title: Acute effects of urocortin 2 on cardiac function and propensity for arrhythmias in an animal model of hypertension-induced left ventricular hypertrophy and heart failure.
abstract: OBJECTIVE
  To test acute effects of the corticotropin-releasing factor-related peptide urocortin 2 (Ucn2) on left ventricular (LV) function and the propensity for ventricular arrhythmias in the isolated heart of an animal model of hypertension-induced heart failure.
  
  
  RESULTS
  Hearts from Dahl salt-sensitive rats with severe LV dysfunction were perfused according to Langendorff. Left ventricular developed pressure and the positive and negative derivatives of LV pressure were analysed before and after perfusion with Ucn2 (n = 15) or normal perfusion solution (control, n = 9). Intracellular calcium cycling parameters were assessed by surface fluorometry. Furthermore, monophasic action potential duration (MAPD) and ventricular fibrillation threshold (VFT) were determined, the latter by a train-of-pulses method at increasing voltage to scan the vulnerable period of repolarization. Urocortin 2 significantly affected intracellular calcium cycling and improved LV contractile function and relaxation. Compared with baseline values, Ucn2 significantly decreased MAPD at 30, 50, and 90% repolarization and significantly increased VFT compared with baseline values. No changes were observed in control experiments.
  
  
  CONCLUSIONS
  Administration of Ucn2 rapidly improves LV function and increases VF threshold in failing, isolated rat hearts with increased propensity for ventricular arrhythmias. These observations suggest a potential use of Ucn2 as a safe and novel agent for the treatment of acute heart failure.
authors.affiliation: CardioBiology, Department of Biomedicine, University of Basel and University Hospital Basel, CH-4031 Basel, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Meili-Butz
authors.forename: Katrin
authors.initials: K
authors.lastname: Bühler
authors.forename: Dietlinde
authors.initials: D
authors.lastname: John
authors.forename: Peter
authors.initials: P
authors.lastname: Buser
authors.forename: Wylie W
authors.initials: WW
authors.lastname: Vale
authors.forename: Kirk L
authors.initials: KL
authors.lastname: Peterson
authors.forename: Marijke
authors.initials: M
authors.lastname: Brink
authors.forename: Thomas
authors.initials: T
authors.lastname: Dieterle
mesh_terms: D000208:Acute Disease; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D004195:Disease Models, Animal; D005470:Fluorometry; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D052139:Intracellular Calcium-Sensing Proteins; D008297:Male; D009206:Myocardium / Q000473:pathology*; D010477:Perfusion; D051381:Rats; D020303:Rats, Inbred Dahl; D012982:Sodium, Dietary; D014463:Ultrasonography; D054832:Urocortins / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000000981:diagnostic imaging / Q000503:physiopathology
chemical_list: D052139:Intracellular Calcium-Sensing Proteins; D012982:Sodium, Dietary; D054832:Urocortins