Biomedical subjects

Tetsuo Betsuyaku

Publications and source records attributed to Tetsuo Betsuyaku.

7 recordsLinked to original sources

PubMed2005

Overexpression of cardiac connexin45 increases susceptibility to ventricular tachyarrhythmias in vivo.

Electrophysiological remodeling involving gap junctions has been demonstrated in failing hearts and may contribute to intercellular uncoupling, delayed conduction, enhanced arrhythmias, and vulnerability to sudden death in patients with heart failure. Recently, we showed that failing human hearts exhibit marked increases in connexin45 (Cx45) expression in addition to previously documented decreases in connexin43 (Cx43) expression. Each of these changes results in reduced gap junction coupling. The objective of the present study was to examine functional consequences of increased Cx45 in cardiac gap junctions. Transgenic mice with cardiac-selective overexpression of the developmentally downregulated cardiac connexin, connexin45 (Cx45OE mice) were subjected to in vivo electrophysiology studies in which an intracardiac catheter was used to induce ventricular arrhythmias in anesthetized mice, and in which ambulatory ECG monitoring was used to detect spontaneous arrhythmias in unanesthetized mice. Hearts were analyzed by TaqMan RT-PCR, immunostaining, immunoblotting, and echocardiography. Lucifer yellow and neurobiotin dye transfer was used to assess coupling in transgenic and control myocyte cultures. Cx45 mRNA was two orders of magnitude greater in Cx45OE mice. Cx45-immunoreactive signal at gap junctions increased twofold and total Cx45 protein by immunoblotting increased 25% in Cx45OE mice compared with nontransgenic littermate controls. Functionally, Cx45OE mice exhibited more inducible ventricular tachycardia than controls but did not exhibit any other functional or structural derangements as assessed by echocardiography. Ventricular myocytes isolated from Cx45OE mice exhibited diminished intercellular transfer of Lucifer yellow dye and increased transfer of neurobiotin, consistent with altered cell-to-cell communication. Thus increased myocardial expression of Cx45 results in remodeling of intercellular coupling and greater susceptibility to ventricular arrhythmias in vivo.

Animals↗

PubMed2004

Positional ventricular tachycardia.

A 60-year-old man showed nonsustained repetitive monomorphic VT in the left lateral position, but this was terminated by deep inspiration. Echocardiography and MRI demonstrated a false tendon extending from the apex to the basal septum where the VT could have originated. Spontaneous remission occurred during the 16-year follow-up.

Follow-Up Studies↗

PubMed2004

Percutaneous coronary intervention for central sleep apnoea with ischaemic cardiomyopathy.

Central sleep apnoea is often recognized in patients with heart failure. Although the medical treatment to improve cardiac function is effective for sleep apnoea, direct evidence that improved cardiac function ameliorates sleep apnoea has not been reported due to the fact that a particular drug may affect a multitude of organs. We present a chronic heart failure patient with central sleep apnoea whose nocturnal desaturation was improved by percutaneous coronary intervention that resulted in improved cardiac function. This is the first case where percutaneous coronary intervention improved sleep apnoea, suggesting that the improved cardiac function led to amelioration of sleep apnoea.

Angioplasty, Balloon, Coronary↗

PubMed2002

Cardiac structure and function in young and senescent mice heterozygous for a connexin43 null mutation.

Downregulation of connexin43 (Cx43) in the failing heart has been implicated not only in arrhythmogenesis but in contractile dysfunction as well. Cx43-deficient mice exhibit reduced baseline conduction velocity and increased arrhythmias in response to ischemia. However, it is not known whether Cx43-deficient mice have any abnormalities in contractile function or, furthermore, whether cardiac dysfunction may be manifested in Cx43-deficient mice with advancing age. Therefore, we analyzed echocardiographic images from young and senescent Cx43-deficient C57BL/6Jx129 mice compared to wild-type littermate controls. Only a few, modest genotype-related differences were observed. LV wall thickness during systole and % fractional shortening were diminished by 8-10% in Cx43-deficient v wild-type mice. Aging alone had a greater effect on cardiac structure and function. LV mass and relative wall thickness were significantly increased in senescent v young mice independent of genotype. Percent fractional shortening and LV internal chamber dimension were significantly reduced in senescent v young mice. Thus, aging in mice, as in humans, is associated with concentric remodeling, mild systolic dysfunction and fibrosis. Although diminished Cx43 expression could contribute to contractile dysfunction in patients with advanced heart failure, genetic deficiency in Cx43 does not appear significantly to alter cardiac structure or function even in aged mice.

Aging↗

PubMed2002

Redistribution of connexin45 in gap junctions of connexin43-deficient hearts.

OBJECTIVE: Adult ventricular myocytes express two gap junction channel proteins: connexin43 (Cx43) and connexin45 (Cx45). Cx43-deficient mice exhibit slow ventricular epicardial conduction, suggesting that Cx43 plays an important role in intercellular coupling in the ventricle. Cx45 is much less abundant than Cx43 in working ventricular myocytes. Its role in ventricular conduction has not been defined, nor is it known whether expression or distribution of Cx45 is altered in Cx43-deficient mice. The present study was undertaken to determine (1) whether expression of Cx45 is upregulated and (2) whether gap junction structure and distribution are altered in Cx43-deficient mice. METHODS: Ventricular tissue from neonatal Cx43(+/+), Cx43(+/-) and Cx43(-/-) and adult Cx43(+/+) and Cx43(+/-) mice was analyzed by immunoblotting and confocal immunofluorescence microscopy. RESULTS: Total Cx45 protein abundance measured by immunoblotting was not different in Cx43-deficient or null hearts compared to wild-type control hearts. However, the amount and distribution of Cx45 immunoreactive signal measured by quantitative confocal analysis were markedly reduced in both Cx43(+/-) and Cx43(-/-) hearts. CONCLUSION: Although the total content of Cx45 is not upregulated in Cx43-deficient hearts, the localization of Cx45 to cardiac gap junctions depends on the expression level of Cx43 and is dramatically altered in mice that express no Cx43.

Animals↗

PubMed2002

Echocardiographic evaluation of ventricular remodeling in a mouse model of myocardial infarction.

Gene-targeting in mice is a powerful tool to define molecular mechanisms of ischemic heart disease that determine infarct size, postinfarct left ventricular (LV) remodeling, and arrhythmogenesis. Coronary ligation in mice is becoming a widely used model of myocardial infarction (MI), but the pathophysiologic consequences of MI in mice and its relevance to human MI have not been fully elucidated. To characterize structural and functional changes during evolving MI, we analyzed 2-dimensional-based reconstruction of the left ventricle by noninvasive echocardiography obtained 1 day and 1 week after surgical ligation of the left anterior descending coronary artery in mice. Sequential 2-dimensional short-axis cineloops of the left ventricle were used to measure LV mass, and LV volumes at end-diastole and end-systole. Echocardiographic infarct size was estimated by measuring the volume of akinetic LV segments. Histologic infarct size was measured by planimetry of 9 transverse sections of each heart. There was close correlation between the 2 methods (31% +/- 20% of LV mass and 34% +/- 17% of LV area, respectively; y =.83x + 7.9, r = 0.96, P <.01). LV volumes at end diastole increased significantly between 1 day and 1 week (51 +/- 17 microL vs 78 +/- 46 microL, respectively, P <.05). The relative change in LV volumes at end diastole varied as a function of infarct size (r = 0.93, P <.01). LV mass and the extent of hypertrophy of noninfarcted segments also varied with infarct size (r = 0.92, P <.01; r = 0.90, P <.01, respectively). Thus, echocardiography is an accurate noninvasive tool for determination of infarct size and quantitative characterization of postinfarct remodeling in the mouse model of MI. Alterations in cardiac structure and function after coronary ligation in mice closely resemble pathophysiologic changes in human ischemic heart disease.

Animals↗

PubMedDate not supplied

Spontaneous and inducible ventricular arrhythmias after myocardial infarction in mice.

INTRODUCTION: Remodeling of gap junctions has been implicated in development of ventricular arrhythmias following myocardial infarction (MI) but the specific contribution of reduced electrical coupling is not known. We addressed this question using hearts from mice heterozygous for a connexin43 null allele (Cx43(+/-)). METHODS: To determine whether Cx43-deficient mice exhibit increased spontaneous ventricular arrhythmias in the setting of chronic ischemic heart disease, radiofrequency transmitters were implanted in wild-type and Cx43(+/-) mice 2 days or 9 weeks after left anterior descending coronary artery ligation or sham operations. ECGs were recorded from unanesthetized, unrestrained mice 1 and 10 weeks after MI. Isolated, perfused hearts excised 1 and 10 weeks after MI were subjected to programmed electrical stimulation to induce arrhythmias. RESULTS AND CONCLUSIONS: Hearts with infarcts exhibited more spontaneous and inducible arrhythmias, but there was no significant difference between wild-type and Cx43-deficient mice. Fewer hearts exhibited spontaneous ventricular tachycardia (VT) in vivo than were inducible in vitro, suggesting that structural and functional substrates for inducible VT in isolated hearts may not be sufficient for initiation and maintenance of sustained VT in vivo. Previous studies have shown that Cx43-deficient mice exhibit more VT than wild-type mice during acute regional ischemia. Mice with MI exhibit increased arrhythmias. However, reduced coupling in Cx43-deficient mice does not significantly enhance spontaneous or inducible VT after MI.

Animals↗