Effect of modification of anandamide plasma levels on ischaemia and reperfusion-induced arrhythmias

Cannabinoid receptor activation has been demonstrated to improve myocardial recovery and reduce arrhythmogenesis during ischaemia and reperfusion.[1] To date it has not been examined if augmentation of the endocannabinoid, anandamide, may also influence ischaemia–reperfusion-induced arrhythmogenesis. We investigated the effect of the anandamide breakdown inhibitor, URB597, anandamide and both in combination on the severity of ischaemia–reperfusion induced arrhythmias in anaesthetised rats subjected to regional coronary occlusion (10 min) and reperfusion (10 min). URB597 (10 mg/kg IP) did not modify mean arterial blood pressure (MABP), at 5 min before occlusion, when given alone but did potentiate the hypotensive effect of exogenously administered anandamide (10 mg/kg IV) (p<0.05 at −7 and −5 min before occlusion). Ventricular fibrillation induced by ischaemia and reperfusion was not significantly affected by anandamide (50%, n = 6), URB597 alone (50%, n = 6) or in combination (50%, n = 6) as compared with controls (50%, n = 12). The total number of ischaemia-induced extrasystoles in surviving animals was also not altered in URB 373 (218) (n = 4), anandamide 180 (50) (n = 3) or URB plus anandamide 367 (101) (n = 4) pretreated animals as compared with 278 (124) (n = 8) in controls. Ischaemic preconditioning did reduce the number of ischaemia-induced ectopic beats from 343 (200) (n = 5) to 43 (27) (n = 6). In conclusion, anandamide’s effect on MABP was potentiated by URB597 but the severity of ischaemia–reperfusion-induced arrhythmias was not modified by increasing anandamide levels.