Pharmacologic preconditioning by delta-opioid agonists occurs via activation of an @entity855 ( @entity855 )-gated @entity972 channel (I(KATP)). Opening of mitochondrial I(KATP) confers pharmacologic preconditioning whereas opening the sarcolemmal I(KATP) shortens action potential duration and is proarrhythmic. This study investigated whether @entity13847 , a selective delta-opioid agonist, is associated with development of @entity943 due to activation of I(KATP). @entity95 isolated hearts were subjected to 12 min of @entity519 and 40 min of reoxygenation after pretreatment with @entity13847 (1 microM, n = 6), @entity1706 (1.25 microM, n = 12), or @entity70400 (6.0 microM, n = 4). Nine additional hearts served as controls. The cytoprotective effects of @entity13847 at a concentration of 1 microM were confirmed using 30 min of regional @entity63 followed by 120 min of reperfusion. @entity2224 ( @entity2224 ) developed in 11 of 12 @entity1706 -treated hearts whereas none of the @entity13847 -treated (zero of six) hearts developed @entity2224 (P < 0.001 compared with @entity1706 pretreatment) and zero of four @entity70400 -pretreated hearts developed @entity2224 . Similarly, zero of nine control hearts developed @entity2224 . @entity13847 reduced @entity1188 size expressed as a percentage of the area at risk from 33 +/- 4% to 14 +/- 3% (P = 0.004) compared with control. @entity13847 , which selectively activates the delta-opioid receptor, provided cytoprotection but did not induce @entity2224 after @entity519 reoxygenation. The results indicate that @entity1706 -induced nonselective activation of I(KATP) results in proarrhythmia that is dependent on activation of the sarcolemmal I(KATP). Selectivity for the mitochondrial I(KATP) is necessary to prevent induction of a proarrhythmic state.

XXXX -induced preconditioning: selective activation of the mitochondrial @entity855 -gated @entity972 channel.

@entity1706 :: ('MESH:D020110', 'Chemical') :: ['pinacidil'] @entity63 :: ('MESH:D007511', 'Disease') :: ['ischemia'] @entity95 :: ('9986', 'Species') :: ['Rabbit'] @entity13847 :: ('MESH:C088464', 'Chemical') :: ['SNC-80'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxia'] @entity1188 :: ('MESH:D007238', 'Disease') :: ['infarct'] @entity2224 :: ('MESH:D014693', 'Disease') :: ['VF', 'Ventricular fibrillation'] @entity972 :: ('MESH:D011188', 'Chemical') :: ['potassium'] @entity70400 :: ('MESH:C428117', 'Chemical') :: ['BMS-191095'] @entity943 :: ('MESH:D001145', 'Disease') :: ['ventricular arrhythmia'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['adenosine triphosphate', 'ATP']
@entity13847 :: (MESH:C088464,Chemical) :: ['SNC-80']
