Potassium channel blocker dofetilide does not abolish ischaemic preconditioning.

  title={Potassium channel blocker dofetilide does not abolish ischaemic preconditioning.},
  author={Jens Munch-Ellingsen and Einar Bugge and Jan Eirik L{\o}keb{\o} and Kirsti Ytrehus},
  journal={Scandinavian journal of clinical and laboratory investigation},
  volume={57 1},
Ischaemic preconditioning (IP) is a powerful mechanism for infarct reduction. Enhanced K+ conductance and shortening of action potential duration in the early phase of the sustained ischaemic episode have been proposed as important factors in the IP mechanism for infarct reduction. We have investigated whether the potassium channel-blocking class III anti-arrhythmic agent dofetilide could abolish IP in an in situ rabbit heart infarct model. Dofetilide is a specific blocker of the delayed… Expand
5-HD abolishes ischemic preconditioning independently of monophasic action potential duration in the heart
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Cardiovascular Drugs
Dofetilide is a new antiarrhythmic drug that recently was recommended for approval by an advisory committee to the Food and Drug Administration (FDA) for treatment of patients with persistent atrialExpand


Limitation of infarct size in the rabbit by ischaemic preconditioning is reversible with glibenclamide.
Whether ischaemic preconditioning occurs through the actions of ATP sensitive potassium (KATP) channels during ischaemia and whether pharmacological antagonism of these channels can reverse the protective effect of preconditionsing is investigated. Expand
Blockade of ischaemic preconditioning in dogs by the novel ATP dependent potassium channel antagonist sodium 5-hydroxydecanoate.
The results further strengthen the hypothesis that activation of myocardial KATP channels is involved in the mechanism of ischaemic preconditioning in dogs. Expand
Ketamine-xylazine anaesthesia permits a KATP channel antagonist to attenuate preconditioning in rabbit myocardium.
When ketamine-xylazine anaesthesia was employed, the protective effects of ischaemic preconditioning in the rabbit heart could be blocked by glibenclamide, and pinacidil could mimic the protection of ischemic preconditionsing. Expand
Blockade of ATP-sensitive potassium channels increases infarct size but does not prevent preconditioning in rabbit hearts.
It is concluded that ATP-sensitive potassium channels are not involved in preconditioning in the rabbit heart; however, blocking those channels does exacerbate ischemia. Expand
Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs.
The results suggest that myocardial preconditioning in the canine heart is mediated by activation of KATP channels and that these channels may serve an endogenous myocardium protective role. Expand
Glibenclamide, but not class III drugs, prevents ischaemic shortening of the refractory period in guinea-pig hearts.
The results suggest that the opening of KATP channels may be responsible for the ischaemia-induced shortening of the effective refractory period in perfused guinea-pig hearts and that the class III effects of UK-66,914, dofetilide and ibutilide are attenuated during ischaemic. Expand
Cardioprotection provided by adenosine receptor activation is abolished by blockade of the KATP channel.
Ado A1-receptor agonists mimicked the cardioprotection of ischemic preconditioning and the Ado-induced limitation of IS was abolished by blockade of the KATP channel. Expand
Cardioprotection with the KATP Opener Cromakalim Is Not Correlated with Ischemic Myocardial Action Potential Duration
The data suggest that APD shortening observed with the KATP opener cromakalim is not correlated with its cardioprotective effects. Expand
Class III antiarrhythmic action by potassium channel blockade: dofetilide attenuates hypoxia induced electromechanical changes.
Dofetilide, like glibenclamide, effectively attenuates hypoxia and nicorandil induced action potential shortening and the associated reduction in contractile force, and would be expected to retain its antiarrhythmic efficacy during myocardial Hypoxia or ischaemia. Expand
Class III Antiarrhythmic Action and Inotropy: Effects of Dofetilide in Acute Ischemic Heart Failure in Dogs
In conclusion, dofetilide, at doses that prolonged repolarization, was devoid of cardiodepressive effects in acute ischemic heart failure. Expand