BACKGROUND/AIMS: The development of therapeutic strategies for the treatment of cirrhosis has become an important focus for basic and clinical researchers. Adrenergic receptor antagonists have been evaluated as antifibrotic drugs in rodent models of carbon tetrachloride (CCl4)-induced cirrhosis. The aim of the present study was to evaluate the effects of carvedilol and doxazosin on fibrosis/cirrhosis in a hamster animal model. METHODS: Cirrhotic-induced hamsters were treated by daily administration of carvedilol and doxazosin for 6 weeks. Hepatic function and histological evaluation were conducted by measuring biochemical markers, including total bilirubin, aspartate aminotransferase, alanine aminotransferase and albumin, and liver tissue slices. Additionally, transforming growth factor beta (TGF-beta) immunohistochemistry was analyzed. RESULTS: Biochemical markers revealed that hepatic function was restored after treatment with doxazosin and carvedilol. Histological evaluation showed a decrease in collagen type I deposits and TGF-beta-secreting cells. CONCLUSIONS: Taken together, these results suggest that the decrease in collagen type I following treatment with doxazosin or carvedilol is achieved by decreasing the profibrotic activities of TGF-beta via the blockage of alpha1- and beta-adrenergic receptor. Consequently, a diminution of fibrotic tissue in the CCl4-induced model of cirrhosis is achieved.
Adrenergic alpha-1 Receptor Antagonists/*pharmacology ; Alanine Transaminase/blood ; Animals ; Aspartate Aminotransferases/blood ; Bilirubin/blood ; Carbazoles/*pharmacology ; Carbon Tetrachloride ; Collagen Type I/drug effects/metabolism ; Cricetinae ; Doxazosin/*pharmacology ; Liver/metabolism/pathology ; Liver Cirrhosis/blood/chemically induced/*drug therapy ; Liver Function Tests ; Propanolamines/*pharmacology ; Serum Albumin/analysis ; Transforming Growth Factor beta/blood/*drug effects

OBJECTIVE: Bedside consultation by cardiologists may facilitate safe discharge of selected patients from the emergency department (ED) even when admission is recommended by the History, Electrocardiogram, Age, Risk factors, Troponin (HEART) pathway. If bedside evaluation is unavailable, phone consultation between emergency physicians and cardiologists would be most impactful if the resultant disposition is discordant with the HEART pathway. We therefore evaluate discordance between actual disposition and that suggested by the HEART pathway in patients presenting to the ED with chest pain for whom cardiology consultation occurred exclusively by phone and to assess the impact of phone-consultation on disposition.METHODS: We performed a single-center, retrospective study of adults presenting to the ED with chest pain whose emergency physician had a phone consultation with a cardiologist. Actual disposition was abstracted from the medical record. HEART pathway category (low-risk, discharge; high-risk, admit) was derived from ED documentation. For discharged patients, major adverse cardiac events were assessed at 30 days by chart review and phone follow-up.RESULTS: For the 170 patients that had cardiologist phone consultation, discordance between actual disposition and the HEART pathway was 17%. The HEART pathway recommended admission for nearly 80% of discharged patients. Following cardiologist phone-consultation, 10% of high-risk patients were discharged, with the majority having undergone a functional study recommended by the cardiologist. At 30 days, discharged patients had experienced no episodes of major adverse cardiac events or rehospitalization for cardiac reasons.CONCLUSION: For patients presenting to the ED with chest pain, cardiology phone-consultation has the potential to safely impact disposition, primarily by facilitating functional testing in high-risk individuals.
Acute Coronary Syndrome ; Adult ; Cardiology ; Chest Pain ; Electrocardiography ; Emergencies ; Emergency Service, Hospital ; Follow-Up Studies ; Heart ; Humans ; Medical Records ; Retrospective Studies ; Risk Factors ; Troponin