title: Functional and histological assessment of an experimental model of Takotsubo's cardiomyopathy.
abstract: BACKGROUND
  Our objectives were to characterize functional and structural features of an experimental model of Takotsubo cardiomyopathy, and its response to beta-blockers.
  
  
  RESULTS
  In protocol 1, a dose-finding study: 69 rats received various doses of isoproterenol (ISO) and echocardiographic and histologic parameters were measured on days 2 to 3 or day 8. There were no dose-dependent effects and, out of 69 ISO-treated rats, 40 (58.0%) survived and 29 (42.0%) died within 24 hours. Of survivors, 30 had apical akinesis averaging 12.1 ± 1.6% of the long axis LV circumference. Out of the 40 survivors, 32.5% showed apical akinesis ≥ 10%, 42.5% showed akinesis<10% and 25% showed no apical akinesis. The basal portion of the LV was always preserved. At 24 hours, histology and ultrastructure showed necrosis, vacuolization, lipid droplets, mononuclear cell infiltration, damaged mitochondria, and edema. On day 8, apical akinesis fully resolved but histologic abnormalities were still present. In protocol 2, rats were randomized to Control; ISO100 mg/kg; propranolol+ISO; and metoprolol+ISO groups. Pretreatment with propranolol and metoprolol improved survival to 90% and 100% respectively, compared with 60% in the ISO group, but did not reduce the incidence and extent of akinesis or the structural damage.
  
  
  CONCLUSIONS
  TC can be mimicked in a rat model of ISO exposure that demonstrates apical akinesis on days 2 to 3 with full recovery of systolic regional wall motion abnormality despite the presence of persistent foci of necrosis and fibrosis on day 8. Pretreatment with beta-blockers improved survival but did not affect structural and functional alterations.
authors: Heart Institute of Good Samaritan Hospital and Division of Cardiovascular Medicine of the Keck School of Medicine, University of Southern California, Los Angeles, CA (J.S., W.D., R.A.K.).
authors: Jaspreet
authors: J
authors: Sachdeva
authors: Heart Institute of Good Samaritan Hospital and Division of Cardiovascular Medicine of the Keck School of Medicine, University of Southern California, Los Angeles, CA (J.S., W.D., R.A.K.).
authors: Wangde
authors: W
authors: Dai
authors: Heart Institute of Good Samaritan Hospital and Division of Cardiovascular Medicine of the Keck School of Medicine, University of Southern California, Los Angeles, CA (J.S., W.D., R.A.K.).
authors: Robert A
authors: RA
authors: Kloner
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D008854:Microscopy, Electron; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D009336:Necrosis; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D054549:Takotsubo Cardiomyopathy / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D008790:Metoprolol
keywords: Takotsubo cardiomyopathy; electron microscopy; histopathology; isoproterenol