RESUMEN
BACKGROUND: The most effective skin antiseptic solution to reduce the incidence of catheter-related bloodstream infections (CRBSI) remains unknown. AIM: To compare solutions with different chlorhexidine (CHG)-based concentrations and povidone-iodine (PVI) in adults with a central venous catheter (CVC) or arterial catheter, and identify an association with the incidence of CRBSI. METHODS: This study evaluated randomized controlled trials comparing CHG and PVI antiseptic agents in patients aged ≥18 years with an underlying illness and a CVC or arterial catheter. The primary outcome was CRBSI rate. Network meta-analysis was performed by a frequentist-based approach with multi-variate random effects meta-analysis, and the effect size was expressed as relative risk (RR) with 95% confidence interval (CI). FINDINGS: The search yielded 1511 records, of which five studies (2815 catheters) were included in the network meta-analysis. The risk of CRBSI was significantly lower with 1% CHG-alcohol than with 0.5% CHG-alcohol (RR 0.40, 95% CI 0.16-0.98; high certainty) or 10% PVI-aqueous (RR 0.31, 95% CI 0.15-0.63; high certainty). There was no significant difference in the risk of CRBSI between 1% CHG-alcohol and 2% CHG-aqueous (RR 0.35, 95% CI 0.12-1.04; moderate certainty) or other antiseptic solutions. The hierarchy of efficacy in reducing CRBSI was 1% CHG-alcohol, 0.5% CHG-alcohol, 2% CHG-aqueous and 10% PVI-aqueous. CONCLUSION: Antiseptic agents containing 1% CHG-alcohol were more strongly associated with reduced risk for CRBSI compared with agents containing 0.5% CHG-alcohol or 10% PVI-aqueous.
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Antiinfecciosos Locales , Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Catéteres Venosos Centrales , Sepsis , Adulto , Alcoholes , Infecciones Relacionadas con Catéteres/prevención & control , Clorhexidina , Humanos , Incidencia , Metaanálisis en Red , Povidona Yodada , Ensayos Clínicos Controlados Aleatorios como Asunto , Sepsis/prevención & controlRESUMEN
BACKGROUND: Although numerous studies on Functional Independence Measure (FIM) analysis in stroke, orthopedic disease, and spinal cord injury patients have been conducted, it has rarely been done in patients undergoing cardiac rehabilitation (CR). AIM: To verify whether the Functional Independence Measure (FIM) score, and its subscale motor FIM and cognitive FIM, during inpatient CR can be a predictor of a patient's readiness for home discharge by establishing an FIM cutoff value. DESIGN: A retrospective, observational cohort study SETTING: This study was conducted at a long-term acute-care hospital. POPULATION: Participants were in-hospital patients undergoing CR (N.=949). METHODS: Measurements included motor FIM, cognitive FIM, CR period, FIM gain per week, and discharge disposition. The strongest predictor for home discharge was analyzed by using multiple logistic regression analysis, and the cutoff value of the FIM score for home discharge was determined by using receiver operating characteristic (ROC) curves. RESULTS: Discharge to home was possible in 723 patients (76.2%), whereas 226 patients (23.8%) had other outcomes. In univariate analysis, a motor FIM gain per week of five points was achieved in the home discharge group. Multiple logistic regression analysis revealed that Body Mass Index, number of comorbidities, motor FIM at discharge, cognitive FIM gain, and CR period were predictive factors with 89.6% predictive ability. ROC curve analysis showed that the cutoff value was a discharge motor FIM score of 63/64 points with 0.912 areas under the curve. CONCLUSION: Discharge motor FIM and cognitive FIM gain were predictive factors for home discharge. A motor FIM gain per week of five points and discharge motor FIM score of 64 points at the end of inpatient CR may be important predictors of a patient's readiness for discharge to home. CLINICAL REHABILITATION IMPACT: The findings of this study indicate an alternative goal to the activities of daily living in inpatients with cardiovascular disease.
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Rehabilitación Cardiaca , Cognición , Evaluación de la Discapacidad , Destreza Motora , Alta del Paciente , Recuperación de la Función , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Advantame is an N-substituted (aspartic acid portion) derivative of aspartame that is similar in structure to neotame, another N-substituted aspartame. An extensive series of studies, were conducted on advantame to define the pharmacokinetics and metabolism in various species, subchronic and chronic toxicity in the rat and dog, carcinogenicity in the rat and mouse, genotoxicity, reproductive, and developmental toxicity, and human tolerability studies. The results of these studies, presented in overview in the present publication, and in greater detail in the accompanying publications, show that advantame is well tolerated by both animals and humans and does not possess systemic toxicity. The metabolic data demonstrate that the animal species used in the toxicity testing are relevant to the evaluation of human safety. The no-observed-adverse-effect levels (NOAELs) identified in the animal studies in which advantame was administered in the diet were generally the highest doses tested. Under the anticipated conditions of use, the predicted intakes of advantame are about 20,000- to 70,000-fold lower than the identified animal study NOAEL values. The results of the animal toxicology and human trial data support the safety of use of advantame in food.
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Aspartame/toxicidad , Edulcorantes/toxicidad , Pruebas de Toxicidad/métodos , Animales , Aspartame/química , Aspartame/metabolismo , Perros , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Masculino , Ratones , Estructura Molecular , Ratas , Edulcorantes/química , Edulcorantes/metabolismoRESUMEN
Advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate), an N-substituted analogue of aspartame, has been developed as a high-intensity sweetener. It is approximately 100 and 20,000 times sweeter than aspartame and sucrose, respectively. In this study the safety of advantame has been evaluated using a series of in vitro and in vivo genotoxicity assays including, bacterial mutation, mammalian cell mutation, and mouse micronucleus tests. Advantame did not induce reverse mutations in Salmonella typhimurium and Escherichia coli at concentrations of up to 5000 µg/plate. In the mammalian cell mutation assay, advantame did not induce mutation at the Hprt locus of L5178Y mouse lymphoma cells in two independent experiments, either in the absence or presence of S9. In vivo, there was no effect on the incidence of micronucleated immature or mature erythrocytes in bone marrow after oral administration of the test substance at any dose level (up to 2000 mg/kg body weight) or sampling time (24 and 48 h). The results of these studies demonstrate that advantame is without genotoxic potential.
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Pruebas de Carcinogenicidad/métodos , Dipéptidos/toxicidad , Edulcorantes/toxicidad , Animales , Línea Celular Tumoral , Relación Dosis-Respuesta a Droga , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Ratones , Pruebas de Micronúcleos , Salmonella typhimurium/efectos de los fármacos , Salmonella typhimurium/genéticaRESUMEN
Groups of 55 male and 55 female Han Wistar rats were administered advantame (98.9-99.8% purity) in the diet at concentrations of 0, 2000, 10,000, or 50,000 ppm for 104 weeks, following parental exposure to the same levels from prior to mating and throughout gestation. Additional groups of 20 rats/sex and 10 rats/sex were dosed for a period of 52 weeks and constituted the toxicity and reversibility phases of the study. Achieved doses of advantame over the carcinogenicity study were 0, 97, 488, and 2621 mg/kg body weight/day in males and 0, 125, 630, and 3454 mg/kg body weight/day in females, respectively. A high incidence of a pale and swollen anus and changes in fecal composition were observed in the high-dose groups. There was no effect of treatment on mortality. Body weight gain in the high-dose males (50,000 ppm) was slightly reduced compared to controls after 52 and 104 weeks of treatment; the decrease was not considered to be of toxicological significance, but due to the non-nutritive nature of the high dietary concentration of advantame. During the toxicity phase, food conversion efficiency was slightly decreased in both sexes, at the 50,000 ppm dose level. Given the non-nutritive content of the diet, this finding was not considered biologically significant. There were no relationships between treatment and the results of hematological or urinalysis investigations. Clinical chemistry evaluations showed consistently lower plasma urea concentrations in both sexes treated at 50,000 ppm, which was reversed during the 6-week recovery phase following 52 weeks of treatment, indicating a lack of permanent effects. Terminal investigations at both the 52 and 104-week revealed a number of intergroup differences in absolute and/or relative organ weights; however, the differences did not show dose-response relationships, were minor in nature, and/or occurred only in one sex, and were not associated with any pathological findings, and they were considered not to be treatment-related. Evaluation of the histopathology of the carcinogenicity phase animals revealed an increased incidence of pancreatic islet cell carcinomas in males (incidence rates of 0/55, 1/55, 2/55, and 3/55 in the 0, 2000, 10,000, or 50,000 ppm groups, respectively) and of mammary gland adenomas in the high-dose females (incidence rates of 0 in the control through 10,000 ppm dose groups and 4/41 in the 50,000 ppm dose group). The incidence rates of these tumors did not attain statistical significance and/or remained within background historical control values, and they were considered to be unrelated to advantame treatment. The no-observed-adverse-effect level was considered to be 50,000 ppm in the diet, the highest concentration tested, equivalent to 2621 and 3454 mg/kg body weight/day in males and females, respectively. Advantame was concluded to be without carcinogenic activity.
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Dipéptidos/administración & dosificación , Dipéptidos/farmacocinética , Dipéptidos/toxicidad , Edulcorantes/administración & dosificación , Edulcorantes/toxicidad , Animales , Pruebas de Carcinogenicidad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Masculino , Neoplasias/inducido químicamente , Ratas , Caracteres Sexuales , Edulcorantes/farmacocinéticaRESUMEN
Advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate), an N-substituted analog of aspartame, has been developed as a high-intensity sweetener. Groups of 4 dogs of each sex were treated at 0, 2000, 10,000, or 50,000 ppm of advantame in the diet for 52 weeks. Additional groups of 2 dogs/sex at the control, and mid- and high-dose groups were treated for 52 weeks followed by a 6-week recovery period. There was no effect of treatment on mortality, body weight, organ weights, food consumption, or the results of ophthalmological, electrocardiographic, haematological, clinical chemistry or urinalysis examinations. No histopathological changes were associated with advantame treatment. The NOAEL was considered to be 50,000 ppm, the highest concentration tested, which was equivalent to 2057 and 2139 mg/kg body weight/day in males, and females, respectively. The results of the study support the safety of advantame for use as a high-intensity sweetener.
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Dipéptidos/administración & dosificación , Dipéptidos/farmacocinética , Dipéptidos/toxicidad , Edulcorantes/administración & dosificación , Edulcorantes/toxicidad , Administración Oral , Animales , Perros , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Masculino , Edulcorantes/farmacocinéticaRESUMEN
To assess its teratogenic potential, advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate) was administered to mated rats (22/group) in the diet at 0, 5000, 15,000, and 50,000 ppm (providing approximately 465, 1418, and 4828 mg/kg body weight/day), and to mated rabbits (24/group) via oral gavage at 0, 500, 1000, and 2000 mg/kg body weight/day throughout gestation. Shortly before delivery (rats: day 20; rabbits: day 29), animals were killed and subjected to a detailed necropsy. Fetuses were examined for external, visceral, and skeletal alterations. Atypical coloration of the feces and cage liners seen with test diets in both rats and rabbits was attributed to excretion of test material/metabolites in the feces and urine. Advantame had no adverse effect on rat offspring survival or development. The no-observed-adverse-effect level (NOAEL) for both maternal and developmental toxicity in rats was 50,000 ppm, the highest dietary concentration tested. Due to adverse effects associated with reduced food intake and fecal output, approximately 20% of mated rabbits receiving 200 0mg/kg body weight/day and 1 animal at 1000 mg/kg body weight/day had to be terminated before scheduled necropsy. A NOAEL of 500 mg/kg body weight/day was established for maternal toxicity in rabbits. No teratogenic effects were observed in any animals, and based on a slightly increased incidence of fetal deaths at 2000 mg/kg body weight/day, a finding that was considered to be indirectly related to advantame treatment, 1000 mg/kg body weight/day was considered the NOAEL for developmental toxicity.
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Anomalías Inducidas por Medicamentos/patología , Dipéptidos/administración & dosificación , Dipéptidos/toxicidad , Reproducción/efectos de los fármacos , Edulcorantes/administración & dosificación , Edulcorantes/toxicidad , Animales , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Muerte Fetal/inducido químicamente , Embarazo , Complicaciones del Embarazo/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Conejos , RatasRESUMEN
Rats received diets containing 0, 2000, 10,000, or 50,000 ppm advantame (N-[N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-α-aspartyl]-L-phenylalanine 1-methyl ester, monohydrate) for 2 generations. F(0) animals (30/sex/group) were treated from 10 weeks before pairing. Males continued until week 16; females through gestation and lactation. Once weaned, F(1) animals (25/sex/group) continued receiving the same diet until F(2) pups were weaned. Mean advantame intakes from each of the diets were 164, 833, and 4410 mg/kg bw/day among F(0) males, and 204, 1036, and 5431 mg/kg bw/day among F(1) males. F(0) and F(1) females had comparable intakes up to lactation, when intakes increased (up to 8447 mg/kg bw/day from 50,000 ppm diet). No treatment-related effects on mortality, body weights, reproduction, litter observations, or postnatal offspring development were noted. Atypical coloration of the feces and cage liners seen with test diets was attributed to excretion of test material/metabolites in the feces and urine. Slightly higher food consumption was seen in F(0) and F(1) animals, especially males, receiving 50,000 ppm. However, these differences were considered to be a secondary response to the high levels of non-nutritive material in the diet. The no-observed-adverse-effect level for reproductive and developmental toxicity was considered to be 50,000 ppm, the highest dietary concentration tested.
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Anomalías Inducidas por Medicamentos , Dipéptidos/toxicidad , Reproducción/efectos de los fármacos , Edulcorantes/toxicidad , Animales , Cruzamiento , Dipéptidos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Estructura Molecular , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Edulcorantes/administración & dosificación , Edulcorantes/químicaRESUMEN
OBJECTIVES: The goal of this study was to examine the implications of the pressure-derived collateral flow index (CFIp) in acute myocardial infarction (AMI). BACKGROUND: Higher CFIp is associated with less severe myocardial ischemia during angioplasty in the non-infarcted heart. It remains unknown whether CFIp also identifies collateral function in AMI patients with and without no-reflow phenomenon. METHODS: The study population included 48 patients with a first AMI. After successful percutaneous transluminal coronary angioplasty (PTCA) stent, we measured mean aortic pressure (Pa), central venous pressure (Pv) and coronary wedge pressure (Pcw) of the infarct-related artery to calculate: CFIp = (Pcw - Pv)/(Pa - Pv). Myocardial contrast echocardiography (MCE) was performed with the intracoronary injection of microbubbles to assess myocardial perfusion. Left ventriculograms at days 1 and 28 were provided for the measurement of the regional wall motion (RWM, SD/chord). RESULTS: There was no difference in CFIp among subsets based on angiographic collateral grades (grade 0, 1, 2, 3; 0.28 +/- 0.07, 0.27 +/- 0.09, 0.27 +/- 0.08, 0.23 +/- 0.08, p = NS). The CFIp was significantly higher in patients with MCE no-reflow (n = 16) than in those with MCE reflow (n = 32) (0.34 +/- 0.07 vs. 0.23 +/- 0.06, p < 0.01). There was a significant inverse correlation between the extent of functional improvement (DeltaRWM[28 d-1 d]) and CFIp (r = 0.56, p < 0.01), implying that higher CFIp is associated with worse functional improvement. CONCLUSIONS: In AMI, CFIp is unlikely to reflect collateral function but seems to increase with the severity of microvascular dysfunction. Because higher CFIp was associated with poorer functional recovery, it provides a simple and useful estimate of clinical outcomes in AMI.
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Velocidad del Flujo Sanguíneo , Presión Sanguínea , Presión Venosa Central , Circulación Colateral , Circulación Coronaria , Microcirculación , Infarto del Miocardio/clasificación , Infarto del Miocardio/fisiopatología , Presión Esfenoidal Pulmonar , Índice de Severidad de la Enfermedad , Anciano , Análisis de Varianza , Angioplastia Coronaria con Balón , Angiografía Coronaria , Ecocardiografía , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/terapia , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Recuperación de la Función , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
UNLABELLED: OBJECTIVES; We assessed the effects of long-term amlodipine administration in a diastolic heart failure (DHF) rat model with preserved systolic function as well as the relationship between changes in left ventricular (LV) myocardial stiffening and alterations in extracellular matrix. BACKGROUND: Although the effect of long-term administration of amlodipine has been shown to be disappointing in patients with systolic failure, the effect is unknown in those with DHF. METHODS: Dahl salt-sensitive rats fed a high-salt diet for seven weeks were divided into three groups: eight untreated rats (DHF group), eight rats given high-dose amlodipine (10 mg/kg/day; HDA group) and seven rats given low-dose amlodipine (1 mg/kg/day; LDA group). RESULTS: High-dose administration of amlodipine decreased systolic blood pressure and controlled excessive hypertrophy, without a decrease in the collagen content, and prevented the elevation of LV end-diastolic pressure at 19 weeks. Low-dose administration of amlodipine with subdeppressive effects did not control either hypertrophy or fibrosis; however, it prevented myocardial stiffening and, hence, the elevation of LV end-diastolic pressure. The ratio of type I to type III collagen messenger ribonucleic acid levels was significantly lower in both the HDA and LDA groups than in the DHF group. CONCLUSIONS: Long-term administration of amlodipine prevented the transition to DHF both at the depressor and subdepressor doses. Amlodipine did not decrease the collagen content, but attenuated myocardial stiffness, with inhibition of the phenotype shift from type III to type I collagen. Thus, amlodipine may exert beneficial effects through amelioration of collagen remodeling in the treatment of DHF.
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Amlodipino/uso terapéutico , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Diástole/efectos de los fármacos , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/prevención & control , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Amlodipino/farmacología , Análisis de Varianza , Animales , Antihipertensivos/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Colágeno/análisis , Colágeno/genética , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Ecocardiografía Transesofágica , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Inmunohistoquímica , Análisis de los Mínimos Cuadrados , Modelos Lineales , Masculino , Miocardio/química , Fenotipo , Distribución Aleatoria , Ratas , Ratas Endogámicas Dahl , Volumen Sistólico/efectos de los fármacos , Factores de Tiempo , Remodelación Ventricular/efectos de los fármacosRESUMEN
The Dyggve-Melchior-Clausen syndrome (DMCS) is a rare autosomal recessive skeletal dysplasia characterized by short-trunk dwarfism and mental retardation. A 49-year-old male with DMCS underwent resection arthroplasty for contracture of the right hip joint under general anesthesia using thiamylal, nitrous oxide, sevoflurane, and vecuronium. Although he was assumed to have difficult airway due to short neck, macroglossia, and disturbance of neck flexion, tracheal intubation was not difficult. No complications including malignant hyperthermia were observed during the 95 min of the operation.
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Anomalías Múltiples , Anestesia General , Huesos/anomalías , Enanismo , Discapacidad Intelectual , Artroplastia , Genes Recesivos , Contractura de la Cadera/cirugía , Humanos , Cuidados Intraoperatorios , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio , SíndromeRESUMEN
OBJECTIVES: Brain natriuretic peptide (BNP) is a strong predictor of left ventricular (LV) hypertrophy (LVH) and dysfunction. However, our recent studies suggested that LVH is not necessarily associated with enhanced production of BNP in hypertension. This study aimed to clarify the relation of the characteristics of hypertrophy with the degree of gene expression of BNP in the developmental process of hypertensive heart failure. METHODS: Serial changes in LV geometry, histology and atrial natriuretic peptide (ANP) and BNP mRNA levels, were assessed in a hypertensive heart failure model using Dahl salt-sensitive rats (n = 24). We further studied effects of alpha1-receptor antagonist (doxazosin: 1 mg/kg per day, n = 5) and angiotensin II type 1 receptor (AT1R) antagonist (candesartan cilexetil: 1 mg/kg per day, n = 5). RESULTS: The BNP mRNA level was not elevated at the compensatory hypertrophic stage when ANP mRNA level was elevated. BNP mRNA level was increased with further progression of hypertrophy and development of fibrosis. AT1R blockade prevented such fibrosis and further progression of hypertrophy with normalization of BNP mRNA levels. Compensatory hypertrophy was not suppressed; therefore, ANP mRNA level, although decreased, was still beyond the normal level. The alpha1-receptor blockade slightly attenuated LV hypertrophy with a slight decrease in ANP mRNA levels. LV fibrosis was not prevented, and the BNP mRNA level was not decreased. CONCLUSIONS: BNP gene expression is not enhanced by initial compensatory hypertrophy, but is enhanced by LV fibrosis and late stage progression of hypertrophy dependent on AT1R-mediated signaling pathway.
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Gasto Cardíaco Bajo/etiología , Gasto Cardíaco Bajo/fisiopatología , Hipertensión/complicaciones , Miocardio/metabolismo , Natriuréticos/biosíntesis , Remodelación Ventricular , Animales , Factor Natriurético Atrial/genética , Gasto Cardíaco Bajo/patología , Ecocardiografía , Fibrosis , Ventrículos Cardíacos , Hemodinámica , Masculino , Miocardio/patología , Péptido Natriurético Encefálico/genética , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas DahlRESUMEN
BACKGROUND: This study sought to investigate how collateral flow changes during myocardial ischemia in patients. METHODS: Myocardial contrast echocardiography (MCE) and rapid atrial pacing were performed in 20 patients with angiographically evidenced coronary collaterals from the right coronary artery (RCA) to the occluded left anterior descending coronary artery. Sonicated contrast medium was injected into the RCA before and immediately after atrial pacing to determine the peak background-subtracted contrast intensity (PI) in the collateral territory (PIA) and its ratio to PI in the control territory (PI ratio) as parameters of collateral blood flow. Lactate production in the coronary circulation during pacing was determined to assess myocardial ischemia in the collateral territory. RESULTS: PIA showed a significant correlation with regional wall motion either before (r(squared)=-0.64, P<0.01) or after pacing (r(squared)=-0.65, P<0.01). Similarly, PI ratio was significantly correlated with regional wall motion either before (r(squared)=-0.54, P<0.05) or after pacing (r(squared)=-0.64, P<0.01). Rapid atrial pacing decreased both PIA and PI ratio significantly greater in patients with lactate production than in those without (PIA: -67+/-53 vs. -15+/-34%, P<0.05; PI ratio: -68+/-49 vs. -8.2+/-32%, P<0.05, respectively), while neither PIA nor PI ratio differ between the two groups of patients before pacing (PIA: 13.8+/-19. vs. 16.2+/-13.3U, P=0.75; PI ratio: 0.70+/-0.71 vs. 0.87+/-0.65, P=0.58, respectively). CONCLUSIONS: We concluded that (1) collateral flow determined by MCE was closely associated with regional cardiac function, and (2) not the amount of collateral flow at rest, but pacing-induced change of collateral flow seemed to be a determinant of regional ischemia in patients with coronary collaterals.
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Circulación Colateral/fisiología , Isquemia Miocárdica/fisiopatología , Anciano , Velocidad del Flujo Sanguíneo/fisiología , Medios de Contraste , Ecocardiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/diagnóstico por imagenRESUMEN
The present study seeks to estimate the difference between coronary zero flow pressure (Pzf) by analysis of the baseline pressure-flow relationship and the Pzf calculated during a long diastole in humans. Although Pzf is likely to provide meaningful information about the characteristics of coronary circulation, there are no available data on Pzf in humans because Pzf is overestimated when it is calculated during normal cardiac cycles. Actual Pzf was determined in 15 subjects by analyzing the coronary pressure-flow relationship during a long cardiac cycle induced by an intracoronary adenosine triphosphate (ATP) infusion, and it was compared with the Pzf calculated during a normal cardiac cycle in order to estimate the difference. Pzf calculated during a normal cardiac cycle was 47 +/- 15 mmHg, which decreased to 36 +/- 9mmHg after intracoronary administration of ATP (0.05 mg) whereas actual Pzf was 21 +/- 7 mmHg. Pzf calculated in a pressure-flow relationship during a normal cardiac cycle under vasodilation correlated well with that during a long diastole (r = 0.75, p < 0.01), although it was 15 +/- 6 mmHg greater than the actual Pzf. It was concluded that Pzf during a normal cardiac cycle could be used to anticipate Pzf.
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Circulación Coronaria/fisiología , Modelos Cardiovasculares , Adenosina Trifosfato/administración & dosificación , Adenosina Trifosfato/farmacología , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Circulación Coronaria/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Resistencia VascularRESUMEN
The diastolic deceleration slope of coronary flow velocity is steeper in patients with substantial 'no reflow' phenomenon than in those without it. This study investigated whether functional outcomes in patients with anterior wall acute myocardial infarction (AMI) can be predicted by analyzing the coronary flow velocity pattern recorded with transthoracic Doppler (TTD) echocardiography. Coronary blood flow velocity in the distal left anterior descending coronary artery was recorded with TTD at day-2 after primary percutaneous transluminal coronary angioplasty/Stent in 51 patients with anterior AMI and the diastolic deceleration half time (DHT, ms) was measured. The wall motion score index (WMSI) was measured at day-1 and -21. In the retrospective study, the DHT was much shorter in those with a poor outcome than in those with good outcome (152 +/- 109 vs 395 +/- 128 ms, p<0.05). Receiver-operating characteristic analysis documented that DHT > or = 300 ms is a suitable cut-off point (sensitivity of 83% and specificity of 93%). In the prospective study (n=30), AWMSI(dl-d21) was significantly higher in those with a DHT > or = 300 ms than those without (0.3 > or = 0.5 vs 1.6 > or = 0.7, p<0.001). DHT correlated significantly with AWMSI(dl-d21) (r=0.76, p<0.001). Patients with a shorter DHT of diastolic coronary flow velocity have a poorer functional outcome among patients with anterior AMI. The TTD-determined DHT is a useful predictor of myocardial viability after an anterior AMI.
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Circulación Coronaria/fisiología , Ecocardiografía Doppler/métodos , Contracción Miocárdica/fisiología , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
OBJECTIVES: This study aimed to characterize the difference between renin angiotensin system (RAS)-dependent and RAS-independent hypertrophy and their differential contribution to the transition to heart failure. BACKGROUND: Hypertensive left ventricular (LV) hypertrophy develops with RAS activation in the heart; however, LV hypertrophy develops even without RAS activation. METHODS: Left ventricular geometry and function were assessed in Dahl salt-sensitive rats placed on an 8% NaCl diet from seven weeks old (hypertensive rats) and in those placed on an 0.3% NaCl diet (control rats, n = 8). The hypertensive rats were randomized to no treatment (n = 8) or treatment with the angiotensin type 1 receptor (AT1R) antagonist candesartan (1 mg/kg per day, n = 10) after the baseline echocardiography study. RESULTS: From 7 to 13 weeks, AT1R blockade at a subdepressor dose did not restrain the development of LV hypertrophy but prevented narrowing of LV diastolic dimension, leading to the normalization of abnormally decreased end-systolic wall stress in the untreated rats. Progressive development of LV hypertrophy in spite of lower than normal end-systolic wall stress (excessive hypertrophy) after 13 weeks was suppressed by the AT1R blockade. Elevation of LV end-diastolic pressure and prolongation of Tau were associated with histological evidence of myocyte hypertrophy and massive interstitial fibrosis in the untreated rats, and none of these was evident in the treated rats. CONCLUSIONS: Renin-angiotensin system activation and AT1R signaling may be dispensable for the development of early adaptive LV hypertrophy and closely linked to the transition to heart failure.
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Insuficiencia Cardíaca/fisiopatología , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Sistema Renina-Angiotensina/fisiología , Animales , Insuficiencia Cardíaca/patología , Hipertensión/patología , Hipertrofia Ventricular Izquierda/patología , Masculino , Contracción Miocárdica/fisiología , Ratas , Ratas Endogámicas DahlRESUMEN
OBJECTIVES: The aim of our study was to explore evolving changes in a mitral flow velocity pattern (MFVP) and its hemodynamic and pathological correlates in hypertensive rats in an isolated diastolic heart failure model. BACKGROUND: Development of left ventricular (LV) hypertrophy and concomitant diastolic dysfunction cause heart failure in hypertensive hearts even with normal systolic function; however, associated evolving change in MFVP is still unclear. METHODS: Mitral flow velocity pattern was recorded every 2 weeks from 7 to 19 weeks in six hypertensive rats. Hemodynamic and pathological correlates of Doppler mitral flow indexes were examined as an additional part of the study using the hypertensive rats at the age of 13 weeks (compensatory stage, n = 7) and at 19 weeks (heart failure stage, n = 8). RESULTS: Initial development of pressure overload LV hypertrophy resulted in a decrease in early diastolic filling wave (E), a reciprocal increase in the filling wave due to atrial contraction (A) and prolongation of deceleration time of E wave (relaxation abnormality pattern). These changes were associated with an increase in tau, an index of LV relaxation, but without a change in LV end-diastolic pressure. Transition to congestive heart failure caused an increase in E, a decrease in A and shortening of deceleration time. These changes were not associated with further increase in tau but with elevation of LV end-diastolic pressure, reflecting marked LV hypertrophy and myocardial fibrosis. CONCLUSIONS: Development of pressure overload LV hypertrophy is associated with evolving changes in MFVP from normal to relaxation abnormality pattern and, in turn, to pseudonormalized to restrictive pattern. Analysis of MFVP may be useful to follow not only functional but also constitutional changes of the myocardium in hypertensive hearts.
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Ecocardiografía Doppler , Hipertrofia Ventricular Izquierda/fisiopatología , Válvula Mitral/fisiopatología , Disfunción Ventricular Izquierda/fisiopatología , Animales , Velocidad del Flujo Sanguíneo , Diástole/fisiología , Masculino , Válvula Mitral/diagnóstico por imagen , Ratas , Ratas Endogámicas Dahl , Presión Ventricular/fisiologíaRESUMEN
BACKGROUND: There is controversy regarding the contribution of calcineurin activation to the development of pressure-overload left ventricular (LV) hypertrophy and heart failure. The aim of this study was to explore whether the inhibition of calcineurin may prevent the transition to heart failure in hypertensive rats and, if so, to clarify in which developmental stage of LV hypertrophy calcineurin plays a key role. METHODS AND RESULTS: Dahl salt-sensitive rats placed on an 8% NaCl diet from the age of 7 weeks (hypertensive rats) were randomized to no treatment (n=6) or treatment with the calcineurin inhibitor FK506 (1 mg x kg(-1) x d(-1)) from 8 weeks (FKE, n=7) or from 17 weeks (FKL, n=7). Rats placed on a 0.3% NaCl diet were defined as control rats (n=6). The administration of FK506 from 8 weeks attenuated, although it did not block, LV hypertrophy observed in the untreated rats and prevented the transition to heart failure. The development of LV fibrosis, however, was not attenuated by the administration of FK506 from 8 weeks. The administration of FK506 from 17 weeks brought no benefit for cardiac remodeling or LV function and failed to prevent heart failure. CONCLUSIONS: Calcineurin inhibition, if started from the initial stage of pressure overload, attenuated the development of LV hypertrophy without any effect on LV fibrosis and prevented the transition to heart failure. The activation of calcineurin is involved in the development of LV hypertrophy but not of LV fibrosis, and this involvement may be crucial at the initial stage.
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Inhibidores de la Calcineurina , Insuficiencia Cardíaca/prevención & control , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/prevención & control , Tacrolimus/administración & dosificación , Animales , Factor Natriurético Atrial/biosíntesis , Factor Natriurético Atrial/genética , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/genética , Modelos Animales de Enfermedad , Esquema de Medicación , Ecocardiografía , Fibrosis/etiología , Fibrosis/patología , Expresión Génica/efectos de los fármacos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/patología , Hemodinámica/efectos de los fármacos , Hipertensión/inducido químicamente , Hipertensión/genética , Hipertrofia Ventricular Izquierda/complicaciones , Hipertrofia Ventricular Izquierda/patología , Inmunosupresores/administración & dosificación , Masculino , Miocardio/patología , Tamaño de los Órganos/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Endogámicas Dahl , Cloruro de SodioRESUMEN
BACKGROUND AND PURPOSE: Rat chromosome 20 is one of special interest because it contains some diabetogenic genes, such as a major histocompatibilitiy complex (MHC)-linked genetic components and quantitative trait loci. We studied rat chromosome 20, using the backcross progeny between BB/Wor and PVG.R23 rats, and confirmed the genetic linkage map by use of another backcross panel. METHODS: Backcross panels were done between BB/Wor and PVG.R23 rats, and BN and KZC rats. Length variations of simple sequence length polymorphism markers were analyzed by use of polymerase chain reaction (PCR) analysis. Alleles of RT1-Bb and RT1-Db were analyzed by use of the PCR-restriction fragment length polymorphism method. Genetic maps of rat chromosome 20 were constructed, using the Map Manager computer program. RESULTS: Fifty-two loci were mapped on rat chromosome 20. Genetic length was 57.9 cM, with average spanning of 1.11 cM between markers. The positions of RT1-N1, Tnf, and RT1-Bb into the MHC region were separated and confirmed by results of two backcross panels in our linkage studies. CONCLUSIONS: The genetic linkage map of rat chromosome 20 was improved, and was a useful tool for genetic analysis of a diabetogenic gene(s) and for producing MHC congenic strains.
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Mapeo Cromosómico , Ligamiento Genético , Ratas Endogámicas/genética , Animales , Cruzamientos Genéticos , Marcadores Genéticos , Ratones , Repeticiones de Microsatélite , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Ratas , Ratas Endogámicas BB/genética , Ratas Endogámicas BN/genética , Programas InformáticosRESUMEN
Left ventricular (LV) longitudinal shortening plays an important role in cardiac contraction and is invariably affected by the presence of coronary artery disease. Third-generation tissue velocity imaging (TVI) color-maps cardiac movement by obtaining mean velocities of LV segments from the same set of beats. The goals of this study were to characterize patterns of longitudinal myocardial motion velocity in healthy subjects and to use these patterns to evaluate abnormal segments of patients with myocardial infarction (MI). Included were 20 healthy subjects and 16 patients with MI who underwent a 2-dimensional Doppler echocardiography study. Myocardial velocity profiles were taken at the anulus, basal, mid, and apical segments of the septal and lateral walls in the apical view. Segmental velocity patterns from healthy subjects were compared with abnormal segments in patients with MI. Both lateral and septal walls of healthy subjects showed significant basal-apical myocardial velocity reductions in systolic shortening (Sm) and early and late diastolic lengthening (Em and Am) and a basal-apical increase in the Em/Am ratio. The lateral wall had greater Sm and Em velocities than the septal wall. The Sm and Em velocities and the Em/Am ratio were significantly reduced in the abnormal segments in patients with MI. Latent lateral wall ischemia may have been detected in 5 of 9 patients with septal infarction, showing reduced Sm velocity in apparently normal lateral walls. In conclusion, TVI objectively quantifies directional and incremental changes in myocardial movement that are useful in evaluating global and regional myocardial function, and it may play a role in the detection of early myocardial ischemia.