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Biomedical subjects

Mitsuaki Isobe

Publications and source records attributed to Mitsuaki Isobe.

At least 37 records · Page 2Linked to original sources

Successful catheter ablation of focal left atrial tachycardia originating from the mitral annulus aorta junction.

Focal left atrial tachycardias (AT) originating from the mitral annulus-aorta (MA-Ao) junction are rare and their mechanisms are unclear. We report a 35-year-old male with successful ablation of an exercise-induced focal AT due to triggered activity originating from the MA-Ao junction. The AT occurred spontaneously during treadmill exercise testing and was easily induced by an atrial extrastimulus and atrial burst pacing after intravenous administration of isoproterenol. The AT was terminated by an atrial extrastimulus as well as a bolus of 5 mg of adenosine 5'-triphosphate. The coupling intervals of the extrastimuli that induced the AT were positively correlated with the interval between the extrastimuli and the first beat of the AT, suggesting the triggered activity as a tachycardia mechanism. The AT was successfully eliminated by a focal ablation at the MA-Ao junction with the earliest atrial activation where fractionated atrial potentials were recorded. The MA-Ao junction should be recognized as an important arrhythmogenic region.

Adenosine Triphosphate↗

[Interstitial pneumonitis followed by syndrome of inappropriate antidiuretic hormone secretion induced by amiodarone therapy for dilated cardiomyopathy: a case report].

An 87-year-old man had been treated under a diagnosis of idiopathic dilated cardiomyopathy and sick sinus syndrome since 1996. His heart failure was worsened by atrial fibrillation in August 2004. He received amiodarone from October 2004. He was admitted to our hospital with shortness of breath in February 2005. Chest radiography revealed a diffuse reticular shadow in the right lung field and pleural effusion. The diagnosis was interstitial pneumonitis induced by amiodarone. However, 10 days after the discontinuation of amiodarone, the serum sodium concentration fell to 114mEq/l. The blood and urine chemical data were consistent with syndrome of inappropriate antidiuretic hormone secretion (SIADH). The serum sodium concentration improved with fluid restriction. Clinicians should be aware that SIADH may occur during amiodarone therapy.

Aged, 80 and over↗

Ultrasound-microbubble-mediated NF-kappaB decoy transfection attenuates neointimal formation after arterial injury in mice.

OBJECTIVE: Decoy transfection is a significant methodology for suppressing gene activation. The decoy can be synthesized easily; however, the major obstacle is the difficulty involved in effective in vivo delivery. METHODS AND RESULTS: We used a fluorescein-labeled decoy to investigate the ultrasound-microbubble-mediated in vivo delivery in normal and injured mouse arteries. We showed that this approach could deliver the decoy into target tissues. In addition, we performed in vivo NF-kappaB decoy transfection into murine injured arteries using the ultrasound-microbubble method. Murine femoral arteries were injured using flexible wires to establish arterial injury. Pathologically, neointima/media areas in the NF-kappaB decoy transfection using ultrasound-microbubble group showed less than those in the control groups. Immunohistochemistry revealed that enhanced expression of inflammatory factors was observed in nontreated injured arteries, while the NF-kappaB decoy suppressed the expression. CONCLUSION: We revealed that ultrasound-microbubble delivery of the decoy is effective for transfection into target organs. We also indicated that NF-kappaB decoy transfection using this method has potential for the suppression of neointimal formation. Ultrasound-mediated transfection of the decoy can be beneficial for the clinical treatment of restenosis after coronary intervention and other cardiovascular diseases.

Animals↗

Cre/loxP-mediated CTLA4IgG gene transfer induces clinically relevant immunosuppression via on-off gene recombination in vivo.

OBJECTIVE: Transfer of the CTLA4IgG gene induces long-term and high levels of CTLA4IgG expression, which can result in generalized immunosuppression. In this study, we utilized Cre/loxP-mediated on-off switch recombination to eliminate transgene expression of CTLA4IgG following acceptance of murine cardiac allografts. METHODS: Fully MHC-mismatched hearts from BALB/c donor mice were transplanted into C3H/He recipient mice. Adenovirus-containing CTLA4IgG flanked between two loxP sites was administered via a recipient tail vein immediately after transplantation. Cre-recombinase gene was subsequently transferred at day 30 posttransplantation. RESULTS: Long-term allograft survival was observed in recipients that received the CTLA4IgG gene. Cre-mediated recombination reduced CTLA4IgG gene expression without any adverse effect on the graft survival. Secondary skin grafts of donor type and of third party were promptly rejected in the recipients that accepted cardiac allografts. In addition, the B cell response against ovalbumin was suppressed during high levels of serum CTLA4IgG, but recovered after Cre-mediated inactivation of CTLA4IgG gene. CONCLUSION: CTLA4IgG gene transfer promoted long-term survival of murine cardiac allografts; however, this was not sufficient to induce tolerance. Cre/loxP-mediated on-off switch recombination was useful to inactivate the CTLA4IgG gene so that recipients' immune responses against neoantigens were restored without an influence on the allograft survival. This system may open novel strategies to orchestrate clinically relevant immunosuppression.

Abatacept↗

Tea catechins attenuate ventricular remodeling and graft arterial diseases in murine cardiac allografts.

OBJECTIVE: Tea catechins have many biological functions; these effects are induced by the suppression of several inflammatory factors. However, effects of catechins on cardiac allograft rejection have not been well investigated. METHODS AND RESULTS: To test the hypothesis that catechins can attenuate ventricular remodeling and graft arterial diseases (GAD) in cardiac rejection, we orally administered catechins to murine cardiac recipients. We analyzed the mechanisms using immunohistochemistry, RNase protection, gel mobility shift, and cell proliferation assays. Although severe myocardial cell infiltration, fibrosis, and GAD with enhancement of inflammatory factors were observed in untreated class II mismatch allografts at day 60, catechins attenuated these changes with altered Th1/Th2 cytokine balance and suppressed NF-kappaB activation and cell proliferation. CONCLUSION: Catechins are potent agents for the suppression of chronic rejection because they are critically involved in the suppression of proinflammatory signaling pathways.

Animals↗

Evaluation of insulin resistance linkage to rat chromosome 4 in SHR of a Japanese colony.

The spontaneously hypertensive rat (SHR) is a model of human insulin resistance syndrome. Quantitative trait loci for cellular defects in glucose and fatty acid metabolism have been mapped to an overlapping region of rat chromosome (RNO) RNO4 in SHR of the National Institute of Health colony, where a deletion in the Cd36 gene has been implicated as the causative mutation of insulin resistance. The present study has examined the potential presence of RNO4 linkage to a series of metabolic phenotypes in F(2) progeny derived from SHR of a Japanese colony (SHR/Izm) without the Cd36 mutation. Our data demonstrate that 'major' insulin resistance gene(s) are unlikely to exist on RNO4 in SHR/Izm and in vitro phenotypes measured in isolated adipocytes do not cosegregate in the F(2) population studied. Thus, it seems to be difficult to explain the underlying genetic mechanisms of insulin resistance by a single major gene on RNO4.

Animals↗

Hepatocyte growth factor ameliorates the progression of experimental autoimmune myocarditis: a potential role for induction of T helper 2 cytokines.

Hepatocyte growth factor (HGF) plays a role in cell protection, antiapoptosis, antifibrosis, and angiogenesis. However, the role of HGF in the immune system is not well defined. We examined the influence of HGF on T cells and the effects of HGF therapy in acute myocarditis. Lewis rats were immunized on day 0 with cardiac myosin to establish experimental autoimmune myocarditis (EAM). Human HGF gene with hemagglutinating virus of the Japan-envelope vector was injected directly into the myocardium on day 0 or on day 14 (two groups of treated rats). Rats were killed on day 21. Expression of c-Met/HGF receptor in splenocytes and myocardial infiltrating cells was confirmed by immunohistochemical staining or FACS analysis. Myocarditis-affected areas were smaller in the treated rats than in control rats. Cardiac function in the treated rats was markedly improved. An antigen-specific T cell proliferation assay was done with CD4-positive T cells isolated from control rats stimulated with cardiac myosin. HGF suppressed T cell proliferation and production of IFN-gamma and increased production of IL-4 and IL-10 secreted from CD4-positive T cells in vitro. Additionally, TUNEL assay revealed that HGF reduced apoptosis in cardiomyocytes. HGF reduced the severity of EAM by inducing T helper 2 cytokines and suppressing apoptosis of cardiomyocytes. HGF has potential as a new therapy for myocarditis.

Animals↗

Electrocardiographic and electrophysiologic characteristics of ventricular tachycardia originating within the pulmonary artery.

OBJECTIVES: We investigated the electrocardiographic (ECG) and electrophysiologic characteristics of ventricular tachycardia (VT) originating within the pulmonary artery (PA). BACKGROUND: Radiofrequency catheter ablation (RFCA) is routinely applied to the endocardial surface of the right ventricular outflow tract (RVOT) in patients with idiopathic VT of left bundle branch block morphology. It was recently reported that this arrhythmia may originate within the PA. METHODS: Activation mapping and ECG analysis were performed in 24 patients whose VTs or ventricular premature contractions (VPCs) were successfully ablated within the PA (PA group) and in 48 patients whose VTs or VPCs were successfully ablated from the endocardial surface of the RVOT (RV-end-OT group). RESULTS: R-wave amplitudes on inferior ECG leads, aVL/aVR ratio of Q-wave amplitude, and R/S ratio on lead V(2) were significantly larger in the PA group than in the RV-end-OT group. On intracardiac electrograms, atrial potentials were more frequently recorded in the PA group than in the RV-end-OT group (58% vs. 12%; p < 0.01). The amplitude of local ventricular potentials recorded during sinus rhythm within the PA was significantly lower than that recorded from the RV-end-OT (0.62 +/- 0.56 mV vs. 1.55 +/- 0.88 mV; p < 0.01). CONCLUSIONS: Ventricular tachycardia originating within the PA has different electrocardiographic and electrophysiologic characteristics from that originating from the RV-end-OT. When mapping the RVOT area, the catheter may be located within the PA if a low-voltage atrial or local ventricular potential of <1-mV amplitude is recorded. Heightened attention must be paid if RFCA is required within the PA.

Adult↗

Long-term efficacy of hybrid pharmacologic and ablation therapy in patients with pilsicainide-induced atrial flutter.

BACKGROUND: Combination therapy with catheter ablation of the cavo-tricuspid isthmus and continued drug therapy, that is, "hybrid therapy," in patients with atrial fibrillation (AF) and drug-induced atrial flutter (AFL) is reported to be an alternative means of achieving and maintaining sinus rhythm. With respect to choosing this method among the rhythm control therapies, its long-term efficacy and the prevalence of AFL in patients with AF are very important and have not been fully elucidated. HYPOTHESIS: The purpose of this study was to investigate the long-term effectiveness of this hybrid therapy and the dose prevalence in Ic drug-induced AFL. METHODS: The subjects were 89 patients (aged 62.4 years, 72 men) with episodes of AF (paroxysmal type: 65, persistent type: 11, permanent type: 13). After 4 weeks of oral pilsicainide administration, the dose was increased in those with no documented AFL. The patients who experienced AFL with pilsicainide (Ic-AFL) underwent ablation. RESULTS: Pilsicainide administration resulted in the common type AFL in 17 patients (19.1%). The pilsicainide plasma concentration in the patients with Ic-AFL was significantly higher than in those without AFL (0.79 +/- 0.41 vs. 0.51 +/- 0.24 microg/ml, respectively, p < 0.01). During a 10-54 (mean 37 +/- 14) month follow-up period, sinus rhythm was maintained in 10 of 12 patients after successful ablation followed by continued antiarrhythmic drug administration. CONCLUSIONS: Hybrid therapy with ablation and high doses of pilsicainide was useful in maintaining sinus rhythm in some selected patients with AF and drug-induced AFL.

Aged↗

Clinical study regarding the anatomical structures of the right atrial isthmus using intra-cardiac echocardiography: implication for catheter ablation of common atrial flutter.

BACKGROUND: The construction of complete bi-directional block in the isthmus (ITH) between the tricuspid annulus and inferior vena cava by radiofrequency energy (RF) applications is sometimes hampered due to anatomical problems such as a thick isthmus or aneurysmal pouch in patients with common atrial flutter (AFL). METHODS AND RESULTS: Fifteen patients were referred for RF ablation of AFL. The anatomical thickness of the right atrial ITH, diameter of the right atrium and thickness of the right atrial free wall were determined using intracardiac echocardiography (ICE), along with the endocardial electrogram recordings at the ITH. RF was applied at the ITH to create a transmural incision to treat the AFL. A significant parallel relationship between the maximum amplitude of the atrial electrogram and the thickness of the ITH, was observed. When the maximum amplitude of the atrial electrogram at the ITH exceeded 1.5 mV, the thickness at the ITH was approximately larger than 5 mm. CONCLUSIONS: Using ICE, the precise measurement of the anatomical structures in the heart, including the ITH, was feasible. From the amplitude of the atrial electrogram, a deduction of the thickness at the ITH was possible, which is indispensable information for the appropriate selection of the RF devices.

Adult↗

Development of novel method of non-viral efficient gene transfer into neonatal cardiac myocytes.

To establish new treatment for cardiovascular disease, the development of safe and highly efficient vectors is necessary. Especially, non-viral vectors are considered to be ideal for human gene therapy, since recent adverse events with retroviral or adenoviral vectors have highlighted the issue of safety. Although we previously reported safety and high efficiency of HVJ-liposome method, we have modified the envelope of HVJ (Sendai virus). In this novel non-viral vector, the envelope of HVJ alone was utilized as a carrier to deliver proteins, genes and oligodeoxynucleotides (ODN). Thus, we optimized the transfection efficiency of HVJ-envelope vector into neonatal cardiac myocytes in this study, since cardiac myocytes is one of the most difficult cells to be transfected. HVJ-envelope, obtained after complete destruction of HVJ genome, containing FITC-labeled ODN or luciferase plasmid was incubated with cardiac myocytes. In addition, the concentration of protamine sulfate was modified (0-700 microg/ml) to increase transfection efficacy. Without HVJ-envelope vector, few cells showed fluorescence, whereas most cells demonstrated fluorescence with HVJ-envelope vector. Consistent with the high transfection efficiency of ODN, high luciferase activity was also detected using HVJ-envelope vector. Moreover, the transfection efficiency varied according to the concentration of protamine sulfate. No obvious cytotoxicity was observed in cells transfected with HVJ-envelope vector. The present study demonstrated the development of a highly efficient novel non-viral vector for cardiac myocytes, suggesting that further development may provide a new useful tool for research and clinical gene therapy in the field of cardiovascular disease.

Animals↗

Curative therapy for swallowing-induced tachycardia by pulmonary vein antrum isolation.

We present a case of a 49-year-old man who experienced invariably reproducible paroxysmal supraventricular tachycardia during swallowing. Because beta-blockers and multiple antiarrhythmic drugs failed to prevent the episodes of this tachycardia, we performed catheter mapping and ablation. After placing multiple decapolar catheters, when the patient swallowed a few sections of an orange, intracardiac mapping revealed atrial premature beats and atrial tachycardia that lasted for a few seconds and arose from an ostial site of the right superior pulmonary vein. After the right superior pulmonary vein antrum was completely isolated, the patient became free from the swallowing-induced tachycardia.

Adrenergic beta-Antagonists↗

Chronic hemodynamic effects after radiofrequency catheter ablation of frequent monomorphic ventricular premature beats.

INTRODUCTION: Radiofrequency catheter ablation (RFCA) of severely symptomatic monomorphic ventricular premature beats (VPBs) is reported to be a safe and effective treatment option. However, the chronic hemodynamic effects of these VPBs have not been precisely evaluated. METHODS AND RESULTS: We sought to investigate chronic effects after decreasing the number of VPBs by RFCA. A total of 47 patients who had no underlying heart disease and frequent monomorphic VPBs, consisting of more than 10,000 beats per day (24,194 +/- 12,516 beats per day), were enrolled. Patients were treated with RFCA and followed up over 6 months as outpatients. Echocardiography and serum B-type natriuretic peptide (BNP) level were repeatedly checked before and after RFCA. In 38 patients, whose VPBs were dramatically decreased to less than 1,000 beats per day by successful RFCA, left ventricular (LV) end-diastolic dimension (LVEDd) and end-systolic dimension (LVESd) measured by echocardiography decreased significantly (LVEDd: 50 +/- 5 to 48 +/- 5 mm, P < 0.01; LVESd: 33 +/- 7 to 30 +/- 6 mm, P < 0.01) in association with improvement of BNP level (39.9 +/- 34.1 to 16.8 +/- 10.3 pg/mL, P = 0.0001). In nine patients, whose VPBs were treated unsuccessfully by RFCA or that recurred, LV dimensions and BNP level did not change during the follow-up period. CONCLUSION: Significant improvement in LV dimensions and serum BNP level appeared to indicate that RFCA of VPBs ameliorated occult cardiac dysfunction induced by frequent VPBs.

Aged↗

Electrocardiographic characteristics of repetitive monomorphic right ventricular tachycardia originating near the His-bundle.

INTRODUCTION: Most idiopathic nonreentrant ventricular tachycardia (VT) and ventricular premature contractions (VPCs) arise from the right or left ventricular outflow tract (OT). However, some right ventricular (RV) VT/VPCs originate near the His-bundle region. The aim of this study was to investigate ECG characteristics of VT/VPCs originating near the His-bundle in comparison with right ventricular outflow tract (RVOT)-VT/VPCs. METHODS AND RESULTS: Ninety RV-VT/VPC patients underwent catheter mapping and radiofrequency ablation. ECG variables were compared between VT/VPCs originating from the RVOT and near the His-bundle. Ten patients had foci near the His-bundle (HIS group), with the His-bundle local ventricular electrogram preceding the QRS onset by 15-35 msec (mean: 22 msec) and His-bundle pacing produced a nearly identical ECG to clinical VT/VPCs. The HIS group R wave amplitude in the inferior leads (lead III: 1.0 +/- 0.6 mV) was significantly lower than that of the RVOT group (1.7 +/- 0.4 mV, P < 0.05). An R wave in aVL was present in 6 of 10 HIS group patients, while almost all RVOT group patients had a QS pattern in aVL. Lead I in HIS group exhibited significantly taller R wave amplitudes than RVOT group. HIS group QRS duration in the inferior leads was shorter than that of the RVOT group. Eight of 10 HIS group patients exhibited a QS pattern in lead V1 compared to 14 of 81 RVOT group patients. HIS group had larger R wave amplitudes in leads V5 and V6 than RVOT group. CONCLUSION: VT/VPCs originating near the His-bundle have distinctive ECG characteristics. Knowledge of the characteristic QRS morphology may facilitate catheter mapping and successful ablation.

Adult↗

Exercise after heparin administration: new therapeutic program for patients with-option arteriosclerosis oblitrans.

BACKGROUND: A prospective study examined whether a combination of an exercise program and heparin administration improves the clinical symptoms of patients with arteriosclerosis obliterans (ASO) without an indication for surgical revascularization because of the lack of distal target vessels or other reasons such as high surgical risk or lack of a vein conduit from previous coronary artery bypass surgery. METHODS AND RESULTS: A total of 19 consecutive patients with symptomatic non-option ASO diagnosed by angiography were randomly assigned to 3 groups: heparin + exercise (walking for 60 min after heparin injection [3,000 units/day IV for 14 days], n = 6), heparin administration only (n = 6), and exercise only (n = 7). Plasma levels of hepatocyte growth factor (HGF) were serially measured before and after intravenous administration of heparin. Ankle brachial pressure index was measured and treadmill exercise test (2.5 km/h, 12% slope) was performed before the 2-week treatment, just after finishing treatment, and 12 weeks after beginning the treatment. Ophthalmic examinations, including visual acuity test, ocular fundoscopy and fluorescein angiographic fundus photography, were performed before and 12 weeks after the treatment program. In all patients, HGF levels increased more than 4-fold of the basal level at 30 min after heparin injection. Maximum walking time was significantly higher in the heparin + exercise group than in the other 2 groups (p < 0.05). There were no patients who showed pathological retinal angiogenesis. CONCLUSION: The combination of an exercise program and heparin administration improves the clinical symptoms of patients with non-option ASO.

Aged↗

Accelerated progression and morbidity in patients with aortic stenosis on chronic dialysis.

BACKGROUND: Progression of aortic stenosis (AS) influences the prognosis in chronic dialysis (CD) patients, but there have been few studies in Japanese patient populations. METHODS AND RESULTS: The progression of AS was examined in 16 CD patients (68+/-10 years) and 82 non-dialysis patients (73+/-11 years). The mean follow-up was 32 and 40 months, respectively. The calcium-phosphate product was increased in CD patients (49+/-14 mg/dl vs 30+/-5 mg/dl; p<0.0001). At entry, the peak transaortic gradient detected by Doppler echocardiography was lower in CD patients (42+/-12 mmHg vs 57+/-22 mmHg; p<0.05). At follow-up, there was no difference between the 2 groups in that value (69+/-31 mmHg vs 71+/-27 mmHg). Decreasing rate of calculated aortic valvular area was increased in CD patients (0.14+/-0.13 cm2/year vs 0.06+/-0.09 cm2/year; p<0.05) and the calcification of the aortic valve was more severe at follow up in CD patients. The mortality was higher in CD patients (75 vs 28%; p<0.001). CONCLUSIONS: AS appeared to progress rapidly in CD patients and therefore early aortic valve replacement may be necessary.

Aged↗

Permanent His-bundle pacing after atrioventricular node ablation in a patient with chronic atrial fibrillation and mitral regurgitation.

Hemodynamic deterioration because of worsening of mitral regurgitation can occur in a small number of patients undergoing atrioventricular node (AVN) ablation and pacing therapy. Patients with moderate mitral regurgitation before ablation seem prone to this complication. Successful permanent His-bundle pacing after AVN ablation was performed in a patient with chronic atrial fibrillation and moderate mitral regurgitation. Pulmonary capillary wedge pressure V-wave amplitude was markedly diminished and the mitral regurgitation area, calculated from the echocardiogram, was decreased by His-bundle pacing compared with that during right ventricular outflow tract or apical pacing.

Aged↗