MODIFICATION BY BRADYKININ B-2 RECEPTOR BLOCKADE OF PROTECTION BY PACING AGAINST ISCHEMIA-INDUCED ARRHYTHMIAS

In dogs, rapid cardiac pacing, by way of a pacing electrode in the rig ht 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 brady kinin in mediating the protective effects of rapid cardiac pacing in t his model was investigated using a selective antagonist of bradykinin at B-2 receptors (icatibant; HOE 140). Ln the presence of icatibant ca rdiac 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 und er such conditions the antiarrhythmic protection afforded by cardiac p acing was not seen although other indices of reduced ischaemia severit y (epicardial ST-segment mapping; changes in the degree of inhomogenei ty of electrical activation within the ischaemic area) were not affect ed by icatibant treatment. These results suggest that bradykinin is an important trigger mediator involved in the protective effects of card iac pacing. Whether this is due to the generation of endothelium-deriv ed protective substances (such as nitric oxide and prostacyclin) or wh ether it results from a direct effect on B-2 receptors in cardiac myoc ytes is unclear.