RESUMEN
Acetogens grow autotrophically and use hydrogen (H2) as the energy source to fix carbon dioxide (CO2). This feature can be applied to gas fermentation, contributing to a circular economy. A challenge is the gain of cellular energy from H2 oxidation, which is substantially low, especially when acetate formation coupled with ATP production is diverted to other chemicals in engineered strains. Indeed, an engineered strain of the thermophilic acetogen Moorella thermoacetica that produces acetone lost autotrophic growth on H2 and CO2. We aimed to recover autotrophic growth and enhance acetone production, in which ATP production was assumed to be a limiting factor, by supplementing with electron acceptors. Among the four selected electron acceptors, thiosulfate and dimethyl sulfoxide (DMSO) enhanced both bacterial growth and acetone titers. DMSO was the most effective and was further analyzed. We showed that DMSO supplementation enhanced intracellular ATP levels, leading to increased acetone production. Although DMSO is an organic compound, it functions as an electron acceptor, not a carbon source. Thus, supplying electron acceptors is a potential strategy to complement the low ATP production caused by metabolic engineering and to improve chemical production from H2 and CO2.
Asunto(s)
Dióxido de Carbono , Moorella , Dióxido de Carbono/metabolismo , Acetona/metabolismo , Electrones , Dimetilsulfóxido/metabolismo , Hidrógeno/metabolismo , Moorella/genética , Moorella/metabolismo , Oxidantes/metabolismo , Adenosina Trifosfato/metabolismoRESUMEN
We performed RNA-seq analyses of mRNA isolated from five organs, liver, bone, heart, kidney and blood at the pre-symptomatic state of klotho mice with/without administration of a Japanese traditional herbal medicine, juzentaihoto (JTT). Data of differentially expressed genes (DEG) with/without JTT was included. Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions. We collected data in which retained-introns were accumulated in a particular set of genes of these organs, and showed that among these retained introns in the liver and bone a subset was recovered to the normal state by the medicine. All of the data present changes of molecular events on the levels of metabolites, proteins and gene expressions observed at the pre- symptomatic state of aging in klotho mice with/without JTT. The research article related to this Data in Brief is published in GENE entitled as "Intron retention as a new pre-symptomatic marker of aging and its recovery to the normal state by a traditional Japanese herbal medicine".
RESUMEN
Intron retention (IR) is an important regulatory mechanism that affects gene expression and protein functions. Using klotho mice at the pre-symptomatic state, we discovered that retained-introns accumulated in several organs including the liver and that among these retained introns in the liver a subset was recovered to the normal state by a Japanese traditional herbal medicine. This is the first report of IR recovery by a medicine. IR-recovered genes fell into two categories: those involved in liver-specific metabolism and in splicing. Metabolome analysis of the liver showed that the klotho mice were under starvation stress. In addition, our differentially expressed gene analysis showed that liver metabolism was actually recovered by the herbal medicine at the transcriptional level. By analogy with the widespread accumulation of intron-retained pre-mRNAs induced by heat shock stress, we propose a model in which retained-introns in klotho mice were induced by an aging stress and in which this medicine-related IR recovery is indicative of the actual recovery of liver-specific metabolic function to the healthy state. Accumulation of retained-introns was also observed at the pre-symptomatic state of aging in wild-type mice and may be an excellent marker for this state in general.
Asunto(s)
Envejecimiento/genética , Perfilación de la Expresión Génica/métodos , Marcadores Genéticos/efectos de los fármacos , Glucuronidasa/genética , Hígado/química , Fitoquímicos/administración & dosificación , Envejecimiento/efectos de los fármacos , Empalme Alternativo , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Respuesta al Choque Térmico , Intrones , Japón , Proteínas Klotho , Hígado/efectos de los fármacos , Medicina Tradicional , Metabolómica , Ratones , Modelos Animales , Fitoquímicos/farmacología , Precursores del ARN/genética , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: Atrial tachycardia (AT) may develop after biatrial surgical ablation of atrial fibrillation. However, the mechanism has not been determined in detail. OBJECTIVE: We aimed to determine the mechanism and treatment of postoperative AT following biatrial surgical ablation in relation to the design and durability of the surgical lesion sets. METHODS: An electrophysiologic study and radiofrequency ablation were performed in 34 consecutive patients (23 male, mean age of 63 ± 9.4 years) who were referred for AT that developed late after biatrial surgical ablation. RESULTS: The mechanism of a total of 53 ATs was macroreentry in 30, a focal mechanism in 20, and localized reentry in 1, and could not be determined in 2. The cause of the macroreentrant AT was residual conduction across a surgical lesion, most of which was located at the annular end of the mitral (n = 18) or tricuspid isthmus incision (n = 7), where cryoablation was applied during the surgery. We did not find any gaps across the cut-and-sew lesions. Radiofrequency (RF) applications to the gap, or an alternative site to transect the circuit, or the earliest activation site of the focus was effective for 48 ATs (91%). After a total of 1.3 ± 0.6 RF sessions, 27 patients (79%) were free of AT (n = 2) or AF (n = 5) during a follow-up period of 50 ± 49 months. CONCLUSIONS: Macroreentry due to a gap in a surgical lesion and focal AT were the major mechanisms of AT in patients after biatrial surgical ablation. Radiofrequency ablation of those ATs is feasible.
Asunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter , Criocirugía , Complicaciones Posoperatorias , Taquicardia Supraventricular , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Mapeo del Potencial de Superficie Corporal/métodos , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Criocirugía/efectos adversos , Criocirugía/métodos , Técnicas Electrofisiológicas Cardíacas/métodos , Femenino , Frecuencia Cardíaca , Humanos , Japón , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/fisiopatología , Estudios Retrospectivos , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/etiología , Taquicardia Supraventricular/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: The T-type Ca(2+) channel (I(CaT)) blocker mibefradil prevents AF-promoting remodeling occurring with atrial tachycardia, an action that has been attributed to I(CaT) inhibition. However, mibefradil has other effects, including ability to inhibit L-type Ca(2+) channels, Na(+) channels and cytochromes. Thus, the relationship between I(CaT) inhibition and remodeling protection in AF is still unknown. OBJECTIVE: To assess the effects of a novel highly selective Cav3 (I(CaT)) blocker, AZ9112, on atrial remodeling induced by 1-week atrial tachypacing (AT-P) in dogs. METHODS: Mongrel dogs were subjected to AT-P at 400 bpm for 7 days, with atrioventricular-node ablation and right-ventricular demand pacing (80 bpm) to control ventricular rate. Four groups of dogs were studied in investigator-blinded fashion: (1) a sham group, instrumented but without tachypacing or drug therapy (n = 5); (2) a placebo group, tachypaced but receiving placebo (n = 6); (3) a positive control tachypacing group receiving mibefradil (n = 6); and (4) a test drug group, subjected to tachypacing during oral treatment with AZ9112 (n = 8). RESULTS: One-week AT-P decreased atrial effective refractory period (ERP) at 6 of 8 sites and diminished rate-dependent atrial ERP abbreviation. Mibefradil eliminated AT-P-induced ERP-abbreviation at 4 of these 6 sites, while AZ9112 failed to affect ERP at any. Neither drug significantly affected AF vulnerability or AF duration. CONCLUSIONS: I(CaT) blockade with the highly selective compound AZ9112 failed to prevent rate-related atrial remodeling. Thus, prevention of atrial electrophysiological remodeling by mibefradil cannot be attributed exclusively to I(CaT) blockade. These results indicate that I(CaT) inhibition is not likely to be a useful approach for AF therapy.
Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Remodelación Atrial/efectos de los fármacos , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo T/efectos de los fármacos , Atrios Cardíacos/efectos de los fármacos , Potenciales de Acción , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/metabolismo , Fibrilación Atrial/fisiopatología , Bloqueadores de los Canales de Calcio/farmacocinética , Canales de Calcio Tipo T/metabolismo , Estimulación Cardíaca Artificial , Modelos Animales de Enfermedad , Perros , Técnicas Electrofisiológicas Cardíacas , Atrios Cardíacos/metabolismo , Atrios Cardíacos/fisiopatología , Mibefradil/farmacología , Periodo Refractario Electrofisiológico/efectos de los fármacos , Factores de TiempoRESUMEN
BACKGROUND: Coronary artery disease predisposes to atrial fibrillation (AF), but the effects of chronic atrial ischemia/infarction on AF-related substrates are unknown. METHODS AND RESULTS: Regional right atrial myocardial infarction (MI) was created in 40 dogs by ligating an artery that supplies the right atrial free wall and not the ventricles; 35 sham dogs with the same artery isolated but not ligated were controls. Dogs were observed 8 days after MI and subjected to open-chest study, in vitro optical mapping, and/or cell isolation for patch-clamp and Ca(2+) imaging on day 8. Holter ECGs showed more spontaneous atrial ectopy in MI dogs (eg, 662±281 on day 7 versus 34±25 ectopic complexes per day at baseline; 52±21 versus 1±1 atrial tachycardia episodes per day). Triggered activity was increased in MI border zone cells, which had faster decay of caffeine-evoked Ca(2+) transients and enhanced (by ≈73%) Na(+)-Ca(2+) exchange current. Spontaneous Ca(2+) sparks (confocal microscopy) occurred under ß-adrenergic stimulation in more MI dog cells (66±9%) than in control cells (29±4%; P<0.01). Burst pacing induced long-lasting AF in MI dogs (1146±259 versus 30±14 seconds in shams). Increased border zone conduction heterogeneity was confirmed by both bipolar electrode mapping in vivo and optical mapping. Optical mapping demonstrated stable border zone reentry in all 9 MI preparations but in none of 6 shams. Border zone tissue showed increased fibrous tissue content. CONCLUSIONS: Chronic atrial ischemia/infarction creates substrates for both spontaneous ectopy (Ca(2+)-release events, increased Na(+)-Ca(2+) exchange current) and sustained reentry (conduction abnormalities that anchor reentry). Thus, chronic atrial infarction in dogs promotes both AF triggers and the substrate for AF maintenance. These results provide novel insights into potential AF mechanisms in patients with coronary artery disease.
Asunto(s)
Fibrilación Atrial/fisiopatología , Estenosis Coronaria/fisiopatología , Infarto del Miocardio/fisiopatología , Animales , Fibrilación Atrial/metabolismo , Calcio/metabolismo , Enfermedad Crónica , Estenosis Coronaria/metabolismo , Modelos Animales de Enfermedad , Perros , Técnicas Electrofisiológicas Cardíacas , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Intercambiador de Sodio-Calcio/metabolismoAsunto(s)
Arritmias Cardíacas/diagnóstico , Mapeo del Potencial de Superficie Corporal/métodos , Técnicas Electrofisiológicas Cardíacas/métodos , Imagenología Tridimensional/métodos , Adolescente , Anciano , Arritmias Cardíacas/cirugía , Ablación por Catéter , Electrocardiografía , Humanos , Magnetismo , MasculinoRESUMEN
BACKGROUND: Other than bundle branch reentry and interfascicular reentry, monomorphic postmyocardial infarction (post-MI) reentrant ventricular tachycardia (VT) including the His-Purkinje system has not been reported. Verapamil-sensitive idiopathic left VT includes the left posterior Purkinje fibers but develops in patients without structural heart disease. OBJECTIVES: The purpose of this study was to describe a novel mechanism of reentrant VT arising from the left posterior Purkinje fibers in patients with a prior MI. METHODS: The study consisted of four patients with a prior MI and symptomatic heart failure who underwent electrophysiologic study and catheter ablation for VT showing right bundle branch block (n = 3) or atypical left bundle branch block (n = 1) morphology with superior axis. In two patients, the VT frequently emerged during the acute phase of MI and required emergency catheter ablation. RESULTS: Clinical VT was reproducibly induced by programmed stimulation. In three patients, both diastolic and presystolic Purkinje potentials were sequentially recorded along the left ventricular posterior septum during the VT, whereas in the fourth patient, only presystolic Purkinje potentials were observed. During entrainment pacing from the right atrium, diastolic Purkinje potentials were captured orthodromically and demonstrated decremental conduction properties, whereas presystolic Purkinje potentials were captured antidromically and appeared between the His and QRS complex. Radiofrequency energy delivered at the site exhibiting a Purkinje-QRS interval of 58 +/- 26 ms successfully eliminated the VTs without provoking any conduction disturbances. CONCLUSION: Reentrant monomorphic VT originating from the left posterior Purkinje fibers, which is analogous to idiopathic left VT, can develop in the acute or chronic phase of MI. Catheter ablation is highly effective in eliminating this VT without affecting left ventricular conduction.
Asunto(s)
Infarto del Miocardio/fisiopatología , Ramos Subendocárdicos/fisiopatología , Taquicardia Ventricular/fisiopatología , Anciano , Mapeo del Potencial de Superficie Corporal , Bloqueo de Rama/etiología , Bloqueo de Rama/fisiopatología , Estimulación Cardíaca Artificial , Ablación por Catéter , Factores de Confusión Epidemiológicos , Diagnóstico Diferencial , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/cirugía , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/epidemiología , Infarto del Miocardio/cirugía , Ramos Subendocárdicos/cirugía , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/epidemiología , Taquicardia Ventricular/etiología , Taquicardia Ventricular/cirugíaRESUMEN
BACKGROUND: Atrial tachycardia (AT) can originate from the proximal coronary sinus (CS). However, detailed electrophysiologic characteristics of the tachycardia are not available. OBJECTIVES: We describe the electrophysiologic characteristics, response to adenosine 5'-triphosphate, and results of radiofrequency ablation of AT with the earliest activation in the proximal CS. METHODS: In 7 of 54 patients (age 57 +/- 18 years) with nonmacroreentrant "focal" AT undergoing electrophysiologic study and radiofrequency ablation, the earliest atrial activation site was located in the proximal CS. RESULTS: The earliest activation site was inside the CS 13 +/- 3 mm from the ostium. The AT could be induced and terminated by atrial extrastimuli or burst pacing. In all patients, the AT was also terminated by a very small dose of adenosine 5'-triphosphate (4.2 +/- 1.1 mg). Rapid ventricular pacing during the tachycardia produced ventriculoatrial dissociation. Radiofrequency ablation directed at the earliest atrial activation site was effective in only three patients (group A). In the remaining four patients (group B), after the radiofrequency energy deliveries, the earliest activation site shifted to an adjacent site with a small increase in the cycle length. Three group B patients underwent successful ablation in the slow pathway region. No recurrence was observed over a follow-up period of 22 +/- 5 months. CONCLUSION: AT with earliest activation in the proximal CS is sensitive to a small dose of adenosine 5'-triphosphate. In some patients, radiofrequency applications in the slow pathway region are effective even if the local activation is not early.