Biomedical subjects

Tatsuaki Matsubara

Publications and source records attributed to Tatsuaki Matsubara.

16 recordsLinked to original sources

PubMed2006

Heart slice NMR.

Nuclear magnetic resonance (NMR) spectroscopy of the heart is normally carried out using whole heart preparations under coronary perfusion. In such preparations, either radical changes in ionic composition of the perfusate or applications of numerous drugs would affect coronary microcirculation. This report communicates the first (31)P NMR spectroscopy study using a heart slice preparation (left ventricular slices) superfused with extracellular medium. The ratio of phosphocreatine concentration to ATP concentration was approximately 2.1. Also, intracellular pH and Mg(2+) concentration ([Mg(2+)](i)), estimated from the chemical shifts of inorganic phosphate and ATP, were comparable with those under retrograde perfusion. [Mg(2+)](i) was significantly increased by the removal of extracellular Na(+), supporting the essential role of Na(+)-coupled Mg(2+) transport in Mg(2+) homeostasis of the heart. Heart slice preparation could also be used to evaluate the potency of cardiac drugs, regardless of their possible effects on coronary microcirculation.

Adenosine Triphosphate↗

PubMed2006

Impact of plasma aldosterone levels for prediction of in-stent restenosis.

Aldosterone promotes vascular smooth muscle cell proliferation and endothelial dysfunction, suggesting the contribution to in-stent restenosis (ISR). This study evaluated any relation between plasma aldosterone levels and ISR 6 months after successful coronary stenting. We enrolled 156 consecutive patients with stable angina who underwent coronary bare metal stenting. Plasma aldosterone levels and other serum markers known to influence cardiovascular events were measured in all patients at baseline. Patients with restenosis were found to have significantly higher plasma aldosterone levels than their counterparts without restenosis (162 +/- 60 vs 122 +/- 60 pg/ml, p = 0.007). On logistic regression analysis, even after adjusting for clinical, angiographic, and other confounding variables, plasma aldosterone level per 10 pg/ml (odds ratio 1.34, 95% confidence interval 1.10 to 1.63, p = 0.006) proved to be the independent predictor of ISR. The area under the receiver-operating characteristic curve for plasma aldosterone level was 0.75, and the optimal cut-off value identified by receiver-operating characteristic analysis was 141.9 pg/ml, which had a predictive accuracy of 69%. In conclusion, the present findings indicate that plasma aldosterone levels at baseline are independent predictors of ISR and may constitute a potential therapeutic target.

Aged↗

PubMed2006

Effects of receipt of chronic statin therapy before the onset of acute myocardial infarction: a retrospective study in patients undergoing primary percutaneous coronary intervention.

BACKGROUND: Studies have reported an association between receipt of statin therapy and a reduction in complications after elective percutaneous coronary intervention (PCI). However, there are limited data on the effects of chronic statin therapy before the occurrence of an acute myocardial infarction (AMI). OBJECTIVE: This study investigated whether administration of chronic statin therapy before AMI was associated with a reduction in reperfusion injury in AMI patients undergoing PCI. METHODS: This was a retrospective study of consecutive patients with a first AMI who underwent successful reperfusion therapy with PCI within 24 hours after the onset of AMI between April 1998 and October 2003. Patients were stratified according to whether they had or had not been receiving chronic statin therapy for > or = 1 month before the onset of AMI. The following end points were compared after PCI: electrocardiographic resolution of ST segment elevation, defined as a reduction of > or = 50% from the initial value; achievement of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow; corrected TIMI frame count (cTFC); maximum serum creatine kinase (CK) level; and the type and frequency of ventricular arrhythmias. RESULTS: The study enrolled 386 patients, 40 of whom had been receiving statin therapy before the onset of AMI. The clinical characteristics of the 2 groups were similar at baseline, with the exceptions of a significantly higher rate of hyperlipidemia in the statin group compared with the nonstatin group (P < 0.001), significantly greater chronic use of aspirin therapy (P < 0.001), and significantly greater chronic use of antihypertensive medications (beta-blockers: P = 0.004; angiotensin-converting enzyme inhibitors/angiotensin II-receptor blockers: P = 0.007; calcium channel blockers: P = 0.006). Electrocardiographic ST segment resolution after PCI was observed in 87.5% and 69.9% of the statin and nonstatin groups, respectively (hazard ratio [HR]: 3.01; 95% CI, 1.15-7.90; P = 0.025). Achievement of TIMI grade 3 flow after PCI was seen in 95.0% of the statin group and 83.5% of the nonstatin group (HR: 3.75; 95% CI, 0.88-16.0; P = NS). Patients treated with a statin had a significantly lower mean (SD) maximum CK level compared with the nonstatin group (2300 [1449] vs 3538 [3170] IU/mL, respectively; P = 0.015) and a lower cTFC after PCI (18.8 [4.0] vs 24.2 [14.2]; P = 0.017). The difference in reperfusion arrhythmias between groups was not statistically significant. After adjustment for baseline covariates, pretreatment with a statin was found to be an independent predictor of ST segment resolution after PCI (HR: 2.95; 95% CI, 1.08-8.09; P = 0.035) and prevention of impaired coronary flow (HR: 3.00; 95% CI, 1.63-5.55; P < 0.001). CONCLUSION: In this study, receipt of chronic statin therapy before the onset of AMI was associated with improvement in epicardial perfusion and a reduction in myocardial necrosis after PCI.

Adrenergic beta-Antagonists↗

PubMed2006

Effects of intravenous nicorandil before reperfusion for acute myocardial infarction in patients with stress hyperglycemia.

OBJECTIVE: Stress hyperglycemia increases the risk of mortality and poor outcomes in patients with acute myocardial infarction (AMI). We aimed to assess effects of intravenous nicorandil administered before reperfusion on AMI patients with stress hyperglycemia. RESEARCH DESIGN AND METHODS: This study consisted of 158 consecutive first AMI patients with stress hyperglycemia who underwent percutaneous coronary intervention (PCI) within 24 h from the onset. They were randomly assigned to receive 12 mg of nicorandil (n = 81) or a placebo (n = 77) intravenously just before reperfusion. Stress hyperglycemia was defined as a blood glucose level > or =10 mmol/l (180 mg/dl). We examined various aspects of epicardial flow and microvascular function as immediate data and major adverse cardiac events (MACEs) (coronary heart disease death or unplanned readmission due to congestive heart failure) as late-phase data. RESULTS: The incidence of slow flow after PCI was lower in the nicorandil group (13.6 vs. 27.3%, P < 0.04). ST segment resolution >50% was observed in 70.4 and 53.2% on nicorandil and placebo, respectively (P < 0.03). Patients treated with nicorandil had a lower peak creatine kinase level (3,137 +/- 2,577 vs. 4,333 +/- 3,608, P < 0.02). Upon Kaplan-Meier analysis, 5 years' freedom from MACEs was 86.4% in the nicorandil group and 74.0% in the placebo (P < 0.05). CONCLUSIONS: Adjunctive therapy with administration of intravenous nicorandil before reperfusion on AMI patients with stress hyperglycemia significantly improves epicardial flow and prevents the occurrence of severe microvascular reperfusion injury, resulting in better outcomes in these patients.

Aged↗

PubMed2005

Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility.

Appropriate gastrointestinal motility is essential to properly control the body energy level. Intracellular Ca2+ ([Ca2+]i) oscillations in interstitial cells of Cajal (ICCs; identified with c-Kit immunoreactivity) are considered to be the primary mechanism for the pacemaker activity in gastrointestinal motility. In the present study, RT-PCR examinations revealed predominant expression of the type 1 isoform of sulphonylurea receptors (SUR1) in ICCs of the mouse ileum, but expression of SUR2 was predominant in smooth muscle. In cell clusters prepared from the same tissue, smooth muscle contractility and pacemaker [Ca2+]i activity in ICCs were found to be differentially modulated by K(ATP) channel openers and sulphonylurea compounds, in accordance with the expression of SUR isoforms. 1 microM cromakalim nearly fully suppressed the mechanical activity in smooth muscle, whereas ICC pacemaker [Ca2+]i oscillations persisted. Greater concentrations (approximately 10 microM) of cromakalim attenuated pacemaker [Ca2+]i oscillations. This effect was not reversed by changing the reversal potential of K+, but was prevented by glibenclamide. Diazoxide at 30 muM terminated ICC pacemaker [Ca2+]i oscillations, but again treatment with high extracellular K+ did not restore them. These results suggest that SUR can modulate pacemaker [Ca2+]i oscillations via voltage-independent mechanism(s), and also that intestinal pacemaking and glucose control are closely associated with SUR.

ATP-Binding Cassette Transporters↗

PubMed2005

Impact of a single intravenous administration of nicorandil before reperfusion in patients with ST-segment-elevation myocardial infarction.

BACKGROUND: Intravenous nicorandil, a hybrid compound of ATP-sensitive potassium channel opener and nitric oxide donor, has been reported to ameliorate early functional and clinical problems in patients with acute myocardial infarction. However, its effects on the late phase remain unclear. METHODS AND RESULTS: This follow-up study to 5 years of a randomized, double-blinded trial was conducted among 368 patients with first ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). They were randomly assigned to receive 12 mg of nicorandil or a placebo intravenously just before reperfusion. We analyzed incidence of cardiovascular death or rehospitalization for congestive heart failure after PCI as well as various aspects of epicardial flow and microvascular function. Mean follow-up was 2.4 years (SD, 1.4). A total of 12 (6.5%) patients receiving nicorandil and 30 (16.4%) receiving placebo had cardiovascular death or hospital admission for congestive heart failure (hazard ratio, 0.39; 95% CI, 0.20 to 0.76; P=0.0058). Postprocedural TIMI 3 flow was obtained in 89.7% of the nicorandil group and in 81.4% of the placebo (hazard ratio, 1.99; 95% CI, 1.09 to 3.65; P=0.025). Corrected TIMI frame count was furthermore lower in the nicorandil group (21.0+/-9.1 versus 25.1+/-14.1; P=0.0009). ST-segment resolution >50% was observed in 79.5% and 61.2% of the nicorandil and placebo groups, respectively (hazard ratio, 2.45; 95% CI, 1.54 to 3.90; P=0.0002). CONCLUSIONS: The addition of intravenous nicorandil to PCI leads to beneficial clinical outcomes and prevents cardiovascular events of long duration and death in patients with ST-segment-elevation myocardial infarction.

Adult↗

PubMed2005

Noninvasive evaluation of the time course of change in cardiac function in spontaneously hypertensive rats by echocardiography.

The spontaneously hypertensive rat (SHR) has been well established as a suitable model for studies of hypertension, but little is known about the processes of left ventricular (LV) hypertrophy and the changes in cardiac function in this model. The present study was designed to provide a noninvasive evaluation of the time-dependent alteration of cardiac function in male SHR at 4 to 24 weeks of age and age-matched Wistar-Kyoto rats (WKY). Echocardiographic studies were performed after blood pressure (BP) and heart rate (HR) were measured by a tail-cuff method. The body weight (BW) of SHR was lighter than that of WKY at all ages, and HR was consistently lower, with significantly elevated systolic BP from 4 weeks of age. In the echocardiographic study, LV mass at 4 weeks of age was similar between WKY and SHR, although the ratio of LV mass to BW was higher in SHR than WKY. The ejection fraction, fractional shortening (FS) and midwall FS did not differ between the two groups at 4 weeks, but after 8 weeks, these parameters were decreased in the SHR. The deceleration time was prolonged in SHR after 16 weeks and the E/A ratio was lowered at 12 weeks. We also analyzed the expression levels of calcineurin, which were found to be increased in both groups with age. These results suggest that calcineurin does not play a major role in the development of LV hypertrophy. Thus, in SHR, cardiac hypertrophy develops by 4 weeks of age, and systolic and diastolic dysfunction is evident at 2 to 3 months.

Animals↗

PubMed2005

Therapeutic neovascularization using cord blood-derived endothelial progenitor cells for diabetic neuropathy.

Diabetic neuropathy is based on the impairment of nerve blood flow and the metabolic disorder. Although the vasodilating agents and anticoagulants improve nerve function and symptoms in diabetic neuropathy, more effective treatments are needed. Because endothelial progenitor cells (EPCs) have been identified in adult human peripheral blood, many studies have shown that transplantation of EPCs improves circulation to ischemic tissues. In this study, we have demonstrated that therapeutic neovascularization using human umbilical cord blood-derived EPCs reversed diabetic neuropathy. EPCs were isolated and expanded on day 7 of culture from cord blood mononuclear cells. Unilateral intramuscular injection of EPCs into hindlimb skeletal muscles significantly ameliorated impaired sciatic motor nerve conduction velocity and sciatic nerve blood flow in the EPC-injected side of streptozotocin-induced diabetic nude rats compared with the saline-injected side of diabetic nude rats. Histological study revealed an increased number of microvessels in hindlimb skeletal muscles in the EPC-injected side of diabetic rats. These findings suggest that transplantation of EPCs from cord blood may be a useful treatment for diabetic neuropathy.

Animals↗

PubMed2004

Requirement of ryanodine receptors for pacemaker Ca2+ activity in ICC and HEK293 cells.

Intracellular Ca(2+) ([Ca(2+)](i)) oscillations seen in interstitial cells of Cajal (ICCs) are considered to be the primary pacemaker activity in the gut. Here, we show evidence that periodic Ca(2+) release from intracellular Ca(2+) stores produces [Ca(2+)](i) oscillations in ICCs, using cell cluster preparations isolated from mouse ileum. The pacemaker [Ca(2+)](i) oscillations in ICCs are preserved in the presence of dihydropyridine Ca(2+) antagonists, which suppress Ca(2+) activity in smooth muscle cells. However, applications of drugs affecting either ryanodine receptors or inositol 1,4,5-trisphosphate receptors terminated [Ca(2+)](i) oscillations at relatively low concentrations. RT-PCR analyses revealed a predominant expression of type 3 RyR (RyR3) in isolated c-Kit-immunopositive cells (ICCs). Furthermore, we demonstrate that pacemaker-like global [Ca(2+)](i) oscillation activity is endowed by introducing RyR3 into HEK293 cells, which originally express only IP(3)Rs. The reconstituted [Ca(2+)](i) oscillations in HEK293 cells possess essentially the same pharmacological characteristics as seen in ICCs. The results support the functional role of RyR3 in ICCs.

Anesthetics, Local↗

PubMed2004

Beneficial effect of rotational atherectomy with low platform speed on late outcomes.

BACKGROUND: Modification of rotational atherectomy (RA) procedures might be expected to alter restenosis rates. METHODS AND RESULTS: From June 1998 (period 2), platform speed was decreased to 150,000-160,000 rpm from the 170,000-190,000 rpm performed from August 1997 to May 1998 (period 1). Patients for the two periods (period 1: 62 patients, 70 lesions; period 2: 85 patients, 91 lesions) demonstrated comparable clinical and angiographic baseline data, allowing immediate and late outcomes to be evaluated for comparison. Restenosis rates in periods 1 and 2 were 57.9% and 33.8%, respectively (P=0.01). Platform speed and lesion length were independent predictors of restenosis by multivariate logistic regression analysis. CONCLUSIONS: RA with a low platform speed (150,000-160,000 rpm) can be performed with a high success rate and with a lower incidence of restenosis than with a high platform speed (170,000-190,000 rpm).

Aged↗

PubMed2004

Antioxidative effects of benidipine hydrochloride in patients with hypertension independent of antihypertensive effects. Relationship between blood pressure and oxidative stress.

This study investigated the significance of measuring plasma level of thiobarbituric acid reactive substance (TBARS) in patients with hypertension and compared the clinical effects of benidipine hydrochloride (CAS 91599-74-5, Coniel) and amlodipine besylate (CAS 111470-99-6) on plasma TBARS. At first, blood pressure and plasma TBARS were measured in 85 untreated patients (48 males and 37 females, 68 years old on average) with at least one risk factor of cardiovascular disease to investigate factors which had influence on plasma TBARS. As the result, plasma TBARS was significantly higher in those with hypertension, which was also true when adjusted for other factors (r = 0.359, p< 0.01). Among these patients, benidipine hydrochloride at the dose of 4 mg/day was administered to 49 patients with hypertension or angina pectoris. All patients stratified for each factor showed significantly decreased plasma TBARS after benidipine hydrochloride treatment. Second, 40 untreated patients with essential hypertension were randomly assigned to the amlodipine group (5-7.5 mg/day) or benidipine group (4-8 mg/day) to compare the plasma TBARS levels. Plasma TBARS levels were significantly decreased in both groups. The amlodipine group showed a positive correlation between the decrease in plasma TBARS level and those in both diastolic and systolic blood pressures after treatment. On the other hand, benidipine hydrochloride decreased plasma TBARS to a greater degree than both diastolic and systolic blood pressures. These findings suggest that patients with hypertension have high plasma TBARS, and benidipine hydrochloride decreases not only blood pressure but also oxidative stress in the clinical practice.

Aged↗

PubMed2003

Ca2+-dependent modulation of intracellular Mg2+ concentration with amiloride and KB-R7943 in pig carotid artery.

It has long been recognized that magnesium is associated with several important diseases, including diabetes, hypertension, cardiovascular, and cerebrovascular diseases. In the present study, we measured the intracellular free Mg2+ concentration ([Mg2+]i) using 31P nuclear magnetic resonance (NMR) in pig carotid artery smooth muscle. In normal solution, application of amiloride (1 mm) decreased [Mg2+]i by approximately 12% after 100 min. Subsequent washout tended to further decrease [Mg2+]i. In contrast, application of amiloride significantly increased [Mg2+]i (by approximately 13% after 100 min) under Ca2+-free conditions, where passive Mg2+ influx is facilitated. The treatments had little effect on intracellular ATP and pH (pHi). Essentially the same Ca2+-dependent changes in [Mg2+]i were produced with KB-R7943, a selective blocker of reverse mode Na+-Ca2+ exchange. Application of dimethyl amiloride (0.1 mM) in the presence of Ca2+ did not significantly change [Mg2+]i, although it inhibited Na+-H+ exchange at the same concentration. Removal of extracellular Na+ caused a marginal increase in [Mg2+]i after 100-200 min, as seen in intestinal smooth muscle in which Na+-Mg2+ exchange is known to be the primary mechanism of maintaining a low [Mg2+]i against electrochemical equilibrium. In Na+-free solution (containing Ca2+), neither amiloride nor KB-R7943 decreased [Mg2+]i, but they rather increased it. The results suggest that these inhibitory drugs for Na+-Ca2+ exchange directly modulate Na+-Mg2+ exchange in a Ca2+-dependent manner, and consequently produce the paradoxical decrease in [Mg2+]i in the presence of Ca2+.

Adenosine Triphosphate↗

PubMed2003

Mechanisms for monovalent cation-dependent depletion of intracellular Mg2+:Na(+)-independent Mg2+ pathways in guinea-pig smooth muscle.

It has been suggested that magnesium deficiency is correlated with many diseases. 31P NMR experiments were carried out in order to investigate the effects of Na+ substitution on Mg2+ depletion in smooth muscle under divalent cation-free conditions. In the taenia of guinea-pig caeci, the intracellular free Mg2+ concentration ([Mg2+]i) was estimated from the chemical shifts of (1) the beta-ATP peak alone and (2) beta- and gamma-ATP peaks. Both estimations indicated that [Mg2+]i decreased only very slowly in Mg(2+)-free, Ca(2+)-free solutions in which Na+ was substituted with large cations such as NMDG (N-methyl-D-glucamine) and choline. Furthermore, the measurements of tension development supported the suggestion of preservation of intracellular Mg2+ with NMDG substitution. Substituting extracellular Na+ with the small cation, Li+, also shifted the beta-ATP peak towards a lower frequency, but the frequency shift was significantly less than that seen upon Na+ substitution with K+. The estimated [Mg2+]i depletion was, however, comparable with that seen after Na+ substitution with K+ using the titration curves of metal-free and Mg(2+)-bound ATP obtained in Li(+)-based model solutions. It was concluded that Mg2+ rapidly decreases only when small cations were the major electrolyte of the extracellular medium. Na+ substitutions with NMDG, choline or Li+ had little effect on intracellular ATP concentration after 100 min treatment.

Adenosine Triphosphate↗

PubMed2002

Dynamics of Ca(2+)/calmodulin-dependent protein kinase II following acute myocardial ischemia-translocation and autophosphorylation.

Ca(2+)/calmodulin-dependent protein kinase (CaMK) family is responsive to changes in the intracellular Ca(2+) concentration. However, their functions have not been well established in the ischemia/reperfusion heart. The effects of myocardial ischemia on CaMKII, the most strongly expressed form, were investigated using isolated rat hearts. Rat hearts were rendered globally ischemic by stopping perfusion for 15 min, and then reperfused, heart ventricles being analyzed in each phase. Western blotting detected a decrease in the cytosolic and concomitant increase in the particulate fraction of CaMKII following transient ischemia. Redistribution to the cytosol was revealed on reperfusion. Northern blot showed CaMKII gene expression decreased by ischemia. Furthermore, autoradiography and confocal immunohistochemical findings provided autophosphorylation of CaMKII in the cytosol, ischemia causing decrease, with gradual recovery on reperfusion. These results indicate a transient partial translocation of CaMKII accompanied by kinase activity, with residual myocardial CaMKII undergoing autophosphorylation during ischemia and reperfusion, demonstrating two different characteristic dynamics of CaMKII.

Animals↗

PubMed2002

Role of medial amygdala in controlling hemodynamics via GABA(A) receptor in anesthetized rats.

Experiments were conducted to determine whether the medial amygdala could control hemodynamics through the GABA receptor in anesthetized rats. Bicuculline (10-100pmol), a GABA(A) antagonist, injected into the anterior basomedial amygdala (medial amygdala) produced dose-related increases in blood pressure (BP) and heart rate (HR). Following microinjection of a 100pmol dose, plasma norepinephrine and epinephrine also rose significantly. In a group that had undergone bilateral adrenalectomy, the same dose of bicuculline into the same region of the amygdala caused similar increases in BP and HR to those produced in normal rats. Pretreatment with an intraperitoneal injection of hexamethonium prevented these responses. When bicuculline was given intravenously (100pmol) it failed to effect these cardiovascular changes. Bicuculline-induced hypertension and tachycardia were inhibited by microinjection of muscimol, a GABA agonist, into the anterior basomedial amygdala. The results thus demonstrate that the influence of bicuculline on BP and HR is through action on the anterior basomedial amygdala and direct sympathetic outflow to heart and vascular smooth muscle. There is tonic GABAergic inhibition of sympathetic outflow in the medial amygdala that plays a part in regulating hemodynamics in the limbic system.

Amygdala↗

PubMed2002

O2 extraction during exercise determines training effect after cardiac rehabilitation in myocardial infarction.

Correlations between baseline hemodynamic and oximetric variables during an invasive exercise test and an improvement in peak oxygen uptake (peak VO2) after exercise training (ET) were examined in 20 patients who participated in a cardiac rehabilitation program after acute myocardial infarction (AMI). Peak VO2 significantly increased by 23 +/- 21% (p < 0.01) after ET and the improvement best correlated with the change in O2 extraction fraction ([arterial O2 content-venous O2 content]/arterial O2 content) during an exercise testbefore ET (r = -0.61, p<0.01). Exercise capacity was improved to a greater extent by ET in patients with a smaller increase in O2 extraction fraction during an exercise test before ET. Thus, O2 extraction fraction during an exercise test before ET may be a useful predictor of the improvement in exercise capacity after ET in post-AMI patients.

Aged↗