Evaluation of cardiac contractility of fetuses from pregestational diabetes mellitus pregnancies by three-dimensional ultrasound

SUMMARY OBJECTIVE: This study aimed to evaluate cardiac contractility in fetuses from pregestational diabetes mellitus pregnancies by three-dimensional ultrasound using spatiotemporal image correlation in rendering mode. METHODS: A retrospective cross-sectional study was performed on 40 fetuses from nondiabetic pregnancies and 28 pregestational diabetic pregnancies between 20 and 33 weeks and 6 days. Cardiac contractility was assessed by measuring the ventricular myocardial area in diastole subtracted from the ventricular myocardial area in systole. RESULTS: Pregestational diabetic pregnancies had a lower maternal age than nondiabetic pregnancies (26.7 vs. 39.9 years, p=0.019). Cardiac contractility in fetuses from diabetic and nondiabetic pregnancies was similar (p=0.293). A moderately positive and significant correlation was observed between gestational age and cardiac contractility (r=0.46, p=0.0004). A 1-week increase in gestational age was responsible for a 0.1386 cm2 increase in cardiac contractility. CONCLUSION: Cardiac contractility as evaluated by three-dimensional ultrasound using spatiotemporal image correlation in rendering mode showed no significant differences across fetuses with and without pregestational diabetes.

Does L-carnitine prevent cadmium-induced damage in gastrointestinal contractility and histological changes in prepubertal rat / ¿La L-carnitina previene el daño inducido por cadmio en la contractilidad gastrointestinal y los cambios histológicos en ratas prepúberes?

SUMMARY: Cadmium (Cd) is the industrial and environmental toxic heavy metal which is found in air, water and soil. Cd, adversely affects many organs in humans such as kidney, intestine, liver, testis and lungs. L-carnitine (LC) is an important agent that plays essential role in energy metabolism. In our study, we aimed to work out whether LC application has any protective effect on intestinal contractility and morphologic damage of prepubertal rat duodenum on Cd-induced toxicity. Twenty eight prepubertal female Wistar rats were divided into four groups. The first group is control (C), second group; Cd group; Cadmium chloride was given 2 mg/kg 28 days with a one-day break by i.p. The third group; Cd+LC, which cadmium chloride was given 2 mg/kg i.p. and LC was given orally by gastric lavage. The LC dose was given as 75 mg/kg. The fourth group; LC, which only LC was given orally. The intestinal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (ACh) and relaxation was achieved with phenylephrine. Also the segments were examined for histological changes by light microscopy. Ach-induced contractions were higher in Cd+LC, LC, and control group compared to the Cd group in duodenal segments. The phenylephrine-induced relaxations were lower in Cd groups as compared with Control, Cd+LC and LC group in duodenal segments. In Cd group intestinal morphology was observed to be severely damaged whereas in Cd+LC group the damage was noticeably lower. Cd administration caused severe cellular damage and decreased gastrointestinal motility. Treatment with the LC has affected the gastrointestinal contractility and reduced the damage in intestinal morphology, which occured after Cd application.

El cadmio (Cd) es el metal pesado tóxico industrial y ambiental que se encuentra en el aire, el agua y el suelo. El Cd afecta negativamente a muchos órganos humanos, como los riñones, los intestinos, el hígado, los testículos y los pulmones. La L-carnitina (LC) es un agente importante que juega un rol esencial en el metabolismo energético. El objetivo de este estudio fue determinar si la aplicación de LC tiene algún efecto protector sobre la contractilidad intestinal y el daño morfológico del duodeno de rata prepuberal sobre la toxicidad inducida por Cd. Veintiocho ratas Wistar hembras prepúberes se dividieron en cuatro grupos. El primer grupo control (C), segundo grupo; grupo cd; Se administró cloruro de cadmio 2 mg/kg durante 28 días con un descanso de un día por vía i.p. El tercer grupo; Cd+LC, al que se administró cloruro de cadmio 2 mg/kg i.p. y LC se administró por vía oral mediante lavado gástrico. La dosis de LC se administró como 75 mg/kg. El cuarto grupo; LC, al cual solo LC se administraba por vía oral. Los segmentos intestinales fueron aislados y suspendieron en baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (ACh) y la relajación se logró con fenilefrina. También se examinaron los segmentos en busca de cambios histológicos mediante microscopía óptica. Las contracciones inducidas por Ach fueron mayores en Cd+LC, LC y el grupo control en comparación con el grupo Cd en los segmentos duodenales. Las relajaciones inducidas por fenilefrina fueron menores en los grupos Cd en comparación con el grupo Control, Cd+LC y LC en los segmentos duodenales. En el grupo Cd se observó que la morfología intestinal estaba severamente dañada mientras que en el grupo Cd+LC el daño fue notablemente menor. La administración de Cd causó daño celular severo y disminución de la motilidad gastrointestinal. El tratamiento con LC afectó la contractilidad gastrointestinal y redujo el daño en la morfología intestinal, que ocurría después de la aplicación de Cd.

Capsaicin fails to produce changes in contractile tension in large gut of neonate rats

Objectives: Capsaicin, the most pungent constituent of chilli pepper (Capsicum annuum L.), is known to alter the physiological activity of the gut. Capsaicin mediates its action through a transient receptor potential vanilloid type 1 (TRPV1) channel. The action of capsaicin on gut smooth muscle varies from segment to segment in different species. The earlier studies were carried out in adult animals only, and its status in the neonate gut, which is in a development stage, is not known. Objective: Therefore, the present study was done to assess the effect of capsaicin on the large gut of neonates. Materials and Methods: In an organ bath preparation, isometric contractions were recorded from segments of dissected rat colon and rectum. The gut segments were exposed to cumulative concentrations of capsaicin (0.01 nM–3 µM) and a capsaicin-induced contractile response was observed. TRPV1 receptor antagonist capsazepine (1 µM) and a nitric oxide synthase inhibitor, L-NAME (100 µM), were used to assess their blocking effect on capsaicin-induced contractile response. Results: Capsaicin raised contractile tension in the colon and rectum of adult rats but not in neonate rats. In adult rats, capsazepine pre-treatment (1 µM) failed to block the capsaicin-induced response in the colon, but in the lower concentrations, it increased contractile tension in the rectum. Pre-application of L-NAME (100 µM) potentiated capsaicin-induced response in the adult rectum and neonate’s colon but had no effect in the neonate rectum and adult colon. Capsaicin with a low concentration (0.01 nM–0.01 µM) increased contractile frequency in both the colon and rectum of adult rats. However, the effect of capsaicin on frequency was abolished at higher concentrations (0.01 µM–3 µM). A capsaicin-evoked change in contractile frequency in adult rats was blocked by capsazepine and L-NAME. At lower concentrations (0.01 nM–0.01 µM), capsaicin did not show any change in frequency in the neonatal colon, while a decrease in contractile frequency was observed with the higher concentrations (0.1 µM–3 µM) of capsaicin. In neonates, capsazepine pre-treatment produced changes in frequency for both the colon and rectum. However, pre-application of L-NAME decreased frequency in the neonate rectum but not in the colon. Conclusion: Capsaicin-induced changes in contractile activity may or may not involve TRPV1 or the Nitric Oxide (NO) pathway, depending on the part of the large gut and developmental maturity.

Prediction of detrusor function in patients with benign prostatic hyperplasia by non-invasive parameters / 现代泌尿外科杂志

【Objective】 To investigate the predictive value of non-invasive parameters in assessing detrusor function in patients with benign prostatic hyperplasia (BPH). 【Methods】 Clinical data of 384 BPH patients to undergo surgery were enrolled and retrospectively analyzed. The patients’ age and medical history time (MHT) were recorded. The free urinary flow rate was measured and maximum flow rate (Qmax) was recorded. Post-void residual (PVR) and voiding volume (VV) were measured with Bladder Scan, and bladder voiding efficiency (BVE) was calculated. Parameters including detrusor pressure (Pdet@Qmax) and Watts factor (WFmax) were collected in invasive urodynamic examination. Patients were grouped as detrusor underactivity (DU) group and non detrusor underactivity (NDU) group according to the results of WFmax, and the factors influencing detrusor function were analyzed with Logistic regression. The optimal cut-off values were confirmed with receiver operating characteristic (ROC) curve. 【Results】 Significant differences were observed in patients’ age, MHT, Qmax, PVR, BVE, Pdet@Qmax between the DU and NDU groups. Logistic regression showed that the overall prediction accuracy was higher when MHT, Qmax and BVE were included. The model prediction formula was Y=6.020-0.451XMHT+0.554XQmax-0.074XBVE. ROC curve showed when age ≥70.5 years and MHT≥ 7.5 years, there was a greater possibility of DU. When Qmax ≥5.7 mL/s and BVE ≥75.5%, the contractile function of detrusor was normal. Model prediction formula Y≥0.72 showed that detrusor contractility was normal. 【Conclusion】 Age, MHT, Qmax and BVE have certain predictive value for assessing detrusor function in BPH patients.

Contribución del acortamiento longitudinal y circunferencial al volumen sistólico y fracción de eyección en la estenosis aórtica grave / Contribution of Longitudinal and Circumferential Shortening to Stroke Volume and Ejection Fraction in Severe Aortic Stenosis

RESUMEN Introducción: El volumen sistólico (VS) del ventrículo izquierdo (VI) es eyectado por una combinación de acortamiento longitudinal (AL), circunferencial (AC) y giro ventricular. El AL se produce por el movimiento del anillo mitral hacia el ápex, lo que ocasiona engrosamiento de la pared (AC y radial), reducción de la cavidad ventricular y eyección del VS. No está definido el rol del AL en la estenosis aórtica (EAo). Objetivo: Analizar la contribución del AL y AC al VS y la fracción de eyección ventricular izquierda (FEVI) en la EAo grave. Materiales y métodos: Se estudiaron 152 pacientes (70 ± 12 años, 64 mujeres) con EAo grave (área valvular <1 cm2) con ecoDoppler cardíaco. La contribución del AL al VS se evalúo considerando a la base del corazón como un cilindro., con volumen = base × altura; la base, un círculo con radio igual a (espesor septal en sístole + espesor pared posterior en sístole + diámetro de fin de sístole)/2; y la altura, el promedio de la excursión sistólica del anillo lateral, septal, anterior e inferior. La contribución del AC al VS se estimó como: VS - contribución del AL al VS. Ambas contribuciones se expresaron en forma absoluta y como porcentajes del VS (% VS-AL y % VS-AC). Resultados: El AL contribuyó con 2 tercios aproximadamente al VS (68 ± 18 %) y el AC con el resto. El VS-AL correlacionó inversamente con el VS (r = - 0,45 p <0,001) y el VS-AC tuvo correlación directa (r = 0,45 p <0,001). La contribución del % VS-AL fue mayor en los pacientes con FEVI <50%. El % VS-AL correlacionó inversamente con el EPR (r = - 0,32 , p <0,01). Conclusión: La contribución del AL al VS es mayor que la del AC, y correlaciona inversamente con el VS. Es mayor el % VS-AL en los pacientes con FEVI <50%. Los hallazgos mencionados podrían tener implicancias al considerar puntos de corte para los índices de función longitudinal (strain) sin considerar la FEVI y/o geometría ventricular.

ABSTRACT Background: Left ventricular (LV) stroke volume (SV) is ejected by a combination of longitudinal shortening (LS), circumferential shortening (CS) and ventricular twist. Longitudinal shortening is caused by the motion of the mitral annulus towards the apex, causing wall thickening (CS and radial thickening), reduction of the ventricular cavity and LV ejection. The role of LS in aortic stenosis (AS) is not defined. Objective: The aim of this study was to analyze the contribution of LS and CS to SV and left ventricular ejection fraction (LVEF) in severe AS. Methods: The study included 152 patients (70 ± 12 years, 64 women) with severe AS (valve area <1 cm2) studied by cardiac Doppler echocardiography. The contribution of LS to SV was evaluated by considering the base of the heart as a cylinder, with volume = base x height; the base was assumed as a circle with radius equal to (systolic septal thickness + systolic posterior wall thickness + end-systolic diameter)/2; and height, as an average of the mitral lateral, septal, anterior and inferior annulus systolic excursion. The contribution of CS to SV was estimated as: SV - contribution of LS to SV. Both contributions were expressed in absolute form and as SV percentages (%SV-LS and %SV-CS). Results: Longitudinal shortening contributed with approximately 2 thirds of SV (68 ± 18 %) and CS with the rest. SV-LS correlated inversely with SV (r = - 0.45 p <0.001) and SV-CS had direct correlation (r = 0.45 p <0.001). The contribution of %SV-LS was greater in patients with LVEF <50%. Percent SV-LS correlated inversely with relative wall thickness (RWT) (r = 0.32, p <0.01). Conclusion: The contribution of LS to SV is greater than that of CS, and correlates inversely with SV. Percent SV-LS is higher in patients with EF <50%. The aforementioned findings could have implications when considering cut-off points for longitudinal function indices (strain) without considering LVEF and/or ventricular geometry.

Canagliflozin reduces the contractile response of isolated heart of normal adult rats / Canagliflozin reduce la respuesta contráctil del corazón aislado de ratas adultas normales

SUMMARY: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent a unique class of glucose-declining renal-targeted drugs. The SGLT2i Canagliflozin (CANA) is an anti-hyperglycemic drug that reduces various cardiovascular and renal outcomes in patients with type 2 diabetes mellitus. This study aimed to explore the potential effects of CANA on the isolated healthy adult rat hearts to show if CANA has positive inotropic or cardiac depressant effects via analyzing the amplitude and frequency of cardiac contractions. In isolated normal adult rat hearts, the effects of CANA on cardiac contractility were examined. In a dose-response curve, CANA led to a significant cardiac depressant effect in a dose-dependent manner. This cardiac depressant effect of CANA (10-6 M) was not prevented by atropine. However, this cardiac depressant effect was partially antagonized by both Isoproterenol (10-5 M) and Calcium chloride (10-6 M), suggesting beta-adrenoceptor and calcium channel blocking actions. In addition, the cardiac depressant effect of CANA (10-6 M) was mitigated in part by Nitric oxide synthase inhibitor, L-NAME, suggesting that its action probably depends to some extent on the accumulation of nitric oxide, which decreases the rise of intracellular Calcium. Data from this study demonstrate that CANA has a significant cardiac relaxant effect in isolated hearts of healthy adult rats by different possible mechanisms. This inhibitory effect on cardiac contractility may help improve the diastolic ventricular filling providing a therapeutic potential to help the other cardioprotective mechanisms of CANA in the prevention and treatment of heart failure.

RESUMEN: Los inhibidores del cotransportador de sodio- glucosa 2 (SGLT2i) representan una clase única de fármacos dirigidos a los riñones que disminuyen la glucosa. El SGLT2i Canagliflozin (CANA) es un fármaco antihiperglucémico que reduce varios resultados cardiovasculares y renales en pacientes con diabetes mellitus tipo 2. Este estudio tuvo como objetivo explorar los efectos potenciales de CANA en corazones aislados de ratas adultas sanas para indicar si CANA tiene efectos inotrópicos o depresores cardíacos positivos mediante el análisis de la amplitud y la frecuencia de las contracciones cardíacas. En corazones aislados de ratas adultas normales, se examinaron los efectos de CANA sobre la contractilidad cardíaca. En una curva de dosis-respuesta, CANA condujo a un efecto depresor cardíaco significativo de manera dependiente de la dosis. Este efecto depresor cardíaco de CANA (10-6 M) no fue impedido por la atropina. Sin embargo, este efecto depresor cardíaco fue parcialmente antagonizado tanto por el isoproterenol (10-5 M) como por el cloruro de calcio (10-6 M), lo que sugiere acciones bloqueadoras de los receptores beta adrenérgicos y de los canales de calcio. Además, el efecto depresor cardíaco de CANA (10-6 M) fue mitigado en parte por el inhibidor de la sintasa de óxido nítrico, L-NAME, lo que sugiere que su acción probablemente depende en cierta medida de la acumulación de óxido nítrico, lo que disminuye el aumento de calcio intracelular. Los datos de este estudio demuestran que CANA tiene un efecto relajante cardíaco significativo en corazones aislados de ratas adultas sanas por diferentes mecanismos posibles. Este efecto inhibitorio sobre la contractilidad cardíaca puede ayudar a mejorar el llenado ventricular diastólico proporcionando un potencial terapéutico para ayudar a los otros mecanismos cardioprotectores de CANA en la prevención y tratamiento de la insuficiencia cardíaca.

The effects of L-carnitine on gastrointestinal contractility and histological changes in rat intestinal ischemia-reperfusion Injury / Efectos de la l-carnitina sobre la contractilidad gastrointestinal y los cambios histológicos en la lesión por isquemia-reperfusión intestinal de rata

SUMMARY: Ischemia-reperfusion (I/R) of the small intestine causes serious abdominal pathologies including tissue dysfunction and organ failure. L-carnitine (L-C), a powerful antioxidant, may help lessen the severity of these pathological effects since it plays a key role in energy metabolism. In this work we aimed to study the effects of L-C on the isolated ileal and duodenal contractility and histological changes in intestinal ischemia and reperfusion injury. Twenty eight Wistar rats were divided into four groups. The first group is the control group. Second group, I/R group, had rats submitted to 45-minutes of intestinal ischemia and to 45-minutes reperfusion. The third group, I/R+ L-C group, rats were treated with L-C 5 minutes before reperfusion and than submitted to ischemia. The fourth group, included rats that were treated with L-C without ischemia or reperfusion. Intestinal ischemia was conducted by obstructing superior mesentery arteries by silk loop. The ileal and duodenal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (Ach) and relaxation was achieved with phenylephrine. At the same time the terminal ileal and duodenal segments were examined for histological changes. Ach-induced contraction responses were higher in the I/R+L-C group, the L-C group, and the control group compared to the I/R group, in both ileal and duodenal segments. On the other hand, the phenylephrine-induced relaxations were higher in the I/R+L-C and L-C groups, especially in duodenal segments. In I/R group intestinal morphology was observed to be severely damaged whereas in I/R+L-C group the damage was noticeably lower possibly due to protective properties of L-C. I/R injury caused severe cellular damage response within the muscularis resulting in decreased gastrointestinal motility. Treatment with the L-C has significantly affected the gastrointestinal contractility. Also L-C treatment reduced the damage in intestinal morphology that occurs after IR injury.

RESUMEN: La isquemia-reperfusión (I/R) del intestino delgado provoca graves patologías abdominales que incluyen disfunción tisular y falla orgánica. La L-carnitina (L-C), un poderoso antioxidante, puede ayudar a disminuir la gravedad de estos efectos patológicos, ya que desempeña un papel clave en el metabolismo energético. El objetivo de este trabajo fue estudiar los efectos de L-C sobre la contractilidad ileal y duodenal aislada y los cambios histológicos en la lesión por isquemia y reperfusión intestinal. Se dividieron 28 ratas Wistar en cuatro grupos. El primer grupo fue el control. El segundo grupo, grupo I/R, de ratas sometidas durante 45 minutos de isquemia intestinal y a 45 minutos de reperfusión. El tercer grupo, grupo I/R+ L-C, las ratas se trataron con L-C, 5 minutos antes de la reperfusión y luego se sometieron a isquemia. El cuarto grupo, las ratas fueron tratadas con L-C sin isquemia ni reperfusión. La isquemia intestinal se realizó obstruyendo la arteria mesentérica superior con un asa de seda. Los segmentos ileal y duodenal se aislaron y suspendieron en un baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (Ach) y la relajación se logró con fenilefrina. Al mismo tiempo, se examinaron cambios histológicos de los segmentos del íleon terminal y del duodeno. Las respuestas de contracción inducidas por Ach fueron mayores en el grupo I/R+L-C, el grupo L-C y el grupo control en comparación con el grupo I/R, tanto en el segmento ileal como en el duodenal. Por otra parte, las relajaciones inducidas por fenilefrina fueron mayores en los grupos I/R+L-C y L-C, especialmente en los segmentos duodenales. En el grupo I/R se observó que la morfología intestinal estaba dañada significativamente, mientras que en el grupo I/R+L-C el daño fue notablemente menor, posiblemente debido a las propiedades protectoras de L-C. La lesión por I/R causó una respuesta de daño celular severo dentro de la capa muscular que resultó en una disminución de la motilidad gastrointestinal. El tratamiento con L-C afectó significativamente la contractilidad gastrointestinal. Por otra parte, el tratamiento L-C redujo el daño en la morfología intestinal que ocurre después de la lesión por IR.

Determinantes de la fracción de eyección ventricular izquierda en pacientes con estenosis aórtica grave / Determinants of left ventricular ejection fraction in severe aortic stenosis

RESUMEN Introducción: En la estenosis aórtica (EAo) grave la fracción de eyección ventricular izquierda (FEVI) reducida (<50%) puede deberse a una disminución de la contractilidad, exceso de poscarga (EP) o a una combinación de ambos mecanismos. Sin embargo, cuando la FEVI es ≥50% algunos pacientes pueden tener la contractilidad disminuida. Objetivo: Evaluar el nivel de contractilidad (NC), EP y geometría ventricular como determinantes de la FEVI en pacientes con EAo grave. Material y métodos: Se estudiaron 184 pacientes con EAo grave y 71 individuos normales (N) mediante eco-Doppler cardíaco. El NC se determinó mediante la diferencia entre la fracción de acortamiento mesoparietal (FAm) medida (EAo) y la FAm predicha (N) menos 2 errores estándar para un valor determinado de estrés meridional de fin de sístole (EFS). Los pac con EAo fueron divididos en 4 grupos: FEVI <50% (n = 78), FEVI 50-59% (n = 27), FEVI 60-69% (n = 45) y FEVI ≥70% (n = 34). Resultados: El NC estuvo disminuido aproximadamente en la mitad de los pac. con FEVI <60% y en menor grado en los pacientes con FEVI ≥60%. El EP se observó en los pacientes con FEVI <50% con NC disminuido (34%) como así también con NC conservado (45%) Conclusiones: La mitad de los pacientes con FEVI <60% presentó NC disminuido y en menor proporción ello ocurrió en el resto de los pacientes, incluso hasta con FEVI ≥70%. La sobrestimación de la función sistólica utilizando la FEVI parece estar relacionada con el grado de hipertrofia concéntrica

ABSTRACT Background: In severe aortic stenosis (AS), reduced left ventricular ejection fraction (LVEF) (<50%) may be attributed to decreased contractility, afterload mismatch (AM) or a combination of both mechanisms. However, when LVEF is ≥50% some patients may have decreased contractility. Objective: The aim of this study was to assess contractility level (CL), AM and ventricular geometry as determinants of LVEF in patients with severe AS. Methods: Doppler echocardiography was used to study 184 patients with severe AS and 71 normal individuals (N). Contractility was assessed as the difference between measured and predicted midwall fractional shortening (mFS) minus 2 standard errors for an established meridional end-systolic stress (ESS). Patients with AS were divided into 4 groups: LVEF <50% (n = 78), LVEF 50-59% (n = 27), LVEF 60-69% (n = 45), and LVEF ≥70% (n = 34). Results: Decreased CL was observed in approximately half of the patients with LVEF <60% and in a lesser degree in patients with LVEF ≥60%. Afterload mismatch was found in patients with LVEF <50% with decreased (34%) as well as preserved (45%) CL. Conclusions: Half of the patients with LVEF <60% presented decreased CL and to a lesser extent this occurred in the rest of the patients, even with LVEF ≥70%. The overestimation of systolic function using LVEF seems to be related to the degree of concentric hypertrophy..

Glabridin alleviates ischemia/reperfusion-induced functional failure of smooth muscle of rat ileum by upregulating the cAMP / Glabridin alivia la falla funcional inducida por isquemia/reperfusión del músculo liso de ileum murino regulando el incremento de cAMP

Despite the development of modern medicine, alternative medicine, which has not lost its timeliness, remains attractive for the treatment of various diseases. Glabridin, a major flavonoid of Glycyrrhiza glabra, is known for its antioxidant and anti-inflammatory activity. The aim of this study was: 1) to determine the possible protective role of glabridin against ischemia/reperfusion (I/R) injury of the intestine; 2) to evaluate the in vitrocontractile responses of ileum smooth muscles to acetylcholine after an intestinal I/R; and 3) to explain the underlying molecular mechanism of its effect. Rats were assigned to groups of six rats each; 1) I/R, 2) gla10, 3) gla20, 4) gla40, 5) N5-[imino(nitroamino)methyl]-L-ornithine, methyl ester monohydrochloride (L-NAME)+gla40, and 6) Sham group. The healing effect of glabridin was abolished by L-NAME. Glabridin did not cause contractility of the smooth muscles to acetylcholine-induced contractile responses in intestinal I/R. Yet, it increased to spontaneous basal activity.

A pesar del desarrollo de la medicina moderna, la medicina alternativa, sin perder su vigencia, sigue siendo atractiva para el tratamiento de varias enfermedades. Glabradina, el flavonoide mayoritario de Glycyrrhiza glabra, es conocido por su actividad antioxidante y antiinflamatoria. Los propósitos de este estudio fueron: 1) Determinar el posible rol protector de glabradina ante daños intestinales por isquemia/reperfusion (I/R) 2) Evaluar in vitrolas respuestas de contracción de los músculos lisos del ileum ante acetilcolina después de I/R intestinal; y 3) Explicar el mecanismo molecular subyacente de este efecto. Se asignaron grupos de seis ratas: 1) I/R, 2) gla10, 3) gla20, 4) gla40, 5) N5-[imino(nitroamino)metil]-L-ornithina, metil ester monohidrochloruro (L-NAME)+gla40, y 6) Grupo testigo. El efecto curativo de glabridina fue abolido por L-NAME. Glabridina no causó contracción en el músculo liso como respuesta acetilcolina-inducida I/R. Además, incrementa la actividad basal expontánea.

Recovery rule of atrial contractility after Maze Ⅳ in patients with valvular atrial fibrillation / 中国胸心血管外科临床杂志

@#Objective    To analyze the recovery rule of atrial contractility (AC) function after Maze Ⅳ procedure of valvular atrial fibrillation (AF). Methods    In our hospital from March 2016 to April 2018, 103 patients who underwent cryoablation Maze Ⅳ procedure due to mitral valve lesions associated with persistent or long-term persistent AF were enrolled. There were 42 males and 61 females, with an average age of 58.5±9.1 years. Electrocardiogram and echocardiography were followed up at discharge and 1, 3, 6, 12 months after procedure. A multivariate Cox analysis of predictive factors for AC recovery was applied. Results    All the 103 patients were followed up for 1 year. The recovery rate of AC increased gradually after operation. It was not until 3 months after procedure that most of the right atrial contractility (RAC) was accompanied by synchronous recovery of the corresponding left atrial contractility (LAC, Kappa coefficient≥0.40, P<0.05). However, the coexistence of sinus rhythm (SR) and bilateral AC was not consistent well until 1 year after operation (Kappa coefficient≥0.40, P<0.05). One year after procedure, the recovery rates of SR and bilateral AC were 86.4% (89/103) and 66.0% (68/103) respectively. By Cox multivariate regression analysis, longer preoperative AF duration (P=0.040), larger preoperative left atrial diameter (LAD, P=0.003), and AC deletion 3 months after surgery (P=0.037) were predictive factors for AF recurrence in the middle and advanced stages (>3 months) after Maze surgery. At the same time, longer preoperative AF duration and larger preoperative LAD were also negative predictors of middle and late recovery of LAC and bilateral AC (All P<0.05). Receiver operating characteristic curve analysis showed that the best critical value of preoperative AF time and preoperative LAD for prediction of AC recovery was 37 months (sensitivity 99.6%, specificity 76.3%) and 60.5 mm (sensitivity 98.5%, specificity 78.9%), respectively. Conclusion    The recovery of AC after Maze procedure is a dynamic improvement process. Early recovery of AC is beneficial to the stable maintenance of SR in the future. Prolonged duration of AF and enlarged LAD have adverse effects on the outcome of Maze Ⅳ procedure.

Effects of leaf extracts of Vernonia amygdalina on the force and rate of contractility of an isolated mammalian heart

Background: Vernonia amygdalina is a common medicinal plant that is widely used by local communities and traditional herbalists in central Uganda in management of various conditions including hypertension that occurs as a result of changes in heart contractility. However, there is limited scientific information of V. amygdalina effects on the force and rate of contractility of the heart. The study evaluated the inotropic and chronotropic effect of methanol, aqueous, ether and total crude leaf extracts of V. amygdalina on isolated perfused rabbit heart.Methods: An experimental laboratory based study determined the effects of V. amygdalina extracts on the rate and force of contraction isolated perfused rabbit using the Langendorff抯 heart perfusion experiment and methods. The heart rate (beats/minute) was counted per minute. The force of contraction of the heart was determined measuring the height of each peak on the kymogram.Results: The findings showed that the force and rate of heart contractility reduced with increasing doses of methanol, aqueous ether and total crude leaf extracts at doses of 0.5, 8.0, 62.0 and 250.0 mg/ml. The force and rate of heart contractility at a dose of 250.0 mg/ml for all the extracts were comparable to that of acetylcholine drug to almost causing cardiac arrest.Conclusions: The leaf extracts of V. amygdalina contain compounds that reduced the force and rate of contraction of an isolated rabbit heart.

Outcomes of the patients of heart failure with reduced ejection fraction receiving inotropic support in initial 6 hours: Insights from Manipal Heart Failure Registry

Heart failure (HF) is responsible for 1.8 million admissions annually in India with an additional burden of mortalityand re-hospitalizations. Positive inotropes with multiple mechanisms, such as dopamine and levosimendan, are beingused for more than three decades to treat the patients of acute HF with reduced ejection fraction (HFrEF). This studycompared the outcomes of the dopamine and the levosimendan up to 180 days. We have selected the patients fromManipal Heart Failure Registry who were diagnosed to have HFrEF (left ventricular EF less than 50%) and wereinitiated on either dopamine or levosimendan in first 6 hours of hospitalization. The study included a total of 187patients; among them, 120 patients were analyzed in the dopamine group, and 67 patients in the levosimendan group.Dopamine was initiated as intravenous infusion with the dose of 2.5 microgram/kilogram/minute (mcg/kg/minute)and up-titrated up to 10 mcg/kg/minute. Levosimendan was also administered intravenously with a dose of 0.1 mcg/kg/minute and up-titrated up to 0.4 mcg/kg/minute. The primary outcomes include a composite of all-cause mortalityand re-hospitalization at 30-days and 180-days follow-ups. The in-hospital mortality, 30-days mortality and 180-daysmortality, and composite outcomes were noted higher in levosimendan treated patients even after matched demographicparameters (age and gender) and comparable comorbidities and risk factors, i.e., smoking, alcohol consumption,hypertension, diabetes mellitus, and atrial fibrillation. However, reduced EF, raised serum creatinine, procalcitonin,and N-terminal pro b-type natriuretic peptide levels and high use of digoxin were noticed in levosimendan groupduring the initial period of index-hospitalization and these can be considered as confounding factors for future studies.

Serum urocortin in preterm labor is it an effective biomarker?

Background: Preterm labor classically defined as delivery before completed 37 gestational weeks. Urocortin a biomarker that have raised recent research interest is a 40-amino acid neuropeptide related to the corticotrophin-releasing factor molecular family. Interestingly urocortin is produced by gestational tissue such as amnion and chorion predictability of preterm labor by biomarker assay could enhance management levels particularly in cases of preterm labor that are considered a frequent clinical scenario in obstetric practice. Aim of the study was to assess and evaluate the serum levels of urocortin predictability capacity in cases that develop preterm labor.Methods: The current research clinical trial was conducted in a prospective way there was two research groups 60 study subjects had threatened preterm labor and 60 normal research study subjects that delivered at term. Comparative analysis was performed for urocortin assay conducted in both research groups in correlation to gathered clinical data obtained from both research groups.Results: Receiver operating characteristic curve (ROC) between preterm and term delivery research groups as regards plasma urocortin level (pg/ml) as a predictor of pre term delivery showing that a cut-off point level >101.3 pg/ml in which statistical sensitivity=88.33%, statistical specificity=75%, positive predictive value=77.9, negative predictive value=86.5.Conclusions: This research finding reveal that maternal serum urocortin is an effective biomarker in predictability of preterm labor; however future research studies should be multicentric in fashion putting in consideration the racial and ethnic differences besides the impact of BMI on maternal serum urocortin indices.

Aspectos novedosos de la intoxicación digitálica / New aspects on digitalis toxicity

Los digitálicos son fármacos con capacidad de aumentar la contractilidad miocárdica (inotrópico positivo), que han desempeñado un rol primordial en el tratamiento de pacientes con insuficiencia cardiaca; su uso inapropiado puede traer complicaciones serias a estos pacientes, incluso, hasta la muerte. La más importante de estas complicaciones es la intoxicación digitálica, originada por la sobredosis de dichos fármacos, a causa de la combinación del efecto inhibitorio en la conducción nodal y la estimulación sobre las fibras individuales auriculares y ventriculares. Debido al uso frecuente de estos medicamentos en todos los niveles de atención de salud y lo difícil que resulta diagnosticar dicha complicación por la complejidad de su cuadro clínico y de su expresión electrocardiográfica, se realizó una revisión bibliográfica exhaustiva sobre el tema para brindar amplia información, que permita una atención adecuada a los pacientes con este diagnóstico

Digitalis are drugs with the capacity of increasing myocardial contractility (inotropic positive agents) which have carried out an important role in the treatment of heart failure; their inappropriate use can bring severe complications to the patient, even, to death. The most important in these complications is the digitalis toxicity, originated by the overdose of these drugs, caused by the combination of the inhibitory effect in the nodal conduction and stimulation on the individual atrial and ventricular fibers. Due to the frequent use of these medications at all levels of medical care and to the difficulty in diagnosing this complication caused by the complexity of their clinical pattern and of their electrocardiographic expression, an exhaustive literature review was carried out on the topic to give a wide information that allows an appropriate care to the patients with this diagnosis

The Inhibitory Mechanism on Acetylcholine-Induced Contraction of Bladder Smooth Muscle in the Streptozotocin-Induced Diabetic Rat

Most diabetic patients experience diabetic mellitus (DM) urinary bladder dysfunction. A number of studies evaluate bladder smooth muscle contraction in DM. In this study, we evaluated the change of bladder smooth muscle contraction between normal rats and DM rats. Furthermore, we used pharmacological inhibitors to determine the differences in the signaling pathways between normal and DM rats. Rats in the DM group received an intraperitoneal injection of 65 mg/kg streptozotocin and measured blood glucose level after 14 days to confirm DM. Bladder smooth muscle contraction was induced using acetylcholine (ACh, 10⁻⁴ M). The materials such as, atropine (a muscarinic receptor antagonist), U73122 (a phospholipase C inhibitor), DPCPX (an adenosine A1 receptor antagonist), udenafil (a PDE5 inhibitor), prazosin (an α₁-receptor antagonist), papaverine (a smooth muscle relaxant), verapamil (a calcium channel blocker), and chelerythrine (a protein kinase C inhibitor) were pre-treated in bladder smooth muscle. We found that the DM rats had lower bladder smooth muscle contractility than normal rats. When prazosin, udenafil, verapamil, and U73122 were pre-treated, there were significant differences between normal and DM rats. Taken together, it was concluded that the change of intracellular Ca²⁺ release mediated by PLC/IP3 and PDE5 activity were responsible for decreased bladder smooth muscle contractility in DM rats.

Effects of Ethyl Acetate Part from Ethanol Extract of Miao Medicine Periploca forrestii on Cardiac Function of Isolated Frog Heart / 中国药房

OBJECTIVE： To study the effects of ethyl acetate part form the ethanol extract of Periploca forrestii on cardiac function of isolated frog heart， and to primarily investigate its potential mechanism. METHODS： The isolated frog heart samples were prepared by using the intube method of steinmann. The Ren’s solution （blank control）， 1.70 mg/mL and 3.48 mg/mL ethyl acetate part from ethanol extract of P. forrestii were used to perfuse the sample. The BL-420 biological function experimental system was used to record the changes in heart rate and myocardial contractility. The effects of ethyl acetate part from ethanol extract of P. forrestii on cardiac function of isolated frog heart were investigated. After perfused with 10 mg/L atropine， 20 μL isoproterenol， 1 μL low calcium （per 1 000 mL pure water contain 0.06 g CaCl2）， high calcium Ren’s solution （per 1 000 mL pure water contain 0.24 g CaCl2）， adding 1.74 mg/mL ethyl acetate part from ethanol extract of P. forrestii， the changes of myocardial contractility in isolated hearts were recorded by BL-420 biological function experimental system. Myocardial tissue was collected after perfused with Ren’s solution （blank control） and ethyl acetate part from ethanol extract of P. forrestii with 1.74 and 3.48   mg/mL. The activity of Na+-K+-ATPase， Ca2+-Mg2+-ATPase and AChE were detected to investigate the potential mechanism of the effects of ethyl acetate extract from ethanol extract of P. forrestii on cardiac function. RESULTS： Compared with blank control， mean myocardial contractility was significantly decreased （P＜0.001） after adding 1.74， 3.48 mg/mL ethyl acetate part form ethanol extract of P. forrestii， but had no significant on heart rate （P＞0.05）. With the increase of extracellular Ca2+ concentration， the inhibitory effect of ethyl acetate part from ethanol extract of P. forrestii on isolated frog heart contraction also increased gradually. After adding atropine and isoproterenol， the inhibitory effect of the ethyl acetate part form ethanol extract of P. forrestii on isolated frog heart contraction decreased to some certain. The activity of Na+-K+-ATPase in cardiac tissue was not significantly changed （P＞0.05）， the activity of Ca2+-Mg2+-ATPase was significantly increased （P＜0.05）， and the activity of AChE was significantly decreased （P＜0.05） after perfused with 1.74， 3.48 mg/mL ethyl acetate part form ethanol extract of P. forrestii. CONCLUSIONS： The ethyl acetate part from the ethanol extract of P. forrestii can inhibit the contractile activity of the isolated frog heart and has a certain negative inotropic effect. The mechanism may be related to the increase of Ca2+-Mg2+-ATPase activity， inhibition of AChE activity， blocking of calcium channel in the cell membrane， the activation of M receptor and blocking of β receptor.

Effects of total flavones of rhododendra on contractility of rat myocardial cells and its mechanism / 安徽医科大学学报

Objective To investigate the total flavones of rhododendra(TFR) on contractility of rat myocardial cells and its possible mechanism. Methods The contraction amplitude and contraction frequency of primary cultured rat myocardial cells were observed by image analysis system. The intracellular free Ca2 + content was measured by calcium ion imaging system. Results 10 and 100 nmol /L hU Ⅱ significantly accelerated the contraction frequency of myocardial cells,and 10 nmol /L hU Ⅱ increased the contraction amplitude of myocardial cells,but 100 nmol /L hU Ⅱ reduced the contraction amplitude of myocardial cells. TFR 300 mg /L significantly slowed the contraction frequency of rat myocardial cells and increased the contraction amplitude. TFR in the range of 33. 3 ～ 300 mg /L could significantly inhibit the increase of contraction frequency,the decrease of contraction amplitude and the increase of intracellular free Ca2 + content induced by 100 nmol /L hU Ⅱ. Conclusion TFR can slow down the contraction frequency of myocardial cells and increase its contractility,which may be related to the decrease of free Ca2 + content in myocardial cells.

Uterotonic Potential of Selected Plants Used by Ugandan Local Communities in the Treatment of Malaria

Malaria is a major cause of death among pregnant women and children under the age of five in Uganda. It is the leading cause of anemia among pregnant women and low birth weight in infants [1]. Majority of the rural population rely on herbs for treatment of various diseases. The leaf extracts of various plants including Bothlioclines longipes, Vernonia amygdalina, Rhus natalensis and Maesa lanceolata are used to treat various diseases including malaria in Uganda. The local communities prefer herbal preparations from the leaves of the plants. Extracts from the leaves of the plants were proven efficacious against P. falciparum in earlier studies in vitro. This study was carried out to investigate the effect of Diethyl ether and methanol extracts on the contractility of an isolated rabbit uterus and also to quantitatively analyze for iron and zinc in the leaves of these plants. The diethyl ether extracts of V. amygdalina, M. lanceolata and R. natalensis at a concentration of 0.4 mg/ml and 0.8 mg/ml exhibited contractility amplitudes of 26.0 mm, 21.5 mm and 27.5 mm and 22.5±1.10 mm, 15.0±1.78 mm and 24.5 ±0.99 mm respectively. The methanol extracts were 25.5±0.70 mm, 23±1.34 mm, 22±1.01 mm and 37.8±1.26 mm, 16.7±2.01 mm, 24.3±0.06 mm respectively, while oxytocin showed 22.8±0.57 mm and 31.0±0.36 mm respectively. The plant leaves were found to have high levels of iron ranging from 2516.587±17.983 (mg/100 g) in B. longipes to 583.317±9.505 (mg/100 g) in V. amygdalina. Rhus natalensis and V. amygdalina had low levels of Zinc. Anti-nutritive phytocompounds such as saponins and Tannins were also detected in some of the test extracts. The study concludes that plants used by pregnant women may have either a positive or negative effect on expectant mothers. There is need to formulate evidence based effective medicines for their safe use in the management of malaria.

The change of signaling pathway on the electrical stimulated contraction in streptozotocin-induced bladder dysfunction of rats

Bladder dysfunction is a common complication of diabetes mellitus (DM). However, there have been a few studies evaluating bladder smooth muscle contraction in DM in the presence of pharmacological inhibitors. In the present study, we compared the contractility of bladder smooth muscle from normal rats and DM rats. Furthermore, we utilized pharmacological inhibitors to delineate the mechanisms underlying bladder muscle differences between normal and DM rats. DM was established in 14 days after using a single injection of streptozotocin (65 mg/kg, intraperitoneal) in Sprague-Dawley rats. Bladder smooth muscle contraction was induced electrically using electrical field stimulation consisting of pulse trains at an amplitude of 40 V and pulse duration of 1 ms at frequencies of 2–10 Hz. In this study, the pharmacological inhibitors atropine (muscarinic receptor antagonist), U73122 (phospholipase C inhibitor), DPCPX (adenosine A₁ receptor antagonist), udenafil (PDE5 inhibitor), prazosin (α₁-receptor antagonist), verapamil (calcium channel blocker), and chelerythrine (protein kinase C inhibitor) were used to pretreat bladder smooth muscles. It was found that the contractility of bladder smooth muscles from DM rats was lower than that of normal rats. In addition, there were significant differences in percent change of contractility between normal and DM rats following pretreatment with prazosin, udenafil, verapamil, and U73122. In conclusion, we suggest that the decreased bladder muscle contractility in DM rats was a result of perturbations in PLC/IP₃-mediated intracellular Ca²⁺ release and PDE5 activity.

Influence of tea pigment on cardiac activity in exsomatized toads of myocardial ischemia / 重庆医学

Objective To observe the influence of tea pigment on myocardial contractility,electrocardiogram(ECG) and heart rate in exsomatized toads under the condition of myocardialischemia.Methods Sixty toads were divided into the normal exsomatized toad heart group(A) and myocardial ischemia toad heart(B).Then the group A was re-divided into the Ringer's solution group (A1),tea pigment low dose(200 mg/L) group(A2) and the high dose(400 mg/L) group(A3);the group B was re-divided into the pituitrin model group(B1),pituitrin + tea pigment low dose(200 mg/L) group(B2) and high dose(400 mg/L) group(B3).The BL-420S biological function experiment system was used to record the myocardial contractile force and ECG change curve of exsomatized toad.Results Compared with the group A1,the myocardial contractility in the group A3 was obviously increased(P＜0.05),the difference in the group A2 had no statistical significance(P＞0.05);the QRS peak value of ECG and heart rate had no statistically significant difference(P＞0.05);compared with the group A1,the myocardial contractility,ECG QRS peak value and heart rate in the group B1 were significantly decreased(P＜0.05);compared with the group B1,the myocardial contractility,ECG QRS peak value and heart rate in the group B2 and B3 were significantly increased(P＜0.05).Conclusion Tea pigment can obviously improve the decrease of the exsomatized toad cardiac activity caused by myocardial ischemia.