Modification by bradykinin B2 receptor blockade of protection by pacing against ischaemia-induced arrhythmias.
In dogs, rapid cardiac pacing, by way of a pacing electrode in the right ventricle, protects against ventricular arrhythmias when a coronary artery is occluded immediately after cessation of the pacing period. This represents a form of ischaemic preconditioning. The role of bradykinin in mediating the protective effects of rapid cardiac pacing in this model was investigated using a selective antagonist of bradykinin at B2 receptors (icatibant; HOE 140). In the presence of icatibant cardiac pacing (220 beats min(-1)) resulted in more severe ischaemia (as assessed by ST-segment elevation from the pacing electrode at the end of the stimulus) and to a higher incidence of ventricular arrhythmias during the pacing protocol. When the coronary artery was occluded under such conditions the antiarrhythmic protection afforded by cardiac pacing was not seen although other indices of reduced ischaemia severity (epicardial ST-segment mapping; changes in the degree of inhomogeneity of electrical activation within the ischaemic area) were not affected by icatibant treatment. These results suggest that bradykinin is an important trigger mediator involved in the protective effects of cardiac pacing. Whether this is due to the generation of endothelium-derived protective substances (such as nitric oxide and prostacyclin) or whether it results from a direct effect on B2 receptors in cardiac myocytes is unclear.
Kaszala
K
K
Department of Pharmacology, Albert Szent-Györgyi Medical University, Szeged, Hungary.
Végh
A
A
Papp
J G
JG
Parratt
J R
JR
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D019194:Ischemic Preconditioning; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000503:physiopathology; D043782:Receptor, Bradykinin B2; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; D043782:Receptor, Bradykinin B2; C065679:icatibant; D001920:Bradykinin