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Biomedical subjects

Ichiro Sakuma

Publications and source records attributed to Ichiro Sakuma.

At least 19 recordsLinked to original sources
PubMed2006

Mechanisms of destabilization and early termination of spiral wave reentry in the ventricle by a class III antiarrhythmic agent, nifekalant.

Nifekalant (NF) is a novel class III antiarrhythmic agent that is effective in preventing life-threatening ventricular tachycardia/fibrillation (VT/VF). We investigated mechanisms of destabilization and early termination of spiral-type reentrant VT by NF in a two-dimensional subepicardial myocardial layer of Langendorff-perfused rabbit hearts (n = 21) using a high-resolution optical action potential mapping system. During basic stimulation, NF (0.1 microM) caused uniform prolongation of action potential duration (APD) without affecting conduction velocity and an increase of APD restitution slope. VTs induced by direct current stimulation in the presence of NF were of shorter duration (VTs > 30 s: 2/54 NF vs. 19/93 control). During VTs in control (with visible rotors), the wave front chased its own tail with a certain distance (repolarized zone), and they seldom met each other. The average number of phase singularity (PS) points was 1.31 +/- 0.14 per 665 ms (n = 7). In the presence of NF, the wave front frequently encountered its own tail, causing a transient breakup of the spiral wave or sudden movement of the rotation center (spatial jump of PS). The average number of PS was increased to 1.63 +/- 0.22 per 665 ms (n = 7, P < 0.05) after NF. The mode of spontaneous termination of rotors in control was in most cases (9/10, 90.0%) the result of mutual annihilation of counterrotating wave fronts. With NF, rotors frequently terminated by wave front collision with the atrioventricular groove (12/19, 63.2%) or by trapping the spiral tip in a refractory zone (7/19, 36.8%). Destabilization and early termination of spiral wave reentry induced by NF are the result of a limited proportion of excitable tissue after modulation of repolarization.

Action Potentials↗
PubMed2006

Cardiopulmonary bypass influences the plasma levels of calcitonin gene-related peptides in dogs: effects of hemofiltration and hemodilution.

Calcitonin gene-related peptides (CGRP), which are potent vasodilators, are elevated during cardiopulmonary bypass (CPB) in humans. We evaluated the plasma levels of CGRP in dogs during CPB with hemofiltration with and without hemodilution. Female beagles were divided into control (n=5) and hemodilution (n=5) groups. The CPB with hemofiltration was performed with or without hemodilution. For the measurement of CGRP, blood samples were collected pre-CPB, during CPB, and post-CPB. The concentrations of CGRP in the hemofiltration solution were measured. Although the CPB elevated the plasma CGRP levels in both groups, its elevation was significant in the hemodilution group when compared to the pre-CPB levels. CGRP levels returned to normal post-CPB. Significant differences were found between the two groups in the CGRP amount in hemofiltration. The results show that hemofiltration should be used during CPB to decrease the plasma levels of CGRP.

Animals↗
PubMed2006

Flow visualization for interactive simulation of drugs injection during chemoembolization.

Chemoembolization is an important therapeutic procedure. A catheter was navigated to the artery that feeds the tumor, and chemotherapy drugs and embolus are injected directly into the tumor. There is a risk that embolus may lodge incorrectly and deprive normal tissue of its blood supply. This paper focuses on visualization of the flow particles in simulation of chemotherapy drugs injection for training of hand-eye coordination skills. We assume that the flow follows a defined path in the hepatic vascular system from the catheter tip. The vascular model is constructed using sweeping and blending operations. Quadrilaterals which are aligned to face the viewer are drawn for the trail of each particle. The quadrilateral in the trail is determined using bilinear interpolation. On simulated fluoroscopic image, the flow is rendered as overlaying and semitransparent quadrilaterals representing the particles' trails. This visualization model achieves a good visual approximation of the flow of particles inside the vessels under fluoroscopic imaging.

Antineoplastic Agents↗
PubMed2006

Low HDL-cholesterol, hypertension and impaired glucose tolerance as predictors of acute myocardial infarction in northern area of Japan.

Acute myocardial infarction (AMI) has gradually been increasing in Japan; however, since the burden of Japanese residents for risk factors (RFs) of AMI, such as hypercholesterolemia, is chronologically less accumulated compared with American and European people, their RFs of AMI may be different from those in western countries. To answer this question, a retrospective community-based study was carried out enrolling 722 first time AMI patients in Hokkaido, the northern island of Japan. As controls, 1748 age-, sex- and residence-matched subjects were randomly chosen from a data-base of a health check-up organization. We assessed associations between premorbid variables and the RFs for AMI. In men, the most important predictor reflected by high odds ratio (OR) was low HDL-cholesterol (HDL-C). Hypertension (HT) and impaired glucose tolerance (IGT) were also independent RFs. In women, HT represented the highest OR, and low HDL-C, high triglyceride (TG) and IGT followed. Total cholesterol (TC) was a negative predictor for AMI in both sexes, because mean TC level of AMI patients was less than that of controls probably because of acute phase reaction. Thus, low HDL-C, HT, IGT and high TG, which represent the state of metabolic syndrome, were important predictors of AMI. And it was suggested that low HDL-C plays a pivotal role in a population whose TC level is not high.

Age Factors↗
PubMed2006

Reversal of elevated cardiac expression of TGFbeta1 and endothelin-1 in OLETF diabetic rats by long-acting calcium antagonist.

The effects of calcium channel blockers (CCBs) on complications associated with diabetes mellitus (DM) have been well studied in clinical and basic science investigations. Cardiovascular complications are a common feature of type 2 DM, and insulin resistance is an early clinical manifestation of type 2 DM. CCBs are widely used to treat cardiovascular diseases in patients with DM. In this study, we used a spontaneous type 2 diabetic rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats, at a highly insulin-resistant stage with modest hyperglycemia. We examined cardiac expression of transforming growth factor-beta(1) (TGFbeta(1)) and endothelin-1 (ET-1) in male OLETF rats. At 8 weeks of age, OLETF rats were treated for 12 weeks with the long-acting CCB benidipine (1 mg/kg/day or 3 mg/kg/day, po, n = 12), with hydralazine hydrochloride (3 mg/kg/day, po, n = 12), or with vehicle (OLETF, n = 12), and male age-matched genetic control Long-Evans Tokushima Otsuka (LETO, n = 12) rats were used. Blood pressure was significantly higher in OLETF rats than in LETO rats, and benidipine treatment at both dosages in OLETF rats for 12 weeks did not significantly reduce blood pressure, whereas hydralazine treatment significantly lowered blood pressure in OLETF rats. Hydralazine and both dosages of benidipine significantly reduced upregulated cardiac ET-1 levels in OLETF rats. Plasma and cardiac TGFbeta1 levels were remarkably higher in OLETF rats compared with LETO rats and were normalized by treatment with benidipine (3 mg/kg/day). Our results suggest that CCBs are effective in normalizing upregulated cardiac TGFbeta1 and ET-1 levels at the insulin-resistant stage in OLETF rats, which may improve cardiac morphology and function in this rat model without altering blood pressure and plasma glucose levels. In contrast, hydralazine treatment also normalizes cardiac ET-1 levels while significantly reducing blood pressure.

Animals↗
PubMed2005

Subdepressor dose of benidipine ameliorates diabetic cardiac remodeling accompanied by normalization of upregulated endothelin system in rats.

We investigated whether benidipine, a long-acting calcium channel blocker (CCB), can normalize cardiac expression profiles of the endothelin (ET)-1 system in insulin-resistant diabetes. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of human Type 2 diabetes, were treated for 12 wk with vehicle or benidipine (3 mg.kg(-1).day(-1)). OLETF rats exhibited a significant increase in ET-1 in plasma and left ventricular (LV) tissues compared with nondiabetic controls. Expression of prepro-ET-1, ET-converting enzyme, and ET(A) and ET(B) receptors in LV tissues was also significantly higher in OLETF rats. The two MAPKs, JNK and p38MAPK, both of which are activated by ET-1, were more abundantly expressed in OLETF rat LV tissues. All these alterations were reversed to nondiabetic levels when OLETF rats were treated with the subdepressor dose of benidipine. Furthermore, benidipine therapy resulted in hindering cardiomyocyte hypertrophy and cardiac perivascular fibrosis in OLETF rats. The beneficial actions of benidipine at the subdepressor dose on cardiac remodeling in insulin-resistant diabetes may involve normalization of the upregulated ET-1 system.

Animals↗
PubMed2005

Temporal effects of edaravone, a free radical scavenger, on transient ischemia-induced neuronal dysfunction in the rat hippocampus.

We examined the effect of a free radical scavenger edaravone on ischemia/reperfusion-induced impairment of long-term potentiation in the perforant path-dentate gyrus synapses of the rat hippocampus, as a measure of functional outcome 4 days after transient global ischemia (2-vessel occlusion, 10 min). Edaravone (3 and 10 mg/kg, i.v.) immediately after reperfusion (Day 0) alleviated ischemia-induced impairment of long-term potentiation in a dose-related manner, whereas treatment on Day 1 or 4 after reperfusion failed to rescue the impaired long-term potentiation. Edaravone administration on Day 0 also prevented the post-ischemic increase in hydroxyl radical formation and the expression of vascular endothelial growth factor, basic fibroblast growth factor and neuronal and inducible nitric oxide synthases of the hippocampus. Thus, edaravone protected the rat hippocampus from ischemia-induced long-term potentiation impairment with a therapeutic time window, suggesting that free radical formation after ischemia/reperfusion is a pivotal trigger of neurofunctional complications after global ischemic stroke.

Animals↗
PubMed2005

Scalable high-resolution integral videography autostereoscopic display with a seamless multiprojection system.

We propose a scalable high-resolution autostereoscopic display that uses integral videography (IV) and a seamless multiprojection system. IV is an animated extension of integral photography (IP). Although IP and IV are ideal ways to display three-dimensional images, their spatial viewing resolution needs improvement; the pixel pitch of the display and the lens pitch are the main factors affecting IV image quality. We improved the quality by increasing the number and density of the pixels. Using multiple projectors, we create a scalable high-resolution image and project it onto a small screen using long-focal-length projection optics. To generate seamless IV images, we developed an image calibration method for geometric correction and color modulation. We also fabricated a lens array especially for the display device. Experiments were conducted with nine XGA projectors and nine PCs for parallel image rendering and displaying. A total of 2868 x 2150 pixels were displayed on a 241 mm x 181 mm (302.4 dots/in.) rear-projection screen. The lens pitch was 1.016 mm, corresponding to 12 pixels of the projected image. Measurement of the geometric accuracy of the reproduced IV images demonstrated that the spatial resolution of the display system matched that of the theoretical analysis.

Journal Article↗
PubMed2005

Compact forceps manipulator using friction wheel mechanism and gimbals mechanism for laparoscopic surgery.

This paper reports evaluation of compact forceps manipulator designed for assisting laparoscopic surgery. The manipulator consists of two miniaturized parts; friction wheel mechanism which rotates and translates forceps (62 x 52 x 150[mm3], 0.6 [kg]), and gimbals mechanism which provides pivoting motion of forceps around incision hole on the abdomen (135 x 165 x 300 [mm3], 1.1 [kg]). The four-DOF motion of forceps around the incision hole on the abdomen in laparoscopic surgery is realized. By integration with robotized forceps or a needle insertion robot, it will work as a compact robotic arm in a master-slave system. It can also work under numerical control based on the computerized surgical planning. This table-mounted miniaturized manipulator contributes to the coexistence of clinical staffs and manipulators in the today's crowded operating room. As the results of mechanical performance evaluation with load of 4 [N], positioning accuracy was less than 1.2 [deg] in pivoting motion, less than 4 [deg] in rotation of forceps, less than 1.2 [mm] in longitudinal translation of forceps. As future works, we will modify mechanism for sterilization and safety improvement, and also integrate this manipulator with robotized forceps to build a surgery assisting robotic system.

Equipment Design↗
PubMed2005

Age-related changes in cardiac expression of VEGF and its angiogenic receptor KDR in stroke-prone spontaneously hypertensive rats.

We examined the age-related changes in cardiac expression of angiogenic molecules during the development of cardiac remodeling in stroke-prone spontaneously hypertensive rats (SHRSP) in comparison with those in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Vascular endothelial growth factor (VEGF) was highly upregulated in SHRSP aged 20 weeks compared with the same age of WKY, but it was downregulated at 40 weeks. On the other hand, KDR, an angiogenic receptor of VEGF, and endothelial nitric oxide synthase, which is important in the VEGF-mediated angiogenic pathway, were markedly downregulated in SHRSP from 20 weeks of age. Such age-related changes in their expression levels seen in SHRSP were quite different from those in SHR. In both SHR and SHRSP, transforming growth factor-beta1 (TGF-beta1) expression was increased with age, although SHRSP showed more marked upregulation. Cardiac remodeling in SHRSP was characterized by decreased coronary capillary density, cardiomyocyte hypertrophy, and cardiac fibrosis. We conclude that, in addition to overexpression of TGF-beta1, which appears to play a pivotal role in promoting cardiac hypertrophy and fibrosis, a defect of the VEGF-KDR system could result in impaired physiologic coronary angiogenesis in SHRSP, contributing to cardiac deteroration associated with myocardial ischemia in this malignant hypertensive model.

Age Factors↗
PubMed2005

Optical imaging of spiral waves: pharmacological modification of spiral-type excitations in a 2-dimensional layer of ventricular myocardium.

Differential effects of sodium channel blockers, an I(Kr) blocker (nifekalant) and amiodarone on the spiral-type reentry, were investigated in rabbit hearts by using a high-resolution optical mapping system. Two-dimensional subepicardial layer of left ventricular myocardium with uniform anisotropy was prepared by endocardial cryoablation. During ventricular tachycardia (VT) elicited by cross-field stimulation, spiral-type excitations rotating around functional block lines (FBLs) were visualized. All the sodium channel blockers stabilized rotors; VT duration was prolonged in association with increases of FBLs and VT cycle length. The rotors in the presence of nifekalant were characterized by large meandering, long FBLs, and frequent front-tail interactions generating wave breaks. Amiodarone (acute application) increased FBLs and VT cycle length, but shortened the VT duration with minimal front-tail interaction. These results suggest that multifaceted drug action on both depolarization and repolarization may be required for the early termination of spiral-type reentry without causing breakup of rotors.

Amiodarone↗
PubMed2005

Reciprocal changes in endothelium-derived hyperpolarizing factor- and nitric oxide-system in the mesenteric artery of adult female rats following ovariectomy.

1. To explore the effects of estrogen on arterial functions, we examined endothelium-derived hyperpolarizing factor (EDHF)- and NO-mediated responses in isolated mesenteric arteries of female rats, 4 weeks after sham-operation (CON), ovariectomy (OVX) and OVX plus chronic estrogen treatment (OVX+E(2)). Tissue levels of connexins-40, 43 (major components of gap junction), inducible NOS (iNOS), endothelial NOS (eNOS) and eNOS regulator proteins such as calmodulin, heat shock protein 90 (hsp90) and caveolin-1 were also examined using Western blot. 2. In OVX, acetylcholine (ACh)-induced EDHF-mediated relaxation and membrane hyperpolarization of arterial smooth muscles were reduced, whereas ACh-induced NO-mediated relaxation was enhanced, leading to no change in ACh-induced relaxation. 3. In OVX, connexin-40 and 43 were decreased. Tissue levels of eNOS and its positive regulators (calmodulin and hsp90) were unchanged, but that of its negative regulator, caveolin-1, was decreased. The levels of iNOS in mesenteric artery and aorta and plasma levels of NO metabolites and cholesterol were elevated. 4. In OVX, contraction of the artery by phenylephrine was reduced, but augmented by nonspecific inhibitor of NOS to the comparable level as that in CON group. The contraction in OVX group unlike that in CON group was augmented by specific iNOS inhibitor, and the difference between contractions in the presence of nonspecific and specific inhibitor as an index of eNOS activity was increased. 5. In OVX+E(2), all these changes were recovered. 6. In all groups, EDHF-mediated relaxation was suppressed by 18beta-glycyrrhetinic acid, an inhibitor of gap junction. 7. These results indicate that estrogen deficiency does not change the diameter of mesenteric artery: it reduces EDHF-mediated relaxation by decreasing gap junction, whereas it augments NO-mediated relaxation via an increase in NO release. Increased NO result from increased activity of eNOS subsequent to a decrease in caveolin-1 and from induction of iNOS. However, excessive NO generation with elevated plasma cholesterol would raise a risk for atherosclerosis.

Acetylcholine↗
PubMed2005

Mechanism of vasodilation to adenosine in coronary arterioles from patients with heart disease.

Adenosine is a key myocardial metabolite that elicits coronary vasodilation in a variety of pathophysiological conditions. We examined the mechanism of adenosine-induced vasodilation in coronary arterioles from patients with heart disease. Human coronary arterioles (HCAs) were dissected from pieces of the atrial appendage obtained at the time of cardiac surgery and cannulated for the measurement of internal diameter with videomicroscopy. Adenosine-induced vasodilation was not inhibited by endothelial denudation, but A(2) receptor antagonism with 3,7-dimethyl-1-propargylxanthine and adenylate cyclase (AC) inhibition with SQ22536 significantly attenuated the dilation. In contrast, A(1) receptor antagonism with 8-cyclopentyl-1,3-dipropylxanthine significantly augmented the sensitivity to adenosine. Moreover, dilation to A(2a) receptor activation with 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido-adenosine hydrochloride was reduced by the A(1) receptor agonist (2S)-N(6)-(2-endo-norbornyl)adenosine. The nonspecific calcium-activated potassium (K(Ca)) channel blocker tetrabutylammonium attenuated adenosine-induced dilation, as did the intermediate-conductance K(Ca) blocker clotrimazole. Neither the large-conductance K(Ca) blocker iberiotoxin nor small-conductance K(Ca) blocker apamin altered the dilation. In conclusion, adenosine endothelium independently dilates HCAs from patients with heart disease through a receptor-mediated mechanism that involves the activation of intermediate-conductance K(Ca) channels via an AC signaling pathway. The roles of A(1) and A(2) receptor subtypes are opposing, with the former being inhibitory to AC-mediated dilator actions of the latter. These observations identify unique fundamental physiological characteristics of the human coronary circulation and may help to target the use of novel adenosine analogs for vasodilation in perfusion imaging or suggest new strategies for myocardial preconditioning.

Adenosine↗
PubMed2005

A rice diet is associated with less fat synthesis/accumulation than a bread diet before exercise therapy.

For effective exercise therapy after waking up, we focused on the staple food in diet therapy, and compared rice and bread diets. The subjects were 10 healthy college male students. After fasting for 12 h or more from the previous day, the subjects had breakfast consisting of rice (protein, 6.3 g; fat, 0.9 g: CHO, 79.3 g; energy, 368 kcal) or bread (protein, 15.7 g; fat, 5.8 g; CHO, 79.2 g; and energy, 450 kcal) containing the same amount of carbohydrates and the same side dishes (protein, 7.0 g; fat, 9.5 g; CHO, 21.3 g; energy, 199 kcal) in the morning 30 min before the initiation of exercise on a bicycle ergometer at an intensity of about 50% VO2max for 60 min. Measurements of the heart rate and expired gas were initiated 15 min before the start of exercise and continued until 10 min after exercise. Blood was collected before the meal, immediately before and 15, 30, and 45 min after the initiation of exercise, and immediately, 15, and 30 min after its termination. After breakfast containing carbohydrates, decreases were observed in the levels of free fatty acid and noradrenalin. Blood insulin (mealxtime, p<0.05 ANOVA) and triglyceride (meal x time, p<0.01, ANOVA) changed at higher levels in the bread diet than in the rice diet. Blood triglyceride is a resource of fat synthesis/accumulation, and insulin promotes its action. Therefore, the bread diet may promote fat synthesis/accumulation compared with the rice diet.

Adult↗
PubMed2005

Experimental studies on artificial blood usage for hemodilution during cardiopulmonary bypass.

BACKGROUND: Although hemodilution is usually utilized during cardiopulmonary bypass (CPB), hemodilution can cause adverse effects such as hypotension and hypoxia. The purpose of this study was to evaluate a novel perfluoro-octyl bromide (PFOB) emulsion, one of perfluorochemicals (PFCs) emulsions, administered during hemodilution CPB. METHODS: Fifteen dogs were subjected to CPB for 2 hours under mild hypothermia. Animals were divided into three groups; control group, hemodilution group and PFOB group. During the experiment, hemodynamics, complete blood count and blood chemistry were monitored. In addition, serum complement titer (CH50), bradykinin and histamine concentrations were also measured. RESULTS: Heart rate (HR) was markedly elevated in the hemodilution groups (p<0.05). Mean arterial pressure (MAP) did not change in the three groups. White blood cell (WBC) and platelet (PLT) count did not significantly differ among the three groups. Plasma lactate concentration was markedly elevated only in hemodilution group during late phase of CPB (p<0.05). In the hemodilution group, CH50, bradykinin and histamine, were markedly elevated during the CPB and just after CPB (p<0.05). CONCLUSIONS: The present study demonstrated possible benefits of the new PFC emulsion during cardiac surgery by counteracting the adverse effects of hemodilution during CPB.

Analysis of Variance↗
PubMed2004

Characterization of regional cerebral blood flow and expression of angiogenic growth factors in the frontal cortex of juvenile male SHRSP and SHR.

Attention-deficit/hyperactivity disorder (AD/HD) is a common pediatric behavioral disorder associated with male preponderance and reduction of regional cerebral blood flow (rCBF). However, lack of an appropriate animal model exhibiting appropriate AD/HD symptoms stands in the way of studying mechanism(s) underlying reduced rCBF and male preponderance. Our group has been investigating the suitability of juvenile male stroke-prone spontaneously hypertensive rats (SHRSP), a substrain of the commonly used AD/HD animal model SHR, as a model for AD/HD because, unlike SHR, SHRSP displays cognitive impairment and male preponderance. Our more recent studies revealed alterations in the synthesis of sex steroid hormones and angiogenic factors in the frontal cortex of male SHRSP compared to the genetic control WKY. Based on these observations, the present study utilizes laser-Doppler flowmetry, histochemistry, enzyme immunoassay, immunoblotting, and real-time PCR to characterize and compare the patterns of regional cerebral blood flow and synthesis of angiogenic molecules [basic fibroblast growth factor; nitric oxide synthase isoforms (endothelial, neuronal and inducible); vascular endothelial growth factor (VEGF) and its signaling molecules (VEGF receptors, phosphorylated Akt, endothelial nitric oxide synthase eNOS] between male SHRSP and SHR. Overall, consistent with our previous data showing alteration in VEGF/Akt/NO signaling, there was a marked reduction in the profile of rCBF (35%) and angiogenic factors of SHRSP, compared to age-matched genetic control Wistar-Kyoto rats (WKY) and SHR. We conclude that, unlike SHR, the profiles of rCBF and angiogenic factors in SHRSP are altered in juvenile male. Thus, SHRSP appears to be a more suitable animal model for studying changes in rCBF in AD/HD.

Age Factors↗
PubMed2004

An S-nitrosylated hemoglobin derivative protects the rat hippocampus from ischemia-induced long-term potentiation impairment with a time window.

Evidence suggests that S-nitrosylation is a biological process involved in cerebral ischemia. The aim of the present study was to elucidate the effects of S-nitrosylated (SNO) polyethylene glycol-conjugated (PEG) hemoglobin (Hb) developed as an artificial oxygen carrier, which can absorb free NO and translocate NO to a sulfhydryl (SH) moiety, on ischemic cerebral dysfunction. Long-term potentiation (LTP) in the perforant path-dentate gyrus synapses of the rat hippocampus was evaluated as functional outcome 4 days after transient incomplete cerebral ischemia (2-vessel occlusion: 2VO, 10 min). SNO-PEG-Hb (250 mg/kg, i.v.) administered on Day 0, 1, 2, or 4 (immediately, 24 h, 48 h, or 96 h after reperfusion, respectively) alleviated 2VO-induced LTP impairment with a therapeutic time window. The effect was significant when SNO-PEG-Hb was administered on Day 1 or 2. SNO-PEG-Hb altered NOS features observed in the vehicle-treated 2VO rat, upregulation of eNOS, nNOS, and iNOS expressions at mRNA and protein levels; SNO-PEG-Hb further upregulated eNOS and nNOS and downregulated iNOS expressions. These findings suggest that SNO-PEG-Hb might have protective effects on the rat hippocampus from ischemia/reperfusion-induced functional damages, thereby increasing the therapeutic potential as an artificial oxygen carrier for use in the area of oxygen therapy.

Animals↗