the results suggest also that the restoration of HSP72 expression and tolerance against ischemia/reperfusion injury by treatment with pioglitazone might be due to an improvement of insulin resistance, leading to restoration of impaired PI3 kinase-dependent Akt activation in response to hyperthermia.

Animals↗
PubMed2006

AT1 receptor blockade prevents microvascular dysfunction induced by ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) in post-arterior post-capillary venules induces an acute inflammatory response, characterized by increased adherence and emigration of leukocytes and vascular permeability, all of which play important roles in cardiovascular disease. The aim of this study was to determine the roles of angiotensin II and AT1 receptor blockade in microvascular I/R injury in rats. Rats were anesthetized and intubated, then the peritoneum was opened and the mesentery was revealed. Small post-capillary venules were examined by in vivo fluorescence microscopy. The flow of erythrocytes and leukocytes was observed under the microscope and video recorded for later dynamic analyses. The superior mesenteric artery (SMA) was ligated with polyethylene tubing and released to induce I/R (20 min of ischemia/60 min of reperfusion). Subsequently, leukocyte adhesion, emigration and albumin leakage were compared with those of non-I/R controls. I/R injury was significantly suppressed by superfusing tissues with the AT1 receptor antagonist losartan (LO; 10 microM). The beneficial effects of LO were inhibited by topical application of either the bradykinin B2 receptor antagonist HOE140 (10 nM) or nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME 10 microM). The effects of LO were lost in the presence of AT2 receptor blocker PD 123319 (PD). In conclusion, LO suppressed and protected against I/R injuries. The possible interaction between AT1 and AT2 receptors was also suggested.

Angiotensin II↗
PubMed2005

Brain natriuretic peptide and cardiac autonomic function in type 2 diabetic patients.

The present study tested the hypothesis that increased plasma brain natriuretic peptide (BNP) levels are related to cardiac autonomic dysfunction in type 2 diabetic patients. A total of 32 consecutive Japanese patients with type 2 diabetes were assigned to either a high-BNP (>or=18 pg/ml) group (n=12; age 57+/-13 years, mean+/-S.D.) or a normal-BNP (<18 pg/ml) group (n=20; 59+/-10 years). No patient had any overt structural heart disease. Cardiac autonomic function was assessed by measurements of baroreflex sensitivity (BRS), heart rate variability (HRV) and cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphic findings. BRS was lower (p<0.005) in the high-BNP group than in the normal-BNP group. However, the components of HRV, and the early and delayed myocardial uptake of (123)I-MIBG and percentage washout rate of (123)I-MIBG were not significantly different between the groups. The plasma level of BNP negatively correlated with BRS (r=0.35, p=0.049). These findings suggest that increased plasma BNP levels were related to cardiac reflex parasympathetic dysfunction in our Japanese type 2 diabetic patients.

3-Iodobenzylguanidine↗
PubMed2005

Effects of insulin resistance on geranylgeranylacetone-induced expression of heat shock protein 72 and cardioprotection in high-fat diet rats.

We investigated the effects of insulin resistance on the expression of heat-shock proteins (HSPs) and myocardial protection against ischemia/reperfusion injury. Male Sprague-Dawley rats received normal chow (CNT) or high-fat (HiF) diet. HiF diet for 6 weeks resulted in the development of insulin resistance, which was evaluated by oral glucose test and insulin tolerance test. Twenty-four hour after oral administration of geranylgeranylacetone (GGA) (200 mg/kg), the heart was isolated and perfused retrogradely with two different doses of insulin (0.1 or 1 mU/ml). Myocardial expression of HSP72 was examined using Western blot analysis. In the HiF group, the expression of HSP72 in response to GGA was decreased. The recovery of left ventricular developed pressure (LVDP) 30 min after reperfusion was tended to be lower in HiF group than in CNT group. Although GGA improved the recovery of LVDP in both CNT and HiF rats, LVDP during reperfusion period was significantly lower in HiF group than in CNT group. High-dose insulin perfusion caused deterioration of post-ischemic functional recovery and LVDP was not different between the two groups, but GGA-induced cardioprotection was preserved irrespective of the dose of insulin both in the CNT and HiF rats. This is the first demonstration that expression of HSP72 was depressed in the heart and that reduced HSP72 was related with less cardioprotection against ischemic insult in high-fat diet-induced insulin resistance rats.

Animals↗
PubMed2005

Effects of valsartan and perindopril combination therapy on left ventricular hypertrophy and aortic arterial stiffness in patients with essential hypertension.

OBJECTIVE: To compare the effects of combined therapy of an angiotensin II receptor blocker (ARB; valsartan) and an angiotensin converting enzyme inhibitor (ACEI; perindopril) on blood pressure (BP), metabolic profiles, plasma brain natriuretic peptide (BNP) levels, echocardiographic findings, and aortic pulse wave velocity (PWV) with those of respective monotherapy in never-treated patients with essential hypertension. METHODS: This was a prospective randomized trial, in which there were 31 patients with essential hypertension and left ventricular hypertrophy (LVH) who visited the outpatient clinic of Oita Red Cross Hospital (14 women and 17 men; mean+/-SD age, 59+/-5 years). Each patient was randomly assigned to receive valsartan (160 mg/day, V group, n=10), perindopril (8 mg/day, P group, n=11), or a combination of valsartan (80 mg/day) and perindopril (4 mg/day, V+P group, n=10) for 40 weeks. Ambulatory BP monitoring (ABPM), echocardiographic findings, metabolic findings, plasma BNP levels, and brachial-ankle PWV (baPWV) were evaluated before and after the 40-week therapy. RESULTS: The baseline and post-therapeutic BP levels were similar among the three groups. At baseline ABPM, non-dipping was observed in 80, 82, and 80% in the V, P, and V+P groups, respectively. Each 40-week therapy regimen comparably reduced ABP. The plasma BNP levels (P<0.0001 for each), left ventricular mass index (LVMI) (P<0.01 for each), and PWV values (P<0.0001 for each) were also reduced. However, when compared with either V or P group, the percentage reduction in LVMI (P<0.05 and P<0.005, respectively), BNP (P<0.05 for each), and baPWV values (P<0.005 and P<0.001, respectively) was greater in the V+P group. CONCLUSIONS: Our findings suggest that, when compared with each monotherapy, perindopril and valsartan combination therapy exerts greater beneficial effects regarding the regression of LVH, reduction in BNP, and improvement of PWV in a selected group of essential hypertensive patients with LVH and high prevalence of non-dipping patterns.

Aged↗
PubMed2005

Heterogeneous expression of connexin 43 in the myocardium of rabbit right ventricular outflow tract.

The right ventricular outflow tract (RVOT) has been demonstrated as an important focus in idiopathic ventricular arrhythmias. However, the role of the gap junction in this region in arrhythmic events has not been fully investigated. The purpose of this study was to evaluate the expression and distribution of the gap junction protein connexin 43 (Cx43) in the myocardium of the RVOT area of normal adult rabbits. Tissue samples were obtained from 6 regions of normal rabbit heart, i.e. the left ventricle (LV) free wall, the LV papillary muscle, the RVOT free wall, and the RVOT septum which was subdivided into the RV side, the central layer, and the LV side. Immunohistochemical analysis was performed to investigate the characteristics of Cx43 distribution in the RVOT area. In the LV free wall and papillary muscle, Cx43 was abundantly, homogeneously, and approximately equally expressed in end-to-end- and side-to-side intercellular connections. In the free wall of the RVOT, Cx43 expression was poor compared to both these LV regions and side-to-side cell connections were predominant. Cx43 was as richly and homogeneously distributed in the central layer and LV side of the RVOT septum as in the two LV regions. However, in the RV side of the RVOT septum, its distribution was scant and an unstained area was noted. The heterogeneous expression of Cx43 in the RVOT area may serve as substrate for idiopathic ventricular arrhythmia.

Animals↗
PubMed2005

High-sensitivity C-reactive protein is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients.

We tested the hypothesis that elevated levels of plasma high-sensitivity C-reactive protein (HSCRP) are associated with insulin resistance/hyperinsulinemia and cardiovascular autonomic dysfunction in type 2 diabetic patients without insulin treatment. The study group consisted of 17 type 2 diabetic patients with high HSCRP (0.3-1.0 mg/dL; age, 59+/-8 years, mean+/-SD; high HSCRP group). The control group consisted of 18 age-matched type 2 diabetic patients with low HSCRP (<0.3 mg/dL; 59+/-7 years; low HSCRP group). Cardiovascular autonomic function was assessed by baroreflex sensitivity, heart rate variability, plasma norepinephrine concentration, and cardiac metaiodobenzylguanidine (MIBG) labeled with iodine 123 scintigraphic findings. Baroreflex sensitivity was lower in the high HSCRP group than in the low HSCRP group (P<.05). Early and delayed 123I-MIBG myocardial uptake values were lower (P<.05 and P<.005, respectively) and the percent washout rate of 123I-MIBG was higher (P<.01) in the high HSCRP group than in the low HSCRP group. Fasting plasma insulin concentration (P<.01) and the homeostasis model assessment index (P<.01) were higher in the high HSCRP group than in the low HSCRP group. Multiple regression analysis revealed that the level of HSCRP was independently predicted by fasting plasma insulin concentration and myocardial uptake of 123I-MIBG at a delayed phase. Our results suggest that high levels of HSCRP are associated with depressed cardiovascular autonomic function and hyperinsulinemia and that fasting plasma insulin concentration and myocardial uptake of 123I-MIBG at a delayed phase are independent predictors of HSCRP level in our Japanese patients with type 2 diabetes mellitus.

3-Iodobenzylguanidine↗
PubMed2005

Gender differences in autonomic modulation of ventricular repolarization in humans.

BACKGROUND: Gender differences in the incidence of ventricular arrhythmias have been reported and torsades de pointes associated with long QT syndrome are more common in women than men. Although increased sympathetic tone has an important role in vulnerability to arrhythmia, little is currently known regarding gender differences in the dynamic electrophysiological response to sympathetic stimulation. Therefore, we investigated whether there is a gender difference in humans with respect to the dynamic response of ventricular repolarization to beta-adrenergic stimulation and to autonomic blockade. METHODS: Twelve-lead ECGs were continuously recorded during isoproterenol infusion (protocol 1) and autonomic blockade with propranolol and atropine infusion (protocol 2) in 24 healthy volunteers (12 men, 23 +/- 2 years; 12 women, 23 +/- 5 years). QT (QTc) intervals were measured at the baseline and at a heart rate of 75, 100, and 120 beats/min. RESULTS: (1) The morphology of the T wave dynamically and transiently changed to bifid or biphasic during the acute phase of isoproterenol infusion. The incidence of these morphologic changes was higher in women than men (P < 0.05). (2) The QTc interval was initially prolonged and then shortened in both men and women during isoproterenol administration. However, QTc prolongation was significantly greater in women (0.44 +/- 0.02 to 0.55 +/- 0.03 sec) than men (0.42 +/- 0.03 to 0.51 +/- 0.04 sec; P < 0.05). (3) The QTc interval was significantly prolonged under autonomic blockade and the intrinsic QTc interval was longer in women than men (P < 0.05). CONCLUSION: While sympathetic stimulation and autonomic blockade modulated the dynamics of ventricular repolarization in both sexes, it was more pronounced in women. This gender difference may partially account for the susceptibility of women to arrhythmogenesis.

Adult↗
PubMed2005

Oral administration of geranylgeranylacetone blunts the endothelial dysfunction induced by ischemia and reperfusion in the rat heart.

It has been shown that geranylgeranylacetone (GGA) protects heart against ischemia/reperfusion injury via enhanced heat shock protein 72 (HSP72) expression in rats. In the present study, we investigated the protective effect of GGA on ischemia/reperfusion-induced endothelial dysfunction. Rats were given oral GGA (GGA group) or vehicle (CON group), and 24 hours later their hearts were removed and placed in the Langendorff apparatus for 30-minute low-flow ischemia followed by 30-minute reperfusion. GGA improved the postischemic functional recovery (P < 0.01), which was abolished by N-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor). NO production during both ischemia and reperfusion were increased in the GGA group, and the acetylcholine (ACh)-induced (endothelium-dependent) vasodilation, measured as the percentage decrease in coronary perfusion pressure after ischemia/reperfusion (14.9 +/- 1.3%), was preserved as compared with that in the CON group (7.9 +/- 1.4%). LY294002, a phosphatidylinositol 3 (PI3) kinase inhibitor, abolished the protective effects of GGA on endothelial-dependent coronary vasodilation and NO production, whereas Y27632 (Rho kinase inhibitor) increased endothelium-dependent coronary vasodilation and NO production in CON group toward the level seen in GGA group. The amount of adrenomedullin in the coronary effluent at basal condition was lower in the GGA group than in the CON group (P < 0.05), and during both ischemia and reperfusion there was no difference in the amount of adrenomedullin between the GGA and CON groups. In addition, no difference was observed in the amount of endothelin-1 between the GGA and CON groups. These results indicate that GGA attenuates the ischemia/reperfusion-induced coronary endothelial dysfunction, which may contribute to its cardioprotective effect. The PI3 kinase and/or Rho kinase pathways appear to be involved in this process, whereas adrenomedullin and endothelin-1 are not necessary for the GGA-induced cardioprotection.

Administration, Oral↗
PubMed2005

Progressive facilitation of antegrade conduction via an accessory pathway in a patient with Wolff-Parkinson-White syndrome and permanent atrial fibrillation.

The case of a 64-year-old man with Wolff-Parkinson-White syndrome and permanent atrial fibrillation (AF) is reported. The patient was admitted due to electrocardiographic feature of AF with rapid conduction over the left-sided accessory pathway. Administration of pirmenol effectively suppressed the ventricular response via an accessory pathway. A transesophageal echocardiography detected an uncertain thrombus in the left atrial appendage. During the 33-month follow-up period, the ventricular response via an accessory pathway was progressively facilitated. Radiofrequency catheter ablation using a transseptal approach was performed during AF, resulting in complete elimination of the antegrade accessory pathway conduction.

Anti-Arrhythmia Agents↗