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The role of mitochondrial K(ATP) channels in antiarrhythmic effects of ischaemic preconditioning in dogs.
Br J Pharmacol. 2002 Dec; 137(7):1107-15.BJ

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 micro g 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; P<0.05), the number of episodes of ventricular tachycardia (VT; 8.3+/-4.2 to 1.6+/-0.9 and 0.2+/-0.1; P<0.05) and the incidences of VT (100 to 43 and 33%; P<0.05) and ventricular fibrilation (VF; 60 to 0 and 17%; P<0.05) during the 25 min occlusion of the LAD. Further, 43% of the PC dogs and 58% of the diazoxide treated dogs survived the combined ischaemia-reperfusion insult (cp. 0% in the controls; P<0.05). The protection afforded by PC and diazoxide was abolished by 5-HD, especially when it was given prior to the PC occlusion. In the presence of 5-HD, three out of 10 dogs fibrillated during the PC occlusion and another three dogs died following reperfusion. Furthermore, there were no survivors in this group from the prolonged ischaemia/reperfusion insult. 5-HD given after PC only attenuated the antiarrhythmic protection. 4. Opening of mitoK(ATP) 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.

Authors+Show Affiliations

Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Faculty of Medicine, Dóm tér 12, P O Box 427, H-6701 Hungary. vegh@phcol.szote.u-szeged.huNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12429584

Citation

Végh, Agnes, and James R. Parratt. "The Role of Mitochondrial K(ATP) Channels in Antiarrhythmic Effects of Ischaemic Preconditioning in Dogs." British Journal of Pharmacology, vol. 137, no. 7, 2002, pp. 1107-15.
Végh A, Parratt JR. The role of mitochondrial K(ATP) channels in antiarrhythmic effects of ischaemic preconditioning in dogs. Br J Pharmacol. 2002;137(7):1107-15.
Végh, A., & Parratt, J. R. (2002). The role of mitochondrial K(ATP) channels in antiarrhythmic effects of ischaemic preconditioning in dogs. British Journal of Pharmacology, 137(7), 1107-15.
Végh A, Parratt JR. The Role of Mitochondrial K(ATP) Channels in Antiarrhythmic Effects of Ischaemic Preconditioning in Dogs. Br J Pharmacol. 2002;137(7):1107-15. PubMed PMID: 12429584.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of mitochondrial K(ATP) channels in antiarrhythmic effects of ischaemic preconditioning in dogs. AU - Végh,Agnes, AU - Parratt,James R, PY - 2002/11/14/pubmed PY - 2003/5/21/medline PY - 2002/11/14/entrez SP - 1107 EP - 15 JF - British journal of pharmacology JO - Br J Pharmacol VL - 137 IS - 7 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 micro g 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; P<0.05), the number of episodes of ventricular tachycardia (VT; 8.3+/-4.2 to 1.6+/-0.9 and 0.2+/-0.1; P<0.05) and the incidences of VT (100 to 43 and 33%; P<0.05) and ventricular fibrilation (VF; 60 to 0 and 17%; P<0.05) during the 25 min occlusion of the LAD. Further, 43% of the PC dogs and 58% of the diazoxide treated dogs survived the combined ischaemia-reperfusion insult (cp. 0% in the controls; P<0.05). The protection afforded by PC and diazoxide was abolished by 5-HD, especially when it was given prior to the PC occlusion. In the presence of 5-HD, three out of 10 dogs fibrillated during the PC occlusion and another three dogs died following reperfusion. Furthermore, there were no survivors in this group from the prolonged ischaemia/reperfusion insult. 5-HD given after PC only attenuated the antiarrhythmic protection. 4. Opening of mitoK(ATP) 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. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/12429584/The_role_of_mitochondrial_K_ATP__channels_in_antiarrhythmic_effects_of_ischaemic_preconditioning_in_dogs_ L2 - https://doi.org/10.1038/sj.bjp.0704966 DB - PRIME DP - Unbound Medicine ER -