required to induce the arrhythmia indexes. In coronary ligationinduced rat arrhythmia model, resveratrol shortened the durationof arrhythmia, decreased the incidence of ventricular tachycar-dia and mortality. Electrophysiological experiments revealedthat resveratrol shortened APD through the inhibition of ICaand selective enhancement of IKs without an effect on IKr.

Acknowledgment

This research is supported by project of NSFC (30430780,30672644).

Keywords: Arrhythmia; Resveratrol; Electrophysiologicalproperty

doi:10.1016/j.yjmcc.2007.03.024

Antiarrhythmic protection by ischemic preconditioningdoes not require activation of Pi3k/Akt in the rat heartTanya Ravingerova, Jana Matejikova, Jan Neckar1, MonikaIvanova, Miro Barancík, Frantisek Kolar1. Inst Heart Res, SAS,Ctr Exc CVR, Bratislava, SR. 1Inst Physiol, AS CR, Ctr ExpCVR, Prague, CR

Emerging data support a view that phosphatidylinositol 3-kinase (PI3K) directly regulates membrane ion channels, andthat activation of PI3K/Akt, besides involvement in protectionconferred by ischemic preconditioning (IP), might be alsoproarrhythmic. To elucidate its role in antiarrhythmic effect of IP(1 cycle of 5 min ischemia/reperfusion), PI3K/Akt inhibitorLY294002 (LY) was given 15 min before 30-min LAD occlu-sion in Langendorff-perfused rat hearts in concentration (5 μM)that completely blunted infarct size limitation and increase inAkt phosphorylation in the preconditioned hearts. To discernnon-specific effects of LY related to changes in action potential,wortmannin (WM; 100 nM) was also applied. IP reduced theincidence of ventricular tachycardia (VT) and total number ofventricular premature beats (VPB) from 100% and 530±80 inthe controls to 22% and 195±40, respectively (P<0.05). Brac-keting of IP with both inhibitors failed to reverse its anti-arrhythmic effect (LY: VT 14%, VPB 77±20; WM: VT 10%,VPB 88±25; P<0.05 vs. controls). Moreover, in non-precon-ditioned hearts, WM did not suppress arrhythmias (VT 89%,VPB 480±50; P>0.05 vs. controls), while LY exhibited asignificant protection comparable with the effect of IP (VT 13%,VPB 155±15, respectively; P>0.05 vs. IP) suggesting the roleof PI3K-independent pathway. Conclusion: these results indi-cate that activation of PI3K/Akt is not required for antiar-rhythmic protection in contrast to its role in the infarct size-limiting mechanisms of IP in the rat heart. VEGA SR 2/5110/25,GACR-305/05/0875, APVT-51-027404, APVV-SK-CZ-02206.

Keywords: Akt; Arrhythmias; Ischemia/Reperfusion

doi:10.1016/j.yjmcc.2007.03.025

Beneficial effects of adaptation to hypoxia in patients withischemic heart disease and extrasystolic arrhythmiasEugenia B. Manukhina1, H. Fred Downey2, Svetlana V.Lyamina3, Nadezhda P. Lyamina3. 1Inst. Gen. Path. andPathophysiol., Moscow, Russia. 2University of N. Tex. Hlth.Sci. Ctr., Ft. Worth, USA. 3Russian Res. Inst. Cardiol., Saratov,Russia

Recent studies have demonstrated that adaptation tointermittent hypoxia minimizes ischemic/reperfusion cardiacinjury and reperfusion arrhythmias in animal experiments (Zonget al., 2004; Neckar et al., 2004; Mallet et al., 2006). The presentstudy evaluated the antianginal and anti-arrhythmic effects ofadaptation to moderate, intermittent, normobaric hypoxia (IHT)in 53 patients with ischemic heart disease (IHD; I–IV functionalclass angina) and extrasystolic arrhythmias. IHTwas performedfor 20 days. Patients inspired 10% O2 for 3-min intervalsinterspersed with inspiration of atmospheric air for 3 min; thetotal duration of daily hypoxic exposure was 20–60 min. Allpatients underwent 24-hour ECG monitoring before and afterIHT. Patients also received drug therapy for IHD, whichincluded nitrates, β-blockers, and long-acting calcium antago-nists. Results of this study showed that 57.4% of patients had afull anti-arrhythmic response to IHT, and all other patients had apartial anti-arrhythmic response. The incidence of anginalattacks decreased 2.2-fold, and their total duration decreased by74%. Antianginal drug intake was reduced by one third of anaverage daily dose. A group of “sham-adapted” patients nottreated with IHT failed to show similar improvements. There-fore, IHT exerts anti-arrhythmic and anti-anginal effects and isan effective, adjunctive therapeutic and rehabilitative modalityin patients with IHD.

Keywords: Cardiology; Hypoxia; Antiarrhythmics

doi:10.1016/j.yjmcc.2007.03.026

Peroxynitrite induces an antiarrhythmic effect inanaesthetised dogsAttila Kiss, László Juhász, Ildikó Huliák*, Péter Ferdinady*,Ágnes Végh. Department of Pharmacology, University ofSzeged, Szeged, Hungary. ⁎Department of Biochemistry,University of Szeged, Szeged, Hungary

There is some evidence that nanomolar concentrations ofexogenously administered peroxynitrite (PN) provide cardio-protection. The objective of the present study was to examinewhether PN in a concentration of 100 nM, modifies theischaemia and reperfusion-induced (I/R) ventricular arrhyth-mias in anaesthetised dogs. Control dogs (C; n=10) weresimply subjected to a 25 min occlusion of the left anteriordescending coronary artery (LAD), followed by reperfusion.In preconditioned dogs (PC; n=10) this was preceded, 5 minearlier, by two 5 min occlusions of LAD. In another group ofdogs peroxynitrite (PN; n=8) was administered in intra-

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coronary infusion two times for 5 min, 5 min prior to theprolonged ischaemia. In some dogs samples were taken forWestern blot analysis to determine 3-nitrotyrosine (3-NT)formation. Compared to the controls both PC and PN signi-ficantly reduced the numbers of ventricular premature beats(VPBs; 289±84 vs. 93±36 and 84±34) and episodes ofventricular tachycardia (VT; 9.6±3.4 vs. 1.9±1.1 and 1.9±1.7)as well as the incidence of ventricular fibrillation (VF; 50% vs.0% and 13%) during prolonged occlusion. Furthermore both PCand PN increased survival (0% vs. 40% and 50%) andattenuated 3-nitrotyrosine formation following reperfusion.We conclude that PN provides protection, similar to PC, andthis protection can be attributed to a reduced PN formationduring the prolonged ischaemia.

Acknowledgment

The work is supported by OTKA (TO 37520).

Keywords: Arrhythmias; Preconditioning; Free radicals

doi:10.1016/j.yjmcc.2007.03.027

The effect of flecainide on conduction is not diminished inhuman atrial fibrillationTorsten Christ, Erich Wettwer, Ursula Ravens. Department ofPharmacology and Toxicology, Dresden University of Tech-nology, Dresden, Germany

Success rate of pharmacological cardioversion of atrialfibrillation (AF) with Class I antiarrhythmic drugs declineswith duration of AF within few months. The reason for thisincreasing resistance of AF against sodium channel blockertreatment is unclear. Therefore, we have studied whether chronicAF influences the effect of the Class IC agent flecainide onaction potentials parameters measured with conventional micro-electrode technique in human right atrial trabeculae obtainedfrom patients who were either in sinus rhythm (SR) or in chronicAF. In AFAPD90 was smaller compared to SR (AF, 207±9 ms,n=6 vs. SR, 245±13 ms, n=6; p<0.05). Resting membranepotential was significantly more negative in AF than in SR (AF,−74±1 mV vs. SR −68±2 mV, n=6, p<0.05). Maximumupstroke velocity (dV/dtmax) was slightly higher in AF than inSR (AF, 244±14 V/s vs. SR 197±15 V/s, n=6; p<0.05)whereas conduction time was not different. Flecainide decreaseddV/dtmax to complete block with no difference in EC50 betweenSR and AF (SR, −log EC50 (M) 4.7±0.2 vs. AF, 4.9±0.3).Flecainide (10 μM) decreased action potential amplitude in SRfrom 93±2 mV to 84±3 mVand in AF from 105±2 mV to 92±4 mV and plateau potential in SR from −15±2 mV to −20±3 mVand in AF from 4±6 mV to −5±5 mV. We conclude thatthe conduction delaying effects of flecainide are well preservedalso in chronic AF. Our data therefore suggest that the Na-channel blocking activity of flecainide in chronic AF persistsand that the lack of the drug's efficacy to cardiovert long-

standing AF is due to additional mechanisms most probablyinduced by ongoing electrical and structural remodeling.

Keywords:Atrial fibrillation; Na+ channels; Antiarhythmic drugs

doi:10.1016/j.yjmcc.2007.03.028

Comparison between the effects of Etomoxir andRanolazine on cardiac arrhythmiasMoslem Najafi, Tahereh Eteraf Oskouei. School of Pharmacyand Drug Applied Research Center, Tabriz University ofMedical Sciences, Tabriz, Iran

Comparison between the effects of Etomoxir (ETM) andRanolazine (RAZ) on ischemia/reperfusion-induced arrhyth-mias was aimed. Isolated rat hearts were subjected to 30 minregional ischemia and 30 min reperfusion. The hearts wereperfused with drug-free (control) or enriched Krebs solutionwith ETM (1 μM) or RAZ (20 μM) during ischemia/reperfusion. The total number of ischemic ventricular ectopicbeats (VEBs) in the control group was 667±116 whileperfusion of RAZ and ETM reduced it to 33±16 (p<0.001)and 501±165, respectively. The number of ischemic ventriculartachycardia (VT) was also lowered by RAZ and ETM from280±50 (control) to 0 (p<0.001) and 146±50, respectively.Similarly, the number of reperfusion VEBs and VT werelowered by RAZ from 349±73 and 154±29 (control) to 86±38 (p<0.01) and 0 (p<0.001), respectively. RAZ also reducedthe incidence of total ventricular fibrillation (VF) and the timespent for reversible VF from 63% and 218±69 s (control) to0% (p<0.05) and 0 sec (p<0.01), respectively. At the sametime, ETM showed significant anti-arrhythmic effects but in thelower extent in comparison with RAZ. Except a significantdifference in the reduction of VEBs by RAZ compared toETM, the effect was not significant between the agents.Regarding the inhibitory role of ETM and RAZ on fatty acidmetabolism, their beneficial anti-arrhythmic effects are prob-ably related to indirect increase in glucose oxidation.

Keywords: Etomoxir; Ranolazine; Arrhythmias

doi:10.1016/j.yjmcc.2007.03.029

Ranolazine normalizes action potential repolarization ofhypertrophied ventricular cardiomyocytesSilvia Suffredini, Simona Brogioni, Elisabetta Cerbai, LuizBelardinelli1, Alessandro Mugelli. CIMMBA, Unifi, Italy. 1CVTherapeutics, CA, USA

Ranolazine (RAN) is a piperazine derivative recentlyapproved as an add-on therapy for the treatment of patientswith stable angina. Recent studies suggest that RAN reducescalcium overload in the ischemic myocyte by inhibiting the latesodium current. Thus, we studied the electrophysiological effect

S10 ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S1–S23