Vladimir Matchkov

Effect of ischemic preconditioning and a Kv7 channel blocker on cardiac ischemia-reperfusion injury in rats

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Effect of ischemic preconditioning and a Kv7 channel blocker on cardiac ischemia-reperfusion injury in rats. / Corydon, Krestine Kjeldsen; Matchkov, Vladimir; Fais, Rafael; Abramochkin, Denis; Hedegaard, Elise Røge; Comerma-Steffensen, Simon; Simonsen, Ulf.

In: European Journal of Pharmacology, Vol. 866, 172820, 05.01.2020.

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Corydon, Krestine Kjeldsen ; Matchkov, Vladimir ; Fais, Rafael ; Abramochkin, Denis ; Hedegaard, Elise Røge ; Comerma-Steffensen, Simon ; Simonsen, Ulf. / Effect of ischemic preconditioning and a Kv7 channel blocker on cardiac ischemia-reperfusion injury in rats. In: European Journal of Pharmacology. 2020 ; Vol. 866.

Bibtex

@article{18cb750cc38c4f97bc7405d1413c9329,
title = "Effect of ischemic preconditioning and a Kv7 channel blocker on cardiac ischemia-reperfusion injury in rats",
abstract = "Recently, we found cardioprotective effects of ischemic preconditioning (IPC), and from a blocker of KCNQ voltage-gated K+ channels (KV7), XE991 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone), in isolated rat hearts. The purpose of the present study was to investigate the cardiovascular effects of IPC and XE991 and whether they are cardioprotective in intact rats. In conscious rats, we measured the effect of the KV7 channel blocker XE991 on heart rate and blood pressure by use of telemetry. In anaesthetized rats, cardiac ischemia was induced by occluding the left coronary artery, and the animals received IPC (2 × 5 min of occlusion), XE991, or a combination. After a 2 h reperfusion period, the hearts were excised, and the area at risk and infarct size were determined. In both anaesthetized and conscious rats, XE991 increased blood pressure, and the highest dose (7.5 mg/kg) of XE991 also increased heart rate, and 44% of conscious rats died. XE991 induced marked changes in the electrocardiogram (e.g., increased PR interval and prolonged QTC interval) without changing cardiac action potentials. The infarct size to area at risk ratio was reduced from 53 ± 2% (n = 8) in the vehicle compared to 36 ± 3% in the IPC group (P < 0.05, n = 9). XE991 (0.75 mg/kg) treatment alone or on top of IPC failed to reduce myocardial infarct size. Similar to the effect in isolated hearts, locally applied IPC was cardioprotective in intact animals exposed to ischemia-reperfusion. Systemic administration of XE991 failed to protect the heart against ischemia-reperfusion injury suggesting effects on the autonomic nervous system counteracting the cardioprotection in intact animals.",
keywords = "Acute myocardial infarction, Blood pressure, Cardioprotection, In vivo, Rat, XE991",
author = "Corydon, {Krestine Kjeldsen} and Vladimir Matchkov and Rafael Fais and Denis Abramochkin and Hedegaard, {Elise R{\o}ge} and Simon Comerma-Steffensen and Ulf Simonsen",
year = "2020",
month = jan,
day = "5",
doi = "10.1016/j.ejphar.2019.172820",
language = "English",
volume = "866",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier BV",

}

RIS

TY - JOUR

T1 - Effect of ischemic preconditioning and a Kv7 channel blocker on cardiac ischemia-reperfusion injury in rats

AU - Corydon, Krestine Kjeldsen

AU - Matchkov, Vladimir

AU - Fais, Rafael

AU - Abramochkin, Denis

AU - Hedegaard, Elise Røge

AU - Comerma-Steffensen, Simon

AU - Simonsen, Ulf

PY - 2020/1/5

Y1 - 2020/1/5

N2 - Recently, we found cardioprotective effects of ischemic preconditioning (IPC), and from a blocker of KCNQ voltage-gated K+ channels (KV7), XE991 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone), in isolated rat hearts. The purpose of the present study was to investigate the cardiovascular effects of IPC and XE991 and whether they are cardioprotective in intact rats. In conscious rats, we measured the effect of the KV7 channel blocker XE991 on heart rate and blood pressure by use of telemetry. In anaesthetized rats, cardiac ischemia was induced by occluding the left coronary artery, and the animals received IPC (2 × 5 min of occlusion), XE991, or a combination. After a 2 h reperfusion period, the hearts were excised, and the area at risk and infarct size were determined. In both anaesthetized and conscious rats, XE991 increased blood pressure, and the highest dose (7.5 mg/kg) of XE991 also increased heart rate, and 44% of conscious rats died. XE991 induced marked changes in the electrocardiogram (e.g., increased PR interval and prolonged QTC interval) without changing cardiac action potentials. The infarct size to area at risk ratio was reduced from 53 ± 2% (n = 8) in the vehicle compared to 36 ± 3% in the IPC group (P < 0.05, n = 9). XE991 (0.75 mg/kg) treatment alone or on top of IPC failed to reduce myocardial infarct size. Similar to the effect in isolated hearts, locally applied IPC was cardioprotective in intact animals exposed to ischemia-reperfusion. Systemic administration of XE991 failed to protect the heart against ischemia-reperfusion injury suggesting effects on the autonomic nervous system counteracting the cardioprotection in intact animals.

AB - Recently, we found cardioprotective effects of ischemic preconditioning (IPC), and from a blocker of KCNQ voltage-gated K+ channels (KV7), XE991 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone), in isolated rat hearts. The purpose of the present study was to investigate the cardiovascular effects of IPC and XE991 and whether they are cardioprotective in intact rats. In conscious rats, we measured the effect of the KV7 channel blocker XE991 on heart rate and blood pressure by use of telemetry. In anaesthetized rats, cardiac ischemia was induced by occluding the left coronary artery, and the animals received IPC (2 × 5 min of occlusion), XE991, or a combination. After a 2 h reperfusion period, the hearts were excised, and the area at risk and infarct size were determined. In both anaesthetized and conscious rats, XE991 increased blood pressure, and the highest dose (7.5 mg/kg) of XE991 also increased heart rate, and 44% of conscious rats died. XE991 induced marked changes in the electrocardiogram (e.g., increased PR interval and prolonged QTC interval) without changing cardiac action potentials. The infarct size to area at risk ratio was reduced from 53 ± 2% (n = 8) in the vehicle compared to 36 ± 3% in the IPC group (P < 0.05, n = 9). XE991 (0.75 mg/kg) treatment alone or on top of IPC failed to reduce myocardial infarct size. Similar to the effect in isolated hearts, locally applied IPC was cardioprotective in intact animals exposed to ischemia-reperfusion. Systemic administration of XE991 failed to protect the heart against ischemia-reperfusion injury suggesting effects on the autonomic nervous system counteracting the cardioprotection in intact animals.

KW - Acute myocardial infarction

KW - Blood pressure

KW - Cardioprotection

KW - In vivo

KW - Rat

KW - XE991

UR - http://www.scopus.com/inward/record.url?scp=85075827210&partnerID=8YFLogxK

U2 - 10.1016/j.ejphar.2019.172820

DO - 10.1016/j.ejphar.2019.172820

M3 - Journal article

C2 - 31760069

VL - 866

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

M1 - 172820

ER -