RESUMEN
BACKGROUND: Numerous studies have demonstrated the accuracy of epiaortic ultrasound scanning (EAS) for assessing ascending aortic disease. It remains unclear whether EAS changes the incidence of perioperative stroke after off-pump coronary artery bypass (OPCAB). METHODS: We studied a retrospective cohort of 2292 patients who underwent isolated OPCAB from January 2001 to December 2011. Patients were retrospectively subdivided into two groups: the non-EAS group (n=1019) who underwent OPCAB under only intraoperative transoesophageal echocardiography and the EAS group (n=1273) who underwent OPCAB under EAS. RESULTS: In the non-EAS group, 317 (31.1%) patients underwent OPCAB with partial aortic clamping and 702 (68.9%) underwent OPCAB without partial aorta clamping. In the EAS group, 301 (23.7%) patients underwent OPCAB with partial aortic clamping and 972 (76.3%) underwent OPCAB without partial aortic clamping. The incidence of early stroke was not different statistically between the EAS and non-EAS groups [non-EAS 1.7% (17/1019) vs EAS 0.8% (10/1273); P=0.052]. However, in the subgroups of patients with partial aorta clamping, the incidence of the early stroke was significantly lower in the EAS group [2.8% (9/317) vs 0.7% (2/301) P=0.041]. CONCLUSIONS: EAS has a significant clinical benefit in reducing the incidence of early stroke in cases of partial aortic clamping in OPCAB. Therefore, EAS should be considered in patients who need partial aortic clamping in OPCAB.
Asunto(s)
Aorta/diagnóstico por imagen , Puente de Arteria Coronaria Off-Pump/métodos , Monitoreo Intraoperatorio/métodos , Accidente Cerebrovascular/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Constricción , Ecocardiografía Transesofágica/métodos , Femenino , Humanos , Incidencia , Corea (Geográfico)/epidemiología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiologíaRESUMEN
BACKGROUND: The aim of this randomized and controlled trial was to investigate the effect of a glucose-insulin-potassium (GIK) solution on myocardial protection in acute coronary syndrome (ACS) patients undergoing urgent multivessel off-pump coronary artery bypass (OPCAB) surgery. METHODS: Sixty-six patients were randomly allocated either to receive 0.3 ml kg(-1) h(-2) GIK solution (potassium 80 mEq and regular insulin 325 IU in 500 ml of 50% glucose) or equivalent volume of normal saline (control) upon anaesthetic induction until 6 h after reperfusion. The primary endpoints were to compare the concentrations of creatine kinase-MB (CK-MB) and troponin-T between the groups after reperfusion. The secondary endpoints were to compare the incidences of postoperative troponin-T >0.8 ng ml(-1) and myocardial infarction (MI) between the groups. RESULTS: Highest CK-MB [8.7 (4.4) vs 13.1 (7.9) ng ml(-1), P=0.006] and troponin-T [0.20 (0.13-0.49) vs 0.48 (0.18-0.91) ng ml(-1), P<0.0001] values after reperfusion were significantly lower in the GIK group compared with the control group. The area under the curve of serially measured troponin-T was also significantly smaller in the GIK group compared with the control group [0.83 (0.43-1.81) vs 0.46 (0.31-1.00), P=0.036]. Significantly fewer patients in the GIK group showed troponin-T >0.8 ng ml(-1) after reperfusion compared with the control group (3 vs 11, P=0.033). The incidence of postoperative MI was similar between the groups. CONCLUSIONS: GIK administration in ACS patients undergoing urgent multivessel OPCAB significantly attenuated the degree of ensuing myocardial injury without complications related to glycaemic control. Clinical Trial Registry. URL: http://clinicaltrials.gov/ct2/show/NCT01384656?term=GIK+AND+OPCAB&rank=1. Unique identification number NCT01384656.
Asunto(s)
Síndrome Coronario Agudo/cirugía , Cardiotónicos , Puente de Arteria Coronaria Off-Pump , Glucosa/uso terapéutico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Potasio/uso terapéutico , Adulto , Anciano , Comorbilidad , Forma MB de la Creatina-Quinasa/sangre , Método Doble Ciego , Determinación de Punto Final , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Atención Perioperativa , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Troponina T/sangreRESUMEN
BACKGROUND: Pulmonary dysfunction related to inflammatory response and radical oxygen species remains a problem in off-pump coronary bypass graft surgery (OPCAB), especially in patients with reduced left ventricular (LV) function. The aim of this study was to evaluate the effect of N-acetylcysteine (NAC) on pulmonary function following OPCAB. METHODS: Patients with LV ejection fraction ≤40% were randomly assigned to receive either a bolus of 100 mg/kg of intravenous NAC over a 15-min period immediately after anesthetic induction, followed by an intravenous infusion at 40 mg/kg/day for 24 h (NAC group, n=24), or a placebo (control group, n=24). Hemodynamic and pulmonary parameters, and the incidence of acute lung injury (PaO(2)/FiO(2)<300 mmHg) were assessed and compared. RESULTS: The pulmonary vascular resistance index (PVRI) did not change during mechanical heart displacement compared with the baseline value in the NAC group while it was significantly increased in the control group. Significantly less number of patients developed acute lung injury at 2 h after the surgery in the NAC group. The other pulmonary parameters and the duration of ventilator care were all similar. CONCLUSIONS: NAC demonstrated promising results in terms of mitigating the increase in PVRI during mechanical heart displacement and attenuating the development of acute lung injury in the immediate post-operative period. However, NAC could not induce a definite improvement in the other important pulmonary variables including PaO(2)/FiO(2) and Q(s)/Q(t), and did not lead to a decreased duration of ventilatory care or length of stay in the intensive care unit.
Asunto(s)
Acetilcisteína/farmacología , Puente de Arteria Coronaria Off-Pump , Depuradores de Radicales Libres/farmacología , Pulmón/fisiología , Lesión Pulmonar Aguda/epidemiología , Lesión Pulmonar Aguda/prevención & control , Anciano , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , Creatina Quinasa/sangre , Método Doble Ciego , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Pulmón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/prevención & control , Circulación Pulmonar/efectos de los fármacos , Pruebas de Función Respiratoria , Resistencia Vascular/efectos de los fármacos , Disfunción Ventricular Izquierda/fisiopatología , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
Dentin collagen is a major component of the hybrid layer, and its stability may have a great impact on the properties of adhesive interfaces. We tested the hypothesis that the use of tannic acid (TA), a collagen cross-linking agent, may affect the mechanical properties and stability of the dentin matrix. The present study evaluated the effects of different concentrations of TA on the modulus of elasticity and enzymatic degradation of dentin matrix. Hence, the effect of TA pre-treatment on resin-dentin bond strength was assessed with the use of two bonding systems. Sound human molars were used and prepared according to each experimental design. The use of TA affected the properties of demineralized dentin by increasing its stiffness. TA treatment inhibited the effect of collagenase digestion on dentin matrix, particularly for 10%TA and 20%TA. The TA-dentin matrix complex resulted in improved bond strength for both adhesive systems.
Asunto(s)
Reactivos de Enlaces Cruzados/farmacología , Dentina/efectos de los fármacos , Taninos/farmacología , Grabado Ácido Dental , Fenómenos Biomecánicos , Bisfenol A Glicidil Metacrilato/química , Colágeno/efectos de los fármacos , Colagenasas/farmacología , Resinas Compuestas/química , Reactivos de Enlaces Cruzados/administración & dosificación , Técnica de Descalcificación , Recubrimiento Dental Adhesivo , Análisis del Estrés Dental/instrumentación , Recubrimientos Dentinarios/química , Módulo de Elasticidad , Humanos , Ácidos Fosfóricos/química , Estrés Mecánico , Taninos/administración & dosificación , Temperatura , Resistencia a la Tracción , Factores de Tiempo , Agua/químicaRESUMEN
We present the clinical and molecular findings of mosaic ring chromosome 4. The patient was referred to us for infertility and short stature. Results of three repeated cytogenetic analyses from lymphocytes showed a similar mosaic karyotype with multiple cell-lines [46,XX,r(4)/45,XX,-4/46,XX,dic r(4)/47,XX,r(4),+r(4)/46,XX]. FISH showed deletion of the 4p subtelomeric region and the 4q telomeric region from the ring chromosome 4. The breakpoints were mapped using molecular analysis. Parental karyotypes were normal. During the course of this study, the patient became pregnant without assisted reproductive technology. The result of amniocentesis performed at 16 weeks gestation showed a normal karyotype. Delivery was uncomplicated. This is the first report, to our knowledge, of the presence of ring chromosome 4 having various mosaic conditions in a female having a chromosomally normal fetus.
Asunto(s)
Cromosomas Humanos Par 4/genética , Cromosomas en Anillo , Adulto , Femenino , Asesoramiento Genético , Humanos , Hibridación Fluorescente in Situ , Recién Nacido , Cariotipificación , Mosaicismo , Embarazo , Resultado del EmbarazoRESUMEN
BACKGROUND: The effect of haemodynamic derangement during coronary artery anastomosis in off-pump coronary artery bypass surgery on cerebral blood flow has not been elucidated. Jugular bulb oxygen saturation is a useful indicator of cerebral blood flow provided that the cerebral metabolic rate is constant. This study was designed to evaluate the changes in jugular bulb oxygen saturation during off-pump coronary artery bypass surgery. METHODS: With IRB approval, 48 patients were included. After anaesthesia, an 18-G catheter was introduced into the jugular bulb. Haemodynamic variables and oxygen profiles from gas analysis of jugular bulb blood and arterial blood were obtained: after sternotomy (baseline); at 5 min after the beginning of the anastomosis of the left anterior descending artery, obtuse marginal artery, and right coronary artery; and after sternal closure. RESULTS: Cardiac index and mixed venous oxygen saturation decreased significantly during anastomosis of all three arteries compared to the baseline value. Although the changes in jugular bulb oxygen saturation during anastomosis were statistically significant compared to its baseline value, jugular bulb oxygen saturation remained within normal limit throughout the study. CONCLUSIONS: Jugular bulb oxygen saturation, which represents the global cerebral oxygenation, was well maintained during the anastomosis of all coronary arteries despite significant haemodynamic changes during off-pump coronary artery bypass (OPCAB).
Asunto(s)
Circulación Cerebrovascular , Puente de Arteria Coronaria , Venas Yugulares/metabolismo , Oxígeno/sangre , Adulto , Anciano , Dióxido de Carbono/sangre , Puente Cardiopulmonar , Humanos , Persona de Mediana EdadRESUMEN
The haemodynamic effects of a continuous infusion of milrinone without an initial bolus dose were evaluated in patients undergoing off-pump coronary artery bypass graft surgery. After internal mammary artery harvest, milrinone 0.5 microg.min(-1).kg(-1) (29 patients) or a normal saline infusion (33 patients) was started and continued until all graft anastomoses were completed. Haemodynamic variables were recorded before application of the tissue stabiliser, at 1, 3, 5 and 10 min after the application of the stabiliser, and after its removal. The administration of a milrinone infusion was associated with a smaller decrease in cardiac output and mixed venous oxygen saturation during all the coronary artery anastomoses, with no severe complications and a decreased dose of norepinephrine infused to maintain systemic arterial pressure.
Asunto(s)
Cardiotónicos/farmacología , Hemodinámica/efectos de los fármacos , Anastomosis Interna Mamario-Coronaria/métodos , Milrinona/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Anciano , Puente Cardiopulmonar , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Cuidados Intraoperatorios/métodos , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Presión ParcialRESUMEN
OBJECTIVES: Hemodynamic derangement during displacement of beating heart in off-pump coronary artery bypass graft (OPCAB) surgery might be related with right ventricular (RV) dysfunction. We evaluated RV function and hemodynamic alterations using a thermodilution pulmonary artery catheter. METHODS: The study included 30 patients undergoing OPCAB, using single pericardial suture and tissue stabilizer. A thermodilution pulmonary artery catheter for continuous monitoring of the cardiac output (CO), right ventricular ejection fraction (RVEF) and RV volume was inserted before anesthesia. The hemodynamic variables were measured after the induction of anesthesia, 5 min after the heart was positioned for each coronary anastomosis and after the sternum was closed. RESULTS: There was no significant change in the RVEF and cardiac index during anastomosis of the left anterior descending artery and right coronary artery. However, the significantly reduced RVEF accompanied by an increase in RV afterload and decrease in the CO was observed during anastomosis of the obtuse marginal (OM) artery. RV volumes did not significantly change during anastomoses, though the right atrial pressure increased during anastomoses of all coronary arteries. CONCLUSIONS: The displacement of beating heart for positioning during anastomosis of the graft to OM artery caused significant derangement of RV function and decrease in CO. A thermodilution catheter continuously measuring the CO and RVEF was useful to monitor the change in RV function and volume during OPCAB.
Asunto(s)
Puente de Arteria Coronaria/métodos , Función Ventricular Derecha/fisiología , Anciano , Puente Cardiopulmonar , Femenino , Hemodinámica , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/métodos , Estudios Prospectivos , Volumen Sistólico , TermodiluciónRESUMEN
BACKGROUND: Little is known about the effect of heart cell transplantation into the dilated cardiomyopathic myocardium. This study was designed to evaluate the effect of heart cell transplantation into dilated cardiomyopathic hamsters. METHODS AND RESULTS: Ventricular heart cells were isolated from 4-week-old BIO 53. 58 hamsters and cultured for 2 weeks before transplantation. The cells were labeled with bromodeoxyuridine (BrdU) before transplantation for identification. Adult hamsters (17 weeks old) were used as recipients. Heart cells (4 x 10(6) cells) or culture medium was transplanted into the left ventricular free wall (transplantation and control groups, respectively, n=12 each). Sham-operated hamsters (n=12) underwent the surgery but not the transplantation. Cyclosporine A was administered subcutaneously to all hamsters daily after the operation. Four weeks after the transplantation, heart function was evaluated with the use of a Langendorff preparation. Histology showed severe focal myocardial necrosis in all groups. BrdU-stained tissue was found at the cell transplantation sites. The transplanted hearts had greater (P:<0. 001) developed pressures at all balloon volumes and improved dP/dt (transplantation 915+/-253 versus control 453+/-120 and sham 530+/-187 mm Hg/s, P:<0.001, balloon volume of 15 microL). No differences in ventricular function were found between control and sham-operated hamsters. CONCLUSIONS: The transplanted ventricular heart cells formed cardiac-like tissue in cardiomyopathic myocardium and improved its contractile function.
Asunto(s)
Cardiomiopatía Dilatada/cirugía , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/trasplante , Miocardio/citología , Animales , Presión Sanguínea , Bromodesoxiuridina , Volumen Cardíaco , Cardiomiopatía Dilatada/patología , Células Cultivadas , Cricetinae , Diástole , Modelos Animales de Enfermedad , Supervivencia de Injerto , Inmunohistoquímica , Técnicas In Vitro , Masculino , Miocardio/metabolismo , Miocardio/patología , Cadenas Pesadas de Miosina/metabolismo , Cadenas Ligeras de Miosina/metabolismo , Troponina/metabolismo , Función Ventricular Izquierda/fisiologíaRESUMEN
BACKGROUND: Transplantation of myocytes into scarred myocardium has been shown to inhibit ventricular remodeling and maintain myocardial contractility. However, the effect of cell transplantation on hearts with global rather than regional dysfunction is unknown. Therefore, we evaluated the effect of transplantation of autologous smooth muscle cells on the morphometry and function of dilated cardiomyopathic hearts. METHODS: Smooth muscle cells were isolated from the ductus deferens of 13-week-old BIO 53.58 hamsters with dilated cardiomyopathy, and cultured for 4 weeks before transplantation. Smooth muscle cells (4 x 10(6) cells) or culture medium were injected into 17-week-old animals in the transplantation and control groups (n = 12 each), respectively. Prelabeling of the smooth muscle cells with 5-bromo-2'-deoxyuridine was performed before transplantation in a group of transplanted hamsters. Another group (sham, n = 12) underwent the operation but did not receive an injection either of smooth muscle cells or of culture medium. Four weeks after transplantation, heart function was evaluated in a Langendorff preparation. RESULTS: Musclelike tissue, labeled with 5-bromo-2'-deoxyuridine, was found at the site of transplantation in the cell-transplanted animals. The cell-transplanted hearts were smaller (p < 0.001), and had greater developed pressures and maximum rate of increase of left ventricular pressure (both p < 0.001) than control and sham hearts. Control hamsters injected with culture medium did not differ from sham-operated animals. CONCLUSIONS: Transplantation of autologous smooth muscle cells prevented cardiac dilatation and improved ventricular function in hamsters with dilated cardiomyopathy.
Asunto(s)
Cardiomiopatía Dilatada/cirugía , Músculo Liso/citología , Músculo Liso/trasplante , Animales , Cardiomiopatía Dilatada/fisiopatología , Células Cultivadas , Cricetinae , Miocardio/citología , Trasplante Autólogo , Función Ventricular IzquierdaRESUMEN
Apoptosis of SK-HEP-1 human hepatoma cells induced by treatment with ginsenoside Rh2 (G-Rh2) is associated with rapid and selective activation of cyclin A-associated cyclin-dependent kinase 2 (Cdk2). Here, we show that in apoptotic cells, the Cdk inhibitory protein p21(WAF1/CIP1), which is associated with the cyclin A-Cdk2 complex, undergoes selective proteolytic cleavage. In contrast, another Cdk inhibitory protein, p27(KIP1), which is associated with cyclin A-Cdk2 and cyclin E-Cdk2 complexes, remained unaltered during apoptosis. Ectopic overexpression of p21(WAF1/CIP1) suppressed apoptosis as well as cyclin A-Cdk2 activity induced by treatment of SK-HEP-1 cells with G-Rh2. The suppressive effects of p21(WAF1/CIP1) were much higher in the cells transfected with p21D112N, an expression vector that encodes a p21(WAF1/CIP1) mutant resistant to caspase 3 cleavage. Overexpression of cyclin A in SK-HEP-1 cells dramatically up-regulated cyclin A-Cdk2 activity and accordingly enhances apoptosis induced by treatment with G-Rh2. These up-regulating effects were blocked by coexpression of a dominant negative allele of cdk2. Furthermore, olomoucine, a specific inhibitor of Cdks, also blocked G-Rh2-induced apoptosis. These data suggest that the induction of apoptosis in human hepatoma cells treated with G-Rh2 occurs by a mechanism that involves the activation of cyclin A-Cdk2 by caspase 3-mediated cleavage of p21(WAF1/CIP1).
Asunto(s)
Apoptosis , Quinasas CDC2-CDC28 , Caspasas/metabolismo , Proteínas de Ciclo Celular , Ciclina A/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/metabolismo , Ginsenósidos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Supresoras de Tumor , Caspasa 3 , Ciclina E/metabolismo , Quinasa 2 Dependiente de la Ciclina , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Ciclinas/genética , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Activación Enzimática , Humanos , Cinetina , Proteínas Asociadas a Microtúbulos/metabolismo , Mutación , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Purinas/farmacología , Saponinas/farmacología , Células Tumorales CultivadasRESUMEN
OBJECTIVE: The purpose of this study was to determine the accuracy of three-dimensional coronary angiography obtained with electron beam CT in the assessment of the patency of coronary artery bypass grafts. SUBJECTS AND METHODS: Twenty-five patients who had undergone coronary artery bypass graft surgery were included. All patients underwent electron beam CT and conventional coronary angiography for the evaluation of the status of their bypass grafts. Three-dimensional reconstructions of the heart and bypass grafts were compared with selective angiographic images of the bypass grafts. RESULTS: Fifty-seven saphenous vein grafts and 22 left internal mammary artery grafts were evaluated for occlusion or patency. Sensitivity and specificity of electron beam CT in revealing left internal mammary artery patency were 80% and 82.4%, respectively. Sensitivity and specificity of electron beam CT in revealing saphenous vein graft patency were 91.7% and 91.1%, respectively. Sensitivity and specificity of electron beam CT for evaluating saphenous vein grafts according to coronary area were as follows: saphenous vein grafts to left anterior descending artery, 100% and 100%, respectively; to diagonal branch, 100% and 100%; to left circumflex artery, 100% and 88.9%; and to right coronary artery, 75% and 85.7%. CONCLUSION: Three-dimensional coronary angiography obtained with electron beam CT is a promising, useful, and relatively accurate diagnostic imaging technique for the evaluation of graft patency in patients who have undergone coronary artery bypass graft surgery.
Asunto(s)
Angiografía Coronaria , Puente de Arteria Coronaria , Procesamiento de Imagen Asistido por Computador , Tomografía Computarizada por Rayos X , Femenino , Humanos , Anastomosis Interna Mamario-Coronaria , Masculino , Persona de Mediana Edad , Vena Safena/diagnóstico por imagen , Vena Safena/trasplante , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos X/métodos , Grado de Desobstrucción VascularRESUMEN
PROBLEM: To determine the expression of vimentin and cytokeratin in eutopic and ectopic endometrium of women with both adenomyosis and ovarian endometrioma and to evaluate their cyclic changes during the menstrual cycle. METHOD OF STUDY: Twenty patients requiring hysterectomy with salpingo-oophorectomy were studied by immunohistochemistry according to their menstrual cycles. RESULTS: Cyclic expression of vimentin was noted in eutopic endometrium and adenomyosis, but not in endometrioma. Cytokeratin expression did not change during the menstrual cycles. The mean intensities of epithelial vimentin were significantly different from each other, being the lowest in endometrioma, intermediate in adenomyosis, and the highest in eutopic endometrium. There was no significant difference in intensities of cytokeratin between adenomyosis and endometrioma, but these intensities were significantly lower than that of eutopic endometrium. CONCLUSIONS: Lower intensities of cytokeratin in adenomyosis and endometrioma than in eutopic endometrium suggest that the ectopic endometria may have a lower degree of differentiation regardless of the site. The lower intensity of epithelial vimentin in endometrioma than in adenomyosis during the proliferative phase may reflect decreased functional activity, probably because of a pressure effect on the lining epithelium within the endometrioma.
Asunto(s)
Neoplasias Endometriales/metabolismo , Endometriosis/metabolismo , Queratinas/metabolismo , Neoplasias Ováricas/metabolismo , Vimentina/metabolismo , Endometrio/metabolismo , Femenino , Humanos , Histerectomía , Inmunohistoquímica , Ciclo MenstrualRESUMEN
A 6 week double-blind placebo-controlled trial of cyproheptadine augmentation of ongoing haloperidol treatment was conducted in 40 chronic schizophrenic in-patients. Cyproheptadine augmentation, compared to administration of haloperidol with placebo, did not produce a statistically significant improvement in psychotic symptoms. Cyproheptadine augmentation caused significant reduction in the extrapyramidal symptoms, which supports the atypical profile of antipsychotics. As to the neuroendocrinological effect, cyproheptadine augmentation did not reduce the plasma prolactin level but did induce a decrease in the plasma cortisol level. Although long-term follow-up studies are needed to confirm the results, this study suggests that cyproheptadine augmentation may be effective in treating chronic schizophrenic patients who are intolerant of extrapyramidal side effects of conventional antipsychotics.
Asunto(s)
Ciproheptadina/uso terapéutico , Haloperidol/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adulto , Enfermedad Crónica , Método Doble Ciego , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Hidrocortisona/sangre , Masculino , Placebos , Prolactina/sangre , Esquizofrenia/sangre , Factores de TiempoRESUMEN
We performed this study in order to verify the heart rate decrease caused by the D2-receptor on cardiac sympathetic nerve endings and its relation to the concentration of norepinephrine in synaptic clefts. Sprague-Dawley rats were pithed and the heart rate was increased either by electrical stimulation of the cardiac accelerator nerve or by intravenous infusion of norepinephrine, tyramine, or isoproterenol. Increased heart rate by electrical stimulation of cardiac accelerator nerve was dose-dependently lowered by lisuride and its effect was blocked by pretreatment with sulpiride but not with yohimbine and SCH 23390. Also, the heart rate was decreased in a dose-dependent manner by clonidine and this effect was blocked by pretreatment with yohimbine, but not with sulpiride. For increased heart rate by infusion of norepinephrine, tyramine, or isoproterenol, the heart rate lowering effect of lisuride was more marked in the norepinephrine-and tyramine-infusion groups, in which the intrasynaptic concentration of norepinephrine was elevated, compared to the isoproterenol-infusion group, in which intrasynaptic concentration of norepinephrine was not elevated. In conclusion, there is a D2-receptor on the cardiac sympathetic nerve endings which decreases the heart rate and is different from the presynaptic alpha 2-receptor. Also, the heart rate lowering effect via stimulation of the D2-receptor by lisuride was more marked with increased concentration of norepinephrine in the synaptic cleft.
Asunto(s)
Frecuencia Cardíaca/fisiología , Receptores de Dopamina D2/fisiología , Animales , Femenino , Corazón/inervación , Frecuencia Cardíaca/efectos de los fármacos , Lisurida/farmacología , Masculino , Norepinefrina/metabolismo , Ratas , Sistema Nervioso Simpático/metabolismo , Sinapsis/metabolismo , Yohimbina/farmacologíaRESUMEN
OBJECTIVES: Hypertension is commonly associated with an endothelial dysfunction that may contribute to the rise in blood pressure. Little information has been available so far on the role of endothelium-derived nitric oxide(EDNO) in renin-dependent, 2-kidney, 1 clip(2KIC) hypertension. The present study was aimed to determine a role for EDNO in the development and maintenance of 2KIC hypertension. METHODS: The effects of blocking synthesis or supplementation with precursor of EDNO on the development of hypertension were determined in 2KIC rats. Vascular responses to acetylcholine, nitroprusside, atrial natriuretic peptide and nifedipine were examined in 7- and 12-week hypertensive 2KIC rats. RESULTS: NG-nitro-L-arginine-methyl ester caused a sustained increase of blood pressure in normal rats, while it was only partially associated with a more pronounced increase of blood pressure in the developmental phase of hypertension in 2KIC rats. In 7-week and 12-week hypertensive rats, phenylephrine-induced contraction of the isolated thoracic aortic rings was more sensitive compared with control. Their acetylcholine-induced relaxation was attenuated while the responses to nitroprusside or atrial natriuretic peptide were unaltered. Although their blood pressure did not differ between 7-week and 12-week hypertensive groups, the attenuation in the acetylcholine-induced relaxation was more prominent in the latter with a longer duration of hypertension. Indomethacin did not affect the attenuated relaxation to acetylcholine. The relaxation response to nifedipine was more pronounced in 2KIC rats. CONCLUSION: These results indicate that ENDO has little influence of the 2KIC hypertension, at least during its developmental phase, which is associated with an activated reninangiotensin system. The chronic stage of 2KIC hypertension, however, is associated with an endothelial dysfunction which may contribute to the enhanced vasoconstriction and sustained high blood pressure.