title: Cardioprotective effects of isoflurane in a rat model of stress-induced cardiomyopathy (takotsubo).
abstract: BACKGROUND
  Stress-induced cardiomyopathy (SIC) is a common syndrome with substantial morbidity and mortality. SIC is common in intensive care units' patients. No therapeutic intervention for SIC has been evaluated in randomized clinical trial so far. Our aim was to investigate whether isoflurane is cardioprotective in an experimental SIC model.
  
  
  METHODS
  We induced SIC-like cardiac dysfunction in rats with intraperitoneal injection of isoprenaline (50 mg/kg) and performed this study in two parts. First, we pre-treated rats with isoflurane (1.5%, n=12), pentobarbital (50 mg/kg, n=12) and ketamine (80 mg/kg, n=12) and compared to controls (n=12). We used glyburide, an ATP-dependent potassium channel blocker (n=6), to test whether isoflurane-protection is mediated through KATPm. In a second set of experiments, we treated rats with two different doses of isoflurane i.e. 0.75% (n=12) and 1.5% (n=12) before induction of SIC and compared to controls. We assessed left ventricular function and morphology in all rats by transthoracic echocardiography. We also measured peak body temperature, blood gases, acid-base homeostasis, blood pressure and heart rate.
  
  
  RESULTS
  The extent of apical akinesia was lowest and cardiac function was best in the isoflurane treated rats. The protective effects were not attenuated by glibenclamide. Higher dose of isoflurane was more cardioprotective than the lower dose. This was persistent after the adjustment for changes in hemodynamics and blood biochemistry induced by anesthesia.
  
  
  CONCLUSIONS
  Isoflurane prevented SIC-like cardiac dysfunction in rats. This protection was not mediated via KATPm. Our study provides an experimental foundation for future clinical trials in SIC.
authors.affiliation: The Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Electronic address: bjorn.redfors@wlab.gu.se.
authors.forename: Bjorn
authors.initials: B
authors.lastname: Redfors
authors.affiliation: The Department of Anaesthesiology and Intensive Care Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Oras
authors.affiliation: The Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Yangzhen
authors.initials: Y
authors.lastname: Shao
authors.affiliation: The Department of Anaesthesiology and Intensive Care Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Helene
authors.initials: H
authors.lastname: Seemann-Lodding
authors.affiliation: The Department of Anaesthesiology and Intensive Care Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Ricksten
authors.affiliation: The Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Elmir
authors.initials: E
authors.lastname: Omerovic
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007530:Isoflurane / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D054549:Takotsubo Cardiomyopathy / Q000000981:diagnostic imaging* / Q000517:prevention & control*; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D002316:Cardiotonic Agents; D007530:Isoflurane
keywords: Echocardiography; Isoflurane; Isoprenaline; Stress-induced cardiomyopathy (SIC)