RESUMO
Hyaluronan (HA) degradation fragments have been linked to inflammation in a wide range of lung diseases. In idiopathic pulmonary arterial hypertension, HA accumulation has been associated with advanced disease. In this study, we investigated the potential role of HA degradation in the early stages of disease by examining HA distribution, molecular mass, synthesis, and enzymatic degradation at different stages of disease progression in a rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH). At 28 days post-MCT, severe PH was associated with increased total lung HA (P = 0.04). In contrast, a significant decrease in total lung HA was observed on day 10, before the onset of PH (P = 0.02). Molecular mass analysis revealed a loss of high molecular mass (HMM) HA at 10 and 24 days post-MCT, followed by an increase in HMM HA at 28 days. Expression of HA synthase 2 (HAS2) was elevated in MCT-challenged animals at 24 and 28 days, consistent with increased synthesis of HMM HA. Analysis by Morgan Elson assay and zymography demonstrated increased hyaluronidase-1 activity in the lungs of MCT-challenged rats, indicating that the observed increases in HAS2 expression and HA synthesis were counterbalanced, in part, by enhanced degradation. The present data demonstrate that, in the MCT model, early-stage PH is associated with enhanced hyaluronidase-1 activity, while both degradation and synthesis are increased at later stages. Thus an early increase in the generation of proinflammatory HA fragments may play a role in the onset and progression of pulmonary arterial hypertension.
Assuntos
Progressão da Doença , Ácido Hialurônico/metabolismo , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Animais , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Hialuronan Sintases , Ácido Hialurônico/química , Hialuronoglucosaminidase/genética , Hialuronoglucosaminidase/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Peso Molecular , Monocrotalina/farmacologia , Ratos , Ratos Endogâmicos F344Assuntos
Infarto do Miocárdio/enzimologia , Miócitos Cardíacos/enzimologia , Condicionamento Físico Animal , Ativador de Plasminogênio Tecidual/metabolismo , Animais , Modelos Animais de Doenças , Ventrículos do Coração/enzimologia , Infarto do Miocárdio/patologia , RNA Mensageiro/metabolismo , Ratos , Fatores de Tempo , Regulação para CimaRESUMO
OBJECTIVES: Current guidelines suggest that most patients who present to an emergency department (ED) with chest pain should be placed on a continuous electrocardiographic monitoring (CEM) device. We evaluated the utility of CEM in ED patients with chest pain. METHODS: We enrolled stable patients who presented to a single ED with chest pain suspected to be ischemic in origin and who were placed on CEM. Patients were classified according to risk of poor outcome using 3 published stratification tools. Trained observers prospectively recorded number of monitored hours, alarms, changes in management, and monitor-detected adverse events (AEs). The primary outcome measure was the rate of AEs detected by CEM. Secondary outcome measures were the rate of alarms that resulted in a change in management and number of false alarms. RESULTS: We enrolled 72 patients, 56% of whom were categorized as very low-risk by Goldman risk criteria. During 371 monitored hours, we recorded 1762 alarms or 4.7 alarms per monitored hour. There were 11 AEs (0.68%; 95% CI, 0.35%-1.2%), 3 of which resulted in a change in management (0.2%; 95% CI, 0.04%-0.5%). Seven AEs were bradydysrhythmias with a heart rate of 45 or higher; the eighth patient had no change in symptoms and was given atropine for a heart rate of 32. The other 3 AEs were an untreated supraventricular tachycardia, a brief sinus pause that triggered a rate change in intravenous nitroglycerin by the patient's nurse, and a run of premature ventricular contractions after which heparin was administered. None of the 3 patients with a change in management was categorized as the lowest-risk. CONCLUSIONS: Routine CEM in low-risk ED patients with chest pain results in an excessive number of alarms, most of which require no change in management. In these patients, the benefit of CEM may be limited, and given that 99.4% of alarms were false, current CEM technology needs to be improved.