title: Direct and interactive effects of cardioplegic arrest and protamine on myocyte contractility.
abstract: BACKGROUND
  Cardioplegic arrest with rewarming and protamine administration have been implicated in causing transient left ventricular dysfunction perioperatively. However, whether interactive effects between cardioplegic arrest and rewarming with protamine occur with respect to myocyte contractile processes remains unclear. Accordingly, using an isolated myocyte model, the present study tested the hypothesis that simulated cardioplegic arrest with rewarming and protamine would have direct and interactive effects on myocyte contractile function.
  
  
  METHODS
  Left ventricular isolated myocyte contractile function was examined using computer-aided videomicroscopy under normothermic conditions (37 degrees C, cell medium; n = 183) and after simulated hypothermic, hyperkalemic cardioplegic arrest with rewarming (4 degrees C, 24 mEq/L K+, 2 hours; then 37 degrees C, cell medium, 5 minutes; n = 268). Myocyte function was then examined in the presence of protamine (10 to 40 micrograms/mL) under normothermic conditions (n = 102) and after cardioplegic arrest with rewarming (n = 175).
  
  
  RESULTS
  Myocyte contractile function decreased by 43% from baseline after simulated cardioplegic arrest with rewarming. Under normothermic conditions, protamine (20 micrograms/mL) reduced myocyte contractile function by 43.9% +/- 4.3%, whereas myocyte contractile function decreased by only 31.1% +/- 2.7% with protamine (20 micrograms/mL) after cardioplegic arrest with rewarming. Thus, the negative effects of protamine on myocyte contractility were attenuated after cardioplegic arrest when compared with normothermic conditions.
  
  
  CONCLUSIONS
  The present study demonstrated that simulated cardioplegic arrest with rewarming and protamine have direct and interactive effects on myocyte contractile function, which are not additive or synergistic.
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: O
authors.forename: M H
authors.initials: MH
authors.lastname: Cox
authors.forename: R
authors.initials: R
authors.lastname: Mukherjee
authors.forename: M J
authors.initials: MJ
authors.lastname: Clair
authors.forename: F A
authors.initials: FA
authors.lastname: Crawford
authors.forename: F G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D000818:Animals; D001831:Body Temperature; D002314:Cardioplegic Solutions / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media; D005260:Female; D006324:Heart Arrest, Induced; D006494:Heparin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007036:Hypothermia, Induced; D007091:Image Processing, Computer-Assisted; D008297:Male; D008853:Microscopy; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D011188:Potassium / Q000008:administration & dosage / Q000494:pharmacology; D011479:Protamines / Q000008:administration & dosage / Q000494:pharmacology*; D017694:Rewarming; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects; D014741:Video Recording
chemical_list: D002314:Cardioplegic Solutions; D003470:Culture Media; D006494:Heparin Antagonists; D011479:Protamines; D011188:Potassium