Bradykinin is a mediator, but unlikely a trigger, of antiarrhythmic effects of ischemic preconditioning.
OBJECTIVE
Brief reversible ischemic episodes (ischemic preconditioning, IPC) protect the heart against arrhythmias during a subsequent prolonged low-flow ischemia. We have recently shown that this protection involves release of bradykinin, activation of bradykinin B2 receptors followed by opening of sarcolemmal, but not mitochondrial ATP-sensitive K+ channels. The goal of this study was to clarify a trigger and/or mediator role of bradykinin in the antiarrhythmic effects of IPC during low-flow ischemia.


METHODS
Isolated perfused rat hearts underwent 60 minutes of low-flow ischemia induced by reducing perfusion pressure followed by 60 minutes of reperfusion. Preconditioning was induced by 2 x 5 minutes episodes of zero-flow ischemia. In yet other groups, preconditioned or non-preconditioned hearts were treated either with bradykinin (10 nmol/L) or with HOE 140 (bradykinin B2 receptor antagonist, 100 nmol/L).


RESULTS
IPC reduced the number of ventricular premature beats, as well as the incidence of ventricular tachycardia and of ventricular fibrillation during low-flow ischemia. In addition, this protection was abolished by HOE 140 given during low-flow ischemia. Pharmacological preconditioning using short bradykinin perfusion instead of IPC did not show antiarrhythmic effects. However, bradykinin administered during low-flow ischemia and reperfusion reduced the number of ventricular premature beats and the incidence of ventricular tachycardia and of ventricular fibrillation during low-flow ischemia.


CONCLUSIONS
Bradykinin is a mediator, but unlikely a trigger, of antiarrhythmic effects of IPC during low-flow ischemia.
Driamov
Sergey V
SV
CardioBiology Research Laboratories, Department of Research, University Hospital Basel, Switzerland.
Bellahcene
Mohamed
M
Butz
Silvia
S
Buser
Peter T
PT
Zaugg
Christian E
CE
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000187:drug effects / Q000378:metabolism* / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D004195:Disease Models, Animal; D018450:Disease Progression; D004562:Electrocardiography; D006339:Heart Rate / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D010865:Pilot Projects; D011379:Prognosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017180:Tachycardia, Ventricular / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control
D065168:Bradykinin Receptor Antagonists; C065679:icatibant; D001920:Bradykinin