Clinical implications of interactions between IK(ATP) activation and IKr blockade during non-ischemic and ischemic conditions:a simulation study
碩士 === 國立成功大學 === 生理學研究所 === 94 === In patients with ischemic heart disease, openers of ATP-sensitive K+ current (IK(ATP)) (e.g., nicorandil) are increasingly used for angina and blockers of the rapidly activating K+ current (IKr) (e.g., E-4031, d-sotalol, dofetilide, and sematilide) are often presc...
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ndltd-TW-094NCKU51160032016-05-30T04:21:58Z http://ndltd.ncl.edu.tw/handle/86564211160402749944 Clinical implications of interactions between IK(ATP) activation and IKr blockade during non-ischemic and ischemic conditions:a simulation study 在心臟組織缺血與非缺血下活化ATP敏感性鉀離子電流與抑制快速活化鉀離子電流交互作用的臨床意義之模擬研究 Han-Dong Chang 張漢東 碩士 國立成功大學 生理學研究所 94 In patients with ischemic heart disease, openers of ATP-sensitive K+ current (IK(ATP)) (e.g., nicorandil) are increasingly used for angina and blockers of the rapidly activating K+ current (IKr) (e.g., E-4031, d-sotalol, dofetilide, and sematilide) are often prescribed for ventricular arrhythmias. Both IK(ATP) openers and IKr blockers possess antiarrhythmic and proarrhythmic properties. Potential interactions between these two classes of drugs may occur. In this study, we used dynamic Luo-Rudy simulation model to study the effects of IK(ATP) activation and IKr blockade, alone and in combination, on action potential duration (APD) of ventricular myocardium during control and under ischemic conditions. Our result showed that IKr blockade by 50% prolonged APD90 from 176 to 385 ms; however, subsequent IK(ATP) activation by 50% reduced the duration from 385 to 124 ms. Ischemic conditions created by varying concentrations of intracellular ATP at 300, 100 and 30 mM progressively decreased APD90 by 11, 42 and 72%, respectively. The half-maximal concentration for intracellular ATP to shorten APD90 and to block IK(ATP) was calculated to be 87.5 mM. Both IK(ATP) activation and IKr blockade did not exert any influence on ischemia. In conclusions, IK(ATP) activation is very potent in shortening ADD90 and may thereby diminish antiarrhythmic while suppress proarrhythmic effects of IKr blockade. Myocardial ischemia induces progressive shortening of APD90 in parallel with reduced ATP concentrations. However, profibrillatory propensity induced by myocardial ischemia would not be affected by either IK(ATP) activation or IKr blockade. Sheng-Nan Wu 吳勝男 2006 學位論文 ; thesis 72 en_US |
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碩士 === 國立成功大學 === 生理學研究所 === 94 === In patients with ischemic heart disease, openers of ATP-sensitive K+ current (IK(ATP)) (e.g., nicorandil) are increasingly used for angina and blockers of the rapidly activating K+ current (IKr) (e.g., E-4031, d-sotalol, dofetilide, and sematilide) are often prescribed for ventricular arrhythmias. Both IK(ATP) openers and IKr blockers possess antiarrhythmic and proarrhythmic properties. Potential interactions between these two classes of drugs may occur. In this study, we used dynamic Luo-Rudy simulation model to study the effects of IK(ATP) activation and IKr blockade, alone and in combination, on action potential duration (APD) of ventricular myocardium during control and under ischemic conditions. Our result showed that IKr blockade by 50% prolonged APD90 from 176 to 385 ms; however, subsequent IK(ATP) activation by 50% reduced the duration from 385 to 124 ms. Ischemic conditions created by varying concentrations of intracellular ATP at 300, 100 and 30 mM progressively decreased APD90 by 11, 42 and 72%, respectively. The half-maximal concentration for intracellular ATP to shorten APD90 and to block IK(ATP) was calculated to be 87.5 mM. Both IK(ATP) activation and IKr blockade did not exert any influence on ischemia. In conclusions, IK(ATP) activation is very potent in shortening ADD90 and may thereby diminish antiarrhythmic while suppress proarrhythmic effects of IKr blockade. Myocardial ischemia induces progressive shortening of APD90 in parallel with reduced ATP concentrations. However, profibrillatory propensity induced by myocardial ischemia would not be affected by either IK(ATP) activation or IKr blockade.
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author2 |
Sheng-Nan Wu |
author_facet |
Sheng-Nan Wu Han-Dong Chang 張漢東 |
author |
Han-Dong Chang 張漢東 |
spellingShingle |
Han-Dong Chang 張漢東 Clinical implications of interactions between IK(ATP) activation and IKr blockade during non-ischemic and ischemic conditions:a simulation study |
author_sort |
Han-Dong Chang |
title |
Clinical implications of interactions between IK(ATP) activation and IKr blockade during non-ischemic and ischemic conditions:a simulation study |
title_short |
Clinical implications of interactions between IK(ATP) activation and IKr blockade during non-ischemic and ischemic conditions:a simulation study |
title_full |
Clinical implications of interactions between IK(ATP) activation and IKr blockade during non-ischemic and ischemic conditions:a simulation study |
title_fullStr |
Clinical implications of interactions between IK(ATP) activation and IKr blockade during non-ischemic and ischemic conditions:a simulation study |
title_full_unstemmed |
Clinical implications of interactions between IK(ATP) activation and IKr blockade during non-ischemic and ischemic conditions:a simulation study |
title_sort |
clinical implications of interactions between ik(atp) activation and ikr blockade during non-ischemic and ischemic conditions:a simulation study |
publishDate |
2006 |
url |
http://ndltd.ncl.edu.tw/handle/86564211160402749944 |
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