Diazoxide protects the rabbit heart following cardioplegic ischemia

Jun Feng; Hongling Li; Eliot R. Rosenkranz

doi:10.1023/A:1015554211010

Diazoxide protects the rabbit heart following cardioplegic ischemia

Jun Feng, Hongling Li, Eliot R. Rosenkranz

Surgery

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

K_ATP channels are present in sarcolemmal and mitochondrial membranes. This study tests the hypothesis that opening mitochondrial K_ATP channels with Diazoxide (DZ) improves tolerance to cardioplegic ischemia during surgery. Twenty-two rabbit hearts were perfused with Krebs-Henseleit buffer (KHB) on a Langendorff apparatus and underwent 50 min of 37°C global ischemia with St Thomas' cardioplegia (STCP). Hearts were divided into three groups. Ten (control) received no pretreatment. Seven (DZ) received 10 min of 30 μM DZ, a selective mitochondrial K_ATP opener, in KHB before arrest with STCP containing 30 μM DZ. Five (5-HD + DZ) received 10 min of 100 μM sodium 5-hydroxydecanoate (5-HD), a selective mitochondrial K_ATP channel blocker, followed by 10 min of 30 μM DZ and 100 μM 5-HD in KHB before arrest with STCP + 30 μM DZ + 100 μM 5-HD. LV developed pressure (LVDP), dP/dt and coronary flow (CF) were measured after 60 min of reperfusion. Diazoxide pretreatment significantly improved the recovery of LV function and coronary flow compared to control (LVDP: 49 ± 5* vs. 31 ± 4; +dP/dt_max 927 ± 93 vs. 507 ± 85 mmHg/sec*; CF 33 ± 4 vs. 22 ± 2 ml/min, *p < 0.05). Mitochondria K_ATP channel blockade with 5-HD prevented DZ's salutary effect on the recovery of LV and vascular function. Diazoxide pretreatment protects the rabbit heart during cardioplegic ischemia by opening mitochondrial K_ATP channels. Opening mitochondrial K_ATP channels may be a new strategy for improving myocardial protection during cardiac surgery.

Original language	English (US)
Pages (from-to)	133-138
Number of pages	6
Journal	Molecular and Cellular Biochemistry
Volume	233
Issue number	1-2
DOIs	https://doi.org/10.1023/A:1015554211010
State	Published - Jan 1 2002

Keywords

Cardioplegia
Diazoxide
Mitochondrial K channel
Preconditioning
Rabbit

ASJC Scopus subject areas

Clinical Biochemistry
Molecular Biology
Genetics
Cell Biology

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title = "Diazoxide protects the rabbit heart following cardioplegic ischemia",

abstract = "KATP channels are present in sarcolemmal and mitochondrial membranes. This study tests the hypothesis that opening mitochondrial KATP channels with Diazoxide (DZ) improves tolerance to cardioplegic ischemia during surgery. Twenty-two rabbit hearts were perfused with Krebs-Henseleit buffer (KHB) on a Langendorff apparatus and underwent 50 min of 37°C global ischemia with St Thomas' cardioplegia (STCP). Hearts were divided into three groups. Ten (control) received no pretreatment. Seven (DZ) received 10 min of 30 μM DZ, a selective mitochondrial KATP opener, in KHB before arrest with STCP containing 30 μM DZ. Five (5-HD + DZ) received 10 min of 100 μM sodium 5-hydroxydecanoate (5-HD), a selective mitochondrial KATP channel blocker, followed by 10 min of 30 μM DZ and 100 μM 5-HD in KHB before arrest with STCP + 30 μM DZ + 100 μM 5-HD. LV developed pressure (LVDP), dP/dt and coronary flow (CF) were measured after 60 min of reperfusion. Diazoxide pretreatment significantly improved the recovery of LV function and coronary flow compared to control (LVDP: 49 ± 5* vs. 31 ± 4; +dP/dtmax 927 ± 93 vs. 507 ± 85 mmHg/sec*; CF 33 ± 4 vs. 22 ± 2 ml/min, *p < 0.05). Mitochondria KATP channel blockade with 5-HD prevented DZ's salutary effect on the recovery of LV and vascular function. Diazoxide pretreatment protects the rabbit heart during cardioplegic ischemia by opening mitochondrial KATP channels. Opening mitochondrial KATP channels may be a new strategy for improving myocardial protection during cardiac surgery.",

keywords = "Cardioplegia, Diazoxide, Mitochondrial K channel, Preconditioning, Rabbit",

author = "Jun Feng and Hongling Li and Rosenkranz, {Eliot R.}",

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T1 - Diazoxide protects the rabbit heart following cardioplegic ischemia

AU - Feng, Jun

AU - Li, Hongling

AU - Rosenkranz, Eliot R.

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N2 - KATP channels are present in sarcolemmal and mitochondrial membranes. This study tests the hypothesis that opening mitochondrial KATP channels with Diazoxide (DZ) improves tolerance to cardioplegic ischemia during surgery. Twenty-two rabbit hearts were perfused with Krebs-Henseleit buffer (KHB) on a Langendorff apparatus and underwent 50 min of 37°C global ischemia with St Thomas' cardioplegia (STCP). Hearts were divided into three groups. Ten (control) received no pretreatment. Seven (DZ) received 10 min of 30 μM DZ, a selective mitochondrial KATP opener, in KHB before arrest with STCP containing 30 μM DZ. Five (5-HD + DZ) received 10 min of 100 μM sodium 5-hydroxydecanoate (5-HD), a selective mitochondrial KATP channel blocker, followed by 10 min of 30 μM DZ and 100 μM 5-HD in KHB before arrest with STCP + 30 μM DZ + 100 μM 5-HD. LV developed pressure (LVDP), dP/dt and coronary flow (CF) were measured after 60 min of reperfusion. Diazoxide pretreatment significantly improved the recovery of LV function and coronary flow compared to control (LVDP: 49 ± 5* vs. 31 ± 4; +dP/dtmax 927 ± 93 vs. 507 ± 85 mmHg/sec*; CF 33 ± 4 vs. 22 ± 2 ml/min, *p < 0.05). Mitochondria KATP channel blockade with 5-HD prevented DZ's salutary effect on the recovery of LV and vascular function. Diazoxide pretreatment protects the rabbit heart during cardioplegic ischemia by opening mitochondrial KATP channels. Opening mitochondrial KATP channels may be a new strategy for improving myocardial protection during cardiac surgery.

AB - KATP channels are present in sarcolemmal and mitochondrial membranes. This study tests the hypothesis that opening mitochondrial KATP channels with Diazoxide (DZ) improves tolerance to cardioplegic ischemia during surgery. Twenty-two rabbit hearts were perfused with Krebs-Henseleit buffer (KHB) on a Langendorff apparatus and underwent 50 min of 37°C global ischemia with St Thomas' cardioplegia (STCP). Hearts were divided into three groups. Ten (control) received no pretreatment. Seven (DZ) received 10 min of 30 μM DZ, a selective mitochondrial KATP opener, in KHB before arrest with STCP containing 30 μM DZ. Five (5-HD + DZ) received 10 min of 100 μM sodium 5-hydroxydecanoate (5-HD), a selective mitochondrial KATP channel blocker, followed by 10 min of 30 μM DZ and 100 μM 5-HD in KHB before arrest with STCP + 30 μM DZ + 100 μM 5-HD. LV developed pressure (LVDP), dP/dt and coronary flow (CF) were measured after 60 min of reperfusion. Diazoxide pretreatment significantly improved the recovery of LV function and coronary flow compared to control (LVDP: 49 ± 5* vs. 31 ± 4; +dP/dtmax 927 ± 93 vs. 507 ± 85 mmHg/sec*; CF 33 ± 4 vs. 22 ± 2 ml/min, *p < 0.05). Mitochondria KATP channel blockade with 5-HD prevented DZ's salutary effect on the recovery of LV and vascular function. Diazoxide pretreatment protects the rabbit heart during cardioplegic ischemia by opening mitochondrial KATP channels. Opening mitochondrial KATP channels may be a new strategy for improving myocardial protection during cardiac surgery.

KW - Cardioplegia

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KW - Mitochondrial K channel

KW - Preconditioning

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