title: Nitric oxide and prostacyclin modulate the alterations in cardiac action potential duration mediated by platelets during ischaemia.
abstract: OBJECTIVE
  To investigate the effects of alterations of nitric oxide (NO) and prostacyclin (PGI2) availability on platelet-mediated electrophysiological effects during myocardial ischaemia.
  
  
  METHODS
  Transmembrane action potentials and electrograms were recorded from isolated, Langendorff-perfused guinea-pig hearts during normal perfusion, global myocardial ischaemia and reperfusion during infusion of washed human platelets. Experiments were performed in the presence of 100 microM NG-nitro-L-arginine methyl ester (L-NAME), 30 microM L-arginine, 10 microM haemoglobin, 100 microM sodium nitroprusside and 2.3 nM iloprost, or using hearts obtained from DL-lysine monoacetylsalicylate (Aspisol, 50 mg.kg-1 i.p.)-treated animals.
  
  
  RESULTS
  Perfusion with L-NAME and haemoglobin increased perfusion pressure by 33% (P = 0.0017) and 23% (P = 0.0026) while sodium nitroprusside and iloprost reduced it (17%, P = 0.0004, and 24%, P = 0.0006). In the absence of platelets, these compounds had no effect on arrhythmogenesis, but in the presence of platelets L-NAME reduced the onset time of ventricular tachycardia during ischaemia from 19.4 (s.e.m. 2.0) min to 12.9 (2.1) min, P = 0.04 and accentuated the ischaemia-induced reduction of action potential duration at 95% repolarization (APD95): 95(6) vs. 115(5) ms, P < 0.05 at 25 min. Sodium nitroprusside in the presence of platelets attenuated the ischaemia-induced reduction in APD95, while iloprost in the presence of platelets was antiarrhythmic (ventricular fibrillation 25 vs. 75%, P = 0.04) and attenuated the reduction in APD95 during ischaemia 115(4) vs. 94(4) ms, P < 0.05 at 20 min. Infusion of platelets into hearts obtained from DL-lysine-monoacetylsalicylate-treated guinea-pigs accentuated the ischaemia-induced reduction in APD95 (94(4) vs. 119(7) ms, P < 0.05 at 20 min) and this was reversed by sodium nitroprusside (117(7) ms, P < 0.05 at 20 min). L-NAME and haemoglobin had no effect on the aggregatory responses of the platelets to 5 microM ADP and 4 micrograms.ml-1 collagen, while sodium nitroprusside and iloprost ablated the responses to ADP and reduced the responses to collagen (maximum height of the aggregatory response reduced by 75 and 84%, respectively, both P = 0.03.)
  
  
  CONCLUSIONS
  Inhibition of NO and PGI2 synthesis exacerbates the reduction in cardiac action potential duration associated with platelet activation during ischaemia, while provision of exogenous NO and PGI2 attenuates the reduction in cardiac action potential duration. Provision of exogenous NO and PGI2 (as iloprost) was associated with inhibition of platelet reactivity.
authors.affiliation: Academic Cardiology Unit, St. Mary's Hospital Medical School, London, UK.
authors.forename: N V
authors.initials: NV
authors.lastname: Goulielmos
authors.forename: Z E
authors.initials: ZE
authors.lastname: Enayat
authors.forename: D J
authors.initials: DJ
authors.lastname: Sheridan
authors.forename: H
authors.initials: H
authors.lastname: Cohen
authors.forename: N A
authors.initials: NA
authors.lastname: Flores
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology; D011464:Epoprostenol / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D006454:Hemoglobins / Q000502:physiology; D016285:Iloprost / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D006454:Hemoglobins; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D003094:Collagen; D001120:Arginine; D011464:Epoprostenol; D016285:Iloprost; D019331:NG-Nitroarginine Methyl Ester