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

E. Robinson, R. Brett, S. Kennedy, K.A. Kane

Research output: Contribution to journalConference Contribution

Abstract

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.
Original languageEnglish
JournalHeart
Volume94
Issue number9
Publication statusPublished - Sep 2008

Fingerprint

Reperfusion
Cardiac Arrhythmias
Ischemia
Arterial Pressure
Premature Cardiac Complexes
anandamide
Cannabinoid Receptors
Endocannabinoids
Ischemic Preconditioning
Coronary Occlusion
Ventricular Fibrillation
cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester

Keywords

  • anandamide plasma levels
  • ischaemia
  • reperfusion-induced arrhythmias

Cite this

Robinson, E., Brett, R., Kennedy, S., & Kane, K. A. (2008). Effect of modification of anandamide plasma levels on ischaemia and reperfusion-induced arrhythmias. Heart, 94(9).
Robinson, E. ; Brett, R. ; Kennedy, S. ; Kane, K.A. / Effect of modification of anandamide plasma levels on ischaemia and reperfusion-induced arrhythmias. In: Heart. 2008 ; Vol. 94, No. 9.
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title = "Effect of modification of anandamide plasma levels on ischaemia and reperfusion-induced arrhythmias",
abstract = "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.",
keywords = "anandamide plasma levels, ischaemia, reperfusion-induced arrhythmias",
author = "E. Robinson and R. Brett and S. Kennedy and K.A. Kane",
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Robinson, E, Brett, R, Kennedy, S & Kane, KA 2008, 'Effect of modification of anandamide plasma levels on ischaemia and reperfusion-induced arrhythmias', Heart, vol. 94, no. 9.

Effect of modification of anandamide plasma levels on ischaemia and reperfusion-induced arrhythmias. / Robinson, E.; Brett, R.; Kennedy, S.; Kane, K.A.

In: Heart, Vol. 94, No. 9, 09.2008.

Research output: Contribution to journalConference Contribution

TY - JOUR

T1 - Effect of modification of anandamide plasma levels on ischaemia and reperfusion-induced arrhythmias

AU - Robinson, E.

AU - Brett, R.

AU - Kennedy, S.

AU - Kane, K.A.

N1 - British Society for Cardiovascular Research: Joint Late Spring Meeting with the British Cardiovascular Society

PY - 2008/9

Y1 - 2008/9

N2 - 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.

AB - 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.

KW - anandamide plasma levels

KW - ischaemia

KW - reperfusion-induced arrhythmias

UR - http://heart.bmj.com/content/94/9/e22.extract

M3 - Conference Contribution

VL - 94

JO - Heart

JF - Heart

SN - 1355-6037

IS - 9

ER -