RESUMO
Metabolic syndrome is a multifaceted condition associated with a greater risk of various disorders (e.g., diabetes and heart disease). In a rat model of metabolic syndrome, an acute in vitro application of rosuvastatin causes relaxation of aortic rings. Since the outcome of a subchronic rosuvastatin treatment is unknown, the present study explored its effect on acetylcholine-induced vasorelaxation of aortic rings from rats with metabolic syndrome. Animals were submitted to a 16-week treatment, including a standard diet, a cafeteria-style diet (CAF-diet), or a CAF-diet with daily rosuvastatin treatment (10 mg/kg). After confirming the development of metabolic syndrome in rats, aortic segments were extracted from these animals (those treated with rosuvastatin and untreated) and the acetylcholine-induced relaxant effect on the corresponding rings was evaluated. Concentration-response curves were constructed for this effect in the presence/absence of L-NAME, ODQ, KT 5823, 4-aminopyridine (4-AP), tetraethylammonium (TEA), apamin plus charybdotoxin, glibenclamide, indomethacin, clotrimazole, and cycloheximide pretreatment. Compared to rings from control rats, acetylcholine-induced vasorelaxation decreased in rings from animals with metabolic syndrome, and was maintained at a normal level in animals with metabolic syndrome plus rosuvastatin treatment. The effect of rosuvastatin was inhibited by L-NAME, ODQ, KT 5823, TEA, apamin plus charybdotoxin, but unaffected by 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. In conclusion, the subchronic administration of rosuvastatin to rats with metabolic syndrome improved the acetylcholine-induced relaxant response, involving stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.
Assuntos
Acetilcolina/farmacologia , Aorta/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Síndrome Metabólica/fisiopatologia , Rosuvastatina Cálcica/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Endotélio Vascular/fisiopatologia , Masculino , Ratos , Ratos Wistar , VasodilatadoresRESUMO
Metabolic syndrome is a multifaceted condition associated with a greater risk of various disorders (e.g., diabetes and heart disease). In a rat model of metabolic syndrome, an acute in vitro application of rosuvastatin causes relaxation of aortic rings. Since the outcome of a subchronic rosuvastatin treatment is unknown, the present study explored its effect on acetylcholine-induced vasorelaxation of aortic rings from rats with metabolic syndrome. Animals were submitted to a 16-week treatment, including a standard diet, a cafeteria-style diet (CAF-diet), or a CAF-diet with daily rosuvastatin treatment (10 mg/kg). After confirming the development of metabolic syndrome in rats, aortic segments were extracted from these animals (those treated with rosuvastatin and untreated) and the acetylcholine-induced relaxant effect on the corresponding rings was evaluated. Concentration-response curves were constructed for this effect in the presence/absence of L-NAME, ODQ, KT 5823, 4-aminopyridine (4-AP), tetraethylammonium (TEA), apamin plus charybdotoxin, glibenclamide, indomethacin, clotrimazole, and cycloheximide pretreatment. Compared to rings from control rats, acetylcholine-induced vasorelaxation decreased in rings from animals with metabolic syndrome, and was maintained at a normal level in animals with metabolic syndrome plus rosuvastatin treatment. The effect of rosuvastatin was inhibited by L-NAME, ODQ, KT 5823, TEA, apamin plus charybdotoxin, but unaffected by 4-AP, glibenclamide, indomethacin, clotrimazole, or cycloheximide. In conclusion, the subchronic administration of rosuvastatin to rats with metabolic syndrome improved the acetylcholine-induced relaxant response, involving stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.
Assuntos
Animais , Masculino , Ratos , Aorta/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Acetilcolina/farmacologia , Síndrome Metabólica/fisiopatologia , Rosuvastatina Cálcica/farmacologia , Vasodilatadores , Endotélio Vascular/fisiopatologia , Ratos Wistar , Modelos Animais de DoençasRESUMO
Background: Stroke is a time-dependent emergency. Most patients with acute ischemic stroke are excluded from reperfusion therapies due to late consultation. Aims: To estimate the arrival times of patients with stroke to the Emergency Room (ER) of a public hospital. To identify factors associated with early consultation. Material and Methods: A convenience sample, 583 patients aged 71 ± 13 years (55% males) consulting for stroke at an emergency room was analyzed in terms of delay between onset of symptoms and arrival to the ER, demographics and etiology of stroke. Results: The admission diagnoses were ischemic stroke in 76%, intracerebral hemorrhage in 12%, transient ischemic attack in 9% and subarachnoid hemorrhage in 3%. The median time of arrival was 8 hours and 11 minutes after the onset of symptoms. Nineteen percent of consultations for ischemic stroke occurred within 3 hours of symptom onset, and 38% within 6 hours. In the logistic regression analysis, having an address near the hospital and the severity of stroke were associated with early consultation with a combined odds ratio of 5.97 (95% confidence intervals 3.23-11.04). Conclusions: There were significant differences in the arrival times of patients with stroke. Only a low proportion of patients with ischemic stroke consulted within the window for reperfusion therapies. Severe strokes and living near the hospital were associated with early consultation.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/epidemiologia , Hemorragia Cerebral , Hospitais PúblicosRESUMO
Resumen Antecedentes: El ataque cerebrovascular (ACV) es una urgencia tiempo-dependiente. La mayoría de los pacientes con infarto cerebral quedan excluidos de las terapias de reperfusión por consultar tardíamente. Se desconocen los factores asociados a llegada y evaluación precoz de pacientes con ACV agudo en nuestra población. Objetivos: Identificar los factores asociados, llegada y evaluación precoz de pacientes con ACV agudo. Pacientes y Métodos: Muestra por conveniencia de las consultas por ACV realizadas en el Turno N° 1, del SU del Hospital Dr. Hernán Henríquez de Temuco, entre enero de 2016 y diciembre de 2017. El análisis estadístico se realizó con el software STATA 14.0. Resultados: Se registraron 584 consultas por ACV. La mediana del tiempo de llegada fue de 8 h y 11 min. La mediana del tiempo para la evaluación por neurólogo(a) fue de 66 min. Tener domicilio en Temuco-Padre Las Casas y una mayor severidad del ACV se asociaron a consultar precozmente con un OR = 5,97 (3,23-11,04). Para evaluación dentro de una hora, las variables severidad, llegada en ambulancia y consulta en menos de 3 h, fueron estadísticamente significativas, con un OR combinado de 10,86 (IC 95%: 5,15-22,94). Conclusiones: Los factores más fuertemente asociados a llegada y evaluación precoz incluyen residir en comunas cercanas al hospital y presentar síntomas más severos de ACV. Se sugiere implementar estrategias para aumentar el grado de reconocimiento de síntomas de ACV y para disminuir las barreras de acceso a hospitales que traten a este tipo pacientes.
Introduction: Stroke is a time-dependent emergency. The majority of patients with Acute Ischemic Stroke are excluded from reperfusion therapies due to late consultation. The factors associated with early arrival and evaluation of patients with acute stroke in our population are unknown. The aim of the study was to identify factors associated with early arrival and evaluation of patients with acute stroke. Methods: A convenience sample of the stroke consultations made during shift # 1 at the ER between January 2016 and December 2017, was analyzed. Results: There were 584 stroke consultations in the period. 55.1% were men. The median time of arrival was 8 hours and 11 minutes. The median time for evaluation by neurologist was 66 minutes. Having an address in Temuco-Padre Las Casas and the severity of stroke was associated with early consultation with a combined OR of 5.97 (CI 95% 3.23-11.04). For an evaluation within one hour, in the logistic regression model, the variables severity, arrival in ambulance and consultation in less than 3 hours were statistically significant with a combined OR of 10.86 (CI 95% 5.15-22.94). Conclusions: The factors associated with early consultation and evaluation include residing in communes near the hospital and presenting more severe symptoms of stroke. It is suggested to implement strategies to increase the degree of recognition of stroke symptoms and to reduce barriers to access hospitals that treat patients with stroke.
Assuntos
Humanos , Masculino , Feminino , Pacientes , Infarto Cerebral , Acidente Vascular Cerebral , Emergências , Hospitais , Estudos Prospectivos , Estudo ObservacionalRESUMO
BACKGROUND: Stroke is a time-dependent emergency. Most patients with acute ischemic stroke are excluded from reperfusion therapies due to late consultation. AIMS: To estimate the arrival times of patients with stroke to the Emergency Room (ER) of a public hospital. To identify factors associated with early consultation. MATERIAL AND METHODS: A convenience sample, 583 patients aged 71 ± 13 years (55% males) consulting for stroke at an emergency room was analyzed in terms of delay between onset of symptoms and arrival to the ER, demographics and etiology of stroke. RESULTS: The admission diagnoses were ischemic stroke in 76%, intracerebral hemorrhage in 12%, transient ischemic attack in 9% and subarachnoid hemorrhage in 3%. The median time of arrival was 8 hours and 11 minutes after the onset of symptoms. Nineteen percent of consultations for ischemic stroke occurred within 3 hours of symptom onset, and 38% within 6 hours. In the logistic regression analysis, having an address near the hospital and the severity of stroke were associated with early consultation with a combined odds ratio of 5.97 (95% confidence intervals 3.23-11.04). CONCLUSIONS: There were significant differences in the arrival times of patients with stroke. Only a low proportion of patients with ischemic stroke consulted within the window for reperfusion therapies. Severe strokes and living near the hospital were associated with early consultation.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral , Feminino , Hospitais Públicos , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapiaRESUMO
BACKGROUND: Neurological emergencies constitute 10-15% of medical emergencies. Doctor Hernán Henríquez Aravena Hospital has in house neurologists present permanently at the Emergency Room since July 2013. AIM: To estimate the waiting times for neurological consultations; to compare the waiting times between neurovascular (UV) and non-vascular (UNV) emergencies; and to compare the waiting times of two prioritization (triage) models. MATERIAL AND METHODS: A convenience sample of the consultations made during shift # 1 at the emergency room between January and December 2016, was analyzed. RESULTS: There were 859 consultations in the period, 570 for UNV and 289 for UV. Mean age of consultants was 57 years and 52% were women. The median time for having an evaluation by a neurologist was 106 min (132 and 81 min for UNV and UV respectively). Twenty seven percent of patients were evaluated in less than one hour (23 and 36% of UNV and UV, respectively). The change of the prioritization model decreased the waiting time by 81 and 32 min for UNV and UV, respectively. CONCLUSIONS: There were significant differences in waiting times between neurovascular and non-vascular emergencies. Most patients were not evaluated in less than 60 minutes. The change in the initial stratification model was associated with a significant reduction in the waiting times for neurological emergencies.
Assuntos
Serviço Hospitalar de Emergência , Doenças do Sistema Nervoso , Encaminhamento e Consulta/estatística & dados numéricos , Tempo para o Tratamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Estudos Prospectivos , Fatores de TempoRESUMO
Background: Neurological emergencies constitute 10-15% of medical emergencies. Doctor Hernán Henríquez Aravena Hospital has in house neurologists present permanently at the Emergency Room since July 2013. Aim: To estimate the waiting times for neurological consultations; to compare the waiting times between neurovascular (UV) and non-vascular (UNV) emergencies; and to compare the waiting times of two prioritization (triage) models. Material and Methods: A convenience sample of the consultations made during shift # 1 at the emergency room between January and December 2016, was analyzed. Results: There were 859 consultations in the period, 570 for UNV and 289 for UV. Mean age of consultants was 57 years and 52% were women. The median time for having an evaluation by a neurologist was 106 min (132 and 81 min for UNV and UV respectively). Twenty seven percent of patients were evaluated in less than one hour (23 and 36% of UNV and UV, respectively). The change of the prioritization model decreased the waiting time by 81 and 32 min for UNV and UV, respectively. Conclusions: There were significant differences in waiting times between neurovascular and non-vascular emergencies. Most patients were not evaluated in less than 60 minutes. The change in the initial stratification model was associated with a significant reduction in the waiting times for neurological emergencies.
Assuntos
Humanos , Masculino , Feminino , Encaminhamento e Consulta/estatística & dados numéricos , Serviço Hospitalar de Emergência , Tempo para o Tratamento , Doenças do Sistema Nervoso , Fatores de Tempo , Estudos Prospectivos , Exame NeurológicoRESUMO
Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7.5-10-5 M). The present outcome was not modified by 10-6 M atropine (an antagonist of muscarinic acetylcholine receptors), 3.1×10-7 M glibenclamide (an ATP-sensitive K+ channel blocker), 10-3 M 4-aminopyridine (4-AP; a voltage-activated K+ channel blocker), 10-5 M indomethacin (a prostaglandin synthesis inhibitor), 10-5 M clotrimazole (a cytochrome P450 inhibitor) or 10-5 M cycloheximide (a general protein synthesis inhibitor). Contrarily, the clobenzorex-induced vasorelaxation was significantly attenuated (P<0.05) by 10-5 M L-NAME (a direct inhibitor of nitric oxide synthase), 10-7 M ODQ (an inhibitor of nitric oxide-sensitive guanylyl cyclase), 10-6 M KT 5823 (an inhibitor of protein kinase G), 10-2 M TEA (a Ca2+-activated K+ channel blocker and non-specific voltage-activated K+ channel blocker) and 10-7 M apamin plus 10-7 M charybdotoxin (blockers of small- and large-conductance Ca2+-activated K+ channels, respectively), and was blocked by 8×10-2 M potassium (a high concentration) and removal of the vascular endothelium. These results suggest that the direct vasorelaxant effect by clobenzorex on phenylephrine-precontracted rat aortic rings involved stimulation of the NO/cGMP/PKG/Ca2+-activated K+ channel pathway.
Assuntos
Anfetaminas/farmacologia , Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Vasodilatação , Vasodilatadores/farmacologia , Animais , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Masculino , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Ratos , Ratos WistarRESUMO
A relationship between thyroid hormones and the cardiovascular system has been well established in the literature. The present in vitro study aimed to investigate the mechanisms involved in the vasodilator effect produced by the acute application of 10-8-10-4 M triiodothyronine (T3) to isolated rat aortic rings. Thoracic aortic rings from 80 adult male Wistar rats were isolated and mounted in tissue chambers filled with Krebs-Henseleit bicarbonate buffer in order to analyze the influence of endothelial tissue, inhibitors and blockers on the vascular effect produced by T3. T3 induced a vasorelaxant response in phenylephrine-precontracted rat aortic rings at higher concentrations (10-4.5-10-4.0 M). This outcome was unaffected by 3.1×10-7 M glibenclamide, 10-3 M 4-aminopyridine (4-AP), 10-5 M indomethacin, or 10-5 M cycloheximide. Contrarily, vasorelaxant responses to T3 were significantly (P<0.05) attenuated by endothelium removal or the application of 10-6 M atropine, 10-5 M L-NG-nitroarginine methyl ester (L-NAME), 10-7 M 1H-(1,2,4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), 10-6 M (9S,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i](1,6)benzodiazocine-10-carboxylic acid, methyl ester KT 5823, 10-2 M tetraethylammonium (TEA), or 10-7 M apamin plus 10-7 M charybdotoxin. The results suggest the involvement of endothelial mechanisms in the vasodilator effect produced by the acute in vitro application of T3 to rat aortic rings. Possible mechanisms include the stimulation of muscarinic receptors, activation of the NO-cGMP-PKG pathway, and opening of Ca2+-activated K+ channels.
Assuntos
Aorta Torácica/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Tri-Iodotironina/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Atropina/farmacologia , Dimetil Sulfóxido/farmacologia , Glibureto/farmacologia , Indometacina/farmacologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Fenilefrina/farmacologia , Canais de Potássio Cálcio-Ativados/efeitos dos fármacos , Ratos WistarRESUMO
Beta-adrenergic receptor (ßAR)-dependent blood vessel relaxation is impaired in older animals and G protein activation has been suggested as the causative mechanism. Here, we investigated the role of ßAR subtypes (ß1AR, ß2AR, and ß3AR) and cAMP in maturation-dependent vasorelaxation impairment. Aortic rings from 15 Sprague-Dawley male rats (3 or 9 weeks old) were harvested and left intact or denuded of the endothelium. Vascular relaxation in aortic rings from younger and older groups was compared in the presence of ßAR subtype agonists and antagonists along with cAMP and cGMP antagonists. Isolated aortic rings were used to evaluate relaxation responses, protein expression was evaluated by western blot or real time PCR, and metabolites were measured by ELISA. Expression of ßAR subtypes and adenylyl cyclase was assessed, and cAMP activity was measured in vascular tissue from both groups. Isoproterenol- and BRL744-dependent relaxation in aortic rings with and without endothelium from 9-week-old rats was impaired compared with younger rats. The ß1AR antagonist CGP20712A (10-7 M) did not affect isoproterenol or BRL744-dependent relaxation in arteries from either group. The ß2AR antagonist ICI-118,551 (10-7 M) inhibited isoproterenol-dependent aortic relaxation in both groups. The ß3AR antagonist SR59230A (10-7 M) inhibited isoproterenol- and BRL744-dependent aortic ring relaxation in younger but not in older rats. All ßAR subtypes were expressed in both groups, although ß3AR expression was lower in the older group. Adenylyl cyclase (SQ 22536) or protein kinase A (H89) inhibitors prevented isoproterenol-induced relaxation in younger but not in older rats. Production of cAMP was reduced in the older group. Adenylyl cyclase III and RyR3 protein expression was higher in the younger group. In conclusion, altered expression of ß3AR and adenylyl cyclase III may be responsible for reduced cAMP production in the older group.