title: Postischemic function and protein kinase C signal transduction.
abstract: BACKGROUND
  The protective effects of myocardial preconditioning may occur by way of multiple mechanisms, with G-protein-mediated protein kinase C (PKC) translocation as a final common pathway. In this study we investigate the pharmacologic induction of preconditioning, by PKC translocation, using PKC agonists/antagonists to reveal its effects on contractile function after myocardial ischemia.
  
  
  METHODS
  Langendorff-perfused rabbit hearts received: (1) control; (2) dimethyl sulfoxide (vehicle); (3) acetylcholine (0.55 mmol/L; PKC agonist); (4) 1,2-s,n-dioctanoylglycerol (DOG; 22 mmol/L; PKC agonist); (5) chelerythrine (0.8 mmol/L; PKC antagonist); or (6) DOG-chelerythrine followed by a 2-hour ischemic period, using modified St. Thomas cardioplegia and a 45-minute reperfusion period. The period of ischemia was chosen so as to allow for improvement by appropriate agonists. To observe metabolic changes, tissue nucleotides and nucleosides were measured. Membrane and cytosolic fractions of PKC were determined by an anti-PKC antibody directed against the PKC delta isozyme. Lactate levels and myocardial pH were measured.
  
  
  RESULTS
  The PKC agonists DOG and acetylcholine showed the greatest recovery of developed pressure (68% +/- 2%, 60% +/- 9%, respectively). Although pH, lactate, and nucleotide levels were similar between groups at all times, myocyte PKC translocation demonstrated 25% of PKC delta isoforms on cell membrane sites during baseline, which shifted to 67% delta 17% with unprotected ischemia. DOG mimicked this shift with 58% delta 12% of PKC delta isoforms on membranes, which was also blocked by chelerythrine to 35% +/- 7%.
  
  
  CONCLUSIONS
  These data demonstrate that PKC translocation results in improved postischemic function, not by alteration of energetics or metabolism, and deserves further investigation.
authors.affiliation: Section of Thoracic Surgery, University of Michigan Medical Center, Ann Arbor, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Rohs
authors.forename: K S
authors.initials: KS
authors.lastname: Kilgore
authors.forename: A J
authors.initials: AJ
authors.lastname: Georges
authors.forename: S F
authors.initials: SF
authors.lastname: Bolling
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001639:Bicarbonates / Q000627:therapeutic use; D002122:Calcium Chloride / Q000627:therapeutic use; D002314:Cardioplegic Solutions / Q000627:therapeutic use; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D004075:Diglycerides / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D019157:Ischemic Preconditioning, Myocardial; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism; D007773:Lactates / Q000032:analysis; D008274:Magnesium / Q000627:therapeutic use; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D009705:Nucleosides / Q000032:analysis; D009711:Nucleotides / Q000032:analysis; D014677:Pharmaceutical Vehicles; D010617:Phenanthridines / Q000494:pharmacology; D011189:Potassium Chloride / Q000627:therapeutic use; D011493:Protein Kinase C / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction; D012965:Sodium Chloride / Q000627:therapeutic use
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D001639:Bicarbonates; D002314:Cardioplegic Solutions; D004075:Diglycerides; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007773:Lactates; D009705:Nucleosides; D009711:Nucleotides; D014677:Pharmaceutical Vehicles; D010617:Phenanthridines; C041711:St. Thomas' Hospital cardioplegic solution; C044295:1,2-dioctanoylglycerol; D012965:Sodium Chloride; D011189:Potassium Chloride; C016299:chelerythrine; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D008274:Magnesium; D002122:Calcium Chloride; D000109:Acetylcholine; D004121:Dimethyl Sulfoxide