PubMed Health⌕ Search

Biomedical subjects

Kenzo Hirao

Publications and source records attributed to Kenzo Hirao.

10 recordsLinked to original sources

A CCR1 antagonist prevents the development of experimental autoimmune myocarditis in association with T cell inactivation.

Chemokines play an important role in induction of chemotaxis of immune cells. CCR1 is a chemokine receptor expressed on neutrophils, monocytes, and T lymphocytes. The role of CCR1 in immunity is not well examined. We demonstrated the role of CCR1 on T lymphocytes and the effect of a CCR1 antagonist, BX471 in myocarditis. Lewis rats were immunized with cardiac myosin on day 0 to establish experimental autoimmune myocarditis. Rats were then administered BX471 subcutaneously every day (group BX0: n = 7) or from day 14 (group BX14: n = 7) and were killed on day 21. We confirmed expression of CCR1 in cells infiltrating the myocardium by immunohistochemistry and FACS analysis. The development of myocarditis was almost completely prevented in group BX0, and myocarditis-affected areas were significantly decreased in size in group BX14. Cardiac function was markedly improved. Ribonuclease protection assay showed that the CCR1 antagonist treatment suppressed mRNA expression for IL-6, IL-1beta, and TNF-alpha in the hearts. An antigen-specific T cell proliferation assay was performed with CD4-positive T cells isolated from control rats immunized with cardiac myosin. T cell proliferation was inhibited by the CCR1 antagonist. Additionally, we showed by Western blot that the CCR1 antagonist suppressed ERK1/2 and JNK activities in T cells stimulated with myosin and that IL-2 reversed this suppression. The CCR1 antagonist reduced the severity of EAM by inhibiting cytokine expression and inducing T cell inactivation. Thus, the CCR1 antagonist may provide a novel therapeutic strategy treatment of myocarditis.

Animals↗

Utility of gallium-67 scintigraphy for evaluation of cardiac sarcoidosis with ventricular tachycardia.

BACKGROUND: The outcome of cardiac sarcoidosis is sometimes very poor. Ventricular tachycardia (VT) associated with cardiac sarcoidosis is the most common cause of sudden death among most patients. However, there is no established method for potential VT in patients with cardiac sarcoidosis. Thus, we investigated the utility of evaluation of gallium-67 scintigraphy for potential VT in patients with cardiac sarcoidosis. METHODS AND RESULTS: Cardiac sarcoidosis was diagnosed in 25 patients at ours or collaborating hospitals during the period 1982 through 2004. Twenty-one of these patients were treated with corticosteroid, and these patients were divided into two groups, depending on whether VT was present: a non-VT group (n=7) and a VT group (n=14). Laboratory and gallium-67 scintigraphy findings were examined in both groups. During the follow-up period, initial and maintenance dosages of corticosteroid did not differ significantly between the groups. Accumulation of gallium-67 in the heart at the time of diagnosis was detected more frequently in the VT group than in the non-VT group (14.3 vs. 71.4%, p<0.05). Six of the seven VT patients who underwent follow-up examination showed improvement on the scintigram obtained after treatment. Five of the six showed no VT recurrence in terms of Holter electrocardiogram, electrophysiologic study, or delivery of implantable cardioverter defibrillator shock. Serum angiotensin-converting enzyme and lysozyme concentrations were within normal limits in most patients in both groups. CONCLUSIONS: Activity of sarcoid granulomas may be associated with the occurrence of VT. Gallium-67 scintigraphy reflects the activity of sarcoid granulomas and thus is useful for evaluation of cardiac sarcoidosis in patients with potential VT.

Adrenal Cortex Hormones↗

Oxygen therapy prevents ventricular arrhythmias in patients with congestive heart failure and sleep apnea.

BACKGROUND: Although ventricular arrhythmia is critical for the prognosis of patients with severe congestive heart failure (CHF), it is difficult to control the arrhythmia using conservative therapies. However, many CHF patients also have sleep apnea syndrome (SAS) and oxygen supply improves their prognosis. The beneficial effects of oxygen treatment for ventricular arrhythmia have not yet been clarified, so the present study was designed to evaluate the effects of oxygen treatment for premature ventricular contraction (PVC). METHODS AND RESULTS: Patients with CHF and SAS were divided into 3 groups: (1) the "PVC declined" group that included patients who had frequent PVCs and oxygen treatment that suppressed the number of PVC; (2) the "PVC not affected" group that included patients who had frequent PVCs and oxygen treatment did not affect the number of PVC; and (3) the "few PVC" group that included patients who had no or few PVCs. The group 1 patients showed higher apnea-hypopnea index, standard deviation of all R-R intervals, left ventricular ejection fraction, and brain natriuretic peptide levels than the patients in group 2. Oxygen treatment in group 3 did not affect the PVC frequency. CONCLUSIONS: Oxygen treatment may be useful for preventing ventricular arrhythmia in selected patients with CHF and SAS.

Aged↗

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↗

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↗

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↗

Oral cibenzoline reduces postoperative atrial fibrillation in coronary artery bypass grafting.

OBJECTIVE: The objective of the present study was to investigate the effectiveness of postoperative oral administration of cibenzoline for the prevention of atrial fibrillation (AF) in coronary artery bypass grafting (CABG). METHODS: A total of 39 patients who underwent isolated CABG from September 2000 to February 2001 and who took oral cibenzoline (300 mg per day for 10 days beginning immediately after surgery) were compared to 59 patients who underwent surgery in our department 8 months prior to the study and who did not take cibenzoline for incidence of postoperative AF. Exclusion criteria encompassed age (>80 years), low ejection fraction (<30%), high serum creatinine level (>2.0 mg/dL), and history of supraventricular arrhythmia with or without treatment by anti-arrhythmic drugs. RESULTS: Postoperative AF occurred in 2 patients in the cibenzoline group (2/35, 5.7%) and 20 patients in the control group (20/59, 33.9%). There were significant differences in the incidence of postoperative AF (p = 0.002). Multivariate analysis revealed that the administration of cibenzoline reduced the incidence of AF significantly, and that a large number of bypass grafts significantly contributed to postoperative AF in CABG. The number of bypass grafts was significantly larger in the cibenzoline group, indicating that cibenzoline administration significantly suppresses the incidence of AF after CABG in high-risk patients. CONCLUSIONS: Postoperative administration of oral cibenzoline for 10 days is one effective method for the prevention of AF after CABG.

Administration, Oral↗

Correlation between electroencephalography and heart rate variability during sleep.

It is known that autonomic nervous activities change in correspondence with sleep stages. However, the characteristics of continuous fluctuations in nocturnal autonomic nerve tone have not been clarified in detail. The study aimed to determine the possible correlation between the electroencephalogram (EEG) and autonomic nervous activities, and to clarify in detail the nocturnal fluctuations in autonomic nerve activities. Overnight EEGs and electrocardiograms of seven healthy males were obtained. These EEGs were analyzed by fast Fourier transformation algorithm to extract delta, sigma and beta power. Heart rate and heart rate variability (HRV) were calculated in consecutive 5-min epochs. The HRV indices of low frequency (LF), high frequency (HF) and LF/HF ratio were calculated from the spectral analysis of R-R intervals. The sleep stages were manually scored according to Rechtschaffen and Kales' criteria. Low frequency and LF/HF were significantly lower during non-rapid eye movement (NREM) than REM, and were lower in stages 3 and 4 than in stages 1 and 2. Furthermore, delta EEG showed inverse correlations with LF (r = - 0.44, P < 0.001) and LF/HF (r = - 0.41, P < 0.001). In contrast, HF differed neither between REM and NREM nor among NREM sleep stages. Detailed analysis revealed that correlation was evident from the first to third NREM, but not in the fourth and fifth NREM. Delta EEG power showed negative correlations with LF and LF/HF, suggesting that sympathetic nervous activities continuously fluctuate in accordance with sleep deepening and lightening.

Adult↗

Delayed thrombogenesis following radiofrequency catheter ablation.

The cause and duration of the thrombogenesis provoked by radiofrequency catheter ablation (RF-CA) was investigated by measuring the thrombin-antithrombin III complex (TAT) in 43 patients who underwent RF-CA and in 20 control subjects who underwent an electrophysiologic study. Blood samples were collected at 7 different times: before introducing the sheaths, during the ablation procedure and at 30 min, 6 and 24h, and 3 and 6 days after the procedure. Hepatocyte growth factor (HGF) was simultaneously measured in the ablation group. Plasma TAT concentration exhibited a double peaked pattern in the ablation group: the first peak occurred during the ablation procedure (42.8+/-15.5 ng/ml), and the second peak 3 days later. Plasma TAT at 3 days after the procedure was significantly higher than that of the control group (21.3+/-19.0 vs 2.5+/-1.4, p=0.0003). The first peak significantly correlated with the procedure time prior to the administration of heparin (r=0.669), but the second peak did not (r=0.132). A subgroup with a serum HGF >0.40 ng/ml at 6 h after the procedure exhibited a significantly high second peak. The thrombogenesis caused by RF-CA has 2 phases; in the acute phase, there is hemostasis during placement of the catheters, and in the delayed phase thrombogenesis is the result of endothelial damage from the RF current.

Adult↗