title: Negative and selective effects of propofol on isolated swine myocyte contractile function in pacing-induced congestive heart failure.
abstract: BACKGROUND
  Although propofol (2-6 di-isopropylphenol) is commonly used to induce and maintain anesthesia and sedation for surgery, systematic hypotension and reduced cardiac output can occur in patients with or without intrinsic cardiac disease. The effect of propofol on myocyte contractility after the development of congestive heart failure (CHF) remains unknown. This study tested the hypothesis that propofol would have direct effects on myocyte contractile function in both healthy and CHF cardiac myocyte preparations.
  
  
  METHODS
  Isolated left ventricular (LV) myocyte contractile function (shortening velocity, micron/s) was examined in myocytes from five control pigs and in five pigs with pacing-induced CHF (240 beats/min, for 3 weeks) in the presence of propofol concentrations ranging from 1-6 micrograms/ml. In addition, myocyte contractility in response to beta-adrenergic receptor stimulation (isoproterenol, 10-50 nM) in the presence of propofol (3 micrograms/ml) was examined.
  
  
  RESULTS
  Three weeks of pacing caused LV dysfunction consistent with CHF as evidenced by increased LV end-diastolic diameter (control 3.3 +/- 0.1 cm vs. CHF 5.6 +/- 0.2 cm; P < 0.05) and reduced LV fractional shortening (control 34 +/- 3% vs. CHF 12 +/- 2%, P < 0.05). Propofol (6 micrograms/ml) caused a concentration-dependent negative effect on velocity of shortening from baseline in both control (67 +/- 2 microns/s vs. 27 +/- 3 microns/s; P < 0.05) and CHF myocytes (29 +/- 1 microns/s vs. 15 +/- 1 microns/s; P < 0.05). Importantly, CHF myocytes were more sensitive than control myocytes to the negative effects of propofol on velocity of shortening at the lower concentration (1 microgram/ml). beta-adrenergic responsiveness was reduced by propofol (3 micrograms/ml) in control myocytes only.
  
  
  CONCLUSIONS
  Propofol has a direct and negative effect on basal myocyte contractile processes in the setting of CHF, which is more pronounced than that on healthy myocytes at reduced propofol concentrations.
authors.affiliation: Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston 29425-2207, USA.
authors.forename: L
authors.initials: L
authors.lastname: Hebbar
authors.forename: B H
authors.initials: BH
authors.lastname: Dorman
authors.forename: M J
authors.initials: MJ
authors.lastname: Clair
authors.forename: R C
authors.initials: RC
authors.lastname: Roy
authors.forename: F G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology* / Q000633:toxicity*; D000818:Animals; D002304:Cardiac Pacing, Artificial; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles / Q000166:cytology / Q000503:physiopathology; D006993:Hypnotics and Sedatives / Q000494:pharmacology* / Q000633:toxicity*; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D015742:Propofol / Q000494:pharmacology* / Q000633:toxicity*; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012680:Sensitivity and Specificity; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D018686:Anesthetics, Intravenous; D002316:Cardiotonic Agents; D006993:Hypnotics and Sedatives; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol; D015742:Propofol