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It has been suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors have cardioprotective effects during myocardial ischemia/reperfusion (I/R) independent of glucose-lowering action. However, the effects of SGLT2 inhibitors on structural damage to cardiomyocytes in the ischemic region during I/R remain unknown. We applied a microdialysis technique to the heart of anesthetized rats and investigated the effects of an SGLT2 inhibitor, dapagliflozin, on myocardial interstitial myoglobin levels in the ischemic region during coronary occlusion followed by reperfusion. Dapagliflozin was administered systemically (40 µg/body iv) or locally via a dialysis probe (100 µM and 1 mM) 30 min before coronary occlusion. In the vehicle group, coronary occlusion increased the dialysate myoglobin concentration in the ischemic region. Reperfusion further increased the dialysate myoglobin concentration. Intravenous administration of dapagliflozin reduced dialysate myoglobin concentration during ischemia and at 0-15 min after reperfusion, but local administration (100 µM and 1 mM) did not. Therefore, acute systemic administration of dapagliflozin prior to ischemia has cardioprotective effects on structural damage during I/R.
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Compuestos de Bencidrilo , Glucósidos , Daño por Reperfusión Miocárdica , Miocitos Cardíacos , Mioglobina , Animales , Compuestos de Bencidrilo/farmacología , Mioglobina/metabolismo , Glucósidos/farmacología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Ratas , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Masculino , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , MicrodiálisisRESUMEN
BACKGROUND: Noninvasive positive pressure ventilation (NIPPV) has been established as an effective treatment for heart failure. Positive airway pressure such as continuous positive airway pressure (CPAP) increases cardiac output (CO) in some patients but decreases it in others. However, the mechanism behind such unpredictable responses remains undetermined. METHODS AND RESULTS: We measured hemodynamic parameters of 38 cases using Swan-Ganz catheter before and after CPAP in chronic heart failure status. In those whose CO increased by CPAP, pulmonary vascular resistance (PVR) was significantly decreased and SpO2 significantly increased, but the other parameters were not changed. On the other hand, PVR was not changed, but systemic vascular resistance (SVR) was increased in those whose CO decreased by CPAP. To explain this phenomenon, we simulated the cardiovascular system using a cardiac model of time-varying elastance. In this model, it was indicated that CPAP decreases CO irrespective of cardiac function or filling status under constant PVR condition. However, when reduction of PVR by CPAP was taken into account, an increase in CO was expected especially in the hypervolemic and low right ventricle (RV) systolic function cases. CONCLUSIONS: CPAP would increase CO only where PVR can be reduced by CPAP therapy, especially in the case with hypervolemia and/or low RV systolic function. Understanding the underlying mechanism should help identify the patients for whom NIPPV would be effective.
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Presión de las Vías Aéreas Positiva Contínua , Insuficiencia Cardíaca , Humanos , Hemodinámica/fisiología , Gasto Cardíaco/fisiología , Corazón , Insuficiencia Cardíaca/terapiaRESUMEN
Background: The use of international telemedicine conferences for doctor-to-doctor education has increased following the coronavirus disease 2019 pandemic to ensure health and safety. Previous studies have shown that administrative tasks are an obstacle to promoting international telemedicine conferences but have not identified the type of system needed to alleviate this burden. Objective: The Asia-Pacific Advanced Network Medical Working Group (APAN-MWG) is an international telemedicine network that includes 1171 medical institutions and 3653 members as of July 21, 2021. The APAN-MWG has supported international telemedicine conferences since 2005 and implemented a program management system in 2014. The present study explores the conference organizers' tasks and evaluates the APAN-MWG management system through a survey of organizers. Methods: We developed a system called med-hok for managing conference programs, international medical institutions, and their members. We investigated all event programs using the med-hok system from June 3, 2015 to July 21, 2021. The target samples included 64 conference programs in 12 series hosted by 13 program organizers. The effectiveness of the system was evaluated using a four-point Likert scale (very good, good, poor, and very poor). The User Experience Questionnaire (UEQ) was used to assess user experience. Results: The survey response rate of the program organizers, who hosted 11 different program series in 7 Asian countries, was 92% (12/13). The administrative tasks for managing the programs were primarily handled by physicians (67%, 8/12), followed by technicians (17%, 2/12). The average program scope encompassed 7 countries, 10 institutions, and 44 members. The largest program comprised 194 members from 49 institutions in 25 countries and was managed by two physicians and one technician. Most program organizers (8/12, 67%) indicated that verifying member information was the most burdensome aspect of organizing teleconferences. Over 90% of respondents positively evaluated med-hok in the following areas: "Confirmation of institution information," "Confirmation of member information," "Confirmation of technical information," "Maintaining the latest status of the program," "Announcing and publicizing the event," and "Formatting and correcting misspellings." They rated user experience positively for all aspects (attractiveness: 1.22; practical quality: 1.42; and hedonic quality: 1.24). Conclusions: Many tasks of organizing casual international telemedicine conferences are handled by physicians and technicians with no operating funds or staff, unlike those in large academic conferences. The proposed system was found to help program organizers manage participants and communicate information effectively. These findings suggest that international telemedicine networks should implement an administrative support system to conduct program operations efficiently.
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Introduction: Telemedicine conferencing is expected to become commonly used internationally. However, national reports on internationally related telemedicine are limited, and related activities and challenges in each country are unclear. In this study, we aimed to clarify the current status and barriers to international telemedicine conferencing in Japan. Methods: The questionnaire was sent to the Internationalization Project Team (I-PT) representatives in all 43 Japanese National University Hospitals. The total of 167 assigned staff comprised 86 medical staff in charge of internationalization (MI) and 81 technical staff in telemedicine (TT). Results: The response rate was 93% (40/43 universities) from 88 staff (44 MI and 44 TT). Most respondents (75%) stated that they had not been active in international telemedicine conferencing during the past 3 years, although a videoconferencing system was installed in 93% of universities. A total of 65% respondents felt that barriers to promoting telemedicine and conferencing existed. Most (43%) respondents reported staff shortage as the most serious barrier overall. Five TT (19%) felt that the most serious barrier was difficulty with English communication, although no MI selected this as a barrier. More MI than TT felt that technical issues were the most serious barrier (MI: 4/29, TT: 1/27). Conclusions: International telemedicine conferencing was found to be insufficiently active in I-PT of Japan, although the installed equipment and technical expertise of TT seemed adequate. This indicates that merely assigning MI and TT to an I-PT is not enough and that improved cooperation between both MI and TT at each university hospital is needed. Establishment of a structured international telemedicine center in each university hospital is to be suggested to accelerate the activities in Japan.
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Telemedicina , Comunicación por Videoconferencia , Hospitales Universitarios , Humanos , Internacionalidad , Japón , Encuestas y Cuestionarios , Comunicación por Videoconferencia/estadística & datos numéricosRESUMEN
INTRODUCTION: PREDICT is a prognostication tool that calculates the potential benefit of various postsurgical treatments on the overall survival (OS) of patients with nonmetastatic invasive breast cancer. Once patient, tumor, and treatment details have been entered, the tool will show the estimated 5-, 10-, and 15-year OS outcomes, both with and without adjuvant therapies. This study aimed to conduct an external validation of the prognostication tool PREDICT version 2.2 by evaluating its predictive accuracy of the 5- and 10-year OS outcomes among female patients with nonmetastatic invasive breast cancer in Japan. METHODS: All female patients diagnosed from 2001 to 2013 with unilateral, nonmetastatic, invasive breast cancer and had undergone surgical treatment at Kyushu University Hospital, Fukuoka, Japan, were selected. Observed and predicted 5- and 10-year OS rates were analyzed for the validation population and the subgroups. Calibration and discriminatory accuracy were assessed using Chi-squared goodness-of-fit test and area under the receiver operating characteristic curve (AUC). RESULTS: A total of 636 eligible cases were selected from 1, 213 records. Predicted and observed OS differed by 0.9% (p = 0.322) for 5-year OS, and 2.4% (p = 0.086) for 10-year OS. Discriminatory accuracy results for 5-year (AUC = 0.707) and 10-year (AUC = 0.707) OS were fairly well. CONCLUSION: PREDICT tool accurately estimated the 5- and 10-year OS in the overall Japanese study population. However, caution should be used for interpretation of the 5-year OS outcomes in patients that are ≥65 years old, and also for the 10-year OS outcomes in patients that are ≥65 years old, those with histologic grade 3 and Luminal A tumors, and in those considering ETx or no systemic treatment.
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Cuidados Posoperatorios/métodos , Neoplasias de Mama Unilaterales/mortalidad , Adulto , Factores de Edad , Anciano , Antineoplásicos/uso terapéutico , Área Bajo la Curva , Distribución de Chi-Cuadrado , Femenino , Humanos , Inmunohistoquímica , Japón , Estimación de Kaplan-Meier , Antígeno Ki-67/análisis , Persona de Mediana Edad , Pronóstico , Curva ROC , Receptor ErbB-2/análisis , Tasa de Supervivencia , Factores de Tiempo , Carga Tumoral , Neoplasias de Mama Unilaterales/química , Neoplasias de Mama Unilaterales/patología , Neoplasias de Mama Unilaterales/terapiaRESUMEN
BACKGROUND: Effective education about endoscopic surgery (ES) is greatly needed for unskilled surgeons, especially at low-volume institutions, to maintain the safety of patients. We have tried to establish the remote educational system using videoconference system through the internet for education about ES to surgeons belonging to affiliate institutions. The aim of this manuscript was to report the potential to establish a comfortable remote educational system and to debate its advantages. METHODS: We established a local remote educational conference system by combining the use of a general web conferencing system and a synchronized remote video playback system with annotation function through a high-speed internet. RESULTS: During 2014-2019, we conducted 14 videoconferences to review and improve surgeons' skills in performing ES at affiliated institutions. At these conferences, while an uncut video of ES that had been performed at one of the affiliated institutions was shown, the surgical procedure was discussed frankly, and expert surgeons advised improvements. The annotation system is useful for easy, prompt recognition among the audience regarding anatomical structures and procedures that are difficult to explain verbally. CONCLUSIONS: This system is of low initial cost and offers easy participation and high-quality videos. It would therefore be a useful tool for regional ES education.
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Telecomunicaciones , Endoscopía , Humanos , Internet , Grabación en Video , Comunicación por VideoconferenciaRESUMEN
Electrical disparity can induce inefficient cardiac performance, representing an uncoordinated wall motion at an earlier activated ventricular wall: an early shortening followed by a systolic rebound stretch. Although regional contractility and distensibility modulate this pathological motion, the effect of a morphological factor has not been emphasized. Our strain analysis in 62 patients with single ventricle revealed that those with an activation delay in 60-70% of ventricular wall area suffered from cardiac dysfunction and mechanical discoordination along with prolonged QRS duration. A computational simulation with a two-compartment ventricular model also suggested that the ventricle with an activation delay in 70% of the total volume was most vulnerable to a large activation delay, accompanied by an uncoordinated motion at an earlier activated wall. Taken together, the ratio of the delayed ventricular wall has a significant impact on the pathophysiology due to an activation delay, potentially highlighting an indicator of cardiac dysfunction.
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Procedimiento de Fontan , Cardiopatías Congénitas/cirugía , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Modelos Cardiovasculares , Contracción Miocárdica , Disfunción Ventricular/fisiopatología , Función Ventricular , Adolescente , Adulto , Fenómenos Biomecánicos , Niño , Preescolar , Ecocardiografía Doppler de Pulso , Femenino , Procedimiento de Fontan/efectos adversos , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/fisiopatología , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/etiología , Humanos , Masculino , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Disfunción Ventricular/diagnóstico por imagen , Disfunción Ventricular/etiología , Adulto JovenRESUMEN
PURPOSE: To identify the incidence of extraction site incisional hernia following gastrectomy for gastric cancer and its significant risk factors, including the subcutaneous fat area. METHODS: We reviewed data gathered prospectively on patients with gastric cancer, who underwent gastrectomy between 2008 and 2012 at Kyushu University Hospital, Fukuoka, Japan. The subcutaneous fat area (SFA) and visceral fat area (VFA) were measured using axial computed tomography at the level of the L4 and L3 transverse processes, and the L2-L3 intervertebral disc. The primary endpoint of the rate of extraction site incisional hernia was based on the computed tomography and clinical data including hospital follow-up reports. RESULTS: After applying the inclusion and exclusion criteria, 320 patients were included in this retrospective analysis: 3.1% (10/320) had extraction site incisional hernias after a mean follow-up of 11 months. Multivariate analysis revealed that age and the SFA were independent risk factors (age ≥ 70.5 years: P = .013, odds ratio: 9.116, 95% confidence interval 1.581-52.553; L4 SFA ≥ 124 cm2: P = .004, odds ratio: 13.752, 95% confidence interval 2.290-82.582). CONCLUSION: Age and the SFA were independent risk factors for extraction site incisional hernia in patients undergoing gastrectomy for gastric cancer.
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Gastrectomía/efectos adversos , Hernia Incisional/etiología , Grasa Intraabdominal , Neoplasias Gástricas/cirugía , Grasa Subcutánea , Factores de Edad , Anciano , Femenino , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/patologíaRESUMEN
PURPOSE: There is no definite evidence of the feasibility and safety of laparoscopic distal gastrectomy (LDG) for patients who have undergone incomplete endoscopic resection (ER). We investigated the influence of ER prior to LDG by a propensity score matching analysis. METHODS: We retrospectively analyzed the outcomes of gastric cancer patients who underwent LDG with or without prior ER from 2000 to 2014. Propensity score matching was performed to compare the two groups of patients. RESULTS: After matching, 47 patients in the ER group and 94 patients in the non-ER group were selected from a total of 365 patients. A residual tumor was observed in 10 of 47 patients (21.3%). The mean number of dissected lymph nodes in the non-ER group (39.4 ± 14.5) was higher than that in the ER group (31.7 ± 13.5) (P = 0.003). However, other perioperative data, such as the operation time and blood loss volume were similar. The complication rate of the ER group (17.0%) and the non-ER group (9.6%) did not differ to a statistically significant extent (P = 0.2). Among these patients, 6 died during the 5-year follow-up period, but no patients showed signs of recurrence. CONCLUSION: ER prior to surgical resection showed no significant influence on postoperative complications or mortality. LDG can be safely performed to achieve radical resection after incomplete ER.
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Endoscopía Gastrointestinal/métodos , Gastrectomía/métodos , Laparoscopía/métodos , Reoperación , Neoplasias Gástricas/cirugía , Anciano , Estudios de Factibilidad , Femenino , Humanos , Escisión del Ganglio Linfático/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Estudios Retrospectivos , Seguridad , Neoplasias Gástricas/mortalidad , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: In biventricular physiology, abnormal septal motion is a hallmark of mechanical dyssynchrony in the left bundle branch block. However, in single-ventricle (SV) physiology, morphologic variations in systemic ventricles pose a challenge in evaluating the negative impact of mechanical dyssynchrony. The present study aimed to characterize the pathologic dyssynchronous contraction patterns in patients with SV. METHODS: In this retrospective study, 70 consecutive postoperative patients with SV anatomy with prolonged QRS duration (25 female patients; median age, 14 years) were enrolled. We divided each SV into two regions and analyzed independent strains using two-dimensional speckle-tracking echocardiography. From an earlier activated ventricular wall, we calculated the strain ratio (Rstrains) of two values (%) during the QRS period and the ejection period: (100 + Strainejection)/(100 + StrainQRS). We reviewed the clinical profiles, B-type natriuretic peptide plasma levels, exercise capacity, and morbidity. Six patients who underwent cardiac resynchronization therapy (CRT) were analyzed regarding changes in strain patterns and ventricular volume. RESULTS: Higher Rstrains, indicating a preceding contraction and subsequent dyskinetic dilation of the earlier activated ventricular wall, was associated with increased B-type natriuretic peptide, reduced exercise capacity, and poor outcome. However, delayed contraction of the later activated ventricular wall was not associated with the effects. Decreases in Rstrains and ventricular volume reductions were observed in all patients after CRT. CONCLUSIONS: A specific strain pattern in an earlier activated ventricular wall indicates mechanical dyssynchrony in patients with SV. This pattern is very similar to the septal flash in adult patients with left bundle branch block. This strategy might be a promising approach for selecting appropriate candidates for CRT in patients with SV.
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Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Adolescente , Bloqueo de Rama/diagnóstico por imagen , Ecocardiografía , Femenino , Insuficiencia Cardíaca/terapia , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Estudios RetrospectivosRESUMEN
Cardiac microdialysis allows the assessment of cardiac efferent vagal nerve activity from myocardial interstitial acetylcholine (ACh) levels with minimal influence on the neural control of the heart; however, a total picture of the baroreflex-mediated myocardial interstitial ACh release including the threshold and saturation pressures has yet to be quantified. In eight anesthetized Wistar-Kyoto rats, we implanted microdialysis probes in the left ventricular free wall and measured the myocardial interstitial ACh release simultaneously with efferent sympathetic nerve activity (SNA) during a carotid sinus baroreceptor pressure input between 60 and 180 mm Hg. The baroreflex-mediated ACh release approximated a positive sigmoid curve, and its threshold and saturation pressures were not significantly different from those of an inverse sigmoid curve associated with the baroreflex-mediated SNA response (threshold: 94.3 ± 8.6 vs. 99.3 ± 6.0 mm Hg; saturation: 150.0 ± 10.3 vs. 158.8 ± 5.8 mm Hg). The sympathetic and vagal systems have certain levels of activities across most of the normal pressure range.
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AIMS: To compare the effects of metoprolol and carvedilol on baroreflex-mediated sympathetic circulatory regulation. METHODS: In anesthetized Wistar-Kyoto rats, carotid sinus baroreceptor regions were isolated. Changes in sympathetic nerve activity (SNA), arterial pressure (AP), heart rate (HR), and aortic flow (AoF) in response to a staircase-wise pressure input were examined before (control) and after intravenous injection of low-dose metoprolol (2â¯mg/kg), high-dose metoprolol (10â¯mg/kg), or carvedilol (0.67â¯mg/kg) (nâ¯=â¯6 each). Peripheral vascular resistance (PVR) was calculated from mean AP divided by mean AoF. RESULTS: Low-dose metoprolol had limited effect on sympathetic AP regulation compared to control [operating-point AP (drug vs. control): 88.7⯱â¯7.1 vs. 98.3⯱â¯3.3â¯mmâ¯Hg, not significant] despite a significant bradycardic effect. Although high-dose metoprolol showed central sympathoinhibition, it increased PVR at a given SNA as a peripheral effect. Consequently, high-dose metoprolol decreased the operating-point AP slightly (96.1⯱â¯2.7 vs. 101.9⯱â¯2.7â¯mmâ¯Hg, Pâ¯<â¯0.01). Carvedilol showed no significant central sympathoinhibition at the dose examined in this study, but significantly reduced PVR at a given SNA, leading to a marked reduction in the operating-point AP (71.9⯱â¯8.2 vs. 112.6⯱â¯7.6â¯mmâ¯Hg, Pâ¯<â¯0.05). CONCLUSION: Low-dose metoprolol has limited hypotensive effect despite blockade of sympathetic HR regulation. Although high-dose metoprolol induces central sympathoinhibition, it also induces peripheral vasoconstriction that antagonizes the hypotensive effect. In contrast, carvedilol exhibits hypotensive effect mainly through peripheral vasodilation. Although carvedilol is frequently classified as a ß-blocker, its vasodilatory effect via α1-adrenergic blockade plays an important role in AP reduction or heart failure treatment.
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Barorreflejo/efectos de los fármacos , Carvedilol/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Metoprolol/administración & dosificación , Sistema Nervioso Simpático/efectos de los fármacos , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Animales , Barorreflejo/fisiología , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Electrocardiografía , Insuficiencia Cardíaca/fisiopatología , Inyecciones Intravenosas , Masculino , Ratas , Ratas Endogámicas WKY , Sistema Nervioso Simpático/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Whether the reduction of heart rate with ivabradine (IVA) could affect sympathetic activation and cardiac innervation in heart failure (HF) remains unknown. PURPOSE: The present study assessed the chronic effects of IVA and ß-blocker on the systemic and local sympathetic nervous systems of hypertensive animals with HF. METHODS AND RESULTS: The Dahl salt-sensitive rats received chronic IVA, bisoprolol (BIS), or placebo (CTL) therapy. The survival of the animal models with IVA and BIS significantly improved (median; 19.7 in IVA and 19.7 in BIS vs 17.0 weeks in CTL, P < .001). A similar decrease in 24-hour heart rate (mean; 305 in IVA and 329 in BIS vs 388 beats/min in CTL, P < .001) without effect on blood pressure, and an improvement in the left ventricular dysfunction (mean fractional shortening; 56.7% in IVA and 47.8% in BIS vs 39.0% in CTL, P < .001) were observed in the animals with IVA and BIS. However, a negative inotropic effect was only observed in the animals with BIS. Excessive urinary noradrenaline excretion in animals with CTL was only suppressed with the use of IVA (mean; 1.35 µg/d in IVA and 1.95 µg/d in BIS vs 2.27 µg/d in CTL, P = .002). In contrast, atrial noradrenaline and acetylcholine depletion in the animals with CTL improved and the tyrosine hydroxylase expression in the both atria were restored with the use of both IVA and BIS. CONCLUSIONS: IVA therapy improved the survival of hypertensive animals with HF. Furthermore, it was associated with the amelioration of systemic sympathetic activation and cardiac sympathetic and parasympathetic nerve innervations. Chronic ß-blocker therapy with negative inotropic effects had beneficial effects only on cardiac innervations.
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Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Bisoprolol/farmacología , Fármacos Cardiovasculares/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Corazón/inervación , Hipertensión/tratamiento farmacológico , Ivabradina/farmacología , Sistema Nervioso Simpático/efectos de los fármacos , Animales , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/etiología , Hipertensión/metabolismo , Hipertensión/fisiopatología , Masculino , Miocardio/metabolismo , Norepinefrina/orina , Sistema Nervioso Parasimpático/efectos de los fármacos , Sistema Nervioso Parasimpático/fisiopatología , Ratas Endogámicas Dahl , Cloruro de Sodio Dietético , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatología , Tirosina 3-Monooxigenasa/metabolismo , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
To elucidate the abnormality of cardiac vagal control in streptozotocin-induced type 1 diabetic rats, we measured left ventricular myocardial interstitial acetylcholine (ACh) release in response to α2-adrenergic stimulation as an index of in vivo cardiac vagal nerve activity. A cardiac microdialysis technique was applied to the rat left ventricle, and the effect of α2-adrenergic stimulation by intravenous medetomidine (100⯵g/kg) on myocardial interstitial ACh levels was examined in anesthetized diabetic rats (4-6â¯weeks after intraperitoneal streptozotocin) and age-matched control rats (protocol 1). The effect of electrical vagal nerve stimulation on ACh levels was also examined in separate rats (protocol 2). In protocol 1, medetomidine increased the ACh levels in control (from 1.76⯱â¯0.65 to 3.13⯱â¯1.41â¯nM, Pâ¯<â¯0.05, nâ¯=â¯7) but not in diabetic rats (from 2.01⯱â¯0.47 to 1.62⯱â¯0.34â¯nM, not significant, nâ¯=â¯7). In protocol 2, electrical vagal nerve stimulation at 20â¯Hz significantly increased the ACh levels in both control (from 1.49⯱â¯0.26 to 6.39⯱â¯1.81â¯nM, Pâ¯<â¯0.001, nâ¯=â¯6) and diabetic rats (from 1.77⯱â¯0.54 to 6.98⯱â¯1.38â¯nM, Pâ¯<â¯0.001, nâ¯=â¯6). In conclusion, medetomidine-induced central vagal activation was impaired in diabetic rats, whereas peripheral cardiac vagal control of ACh release was preserved. The impairment of central vagal activation may lead to relative sympathetic predominance and promote cardiovascular complications in diabetes.
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Diabetes Mellitus Experimental/fisiopatología , Medetomidina/farmacología , Nervio Vago/fisiopatología , Acetilcolina/metabolismo , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Estimulación Eléctrica , Ventrículos Cardíacos/metabolismo , Ratas , EstreptozocinaRESUMEN
Ivabradine is a selective bradycardic agent that inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. HCN channels play a key role in mediating the positive chronotropic response to sympathetic nerve stimulation (SNS). We examined whether ivabradine would interfere with dynamic sympathetic control of heart rate (HR). The effect of intravenous ivabradine (2 mg/kg, n = 7) or metoprolol (10 mg/kg, n = 6) on the transfer function from SNS to HR was examined in anesthetized rats. Ivabradine preserved the asymptotic dynamic gain of the HR transfer function and nearly doubled the asymptotic dynamic gain of the transfer function from SNS to the R-R interval. In contrast, metoprolol abolished dynamic sympathetic control of HR. Preserved dynamic sympathetic control of HR, with coexisting bradycardia, may contribute to some of the beneficial effects of ivabradine previously reported in clinical application.
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Bradicardia/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Ivabradina/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Bradicardia/metabolismo , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Masculino , Metoprolol/farmacología , Ratas , Ratas Endogámicas WKY , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/metabolismoRESUMEN
Pulmonary artery impedance (PAZ) that measures the pulsatile properties of the vasculature provides diagnostic and prognostic information in patients with pulmonary vascular diseases. While downstream pressure [i.e., left atrial (LA) pressure] should be considered when calculating static properties of pulmonary vasculature, PAZ is commonly estimated without taking into account the pulsatile component of LA pressure. We examined whether PAZ can be estimated with reasonable accuracy without using LA pressure. Pulmonary artery (PA) flow, PA pressure, and LA pressure were measured under irregular pacing in eight normal Sprague-Dawley rats. PAZ was estimated by analyzing a one-input, one-output system (I1O1 analysis) that does not include LA pressure, and a two-input, one-output system (I2O1 analysis) that includes LA pressure. Using a tube and 3-element Windkessel model, PAZ was parameterized as peripheral resistance (RP ), arterial compliance (CP ), characteristic impedance (ZC ), and transmission time to the reflection site (TD ). These parameters were not significantly different between the I1O1 and I2O1 analyses (RP : 0.286 ± 0.040 vs. 0.274 ± 0.038 mmHg·min/mL, CP : 0.352 ± 0.049 vs. 0.343 ± 0.041 mL/mmHg, ZC : 0.115 ± 0.005 vs. 0.117 ± 0.005 mmHg·min/mL, TD : 13.2 ± 1.8 vs. 12.9 ± 1.7 msec). In conclusion, the I1O1 analysis that does not use LA pressure estimates PAZ with reasonable accuracy compared with the I2O1 analysis that uses LA pressure in normal rats. Our finding that the pulsatile component of LA pressure contributes little to PAZ estimation may justify the clinical use of the I1O1 analysis.
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Función del Atrio Izquierdo , Presión Sanguínea , Arteria Pulmonar/fisiología , Flujo Pulsátil , Animales , Masculino , Modelos Cardiovasculares , Contracción Miocárdica , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND/OBJECTIVES: It is often difficult to determine an adequate resection line during pancreatectomy for intraductal papillary mucinous neoplasm involving the main pancreatic duct during partial pancreatectomy. The aim of this study was to evaluate the usefulness of improved peroral pancreatoscopy using SpyGlass-DStm in the preoperative assessment of intraductal papillary mucinous neoplasm involving the main pancreatic duct. METHODS: We collected and retrospectively analyzed clinicopathological data from seven consecutive patients who underwent preoperative assessment of intraductal papillary mucinous neoplasm involving the main duct using SpyGlass-DStm. RESULTS: Good imaging quality of the intraductal protruding lesion was obtained in all seven patients, and only one adverse event was noted wherein a patient had mild pancreatitis. Six patients underwent pancreatectomy. In one patient, masked-type concomitant pancreatic ductal adenocarcinoma and low-length dysplastic lesion was found near the surgical margin, which was not detected by preoperative imaging modalities including SpyGlass-DStm. The sensitivity of targeting biopsy during SpyGlass-DStm to diagnose high-grade dysplasia was 0%. CONCLUSIONS: SpyGlass-DStm can be safely performed in patients with intraductal papillary mucinous neoplasm involving the main duct, and has excellent visualization of the target lesion. However, challenges include poor diagnostic ability of targeting biopsy, and, therefore, intraoperative frozen section is still needed to obtain negative surgical margins.
RESUMEN
Although diabetes mellitus (DM) is a major risk factor for cardiovascular diseases, changes in open-loop static and dynamic characteristics of the arterial baroreflex in the early phase of DM remain to be clarified. We performed an open-loop systems analysis of the carotid sinus baroreflex in type 1 DM rats 4 to 5 wk after intraperitoneal streptozotocin injection ( n = 9) and we compared the results with control rats ( n = 9). The operating-point baroreflex gain was maintained in the DM rats compared with the control rats (2.07 ± 0.67 vs. 2.66 ± 0.22 mmHg/mmHg, P = 0.666). However, the range of arterial pressure (AP) control was narrower in the DM than in the control group (48.0 ± 5.0 vs. 77.1 ± 4.5 mmHg, P = 0.001), suggesting that the reserve for AP buffering is lost in DM. Although baroreflex dynamic characteristics were relatively preserved, coherences were lower in the DM than in the control group. The decreased coherence in the neural arc may be related to the narrowed quasi-linear range in the static relationship between carotid sinus pressure and sympathetic nerve activity in the DM group. Although the reason for the decreased coherences in the peripheral arc and the total reflex arc was inconclusive, the finding may indicate a loss of integrity of the baroreflex-mediated sympathetic AP control in the DM group. The derangement of the baroreflex dynamic characteristics is progressing occultly in this early stage of type 1 DM in a manner where dynamic gains are relatively preserved around the normal operating point.
Asunto(s)
Presión Arterial , Barorreflejo , Seno Carotídeo/inervación , Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Neuropatías Diabéticas/fisiopatología , Estreptozocina , Sistema Nervioso Simpático/fisiopatología , Animales , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Tipo 1/inducido químicamente , Neuropatías Diabéticas/inducido químicamente , Masculino , Modelos Neurológicos , Ratas Endogámicas WKY , Factores de TiempoRESUMEN
AIMS: To assess the acute effects of intravenous ivabradine, a selective bradycardic agent, on carotid sinus baroreflex-mediated sympathetic arterial pressure (AP) and heart rate (HR) responses. METHODS AND RESULTS: In anesthetized and vagotomized Wistar-Kyoto rats (n=6), carotid sinus baroreceptor regions were isolated. Changes in splanchnic sympathetic nerve activity (SNA), AP, and HR in response to a step-wise pressure input were examined before and after intravenous ivabradine (2mg/kg). Ivabradine did not affect the response range of SNA (91.8±6.5 vs. 93.5±9.8%) or AP (89.6±10.6 vs. 91.0±9.7mmHg). Ivabradine significantly reduced the minimum HR from 369.4±8.4 to 223.3±13.2 (P<0.001) but did not attenuate the HR response range (69.1±7.0 vs. 82.5±9.6beats/min). CONCLUSIONS: Ivabradine does not acutely affect baroreflex-mediated sympathetic AP regulation and also spares the magnitude of the sympathetic HR response, despite significant bradycardia. The preserved sympathetic HR response, which could not be afforded by beta-blockers, may contribute to some beneficial clinical effects of ivabradine.
Asunto(s)
Barorreflejo/efectos de los fármacos , Benzazepinas/farmacología , Presión Sanguínea/efectos de los fármacos , Fármacos Cardiovasculares/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Presorreceptores/efectos de los fármacos , Animales , Barorreflejo/fisiología , Presión Sanguínea/fisiología , Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca/fisiología , Ivabradina , Presorreceptores/fisiología , Ratas , Ratas Endogámicas WKY , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/fisiologíaRESUMEN
The aim of this study was to assess the feasibility of prophylactic pancreatojejunostomy after enucleation or limited pancreatic resection regarding the risk of postoperative pancreatic fistula (PF). We retrospectively reviewed the medical records of 32 patients who underwent enucleation or limited pancreatic resection and compared the clinical parameters between patients with (n = 10) and without (n = 22) prophylactic pancreatojejunostomy. Prophylactic pancreatojejunostomy was performed in patients with a possible high risk ofPF. No operation-related mortality occurred. Operation time was significantly longer (P < 0.01) and blood loss significantly greater (P < 0.01) in patients with pancreatojejunostomy. Overall complications were more frequent (P = 0.02) and postoperative hospital stay was significantly longer (P = 0.02) in patients with pancreatojejunostomy. However, other assessed factors including the prevalence of postoperative PF did not differ between groups. In conclusion, prophylactic pancreatojejunostomy is feasible, and its efficacy in preventing PF after enucleation or limited pancreatic resection in high-risk patients will require further study.