The specialized myocytes of the ventricular conduction system (VCS) coordinate ventricular contraction and are critical for efficient pumping by the heart. Impaired VCS conduction is characteristic of inherited forms of cardiac conduction disorders. Here we show that the Iroquois homeobox 3 (Irx3) transcription factor is preferentially expressed in the developing and mature VCS. Loss of Irx3 in mice results in slowed VCS conduction and prolonged QRS duration with right bundle branch block, caused by reduction (42%) in VCS-specific connexin 40 (Cx40) expression and VCS fiber hypoplasia, absent in littermate controls. Therefore, we show that the role of Irx3 in the heart is two-fold, whereby Irx3 (1) indirectly regulates Cx40 gene expression, by repressing a repressor of Cx40 transcript, and (2) controls VCS maturation, possibly in an Nkx2-5-dependent manner. To our knowledge, this is the first report of a role for Irx3 in regulating the development and function of the VCS.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成4年10月19日 狩野良雄氏の博士論文として提出された

Thesis (Ph. D.)--Cornell University, January, 2007. / Vita. Includes bibliographical references.

Thesis (M.S.)--University of Alabama at Birmingham, 2006. / Thesis not released until Summer 2007. Description based on contents viewed Oct. 5, 2007; title from title screen. Includes bibliographical references.

Restrictive cardiomyopathy (RCM) is a heart muscle disease, characterized by diastolic dysfunction. The present dissertation is to understand the mechanisms underlyijng the initiation of diastolic dysfunction and the fast disease progression to early death in a RCM mouse model, the transgenic cTnI193His mouse... These data showed that myocardial ischemia occurred after diastolic dysfunction and before systolic dysfunction which proceeded congestive heart failure. The results demonstrate that myocardial ischemia causing cardiomycete death is a link between the initial diastolic dysfunction and late-stage systolic dysfunction, and accelerates the disease progression to fatal heart failure in the early age. / by Yuejin Li. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Utilizou-se 30 corações de gatos sem raça definida, machos e fêmeas, adultos de idades variadas que não portavam nenhuma afecção cardíaca. Os corações foram injetados pela aorta torácica com Neoprene Latex 450, corados com pigmento vermelho. Verificou-se quando do predomínio da vascularização ventricular do tipo esquerda (63,34%) que a região irrigada pelo nó sinoatrial fica predominantemente na dependência do ramo proximal atrial direito (78,9%) ou com menor freqüência pelo ramo proximal atrial esquerdo (21,1%). Quando ocorreu a vascularização ventricular do tipo equilibrada (33,34%), a região ocupada pelo nó sinoatrial ficou na dependência mais frequentemente do ramo proximal atrial direito (80%), ou com menor freqüência a nutrição do nó se deu pelo ramo proximal atrial esquerdo (20%). Em um caso isolado, onde ocorreu a vascularização ventricular do tipo direita (3,34%), a nutrição da área ocupada pelo nó sinoatrial, ficou na dependência exclusiva do ramo intermédio atrial direito. Estes resultados indicam que nesta espécie não existe nenhuma relação entre a irrigação do nó sinoatrial e o tipo de vascularização ventricular. / We analyzed 30 hearts of cats without pedigree, males and females, adults of several ages. They were not carrying any heart problems. The hearts were injected by the thoracic aorta with Neoprene Latex 450 and stained with red pigment. We analyzed the prevalence of ventricular vascularization of the left type (63.34%) the irrigated region by the sinoatrial node was predominantly in the dependency of the Ramus proximalis atrii dextri (78.9%) or with less frequency by Ramus proximalis atrii sinister (21.1%). When occurred the ventricular vascularization of the type balanced (33.34%), the region occupied by the sinoatrial node was in the responsibility more often of the Ramus proximalis atrii dextri (80%) or with less frequency the nutrition of the sinoatrial node occurred by Ramus proximalis atril sinister (20%). In a singlecase, where we observed the ventricular vascularization of the right type (3.34%), the nutrition of the area occupied by the sinoatrial node, was the exclusive dependence of the Ramus intermedius atril dextri. These results showed that this specie there are no relationship between both the sinoatrial node irrigation and the type of ventricular vascularization, therefore, the nutrition of the sinoatrial node does not depend on the type of the ventricles vascularization.

Tvarkingą širdies darbą užtikrina širdies laidžioji sistema (ŠLS). Ją pažeidus sutrinka širdies darbas. Pažeidimo rizika atsiranda operacijos metu, kadangi ŠLS yra raumeninės kilmės audinys ir vizualiai neatskiriamas nuo aplinkinių audinių. ŠLS pažeidimo galima būtų išvengti, jei būtų žinomas tikslus ŠLS išsidėstymas arba egzistuotų ŠLS vaizdinimo metodika. Deja, bet atskirų ŠLS dalių tikslus išsidėstymas vis dar tikslinamas, o patologijų atvejais apskritai nėra žinomas. ŠLS vaizdinimo metodikos, tinkančios in vivo taikymams, taipogi nėra. Atlikus širdies audinių tyrimus nustoviąja fluorescencine spektroskopija nustatyti charakteringi intensyvumų skirtumai. Remiantis šiais skirtumais sukurta ŠLS atskyrimo metodika, paremta intensyvumų santykių skaičiavimu. Suskaičiuota vertė R = I(330)/I(380) yra skirtinga ŠLS, miokardui (MK) ir jungiamąjam audiniui (JA).Tokia metodika yra nejautri tyrimo sąlygoms ir gali būti naudojama ŠLS nustatymui. Ištyrus širdies audinius laikinės skyros spektroskopija nustatyta, kad ŠLS ir MK fluorescencijos gyvavimo trukmė bei santykinė sudėtis reikšmingai nesiskiria, tuo tarpu JA ir ŠLS tiek fluorescencijos gyvavimo trukmės, tiek santykinė komponentinė sudėtis yra skirtinga. Ištyrus širdies audinius konfokaliniu atspindžio mikroskopu nustatyta, jog dėl skirtingų šviesą atspindinčių komponentų bei skirtingo jų išsidėstymo galima identifikuoti MK, JA, Purkinje ląsteles ir ŠLS pluoštus. Atlikus tyrimus in vivo nustatyta, jog operacijos metu... [toliau žr. visą tekstą] / Rhythmical contraction of the heart is controlled by the cardiac conduction system (CCS). However, this highly important system visually could not be distinguished from the surrounding heart tissues – myocardium (MC) and connective tissue (CT); therefore during surgical procedures CCS could be damaged. The reliable method for CCS identification either in vivo or ex vivo does not exist therefore there is a definite need for developing a CCS imaging method. Fluorescence spectroscopy studies of cardiac tissues revealed, that most distinct spectral differences between CCS and the surrounding tissues were observed in 400 nm – 550 nm region under excitation from 330 nm – 380 nm region. The visualization method, based on the intensity ratios calculated for two excitation wavelengths, has been established. The calculated ratio R = I(330)/I(380) is different for CCS, CT and MC tissues, therefore the method may be used for identification of CCS. Time resolved fluorescence spectroscopy revealed no significant difference in composition and lifetimes between CCS and MC. On the other hand, the lifetimes and the relative spectral composition of CT differed significantly from those of CCS. Reflection confocal microscopy allows visualizing MC, CT, Purkinje cells and CCS bundles because of different reflection properties of tissue components and their specific distribution inside the tissue. The results of in vivo performed procedure revealed, that the distribution of fluorescence intensities... [to full text]

Rhythmical contraction of the heart is controlled by the cardiac conduction system (CCS). However, this highly important system visually could not be distinguished from the surrounding heart tissues – myocardium (MC) and connective tissue (CT); therefore during surgical procedures CCS could be damaged. The reliable method for CCS identification either in vivo or ex vivo does not exist therefore there is a definite need for developing a CCS imaging method. Fluorescence spectroscopy studies of cardiac tissues revealed, that most distinct spectral differences between CCS and the surrounding tissues were observed in 400 nm – 550 nm region under excitation from 330 nm – 380 nm region. The visualization method, based on the intensity ratios calculated for two excitation wavelengths, has been established. The calculated ratio R = I(330)/I(380) is different for CCS, CT and MC tissues, therefore the method may be used for identification of CCS. Time resolved fluorescence spectroscopy revealed no significant difference in composition and lifetimes between CCS and MC. On the other hand, the lifetimes and the relative spectral composition of CT differed significantly from those of CCS. Reflection confocal microscopy allows visualizing MC, CT, Purkinje cells and CCS bundles because of different reflection properties of tissue components and their specific distribution inside the tissue. The results of in vivo performed procedure revealed, that the distribution of fluorescence intensities... [to full text] / Tvarkingą širdies darbą užtikrina širdies laidžioji sistema (ŠLS). Ją pažeidus sutrinka širdies darbas. Pažeidimo rizika atsiranda operacijos metu, kadangi ŠLS yra raumeninės kilmės audinys ir vizualiai neatskiriamas nuo aplinkinių audinių. ŠLS pažeidimo galima būtų išvengti, jei būtų žinomas tikslus ŠLS išsidėstymas arba egzistuotų ŠLS vaizdinimo metodika. Deja, bet atskirų ŠLS dalių tikslus išsidėstymas vis dar tikslinamas, o patologijų atvejais apskritai nėra žinomas. ŠLS vaizdinimo metodikos, tinkančios in vivo taikymams, taipogi nėra. Atlikus širdies audinių tyrimus nustoviąja fluorescencine spektroskopija nustatyti charakteringi intensyvumų skirtumai. Remiantis šiais skirtumais sukurta ŠLS atskyrimo metodika, paremta intensyvumų santykių skaičiavimu. Suskaičiuota vertė R = I(330)/I(380) yra skirtinga ŠLS, miokardui (MK) ir jungiamąjam audiniui (JA).Tokia metodika yra nejautri tyrimo sąlygoms ir gali būti naudojama ŠLS nustatymui. Ištyrus širdies audinius laikinės skyros spektroskopija nustatyta, kad ŠLS ir MK fluorescencijos gyvavimo trukmė bei santykinė sudėtis reikšmingai nesiskiria, tuo tarpu JA ir ŠLS tiek fluorescencijos gyvavimo trukmės, tiek santykinė komponentinė sudėtis yra skirtinga. Ištyrus širdies audinius konfokaliniu atspindžio mikroskopu nustatyta, jog dėl skirtingų šviesą atspindinčių komponentų bei skirtingo jų išsidėstymo galima identifikuoti MK, JA, Purkinje ląsteles ir ŠLS pluoštus. Atlikus tyrimus in vivo nustatyta, jog operacijos metu... [toliau žr. visą tekstą]

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 5 uppsatser.

Utilizou-se 30 corações de gatos sem raça definida, machos e fêmeas, adultos de idades variadas que não portavam nenhuma afecção cardíaca. Os corações foram injetados pela aorta torácica com Neoprene Latex 450, corados com pigmento vermelho. Verificou-se quando do predomínio da vascularização ventricular do tipo esquerda (63,34%) que a região irrigada pelo nó sinoatrial fica predominantemente na dependência do ramo proximal atrial direito (78,9%) ou com menor freqüência pelo ramo proximal atrial esquerdo (21,1%). Quando ocorreu a vascularização ventricular do tipo equilibrada (33,34%), a região ocupada pelo nó sinoatrial ficou na dependência mais frequentemente do ramo proximal atrial direito (80%), ou com menor freqüência a nutrição do nó se deu pelo ramo proximal atrial esquerdo (20%). Em um caso isolado, onde ocorreu a vascularização ventricular do tipo direita (3,34%), a nutrição da área ocupada pelo nó sinoatrial, ficou na dependência exclusiva do ramo intermédio atrial direito. Estes resultados indicam que nesta espécie não existe nenhuma relação entre a irrigação do nó sinoatrial e o tipo de vascularização ventricular. / We analyzed 30 hearts of cats without pedigree, males and females, adults of several ages. They were not carrying any heart problems. The hearts were injected by the thoracic aorta with Neoprene Latex 450 and stained with red pigment. We analyzed the prevalence of ventricular vascularization of the left type (63.34%) the irrigated region by the sinoatrial node was predominantly in the dependency of the Ramus proximalis atrii dextri (78.9%) or with less frequency by Ramus proximalis atrii sinister (21.1%). When occurred the ventricular vascularization of the type balanced (33.34%), the region occupied by the sinoatrial node was in the responsibility more often of the Ramus proximalis atrii dextri (80%) or with less frequency the nutrition of the sinoatrial node occurred by Ramus proximalis atril sinister (20%). In a singlecase, where we observed the ventricular vascularization of the right type (3.34%), the nutrition of the area occupied by the sinoatrial node, was the exclusive dependence of the Ramus intermedius atril dextri. These results showed that this specie there are no relationship between both the sinoatrial node irrigation and the type of ventricular vascularization, therefore, the nutrition of the sinoatrial node does not depend on the type of the ventricles vascularization.