title: Adenosine prevents hyperkalemia-induced calcium loading in cardiac cells: relevance for cardioplegia.
abstract: BACKGROUND
  Hyperkalemic cardioplegic solutions effectively arrest the heart but also induce membrane depolarization, which could lead to intracellular Ca2+ loading and contribute to ventricular dysfunction associated with cardiac operations. Adenosine, which possesses cardioprotective properties, has been proposed as an adjunct to conventional cardioplegic solutions. However, it is not known whether adenosine supplementation enables cardiac cells to withstand hyperkalemia-induced Ca2+ loading.
  
  
  METHODS
  Single ventricular cardiomyocytes were isolated from guinea pig hearts, loaded with a Ca(2+)-sensitive fluorescent probe, and imaged by digital epifluorescent microscopy. The emitted fluorescence of the probe, a measure of the intracellular Ca2+ concentration, was recorded from single myocytes during hyperkalemic challenges in the absence and the presence of adenosine to assess the protective effectiveness of this agent.
  
  
  RESULTS
  Hyperkalemic solutions induced intracellular Ca2+ loading (estimated intracellular Ca2+ concentration, 88 +/- 5 nmol/L before and 1,825 +/- 112 nmol/L after addition of 16 mmol/L KCl). Adenosine (1 mmol/L) prevented K(+)-induced Ca2+ loading (intracellular Ca2+ concentration, 86 +/- 6 nmol/L before and 85 +/- 8 nmol/L after exposure to K+). Whereas glyburide (3 mumol/L), an antagonist of adenosine triphosphate-sensitive K+ channels, had no effect, staurosporine (200 nmol/L) and chelerythrine (5 mumol/L), two inhibitors of protein kinase C, did abolish the action of adenosine.
  
  
  CONCLUSIONS
  Adenosine prevents hyperkalemia-induced Ca2+ loading in cardiomyocytes. This effect is due to a direct action on ventricular cells, as the preparation employed was free from atrial, neuronal, and vascular elements, and appears to be mediated through a protein kinase C-dependent mechanism. The property of adenosine to prevent hyperkalemia-induced Ca2+ loading may contribute to the cytoprotective efficacy of this agent as an adjunct to conventional hyperkalemic cardioplegic solutions.
authors.affiliation: Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jovanović
authors.forename: A E
authors.initials: AE
authors.lastname: Alekseev
authors.forename: J R
authors.initials: JR
authors.lastname: López
authors.forename: W K
authors.initials: WK
authors.lastname: Shen
authors.forename: A
authors.initials: A
authors.lastname: Terzic
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006324:Heart Arrest, Induced; D006947:Hyperkalemia / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology
chemical_list: D002314:Cardioplegic Solutions; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D000241:Adenosine; D011188:Potassium; D002118:Calcium