The role of mitochondrial K ATP channels in antiarrhythmic effects of ischaemic preconditioning in dogs

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Abstract

1. In the canine a single brief (5 min) coronary artery occlusion protects the myocardium against the severe ventricular arrhythmias and reduces the ischaemic changes that result from a subsequent, more prolonged (25 min) occlusion. The main purpose of the present study was to examine whether mitochondrial K ATP channels are involved in this protection. 2. In chloralose-urethane anaesthetized dogs, preconditioning (PC) was induced by a single 5 min period occlusion of the left anterior descending (LAD) coronary artery, 20 min prior to a 25 min occlusion of the same artery. In some of these PC dogs 5-hydroxydecanoate (5-HD; 150 μg kg -1 min -1 by intracoronary infusion) was given over a period of 30 min either before, or after PC. In other dogs the mitochondrial K ATP channel opener diazoxide (1 mg kg -1; i.c.) was given, either alone or in the presence of 5-HD. Control dogs (infused with saline) were simply subjected to a 25 min occlusion and reperfusion. 3. Compared to controls, both PC and diazoxide significantly reduced the number of ventricular premature beats (VPBs; 295 ± 67 to 89 ± 28 and 19 ± 11, respectively; PATP channels prior to ischaemia by preconditioning and diazoxide protects the myocardium against ischaemia and reperfusion-induced arrhythmias. This protection is abolished if the opening of these channels is prevented by the prior administration of 5-HD but only attenuated if 5-HD is given after preconditioning. The results indicate that opening of mitoK ATP channels prior to ischaemia is mandatory for protection against ischaemia and reperfusion-induced arrhythmias.

Original languageEnglish
Pages (from-to)1107-1115
Number of pages9
JournalBritish Journal of Pharmacology
Volume137
Issue number7
DOIs
Publication statusPublished - Dec 2002

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Ischemic Preconditioning
Diazoxide
Ischemia
Dogs
Reperfusion
Cardiac Arrhythmias
Coronary Vessels
Myocardium
Chloralose
Ventricular Premature Complexes
Coronary Occlusion
Urethane
Canidae
Arteries
mitochondrial K(ATP) channel

Keywords

  • 5-hydroxydecanoate
  • Diazoxide
  • Ischaemia
  • Mitochondrial K channels
  • Sudden death
  • Ventricular arrhythmia

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "The role of mitochondrial K ATP channels in antiarrhythmic effects of ischaemic preconditioning in dogs",
abstract = "1. In the canine a single brief (5 min) coronary artery occlusion protects the myocardium against the severe ventricular arrhythmias and reduces the ischaemic changes that result from a subsequent, more prolonged (25 min) occlusion. The main purpose of the present study was to examine whether mitochondrial K ATP channels are involved in this protection. 2. In chloralose-urethane anaesthetized dogs, preconditioning (PC) was induced by a single 5 min period occlusion of the left anterior descending (LAD) coronary artery, 20 min prior to a 25 min occlusion of the same artery. In some of these PC dogs 5-hydroxydecanoate (5-HD; 150 μg kg -1 min -1 by intracoronary infusion) was given over a period of 30 min either before, or after PC. In other dogs the mitochondrial K ATP channel opener diazoxide (1 mg kg -1; i.c.) was given, either alone or in the presence of 5-HD. Control dogs (infused with saline) were simply subjected to a 25 min occlusion and reperfusion. 3. Compared to controls, both PC and diazoxide significantly reduced the number of ventricular premature beats (VPBs; 295 ± 67 to 89 ± 28 and 19 ± 11, respectively; PATP channels prior to ischaemia by preconditioning and diazoxide protects the myocardium against ischaemia and reperfusion-induced arrhythmias. This protection is abolished if the opening of these channels is prevented by the prior administration of 5-HD but only attenuated if 5-HD is given after preconditioning. The results indicate that opening of mitoK ATP channels prior to ischaemia is mandatory for protection against ischaemia and reperfusion-induced arrhythmias.",
keywords = "5-hydroxydecanoate, Diazoxide, Ischaemia, Mitochondrial K channels, Sudden death, Ventricular arrhythmia",
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AU - Parratt, J.

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N2 - 1. In the canine a single brief (5 min) coronary artery occlusion protects the myocardium against the severe ventricular arrhythmias and reduces the ischaemic changes that result from a subsequent, more prolonged (25 min) occlusion. The main purpose of the present study was to examine whether mitochondrial K ATP channels are involved in this protection. 2. In chloralose-urethane anaesthetized dogs, preconditioning (PC) was induced by a single 5 min period occlusion of the left anterior descending (LAD) coronary artery, 20 min prior to a 25 min occlusion of the same artery. In some of these PC dogs 5-hydroxydecanoate (5-HD; 150 μg kg -1 min -1 by intracoronary infusion) was given over a period of 30 min either before, or after PC. In other dogs the mitochondrial K ATP channel opener diazoxide (1 mg kg -1; i.c.) was given, either alone or in the presence of 5-HD. Control dogs (infused with saline) were simply subjected to a 25 min occlusion and reperfusion. 3. Compared to controls, both PC and diazoxide significantly reduced the number of ventricular premature beats (VPBs; 295 ± 67 to 89 ± 28 and 19 ± 11, respectively; PATP channels prior to ischaemia by preconditioning and diazoxide protects the myocardium against ischaemia and reperfusion-induced arrhythmias. This protection is abolished if the opening of these channels is prevented by the prior administration of 5-HD but only attenuated if 5-HD is given after preconditioning. The results indicate that opening of mitoK ATP channels prior to ischaemia is mandatory for protection against ischaemia and reperfusion-induced arrhythmias.

AB - 1. In the canine a single brief (5 min) coronary artery occlusion protects the myocardium against the severe ventricular arrhythmias and reduces the ischaemic changes that result from a subsequent, more prolonged (25 min) occlusion. The main purpose of the present study was to examine whether mitochondrial K ATP channels are involved in this protection. 2. In chloralose-urethane anaesthetized dogs, preconditioning (PC) was induced by a single 5 min period occlusion of the left anterior descending (LAD) coronary artery, 20 min prior to a 25 min occlusion of the same artery. In some of these PC dogs 5-hydroxydecanoate (5-HD; 150 μg kg -1 min -1 by intracoronary infusion) was given over a period of 30 min either before, or after PC. In other dogs the mitochondrial K ATP channel opener diazoxide (1 mg kg -1; i.c.) was given, either alone or in the presence of 5-HD. Control dogs (infused with saline) were simply subjected to a 25 min occlusion and reperfusion. 3. Compared to controls, both PC and diazoxide significantly reduced the number of ventricular premature beats (VPBs; 295 ± 67 to 89 ± 28 and 19 ± 11, respectively; PATP channels prior to ischaemia by preconditioning and diazoxide protects the myocardium against ischaemia and reperfusion-induced arrhythmias. This protection is abolished if the opening of these channels is prevented by the prior administration of 5-HD but only attenuated if 5-HD is given after preconditioning. The results indicate that opening of mitoK ATP channels prior to ischaemia is mandatory for protection against ischaemia and reperfusion-induced arrhythmias.

KW - 5-hydroxydecanoate

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