EFFECTS OF BORDETELLA-PERTUSSIS TOXIN PRETREATMENT ON THE ANTIARRHYTHMIC ACTION OF ISCHEMIC PRECONDITIONING IN ANESTHETIZED RATS

1 Bordetella pertussis toxin, which catalyses the ADP-ribosylation of certain guanine nucleotide binding proteins (G proteins), thus functio nally uncoupling them from associated receptors, was examined to deter mine whether it modified the antiarrhythmic effect of ischaemic precon ditioning in anaesthetized rats.2 Pertussis toxin (25 mu g kg(-1), i.p ., 48 h prior to heart isolation) attenuated the negative chronotropic effect of acetylcholine (ACh) in rat isolated Langendorff perfused he arts. ACh (10 mu M) reduced heart rate by 4% in hearts taken from pert ussis toxin-treated animals, compared to a reduction of 57% in hearts taken from animals treated only with vehicle. 3 In anaesthetized rats, ischaemic preconditioning (a single 3 min occlusion of the left main coronary artery followed by 10 min reperfusion) had a pronounced antia rrhythmic effect during a subsequent 30 min period of regional myocard ial ischaemia. Compared to hearts receiving only a 30 min period of le ft coronary occlusion, there was a reduced mortality (67% and 0% for c ontrol and preconditioned groups, respectively; P < 0.01) and decrease d incidences of ventricular tachycardia (VT) and ventricular fibrillat ion (VF). Pretreatment with pertussis toxin (25 mu g kg(-1), i.p., 48 h previously) did not modify the arrhythmias associated with a 30 min period of regional myocardial ischaemia, neither did it modify the red uction in mortality (from 56% to 0%; P < 0.05) associated with precond itioning. Furthermore, the decrease in total ventricular premature bea t count induced by preconditioning seen in controls (from 427 +/- 130 to 95 +/- 45) was also seen in pertussis toxin-treated rats (from 252 +/- 190 to 57 +/-:25). 4 These results suggest that receptor coupling to pertussis toxin-sensitive G proteins is not necessary for the antia rrhythmic effect of ischaemic preconditioning in this model.