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1.
Environ Health Prev Med ; 25(1): 77, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33261557

RESUMEN

BACKGROUND: Decreased heart rate variability (HRV) is a predictor of autonomic system dysfunction, and is considered as a potential mechanism of increased risk of cardiovascular disease (CVD) induced by exposure to particulate matter less than 2.5 µm in diameter (PM2.5). Previous studies have suggested that exposure to PM2.5 may lead to decreased HRV levels, but the results remain inconsistent. METHODS: An updated systematic review and meta-analysis of panel studies till November 1, 2019 was conducted to evaluate the acute effect of exposure to ambient PM2.5 on HRV. We searched electronic databases (PubMed, Web of Science, and Embase) to identify panel studies reporting the associations between exposure to PM2.5 and the four indicators of HRV (standard deviation of all normal-to-normal intervals (SDNN), root mean square of successive differences in adjacent normal-to-normal intervals (rMSSD), high frequency power (HF), and low frequency power (LF)). Random-effects model was used to calculate the pooled effect estimates. RESULTS: A total of 33 panel studies were included in our meta-analysis, with 16 studies conducted in North America, 12 studies in Asia, and 5 studies in Europe. The pooled results showed a 10 µg/m3 increase in PM2.5 exposure which was significantly associated with a - 0.92% change in SDNN (95% confidence intervals (95%CI) - 1.26%, - 0.59%), - 1.47% change in rMSSD (95%CI - 2.17%, - 0.77%), - 2.17% change in HF (95%CI - 3.24%, - 1.10%), and - 1.52% change in LF (95%CI - 2.50%, - 0.54%), respectively. Overall, subgroup analysis suggested that short-term exposure to PM2.5 was associated with lower HRV levels in Asians, healthy population, and those aged ≥ 40 years. CONCLUSION: Short-term exposure to PM2.5 was associated with decreased HRV levels. Future studies are warranted to clarity the exact mechanism of exposure to PM2.5 on the cardiovascular system through disturbance of autonomic nervous function.


Asunto(s)
Frecuencia Cardíaca/efectos de los fármacos , Material Particulado/análisis , Adulto , Anciano , Anciano de 80 o más Años , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
2.
PLoS One ; 15(11): e0241818, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33152041

RESUMEN

Currently no drugs are employed clinically to reverse the unconsciousness induced by general anesthetics. Our previous studies showed that caffeine, when given near the end of an anesthesia session, accelerated emergence from isoflurane anesthesia, likely caused by caffeine's ability to elevate intracellular cAMP levels and to block adenosine receptors. These earlier studies showed that caffeine did not rouse either rats or humans from deep anesthesia (≥ 1 minimum alveolar concentration, MAC). In this current crossover study, we examined whether caffeine reversed the unconsciousness produced by light anesthesia (< 1 MAC) in the continued presence of isoflurane. The primary endpoint of this study was to measure isoflurane levels at the time of recovery of righting reflex, which was a proxy for consciousness. Rats were deeply anesthetized with 2% isoflurane (~1.5 MAC) for 20 minutes. Subsequently, isoflurane was reduced to 1.2% for 10 minutes, then by 0.2% every 10 min; animals were monitored until the recovery of righting reflex occurred, in the continued presence of isoflurane. Respiration rate, heart rate and electroencephalogram (EEG) were monitored. Our results show that caffeine-treated rats recovered their righting reflex at a significantly higher inspired isoflurane concentration, corresponding to light anesthesia, than the same rats treated with saline (control). Respiration rate and heart rate increased initially after caffeine injection but were then unchanged for the rest of the anesthesia session. Deep anesthesia is correlated with burst suppression in EEG recordings. Our data showed that caffeine transiently reduced the burst suppression time produced by deep anesthesia, suggesting that caffeine altered neuronal circuit function but not to a point where it caused arousal. In contrast, under light anesthesia, caffeine shifted the EEG power to high frequency beta and gamma bands. These data suggest that caffeine may represent a clinically viable drug to reverse the unconsciousness produced by light anesthesia.


Asunto(s)
Anestésicos por Inhalación/administración & dosificación , Cafeína/administración & dosificación , Isoflurano/administración & dosificación , Reflejo de Enderezamiento/efectos de los fármacos , Periodo de Recuperación de la Anestesia , Anestesia General , Animales , Cafeína/farmacología , Estudios Cruzados , Electroencefalografía , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Modelos Animales , Ratas , Frecuencia Respiratoria/efectos de los fármacos
3.
Medicine (Baltimore) ; 99(45): e23061, 2020 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-33157963

RESUMEN

OBJECTIVE: This study is aims to compare the anesthetic safety of propofol combined with etomidate for painless gastroscopy. METHODS: Three hundred patients undergoing painless gastroscopy were randomly assigned to P, PE1, and PE2 groups. Patients were anesthetized with propofol (P group) or propofol combined with etomidate (volume ratio 1: 1, PE1 group; volume ratio 2: 1, PE2 group). The hemodynamics and adverse reactions were observed. The sleep quality satisfaction and nature of dreams were recorded. RESULTS: Compared with pre-anesthesia, the mean arterial pressure and heart rate of the 3 groups were significantly slower during the examination and at the end of the examination. PE1 group had a higher incidence of muscle spasm, body moving, choking, and deglutition. The incidence of hypoxemia and injection pain was higher in P group. P and PE2 group had higher sleep quality satisfaction and dream incidence after awaking. However, there was no difference in the nature of dreams among 3 groups. CONCLUSION: Our data indicate that the combination of 10 ml 1.0% propofol and 5 ml 0.2% etomidate for painless gastroscopy reduces adverse reactions while not affecting the patients respiratory function. Moreover, it is safe and effective, which is worthy of clinical application and promotion.


Asunto(s)
Anestésicos Intravenosos/efectos adversos , Etomidato/efectos adversos , Gastroscopía/métodos , Propofol/efectos adversos , Adulto , Obstrucción de las Vías Aéreas/inducido químicamente , Anestésicos Intravenosos/administración & dosificación , Presión Arterial/efectos de los fármacos , Estudios de Casos y Controles , Quimioterapia Combinada , Etomidato/administración & dosificación , Femenino , Gastroscopía/tendencias , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Humanos , Hipoxia/inducido químicamente , Incidencia , Reacción en el Punto de Inyección , Masculino , Persona de Mediana Edad , Mioclonía/inducido químicamente , Propofol/administración & dosificación , Seguridad , Espasmo/inducido químicamente , Espasmo/epidemiología , Resultado del Tratamiento
4.
Nat Commun ; 11(1): 5555, 2020 11 03.
Artículo en Inglés | MEDLINE | ID: mdl-33144559

RESUMEN

It is highly debated how cyclic adenosine monophosphate-dependent regulation (CDR) of the major pacemaker channel HCN4 in the sinoatrial node (SAN) is involved in heart rate regulation by the autonomic nervous system. We addressed this question using a knockin mouse line expressing cyclic adenosine monophosphate-insensitive HCN4 channels. This mouse line displayed a complex cardiac phenotype characterized by sinus dysrhythmia, severe sinus bradycardia, sinus pauses and chronotropic incompetence. Furthermore, the absence of CDR leads to inappropriately enhanced heart rate responses of the SAN to vagal nerve activity in vivo. The mechanism underlying these symptoms can be explained by the presence of nonfiring pacemaker cells. We provide evidence that a tonic and mutual interaction process (tonic entrainment) between firing and nonfiring cells slows down the overall rhythm of the SAN. Most importantly, we show that the proportion of firing cells can be increased by CDR of HCN4 to efficiently oppose enhanced responses to vagal activity. In conclusion, we provide evidence for a novel role of CDR of HCN4 for the central pacemaker process in the sinoatrial node.


Asunto(s)
Relojes Biológicos , AMP Cíclico/metabolismo , Canales Regulados por Nucleótidos Cíclicos Activados por Hiperpolarización/metabolismo , Nodo Sinoatrial/patología , Potenciales de Acción/efectos de los fármacos , Animales , Arritmias Cardíacas/complicaciones , Arritmias Cardíacas/patología , Relojes Biológicos/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Bradicardia/complicaciones , Bradicardia/patología , Carbacol/farmacología , Electrocardiografía , Femenino , Células HEK293 , Corazón/efectos de los fármacos , Corazón/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Ratones Endogámicos C57BL , Subunidades de Proteína/metabolismo , Reproducibilidad de los Resultados , Nodo Sinoatrial/fisiopatología , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiopatología
5.
Sci Rep ; 10(1): 16243, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33004964

RESUMEN

Food coloring is often used as a coloring agent in foods, medicines and cosmetics, and it was reported to have certain carcinogenic and mutagenic effects in living organisms. Investigation of physiological parameters using zebrafish is a promising methodology to understand disease biology and drug toxicity for various drug discovery on humans. Zebrafish (Danio rerio) is a well-acknowledged model organism with combining assets such as body transparency, small size, low cost of cultivation, and high genetic homology with humans and is used as a specimen tool for the in-vivo throughput screening approach. In addition, recent advances in microfluidics show a promising alternative for zebrafish manipulation in terms of drug administration and extensive imaging capability. This pilot work highlighted the design and development of a microfluidic detection platform for zebrafish larvae through investigating the effects of food coloring on cardiovascular functionality and pectoral fin swing ability. The zebrafish embryos were exposed to the Cochineal Red and Brilliant Blue FCF pigment solution in a concentration of (0.02‰, 0.2‰) cultured in the laboratory from the embryo stage to hatching and development until 9 days post fertilization (d.p.f.). In addition, zebrafish swimming behaviors in terms of pectoral fin beating towards the toxicity screening were further studied by visualizing the induced flow field. It was evidenced that Cochineal Red pigment at a concentration of 0.2‰ not only significantly affected the zebrafish pectoral fin swing behavior, but also significantly increased the heart rate of juvenile fish. The higher concentration of Brilliant Blue FCF pigment (0.2%) increased heart rate during early embryonic stages of zebrafish. However, zebrafish exposed to food coloring did not show any significant changes in cardiac output. The applications of this proposed platform can be further extended towards observing the neurobiological/hydrodynamic behaviors of zebrafish larvae for practical applications in drug tests.


Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Aditivos Alimentarios/farmacología , Hemodinámica/efectos de los fármacos , Animales , Compuestos Azo/efectos adversos , Compuestos Azo/farmacología , Bencenosulfonatos/efectos adversos , Bencenosulfonatos/farmacología , Relación Dosis-Respuesta a Droga , Aditivos Alimentarios/efectos adversos , Colorantes de Alimentos/efectos adversos , Colorantes de Alimentos/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Ensayos Analíticos de Alto Rendimiento/métodos , Técnicas Analíticas Microfluídicas , Naftalenosulfonatos/efectos adversos , Naftalenosulfonatos/farmacología , Pez Cebra
6.
J Clin Psychiatry ; 81(6)2020 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-33049804

RESUMEN

OBJECTIVE: To assess the effects of a supratherapeutic dose of SPN-812, a drug currently under investigation as a treatment for attention-deficit/hyperactivity disorder, on cardiac repolarization (QTc) in healthy adults. METHODS: The study was conducted from June 27, 2018, to July 10, 2018. It had a double-blind, randomized, crossover design in which subjects received a 3-treatment sequence-placebo, 400 mg moxifloxacin, and 1,800 mg SPN-812 for 2 consecutive days (separated by at least a 3-day washout). The primary endpoint was the correlation between the change from baseline (CFB) in individual heart rate corrected QT interval (QTcI) (ΔQTcI) and viloxazine and 5-hydroxyviloxazine glucuronide (5-OH-VLX-gluc) plasma concentrations (Cps). The secondary endpoint was the time point placebo-adjusted CFB in QTcI (ΔΔQTcI) for viloxazine. For assay sensitivity, the correlations between moxifloxacin Cp and the ΔQTcI, and moxifloxacin and time point ΔΔQTcI were evaluated. Additional evaluations included Fridericia's formula QT correction, heart rate, and the PR and QRS intervals. Changes in electrocardiogram (ECG) morphology along with other safety parameters were also analyzed and reported. RESULTS: The correlation between ΔQTcI and viloxazine Cp demonstrated a statistically significant negative slope (P = .0012). 5-OH-VLX-gluc Cp and ΔQTcI also demonstrated a statistically significant negative slope (P = .0007). Secondary time point analyses showed no effect of SPN-812 on QTcI. Assay sensitivity with moxifloxacin was confirmed. Safety parameters were acceptable. CONCLUSIONS: This study demonstrated that SPN-812 had no effect on cardiac repolarization or other ECG parameters in healthy adults, suggesting that it is not associated with a risk for cardiac arrhythmias or other electrocardiographic parameters.


Asunto(s)
Inhibidores de Captación Adrenérgica/farmacología , Electrocardiografía/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Viloxazina/farmacología , Inhibidores de Captación Adrenérgica/administración & dosificación , Inhibidores de Captación Adrenérgica/efectos adversos , Adulto , Estudios Cruzados , Preparaciones de Acción Retardada , Método Doble Ciego , Femenino , Humanos , Masculino , Moxifloxacino/farmacología , Inhibidores de Topoisomerasa II/farmacología , Viloxazina/administración & dosificación , Viloxazina/efectos adversos
7.
Rev Cardiovasc Med ; 21(3): 419-432, 2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-33070546

RESUMEN

Several observational studies have shown a survival benefit for patients with atrial fibrillation (AF) who are treated with catheter ablation (CA) rather than medical management (MM). However, data from randomized controlled trials (RCTs) are uncertain. Therefore, we performed a meta-analysis of RCTs that compared the benefits of CA and MM in treatment of AF. We searched the Cochrane Library, PubMed, and EMBASE databases for RCTs that compared AF ablation with MM from the time of database establishment up to January 2020. The risk ratio (RR) with a 95% confidence interval (CI) was used as a measure treatment effect. Twenty-six RCTs that enrolled a total of 5788 patients were included in the meta-analysis. In this meta-analysis, the effect of AF ablation depended on the baseline level of left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. AF ablation appears to be of benefit to patients with a lesser degree of advanced HF and better LVEF by reducing mortality. Meanwhile, this mortality advantage was manifested in long-term follow-up. CA increased the risk for hospitalization when it was used as first-line therapy and decreased the risk when used as second-line therapy. CA reduced recurrence of atrial arrhythmia for different types of AF (paroxysmal or persistent AF) and CA-related complications were non-negligible. There was no convincing evidence for a reduction in long-term stroke risk after AF ablation, and additional high quality RCTs are needed to address that issue.


Asunto(s)
Antiarrítmicos/uso terapéutico , Fibrilación Atrial/terapia , Ablación por Catéter , Frecuencia Cardíaca/efectos de los fármacos , Adulto , Anciano , Antiarrítmicos/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Fibrilación Atrial/fisiopatología , Ablación por Catéter/efectos adversos , Ablación por Catéter/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/prevención & control , Factores de Tiempo , Resultado del Tratamiento
8.
Rev Cardiovasc Med ; 21(3): 473-480, 2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-33070551

RESUMEN

Pacemakers are more commonly recommended than theophylline for sick sinus syndrome (SSS) treatment. The positive effects of cilostazol on bradyarrhythmias also have been reported. However, no comparison of cilostazol and theophylline has been previously reported found. We retrospectively enrolled SSS patients, who refused a pacemaker implantation. Theophylline or cilostazol was administered, and the heart rate (HR) was evaluated in 4-8 weeks using a digital sphygmomanometer and the electrocardiogram (ECG). A 200-400 mg of theophylline or 100-200 mg of cilostazol were administered per day in 50 and 30 patients, respectively. The baseline HR was 54.8 ± 13.5 beats per minute (bpm) on using sphygmomanometry and 51.9 ± 11.8 bpm using the ECG. In the theophylline group, the HR increased by 12.0 ± 16.3 bpm by sphygmomanometry (P < 0.001) and 8.4 ± 12.0 bpm by the ECG (P < 0.001). In the cilostazol group, the HR increased by 16.8 ± 13.9 bpm by sphygmomanometry (P < 0.001) and 12.4 ± 13.4 bpm using the ECG (P < 0.001). In 15 of the 50 theophylline patients, the medication was switched to cilostazol. The HR increased from 61.4 ± 13.8 bpm to 64.0 ± 12.6 bpm (P = 0.338). Symptoms such as dyspnea, chest discomfort, dizziness, and syncope significantly improved after the administration of the medications. There were no significant differences in the improvement in the symptoms except for dizziness between the two agents. Cilostazol was as effective as theophylline for increasing the HR in SSS patients.


Asunto(s)
Fármacos Cardiovasculares/uso terapéutico , Cilostazol/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Síndrome del Seno Enfermo/tratamiento farmacológico , Teofilina/uso terapéutico , Anciano , Estimulación Cardíaca Artificial , Fármacos Cardiovasculares/efectos adversos , Cilostazol/efectos adversos , Sustitución de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Síndrome del Seno Enfermo/diagnóstico , Síndrome del Seno Enfermo/fisiopatología , Teofilina/efectos adversos , Factores de Tiempo , Resultado del Tratamiento , Negativa del Paciente al Tratamiento
9.
Toxicol Lett ; 335: 28-36, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33091562

RESUMEN

Endotoxic manifestations are diminished in female populations due to immune boosting actions of sex steroids. Considering that tobacco constituents including nicotine inhibit estrogen synthesis, we tested the hypothesis that nicotine exposure unveils cardiovascular anomalies of endotoxemia in female rats. Studies were undertaken in conscious female rats treated with i.v. lipopolysaccharide (LPS, 10 mg/kg) in absence and presence of nicotine. In contrast to no effects for LPS when used alone, dose-related decreases in blood pressure (BP) and serum estrogen were noted in endotoxic rats treated consequently with nicotine (25, 50, or 100 µg/kg i.v.). Signs of cardiac autonomic dysfunction appeared in LPS/nicotine-treated rats such as (i) decreased time-domain indices of heart rate variability (HRV), e.g. standard deviation of R-R intervals (SDNN) and root mean square of successive differences in R-R interval durations (rMSSD), and (ii) reduced total power of the frequency spectrum and shifted cardiac sympathovagal balance toward sympathetic dominance. Nicotine reversed the LPS-evoked modest rises in serum TNFα and IL-1ß while had no effect on associated arterial baroreflex dysfunction, inferring no roles for inflammation or baroreflexes in LPS-nicotine interaction. Estrogen or aminoguanidine (iNOS inhibitor), but not pentoxifylline (TNFα inhibitor), abolished LPS/nicotine hypotension. Together, nicotine acts probably via reducing estrogen availability to uncover nitric oxide-dependent hypotension and autonomic dysregulation in endotoxic female rats.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Endotoxemia/inducido químicamente , Estrógenos/sangre , Frecuencia Cardíaca/efectos de los fármacos , Corazón/efectos de los fármacos , Nicotina/toxicidad , Óxido Nítrico/sangre , Animales , Sistema Nervioso Autónomo/efectos de los fármacos , Barorreflejo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Endotoxemia/sangre , Endotoxemia/inmunología , Endotoxemia/fisiopatología , Endotoxinas/toxicidad , Femenino , Corazón/inervación , Interleucina-1beta/sangre , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/sangre
10.
Circ Arrhythm Electrophysiol ; 13(11): e008937, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33003964

RESUMEN

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2) has resulted in a global pandemic. Hydroxychloroquine±azithromycin have been widely used to treat coronavirus disease 2019 (COVID-19) despite a paucity of evidence regarding efficacy. The incidence of torsade de pointes remains unknown. Widespread use of these medications forced overwhelmed health care systems to search for ways to effectively monitor these patients while simultaneously trying to minimize health care provider exposure and use of personal protective equipment. METHODS: Patients with COVID-19 positive who received hydroxychloroquine±azithromycin across 13 hospitals between March 1 and April 15 were included in this study. A comprehensive search of the electronic medical records was performed using a proprietary python script to identify any mention of QT prolongation, ventricular tachy-arrhythmias and cardiac arrest. RESULTS: The primary outcome of torsade de pointes was observed in 1 (0.015%) out of 6476 hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin. Sixty-seven (1.03%) had hydroxychloroquine±azithromycin held or discontinued due to an average QT prolongation of 60.5±40.5 ms from a baseline QTc of 473.7±35.9 ms to a peak QTc of 532.6±31.6 ms. Of these patients, hydroxychloroquine±azithromycin were discontinued in 58 patients (86.6%), while one or more doses of therapy were held in the remaining nine (13.4%). A simplified approach to monitoring for QT prolongation and arrythmia was implemented on April 5. There were no deaths related to the medications with the simplified monitoring approach and health care provider exposure was reduced. CONCLUSIONS: The risk of torsade de pointes is low in hospitalized patients with COVID-19 receiving hydroxychloroquine±azithromycin therapy.


Asunto(s)
Antivirales/efectos adversos , Azitromicina/efectos adversos , Prestación de Atención de Salud , Sistema de Conducción Cardíaco/efectos de los fármacos , Hidroxicloroquina/efectos adversos , Torsades de Pointes/inducido químicamente , Potenciales de Acción/efectos de los fármacos , Adolescente , Adulto , Anciano , Antivirales/administración & dosificación , Azitromicina/administración & dosificación , Cardiotoxicidad , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Hospitalización , Humanos , Hidroxicloroquina/administración & dosificación , Masculino , Persona de Mediana Edad , New York , Seguridad del Paciente , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Torsades de Pointes/diagnóstico , Torsades de Pointes/fisiopatología , Resultado del Tratamiento , Adulto Joven
11.
Medicine (Baltimore) ; 99(43): e22288, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33120732

RESUMEN

INTRODUCTION: Dexmedetomidine and midazolam have become important approaches for the sedation of dental surgery. However, the comparison of these 2 drugs for the sedation of dental surgery has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of dexmedetomidine versus midazolam for dental surgery. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of dexmedetomidine versus midazolam on dental surgery are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. Meta-analysis is performed using the random-effect model. RESULTS: Five RCTs and 420 patients are included in the meta-analysis. Compared with midazolam intervention for dental surgery, dexmedetomidine intervention has similar lowest SpO2, lowest heart rate and lowest systolic blood pressure, duration of surgery, and total volume of local anesthetic, but is associated with stable and reduced lowest diastolic blood pressure. CONCLUSIONS: Similar benefits of dexmedetomidine and midazolam intervention are observed for the sedation of dental surgery in terms of SpO2, heart rate, systolic blood pressure, and the volume of local anesthetic, but dexmedetomidine may result in more stable diastolic blood pressure.


Asunto(s)
Dexmedetomidina/uso terapéutico , Hipnóticos y Sedantes/uso terapéutico , Midazolam/uso terapéutico , Procedimientos Quirúrgicos Orales , Anestésicos Locales/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Diástole/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Tempo Operativo , Oxígeno/sangre , Sístole/efectos de los fármacos
12.
J Cardiothorac Surg ; 15(1): 296, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33008451

RESUMEN

BACKGROUND: The Surgical Pleth Index (SPI) is a monitoring method that reflects painful stimuli during general anesthesia, and dexmedetomidine is an analgesic adjuvant with an opioid-sparing effect. But up to now, it is still unclear whether dexmedetomidine has any influence on SPI. To investigate whether dexmedetomidine has an effect on SPI during video-assisted thoracoscopic surgery. METHODS: We enrolled 94 patients who underwent video-assisted thoracoscopic lung lobectomy. Patients were randomly assigned to a dexmedetomidine group (dexmedetomidine: 0.8 µg/kg administered for 10 min before anesthesia) or normal saline group (equal volume of normal saline). SPI and vital signs were recorded. The number rating scale (NRS) pain score was also evaluated. RESULTS: SPI values were significantly lower in the dexmedetomidine group than in the normal saline group at intubation and at discharge from the postanesthesia care unit. Compared with the normal saline group, mean arterial pressure and heart rate were both significantly lower in the dexmedetomidine group at intubation. Heart rate was lower at skin incision in the dexmedetomidine group. The NRS score in the normal saline group was noticeably higher vs. the dexmedetomidine group at discharge from the postanesthesia care unit. CONCLUSIONS: Dexmedetomidine decreased intraoperative SPI and NRS scores. Our results showed that dexmedetomidine attenuated noxious stimuli. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): ChiCTR-OOC-16009450 , Registered 16 October, 2016.


Asunto(s)
Analgésicos no Narcóticos/uso terapéutico , Dexmedetomidina/uso terapéutico , Enfermedades Pulmonares/cirugía , Adolescente , Adulto , Anciano , Anestesia General , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Dolor Postoperatorio , Neumonectomía , Estudios Prospectivos , Cirugía Torácica Asistida por Video , Adulto Joven
13.
Am J Physiol Regul Integr Comp Physiol ; 319(6): R653-R665, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33074015

RESUMEN

Antenatal glucocorticoids improve outcomes among premature infants but are associated with hyperglycemia, which can exacerbate hypoxic-ischemic injury. It is still unclear how antenatal glucocorticoids or hyperglycemia modulate fetal cardiovascular adaptations to severe asphyxia. In this study, preterm fetal sheep received either saline or 12 mg im maternal dexamethasone, followed 4 h later by complete umbilical cord occlusion (UCO) for 25 min. An additional cohort of fetuses received titrated glucose infusions followed 4 h later by UCO to control for the possibility that hyperglycemia contributed to the cardiovascular effects of dexamethasone. Fetuses were studied for 7 days after UCO. Maternal dexamethasone was associated with fetal hyperglycemia (P < 0.001), increased arterial pressure (P < 0.001), and reduced femoral (P < 0.005) and carotid (P < 0.05) vascular conductance before UCO. UCO was associated with bradycardia, femoral vasoconstriction, and transient hypertension. For the first 5 min of UCO, fetal blood pressure in the dexamethasone-asphyxia group was greater than saline-asphyxia (P < 0.001). However, the relative increase in arterial pressure was not different from saline-asphyxia. Fetal heart rate and femoral vascular conductance fell to similar nadirs in both saline and dexamethasone-asphyxia groups. Dexamethasone did not affect the progressive decline in femoral vascular tone or arterial pressure during continuing UCO. By contrast, there were no effects of glucose infusions on the response to UCO. In summary, maternal dexamethasone but not fetal hyperglycemia increased fetal arterial pressure before and for the first 5 min of prolonged UCO but did not augment the cardiovascular adaptations to acute asphyxia.


Asunto(s)
Asfixia Neonatal/tratamiento farmacológico , Glucemia/efectos de los fármacos , Dexametasona/toxicidad , Corazón Fetal/efectos de los fármacos , Glucocorticoides/toxicidad , Hemodinámica/efectos de los fármacos , Hiperglucemia/inducido químicamente , Nacimiento Prematuro/tratamiento farmacológico , Animales , Animales Recién Nacidos , Presión Arterial/efectos de los fármacos , Asfixia Neonatal/sangre , Asfixia Neonatal/fisiopatología , Biomarcadores/sangre , Glucemia/metabolismo , Dexametasona/administración & dosificación , Modelos Animales de Enfermedad , Corazón Fetal/fisiopatología , Edad Gestacional , Glucocorticoides/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Hiperglucemia/sangre , Hiperglucemia/fisiopatología , Nacimiento Prematuro/sangre , Nacimiento Prematuro/fisiopatología , Oveja Doméstica , Factores de Tiempo
14.
Cochrane Database Syst Rev ; 10: CD012569, 2020 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-33089502

RESUMEN

BACKGROUND: Renin inhibitors (RIs) reduce blood pressure more than placebo, with the magnitude of this effect thought to be similar to that for angiotensin converting enzyme (ACE) inhibitors. However, a drug's efficacy in lowering blood pressure cannot be considered as a definitive indicator of its effectiveness in reducing mortality and morbidity. The effectiveness and safety of RIs compared to ACE inhibitors in treating hypertension is unknown. OBJECTIVES: To evaluate the benefits and harms of renin inhibitors compared to ACE inhibitors in people with primary hypertension. SEARCH METHODS: The Cochrane Hypertension Group Information Specialist searched the following databases for randomized controlled trials up to August 2020: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers about further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We included randomized, active-controlled, double-blinded studies (RCTs) with at least four weeks follow-up in people with primary hypertension, which compared renin inhibitors with ACE inhibitors and reported morbidity, mortality, adverse events or blood pressure outcomes. We excluded people with proven secondary hypertension. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the included trials, evaluated the risks of bias and entered the data for analysis. MAIN RESULTS: We include 11 RCTs involving 13,627 participants, with a mean baseline age from 51.5 to 74.2 years. Follow-up duration ranged from four weeks to 36.6 months. There was no difference between RIs and ACE inhibitors for the outcomes: all-cause mortality: risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.18; 5 RCTs, 5962 participants; low-certainty evidence; total myocardial infarction: RR 0.86, 95% CI 0.22 to 3.39; 2 RCTs, 957 participants; very low-certainty evidence; adverse events: RR 0.98, 95% CI 0.93 to 1.03; 10 RTCs, 6007 participants;  moderate-certainty evidence; serious adverse events: RR 1.21, 95% CI 0.89 to 1.64; 10 RTCs, 6007 participants; low-certainty evidence; and withdrawal due to adverse effects: RR 0.85, 95% CI 0.68 to 1.06; 10 RTCs, 6008 participants; low-certainty evidence. No data were available for total cardiovascular events, heart failure, stroke, end-stage renal disease or change in heart rate. Low-certainty evidence suggested that RIs reduced systolic blood pressure: mean difference (MD) -1.72, 95% CI -2.47 to -0.97; 9 RCTs, 5001 participants;  and diastolic blood pressure: MD -1.18, 95% CI -1.65 to -0.72; 9 RCTs, 5001 participants,  to a greater extent than ACE inhibitors, but we judged this to be more likely due to bias than a true effect.  AUTHORS' CONCLUSIONS: For the treatment of hypertension, we have low certainty that renin inhibitors (RI) and angiotensin converting enzyme (ACE) inhibitors do not differ for all-cause mortality and myocardial infarction. We have low to moderate certainty that they do not differ for adverse events. Small reductions in blood pressure with renin inhibitors compared to ACE inhibitors are of low certainty.  More independent, large, long-term trials are needed to compare RIs with ACE inhibitors, particularly assessing morbidity and mortality outcomes, but also on blood pressure-lowering effect.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antihipertensivos/uso terapéutico , Renina/antagonistas & inhibidores , Anciano , Amidas/efectos adversos , Amidas/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Enfermedades Cardiovasculares/epidemiología , Causas de Muerte , Femenino , Fumaratos/efectos adversos , Fumaratos/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Irbesartán/uso terapéutico , Fallo Renal Crónico/epidemiología , Lisinopril/uso terapéutico , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Ramipril/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto
15.
Anesth Analg ; 131(5): 1599-1606, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33079884

RESUMEN

BACKGROUND: Oxycodone has been shown to be an effective analgesic for early postoperative analgesia, especially for abdominal operations associated with severe visceral pain. However, the dose needed varies depending on the operation and application of multimodal analgesia, such as local ropivacaine wound infiltration. Therefore, we conducted this study to estimate the median effective dose (ED50) of oxycodone that provides analgesia for hysterectomy and myomectomy with local ropivacaine wound infiltration. METHODS: In this dose-finding study, the ED50 of oxycodone for postoperative analgesia was estimated separately for laparoscopic hysterectomy, transabdominal hysterectomy, laparoscopic myomectomy, and transabdominal myomectomy. We used the sequential allocation designed by Dixon. Trials were conducted simultaneously in the 4 surgical type groups. A predefined dose of oxycodone was injected 30 minutes before the end of the operation with an initial dose of 0.1 mg/kg. A series of trials were performed following the rule of a relative 10% increase in dose after inadequate analgesia and a relative 10% decrease in dose after adequate analgesia. The study was conducted until the collection of 7 crossover points was achieved. Local ropivacaine wound infiltration was administered during abdominal stitching. The mean blood pressure (MBP) and heart rate (HR) were analyzed to assess the hemodynamic changes associated with oxycodone administration. RESULTS: A total of 113 patients were included in the estimation of ED50: 28 each in the laparoscopic hysterectomy group and transabdominal myomectomy group, 27 in the transabdominal hysterectomy group, and 30 in the laparoscopic myomectomy group. The estimated oxycodone ED50 (95% confidence interval [CI]) after laparoscopic hysterectomy, transabdominal hysterectomy, laparoscopic myomectomy, and transabdominal myomectomy was 0.060 mg/kg (0.053-0.068), 0.079 mg/kg (0.072-0.086), 0.060 mg/kg (0.051-0.071), and 0.092 mg/kg (0.086-0.098), respectively, for postoperative analgesia with local ropivacaine wound infiltration. The ED50 of oxycodone was different between laparoscopic surgeries and transabdominal surgeries (P < .001). The MBP and HR before and after oxycodone injection were different, regardless of surgical type. CONCLUSIONS: The oxycodone ED50 for postoperative analgesia was lower for laparoscopic hysterectomy (0.060 mg/kg) and laparoscopic myomectomy (0.060 mg/kg) than for transabdominal hysterectomy (0.079 mg/kg) and transabdominal myomectomy (0.092 mg/kg) when combined with local ropivacaine wound infiltration. A single intravenous injection of oxycodone is associated with an acceptable decrease in MBP and HR within a short time.


Asunto(s)
Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/uso terapéutico , Anestésicos Locales/uso terapéutico , Histerectomía/efectos adversos , Oxicodona/administración & dosificación , Oxicodona/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Ropivacaína/uso terapéutico , Miomectomía Uterina/efectos adversos , Adulto , Anestesia Local , Anestésicos Locales/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Inyecciones Intravenosas , Laparoscopía , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Ropivacaína/administración & dosificación
16.
Cardiovasc Ther ; 2020: 8563135, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33123219

RESUMEN

Metabolic syndrome (MetS) is a combination of factors which, collectively, increase cardiovascular risk to a greater extent than each of them separately. Previous studies showed high cardiovascular risk to be associated with autonomic nervous system dysfunction. The purpose of this study was to assess the effects of antihypertensive treatment on heart rate variability (HRV) in patients with hypertension (HTN), depending on cooccurrence of MetS. 118 patients with uncontrolled HTN were enrolled to the study. HRV was compared among patients with and without MetS (MetS [+], n = 70) at baseline and following 12 months antihypertensive treatment. The HRV indices measured from RR intervals recorded form using 24-hour ambulatory electrocardiography. The measured HRV domains were the standard deviation of the average of NN intervals [SDNN], square root of the mean of the sum of the squares of differences between adjacent NN intervals [rMSSD], percentage of NN50 [pNN50], low frequency [LF], high frequency [HF], total power of variance of all NN intervals [TP], and LF/HF ratio. Baseline parameters: SDNN, rMSSD, pNN50, and HF were significantly lower in the MetS[+] compared to the MetS[-] subgroup (p < 0.05). After a 12-month antihypertensive treatment, MetS[+] patients achieved a significant improvement in parameters: SDNN, rMSSD, pNN50, and TP (p < 0.05), while the changes in HRV observed in the MetS[-] subgroup were not statistically significant. The cooccurrence of HTN and other components of MetS is associated with disturbances of the autonomic balance. HTN control has a beneficial effect on HRV, with the effect being more evident in patients with MetS.


Asunto(s)
Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Síndrome Metabólico/tratamiento farmacológico , Adulto , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Masculino , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/fisiopatología , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
17.
Aquat Toxicol ; 229: 105653, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33080536

RESUMEN

Oil spill accidents are a major concern for aquatic organisms. In recent history, the Deepwater Horizon blowout spilled 500 million liters of crude oil into the Gulf of Mexico. Corexit 9500A was used to disperse the oil since it was the method approved at that time, despite safety concerns about its use. A better solution is necessary for dispersing oil from spills that reduces the toxicity to exposed aquatic organisms. To address this challenge, novel engineered nanoparticles were designed using silica cores grafted with hyperbranched poly(glycidol) branches. Because the silica core and polymers are known to be biocompatible, we hypothesized that these particles are nontoxic to fathead minnows (Pimephales promelas) and would decrease their exposure to oil polyaromatic hydrocarbons. Fathead minnow embryos, juveniles and adult stages were exposed to the particles alone or in combination with a water-accommodated fraction of oil. Acute toxicity of nanoparticles to fish was tested by measuring mortality. Sub-lethal effects were also measured including gene expression of cytochrome P450 1a (cyp1a) mRNA and heart rate in embryos. In addition, a mixture of particles plus the water-accommodated fraction was directly introduced to adult female fathead minnows by gavage. Three different nanoparticle concentrations were used (2, 10, and 50 mg/L) in either artificial fresh water or the water-accommodated fraction of the oil. In addition, nanoparticle-free controls were carried out in the two solutions. No significant mortality was observed for any age group or nanoparticle concentration, suggesting the safety of the nanoparticles. In the presence of the water-accommodated fraction alone, juvenile and adult fathead minnows responded by increasing expression of cyp1a. The addition of nanoparticles to the water-accommodated fraction reduced cyp1a gene expression in treatments. Heart rate was also restored to normal parameters in embryos co-exposed to nanoparticles and to the water-accommodated fraction. Measurement of polyaromatic hydrocarbons confirmed their presence in the tested solutions and the reduction of available PAH in WAF treated with the nanoparticles. Our findings suggest the engineered nanoparticles may be protecting the fish by sequestering polyaromatic hydrocarbons from oil, measured indirectly by the induction of cypa1 mRNAs. Furthermore, chemical analysis showed a reduction in PAH content in the water accommodated fraction with the presence of nanoparticles.


Asunto(s)
Cyprinidae/metabolismo , Nanopartículas/toxicidad , Contaminación por Petróleo/análisis , Dióxido de Silicio/toxicidad , Pruebas de Toxicidad , Animales , Cyprinidae/embriología , Cyprinidae/genética , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Embrión no Mamífero/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Golfo de México , Frecuencia Cardíaca/efectos de los fármacos , Micelas , Nanopartículas/química , Petróleo/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Dióxido de Silicio/química , Contaminantes Químicos del Agua/toxicidad
18.
Life Sci ; 263: 118574, 2020 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-33049280

RESUMEN

AIMS: We investigated the involvement of the renin angiotensin system (RAS) on the cardiorespiratory control in rats from dams fed with a low-protein diet. MAIN METHODS: Male offspring were obtained from dams fed a normoprotein diet (NP, 17% casein) and low-protein diet (LP, 8% casein) during pregnancy and lactation. Direct measurements of arterial pressure (AP), heart rate (HR) and respiratory frequency (RF) were recorded in awake 90-day-old at resting and after losartan potassium through either intracerebroventricular (ICV) microinjections or intravenous (IV) administration. Cardiovascular variability was evaluated by spectral analysis. Peripheral chemoreflex sensitivity was assessed through the potassium cyanide (KCN; 40 µg/0.1 ml/rat, IV). Gene expression was evaluated by qPCR, and MAPK (Mitogen Activated Protein Kinase) expression was evaluated by western blot. KEY FINDINGS: The LP offspring had higher mean AP (MAP) and RF than NP offspring. In the spectral analysis, the LP rats also showed higher low frequency of systolic AP (NP: 2.7 ± 0.3 vs. LP: 5.0 ± 1.0 mmHg). After ICV losartan, MAP and RF in LP rats remained higher than those in NP rats, but without changes in HR. The peripheral chemoreflex was similar between the groups. LP group had lower gene expression of Rac1 (Ras-related C3 botulinum toxin substrate 1) (NP: 1.13 ± 0.06 vs. LP: 0.88 ± 0.08). Peripherally, LP rats had larger delta of MAP after IV losartan (NP: -9.8 ± 2 vs. LP: -23 ± 6 mmHg), without changes in HR and RF. SIGNIFICANCE: In rats, the RAS participates peripherally, but not centrally, in the maintenance of arterial hypertension in male offspring induced by maternal protein restriction.


Asunto(s)
Dieta con Restricción de Proteínas/efectos adversos , Hipertensión/fisiopatología , Fenómenos Fisiologicos Nutricionales Maternos/fisiología , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Sistema Renina-Angiotensina/fisiología , Animales , Presión Arterial/efectos de los fármacos , Presión Arterial/fisiología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Lactancia/fisiología , Losartán/farmacología , Masculino , Embarazo , Ratas , Ratas Wistar , Frecuencia Respiratoria/efectos de los fármacos , Frecuencia Respiratoria/fisiología
19.
Sci Rep ; 10(1): 15701, 2020 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-32973263

RESUMEN

Heart failure with preserved ejection fraction (HFpEF) is currently untreated. Therapeutics development demands effective diagnosis of diastolic dysfunction in animal models mimicking human pathology, which requires appropriate anaesthetics. Here, we investigated which anaesthetic, ketamine/xylazine or isoflurane, could be used to reveal diastolic dysfunction in HFpEF-diseased obese ZSF1 rats by echocardiography. First, diastolic dysfunction was confirmed by pressure-volume loops in obese compared to lean control ZSF1 rats. In echocardiography, ketamine/xylazine, unlike isoflurane, was able to demonstrate impaired relaxation in obese ZSF1 rats, as reflected by impaired early (E) and late (A) filling peak velocities, decreased E/A ratio, and a prolonged deceleration and isovolumic relaxation time. Interestingly, ketamine/xylazine induced a wider separation of both tissue and pulsed wave Doppler-derived echocardiographic waves required for diastolic dysfunction diagnosis, potentially by reducing the heart rate (HR), while isoflurane resulted in merged waves. To assess whether HR-lowering alone explained the differences between the anaesthetics, echocardiography measurements under isoflurane with and without the HR-lowering drug ivabradine were compared. However, diastolic dysfunction could not be diagnosed in ivabradine-treated obese ZSF1 rats. In summary, ketamine/xylazine compared to isoflurane is the anaesthetic of choice to detect diastolic dysfunction by echocardiography in rodent HFpEF, which was only partly mediated by HR-lowering.


Asunto(s)
Anestésicos/administración & dosificación , Diástole/efectos de los fármacos , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Isoflurano/administración & dosificación , Ketamina/administración & dosificación , Xilazina/administración & dosificación , Animales , Diástole/fisiología , Ecocardiografía , Frecuencia Cardíaca/fisiología , Masculino , Obesidad/fisiopatología , Ratas , Disfunción Ventricular Izquierda/fisiopatología
20.
Am J Respir Cell Mol Biol ; 63(6): 843-855, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32915674

RESUMEN

The potential benefit of heart rate reduction (HRR), independent of ß-blockade, on right ventricular (RV) function in pulmonary hypertension (PH) remains undecided. We studied HRR effects on RV fibrosis and function in PH and RV pressure-loading models. Adult rats were randomized to 1) sham controls, 2) monocrotaline (MCT)-induced PH, 3) SU5416 + hypoxia (SUHX)-induced PH, or 4) pulmonary artery banding (PAB). Ivabradine (IVA) (10 mg/kg/d) was administered from 2 weeks after PH induction or PAB. Exercise tolerance, echocardiography, and pressure-volume hemodynamics were obtained at a terminal experiment 3 weeks later. RV myocardial samples were analyzed for putative mechanisms of HRR effects through fibrosis, profibrotic molecular signaling, and Ca++ handling. The effects of IVA versus carvedilol on human induced pluripotent stem cell-derived cardiomyocytes beat rate and relaxation properties were evaluated in vitro. Despite unabated severely elevated RV systolic pressures, IVA improved RV systolic and diastolic function, profibrotic signaling, and RV fibrosis in PH/PAB rats. RV systolic-elastance (control, 121 ± 116; MCT, 49 ± 36 vs. MCT+IVA, 120 ± 54; PAB, 70 ± 20 vs. PAB+IVA, 168 ± 76; SUHX, 86 ± 56 vs. SUHX +IVA, 218 ± 111; all P < 0.05), the time constant of RV relaxation, echo indices of RV function, and fibrosis (fibrosis: control, 4.6 ± 1%; MCT, 13.4 ± 6.5 vs. MCT+IVA, 6.7 ± 2.6%; PAB, 11.4 ± 4.5 vs. PAB+IVA, 6.4 ± 5.1%; SUHX, 10 ± 4.6 vs. SUHX+IVA, 3.9 ± 2.2%; all P < 0.001) were improved by IVA versus controls. IVA had a dose-response effect on induced pluripotent stem cell-derived cardiomyocytes beat rate by delaying Ca++ loss from the cytoplasm. In experimental PH or RV pressure loading, HRR improves RV fibrosis, function, and exercise endurance independent of ß-blockade. The balance between adverse tachycardia and bradycardia requires further study, but judicious HRR may provide a promising strategy to improve RV function in clinical PH.


Asunto(s)
Frecuencia Cardíaca/efectos de los fármacos , Hipertensión Pulmonar/inducido químicamente , Ivabradina/farmacología , Función Ventricular Derecha/efectos de los fármacos , Animales , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Hemodinámica , Humanos , Hipertensión Pulmonar/patología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Arteria Pulmonar/fisiopatología , Ratas Sprague-Dawley , Presión Ventricular/efectos de los fármacos
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