title: Effects of triiodothyronine pretreatment on beta-adrenergic responses in stunned cardiac myocytes.
abstract: OBJECTIVE
  To investigate whether triiodothyronine pretreatment enhanced beta-adrenergic responses in stunned myocardium and whether this acute effect of triiodothyronine was mediated through the cyclic adenosine 3',5'-monophosphate (AMP) system.
  
  
  METHODS
  A prospective study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Rabbits.
  
  
  METHODS
  Rabbit ventricular myocytes were isolated and placed in a medium equilibrated with either air (control) or with 95% N(2) and 5% CO(2) (stunned) for 15 minutes at 37 degrees C. The stunned myocytes were reoxygenated with air for 30 minutes. Triiodothyronine (10 nmol/L) and/or isoproterenol (0.1 nmol/L) was added to the myocytes. Myocyte shortening was measured by using a video-edge detector.
  
  
  RESULTS
  In electrically stimulated cells, the basal values of the percent shortening (22%-30%) and the maximum rate of shortening (22%-25%) were significantly reduced in the stunned myocytes. Isoproterenol (5 minutes) alone significantly increased the percent shortening in the control (from 3.70 +/- 0.36 to 4.14 +/- 0.37) but not in the stunned myocytes (from 2.60 +/- 0.30 to 3.15 +/- 0.27). Triiodothyronine (5 minutes) alone significantly increased the percent shortening in the control (from 3.75 +/- 0.36 to 4.34 +/- 0.45) and in the stunned myocytes (from 2.91 +/- 0.2 to 3.85 +/- 0.26). After triiodothyronine pretreatment for 5 minutes, isoproterenol caused greater increases in the percent shortening in both the control (37%) and the stunned myocytes (62%) than either agent alone. Isoproterenol or triiodothyronine caused small increases in the maximum rate of shortening in the control (14%-16%) and the stunned myocytes (34%-49%). After triiodothyronine pretreatment, isoproterenol caused greater increases in the maximum rate of shortening in both groups (control: 41%, stunned: 73%) than either agent alone. Isoproterenol caused an increase in the level of cyclic AMP (rho;moles/10(5) myocytes) in the control (from 2.92 +/- 0.47 to 3.77 +/- 0.43) but not in the stunned myocytes (from 2.42 +/- 0.25 to 2.42 +/- 0.20). Triiodothyronine pretreatment did not cause any change in cyclic AMP levels in the control (2.50 +/- 0.29) or in the stunned myocytes (2.60 +/- 0.40). After triiodothyronine pretreatment, isoproterenol caused a small increase in the cyclic AMP level in the control but not in the stunned myocytes.
  
  
  CONCLUSIONS
  The data showed that the myocardial beta-adrenergic responses were more sensitive to ischemic insult than the triiodothyronine responses. Triiodothyronine pretreatment enhanced beta-adrenergic responses in both the control and the stunned myocytes. However, this acute positive inotropic effect of triiodothyronine might not be mediated through the cyclic AMP system.
authors.affiliation: Department of Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ 08901-1977, USA. tsejt@umdnj.edu
authors.forename: James
authors.initials: J
authors.lastname: Tse
authors.forename: Ankur
authors.initials: A
authors.lastname: Gandhi
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Yi Qi
authors.initials: YQ
authors.lastname: He
authors.forename: Harvey R
authors.initials: HR
authors.lastname: Weiss
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000187:drug effects; D017682:Myocardial Stunning / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011446:Prospective Studies; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D014284:Triiodothyronine; D000242:Cyclic AMP; D007545:Isoproterenol