© 1995 by European Society of Cardiology
Copyright © 1995, European Society of Cardiology
Nitric oxide and prostacyclin modulate the alterations in cardiac action potential duration mediated by platelets during ischaemia
aAcademic Cardiology Unit, St. Mary's Hospital Medical School, 10th floor QEQM Wing, South Wharf Road, London W2 1NY, UK
bDepartment of Haematology, St. Mary's Hospital Medical School, Norfolk Place, London W2 1PG, UK
* Corresponding author. Tel.: (+ 44-171) 725 6129; fax: (+ 44-171) 725 6732.
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 µM NG-nitro-L-arginine methyl ester (L-NAME), 30 µM L-arginine, 10 µM haemoglobin, 100 µM 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-mono-acetylsalicylate-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 µM ADP and 4 µg · 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.
KEYWORDS Myocardial ischemia; Reperfusion; Repolarization; Platelets; Nitric oxide; L-NAME; Prostacyclin; Nitrates; Guinea pig, heart
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Heindl, S. Zahler, U. Welsch, and B. F Becker Disparate effects of adhesion and degranulation of platelets on myocardial and coronary function in postischaemic hearts Cardiovasc Res, May 1, 1998; 38(2): 383 - 394. [Abstract] [Full Text] [PDF]
|
|