Cardiac sympathetic nerve activity and ventricular fibrillation during acute myocardial infarction in ambulent sheep

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ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S1–S23

in the total duration of TdP. QT intervals corrected for heart rate (QTc) were maximally prolonged by 24 ± 5%, 25 ± 3% and 27 ± 7% for ATX-II, E-4031 and the combination, respectively. Conduction block was not observed with ATX-II, but was seen in 17% of rabbits given E-4031 and in all rabbits receiving the combination (p < 0.05 vs. other groups). The change in short-term variability (STV) of the monophasic action potential duration at 90% repolarisation from baseline to just before the first arrhythmia was 2.7 ± 1.9 ms in rabbits with TdP (n = 7) and 2.1 ± 1.8 ms in rabbits that did not have TdP (n = 8). The present findings suggest that the INa opener ATX-II does not significantly potentiate the torsadogenic action of the IKr blocker E-4031, and STV does not appear to help predict the likelihood of TdP occurring in this anaesthetized rabbit model. Keywords: Arrhythmias; Heart; Ion channel doi:10.1016/j.yjmcc.2007.03.021

Cardiac sympathetic nerve activity and ventricular fibrillation during acute myocardial infarction in ambulent sheep C.J. Charles, D.L. Jardine, A.M. Richards. Christchurch Cardioendocrine Research Group, Christchurch, New Zealand The association between cardiac sympathetic nerve activity (CSNA) and ventricular fibrillation (VF) following acute myocardial infarction (MI) has not been assessed in a conscious animal model. For 60 minutes post-MI, blood pressure (BP), heart rate (HR) and CSNA were recorded continuously. Resistant sheep (group A, n = 10) were compared to susceptible sheep (group B, n-10) who developed fatal VF or sustained ventricular tachycardia VT. MI was induced under pethidine/ diazepam analgesia by applying sustained tension to a coronary suture. Time to VF (n = 7) or VT (n = 3) was 28.1 ± 3.3 min. In group B, MBP, HR and CSNA were averaged each consecutive minute from baseline (14 minutes prior to onset of VF/VT) and compared to time-matched values in group A. In both groups, BP and HR remained constant. Compared to group A, all normalized indices of CSNA (%baseline) increased in group B: burst frequency (p = 0.017), burst incidence (p = 0.007), burst area/min (p = 0.011) and burst area/100 beats (p = 0.013). During the last five minutes immediately prior to VF/VT, respective values in group A vs. group B were: 101% ± 7 vs. 120 ± 5 (p = 0.04), 91% ± 4 vs. 117 ± 8 (p = 0.008), 91% ± 4 vs. 120 ± 10 (p = 0.012), 101% ± 7 vs. 112 ± 5 (p = 0.04). In conclusion, sheep that develop VF or sustained VT post-MI exhibit significant increases in all indices of CSNA during the first 30 min of infarction. CSNA may be of pivotal importance in the genesis of lethal ventricular tachyarrhythmia post-MI. Keywords: Sympathetic nerve activity; Myocardial infarction; Ventricular arrhythmia doi:10.1016/j.yjmcc.2007.03.022

Hypetriglycerolemia affects myocardial connexin-43 remodelling and increased incidence of lethal arrhythmias Marcela Fialova, Katarina Dlugosova, Vladimir Knezl1 , Ludmila Okruhlicova, Narcis Tribulova. Inst. for Heart Res., SAS, Bratislava, Slovakia. 1Inst. Exper. Pharmacol. SAS, Bratislava, Slovakia Aim of this work was to examine whether hypetriglycerolemia (hHTG) affects distribution and/or expression of major cell-to-cell gap junction protein, connexin-43 (Cx43), since Cx43 remodelling is known to facilitate occurrence of malignant arrhythmias. Ventricular tissues taken from the heart of 4 month-old male hHTG and age-matched Wistar rats were processed for in situ coronary and capillary enzyme histochemistry, immunolabelling of Cx43 and for electron microscopy examination. Isolated perfused heart model was used to test vulnerability of the heart to electrically-induced ventricular fibrillation (VF). Results showed that hHTG rat hearts exhibited decreased coronary artery-related ATPase and capillary-related alkaline phosphatase activities as well as subcellular alterations suggesting endothelial impairment. Moreover, myocardial fibres disarrays and interstitial fibrosis indicated ventricular structural remodelling. Notably, an immunolabelling of Cx43 revealed pronounced changes in distribution of gap junctions, i. e. increased number of Cx43-positive gap junctions on lateral surfaces of the cardiomyocytes, cytoplasmic annular profiles of the gap junctions in the vicinity of intercalated discs were observed. These changes, i.e. “lateralisation” and “internalisation” of Cx43 containing gap junctions were linked with significantly higher incidence of VF in hHTG rat hearts (7 of 8) when compared to Wistar controls (2 of 8). Acknowledgment Supported by APVV 51-059505. Keywords: Hypertriglycerolemia; Connexin-43 gap junction channels; Ventricular fibrillation doi:10.1016/j.yjmcc.2007.03.023

Resveratrol, a natural ingredient of grape skin: Antiarrhythmic efficacy and ionic mechanisms Yanjie Lu, Baofeng Yang. Department of Pharmacology, Harbin Medical University, Harbin, Heilongjiang, China Resveratrol has been demonstrated to produce a variety of biological actions. Accumulating line of evidence supported the view that resveratrol may exert protective effect on the cardiovascular system. The aim of the study was to assess the antiarrhythmic profile of resveratrol as well as its electrophysiological mechanism. We observed the antiarrhythmic effects of resveratrol on aconitine induced rat arrhythmia, ouabain induced guinea pig arrhythmia, and coronary ligation induced rat arrhythmia models. Resveratrol significantly and dosedependently increased the doses of aconitine and ouabain