The effect of acute simvastatin administration on the ischaemia and reperfusion-induced ventricular arrhythmias in anesthetized dogs

Kisvári Gábor
The effect of acute simvastatin administration on the ischaemia and reperfusion-induced ventricular arrhythmias in anesthetized dogs.
PhD, University of Szeged.
(2016)

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Abstract in foreign language

Ventricular tachyarrhythmia is one of the main causes responsible for sudden cardiac death. The prevention and treatment of these severe tachyarrhythmias is still remained a big challenge of cardiology in the industrialized countries. There is increasing evidence that statins, which represent the first-line therapy for hyperlipidaemia, may possess lipid-independent pleiotropic actions, which are associated with an increased release of nitric oxide (NO) through the activation of eNOS, and contribute to cardioprotection following chronic statin treatment. There is lack of evidence, however, whether statins administered acutely influence the severity of arrhythmias, resulting from ischaemia and reperfusion (I/R). Therefore, the aim of the present study was to examine the effects and mechanisms of acute statin administration on arrhythmias resulting from a 25 min coronary artery occlusion and reperfusion (I/R) in chloralose/urethane anaesthetized dogs. In a group of dogs activated simvastatin (0.1 mg/kg) was administrated in slow intracoronary injection just prior to the occlusion of the left anterior descending coronary artery. The severity of ischaemia (degree of inhomogeneity of electrical activation, epicardial ST-segment) and of arrhythmias, as well as the plasma NOx levels in blood samples taken from the coronary sinus were assessed. From the myocardial tissue samples the activity of eNOS (Western blot) and superoxide production (confocal microscopy) were determined. We have shown that compared to the control group, in which the dogs were treated only with the solvent of simvastatin, the administration of simvastatin significantly decreased the severity of ischaemia and of ventricular arrhythmias, increased the activity of eNOS and the plasma concentration of NO metabolites, and significantly reduced the production of superoxide during reperfusion. We have also pointed out that the protective effects of simvastatin are mediated through the rapid activation of eNOS, most probably via the stimulation of PI-3 kinase/Akt pathway, since the inhibition of NOS by L-NAME, and the inhibition PI-3 kinase by wortmannin abolished the protective effects of simvastatin. Thus we conclude that the antiarrhythmic effect of acute simvastatin administration can certainly be associated with an increased NO bioavailability during occlusion, due to the rapid activation of eNOS via the stimulation of the PI3/Akt pathway by simvastatin.

Item Type: Thesis (PhD)
Creators: Kisvári Gábor
Hungarian title label: Az akut simvastatin kezelés hatása az iszkémia/reperfúzió okozta kamrai aritmiákra altatott kutya modellben
Title of the thesis in foreign language: The effect of acute simvastatin administration on the ischaemia and reperfusion-induced ventricular arrhythmias in anesthetized dogs
Divisions: Doctoral School of Multidisciplinary Medicine
Discipline label: orvostudományok > elméleti orvostudományok
Defence date label: 2016
Item ID: 3162
Identification Number: 3267809
doi: https://doi.org/10.14232/phd.3162
Date Deposited: 2016. Oct. 18. 13:42
Last Modified: 2017. Sep. 19. 14:01
Depository no.: B 6214
Supervisor label:
Supervisor Supervisor scientific name label
Prof. Végh Ágnes
Egyetemi tanár, Farmakológiai és Farmakoterápiai Intézet, Általános Orvostudományi Kar, Szegedi Tudományegyetem
Reviewer label:
Reviewer name label Reviewer scientific name label
Dr. Jancsó Gábor
Dr. Varga Albert
Intézetvezető, egyetei docens, PTE ÁOK Sebészeti Oktató és Kutató Intézet
Egyetemi tanár, SZTE ÁOK II. sz. Belgyógyászati Klinika
President label:
President name label President scientific name label
Dr. Boros Mihály
Tanszékvezető egyetemi tanár, SZTE ÁOK, Sebészeti és Műtéttani Intézet
Member label:
Member name label Member scientific name label
Dr. Tósaki Árpád
Dr. Csont Tamás
Dr. Csonka Csaba
Tanszékvezető egyetemi tanár, DE OEC GYTK Gyógyszethatástani Tanszék
Egyetemi docens, SZTE ÁOK Biokémiai Intézet
Tudományos főmunkatárs, SZTE ÁOK Biokémiai Intézet
URI: http://doktori.bibl.u-szeged.hu/id/eprint/3162
Defence/Citable status: Defended.

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