L. Piacentini et al., THE ANTIARRHYTHMIC EFFECT OF ISCHEMIC PRECONDITIONING IN ISOLATED RAT-HEART INVOLVES A PERTUSSIS TOXIN-SENSITIVE MECHANISM, Cardiovascular Research, 27(4), 1993, pp. 674-680
Objective: The aims were to examine the effect of pretreatment with Bo
rdetella pertussis toxin on the antiarrhythmic effect of ischaemic pre
conditioning in order to determine the possible involvement of inhibit
ory G proteins in this phenomenon; and (2) to characterise the model u
sed by varying the duration of a single preconditioning occlusion of t
he left coronary artery, the reperfusion time, and the duration of the
subsequent prolonged coronary artery occlusion. Methods: Isolated rat
hearts perfused with Krebs Henseleit solution at constant flow (8-10
ml.min-1) were subjected to a single preconditioning occlusion of the
left coronary artery (either 1 or 3 min) followed, up to 60 min later,
by a prolonged occlusion of 30 or 60 min (n=56). The ventricular arrh
ythmias during occlusion were compared to those from control rats in w
hich the artery was occluded for 30 or 60 min but without precondition
ing (n=29 and 14 respectively). Results: Protection against ventricula
r arrhythmias was most pronounced when a 3 min preconditioning occlusi
on was used followed by a 10 min reperfusion period: reduction in vent
ricular premature beats (VPB) during the 30 min occlusion from 514(SEM
119) in control hearts to 79(29) in preconditioned hearts (p<0.01). T
his protection was still apparent when the reperfusion time was extend
ed to 30 min [VPB 52(16); p<0.01] but lost when reperfusion was extend
ed to 1 h. Rendering G(i) proteins non-functional (ascertained by resp
onses to acetylcholine) resulted in loss of this antiarrhythmic effect
of preconditioning [VPB 241(93) v 226(120) for non-preconditioned hea
rts]. Conclusions: The antiarrhythmic effects of preconditioning can b
e demonstrated in isolated rat hearts perfused at constant flow with a
n artificial medium and this protection is lost following treatment wi
th Bordetella pertussis toxin 48 h previously.