Ischaemic preconditioning in the XXXX heart: the role of G-proteins and adrenergic stimulation.

@entity268 @entity1165 @entity1920 @entity3980 @entity35 @entity1063 @entity857 @entity943
Since recent findings indicate the involvement of G-proteins in the mechanism of ischaemic preconditioning (PC), the present study was aimed to investigate the role of adrenergic mechanisms, such as G-proteins and stimulation of adrenergic receptors, in this phenomenon. For this purpose, isolated Langendorff-perfused @entity35 hearts were subjected to regional ischaemia (30 min occlusion of @entity3980 ) followed by reperfusion. The effect of PC (a single 5 min occlusion/reperfusion before a long occlusion) on ischaemia- and reperfusion induced @entity943 was studied in conjunction with an assessment of G-proteins in the myocardial tissue by means of Western blotting and @entity857 -ribosylation with bacterial toxins. To follow the link between G-proteins and adrenergic receptors, their stimulation by exogenous @entity1063 (NE) was applied to test whether it can mimic the effect of PC on @entity943 . Thirty min ischaemia and subsequent reperfusion induced high incidence of @entity1165 ( @entity1165 ) and fibrillation (VF). PC significantly reduced a total number of extrasystoles, incidence of @entity1165 and abolished VF. It was, however, insufficient to suppress reperfusion-induced sustained VF. Measurement of G-proteins revealed that PC led to a reduction of stimulatory Gs proteins, whereas inhibitory Gi proteins were increased. NE (50 nmol) introduced a manner of similar to PC (5 min infusion, 10 min normal reperfusion) reduced @entity943 in the same way, as PC. In addition, in NE-pretreated hearts reperfusion induced mostly transient VF, which was spontaneously reverted to normal sinus rhythm. A transient increase in heart rate and perfusion pressure during NE infusion completely waned before the onset of ischaemia, indicating that antiarrhythmic effect was not related to haemodynamic changes and to conditions of myocardial perfusion. CONCLUSION: antiarrhythmic effect of PC may be mediated by a stimulation of adrenergic receptors coupled to appropriate G-proteins. Consequently, the inhibition of @entity1920 cyclase activity and reduction in @entity268 level, as well as the activation of protein kinase C may be considered as two possible pathways leading to a final response.
