P.1.8 Uncoupling myocardial gap junctions: A new antiarrhythmic drug mechanism

EP Europace, Oct 2003

Cervantes, D., Coromilas, J., Wit, A.

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P.1.8 Uncoupling myocardial gap junctions: A new antiarrhythmic drug mechanism

A. Głowniak 0 1 2 3 4 5 A. Kutarski 0 1 2 3 4 5 D. Szcze˛s´niak 0 1 2 3 4 5 P. Ruci n´ski. Department of 0 1 2 3 4 5 0 Ext. P dur. Ext. RMS20 Ext. ALP Int. RA P dur. Int. RA RMS20 Int. RA ALP Int. LA P dur. Int. LA RMS20 Int. LA ALP , USA 1 Cardiology; University Medical School of Lublin , Poland 2 A. Kutarski, A. Głowniak , D. Szcze ̨s ́niak, P. Ruci n ́ski, T. Widomska- Czekajska. Department of Cardiology, University Medical School of Lublin , Poland 3 O. Sychev, E. Romanova, A. Frolov, H. Bobrova, N. Pelech. Institute of Cardiology , Kiev , Ukraine 4 L. Borghi , O. Kutsogiannis, M. Karachiriu, A. Deri, A. Gotsis, S. Terzi , A. Panaiotidu. Clinic of Cardiology, General Hospital of Komotini , Greece 5 D. Cervantes, J. Coromilas, A. Wit. Department of Pharmacology, Columbia University , New York , USA Conclusion: the indices of P wave signal-averaged electrocardiogram are more dependent from level of systolic dysfunction then from diastolic dysfunction of left ventricle. - P.1.6 COMPARISON OF THE INTRAATRIAL A WAVE HIGH GAIN SA IEGM WITH P WAVE SA ECG Conventional time-domain analysis of signal-averaged ECG recorded from chest leads is accepted method of evaluation of inhomogeneity of atrial excitation, predictive for atrial arrhythmias. Its main disadvantages are poor atrial signal, QRS complex discrimination and necessity of synchronization using R wave. We put the hypothesis that analysis of high gain SA righ and left atrial potentials leads to better recognition of local conduction disturbances with micro-voltage oscillations during final part of atrial excitation than conventional external SA ECG method. The aim of the study was to determine the value of intraatrial SA signals technique for recognition of atrial late potentials and its comparison to conventional SA ECG P wave analysis method. Methods: intraatrial signals were recorded in 24 pts during implantation of BiA pacemaker, using leads located in RAA, LRA and CS. Standard surface SA ECG from Frank leads was obtained before procedure. We analyzed: P wave duration, RMS20 and LAS5 and presence of ALP criteria. Conclusion: intraatrial SA IEGM provides an accurate data for ALP study, mostly due to better signal quality. P duration and RMS20 seem to be substantial parameters with good correlation between external SA ECG and internal SA IEGM. The method requires definite evaluation criteria establishment. Leads \ parameters P dur. Extern. (1) Int. RA (2) Int. LA (3) Signif. differrence Correlation 155,9 174,6 175,3 1–2, 1–3 1–2, 1–3, 2–3 RMS20 ALP P.1.7 ANTIARRHYTHMIC THERAPY – DOES IT INFLUENCE ON SA ECG P WAVE PARAMETERS? The aim of the study was to compare time domain high gain SA P wave (recorded from conventional and intraatrial leads) in pts with atrial arrhythmias treated with different AA drugs. Methods: We examined 24 pts during BiA pacing system implantation procedure. Intraatrial signals were recorded separately from right and left atrium, using bipolar pacing leads placed in RAA and CS and a lead temporarily placed in low right atrium site. External signals were obtained from Frank orthogonal leads. Signals were gathered during sinus rhythm. We analyzed following SAECG parameters: P wave duration, RMS20 and LAS5. ALP were considered as positive if Pdur>125ms and RMS20<2,40uV 11 pts were treated without AA drugs, 5 pts received one AA drug and 8 pts received two drugs. Conclusion: Therapy with AA drugs seems not to have significant influence on SA P wave duration, root mean square voltages of RMS20 and LAS5 in SA ECG both in external and intraatrial leads. Param. \ N of drugs 144,6 2,39 6/11 168,3 1,81 10/11 171,6 2,06 9/11 163,2 2,33 5/5 187,0 2,09 5/5 184,4 2,29 4/4 160,9 1,87 8/8 176,0 1,51 8/8 174,6 2,54 6/7 Statist. P.1.8 UNCOUPLING MYOCARDIAL GAP JUNCTIONS; A NEW ANTIARRHYTHMIC DRUG MECHANISM Reentry causing ventricular tachycardia has been shown to occur in the epicardial border zone (EBZ) of healing canine infarcts. Hypothesis: a drug that specifically uncouples gap junction connections in the EBZ would cause conduction block and not allow reentrant circuits to occur. To test the concept, and since no drug for this purpose has been developed, we used halothane since it has been shown to be a gap junction uncoupler. Canine hearts, 4 days post-coronary occlusion, were instrumented with a 312 bipolar electrode array for mapping propagation in the EBZ. Halothane was administered directly into the EBZ through a branch of the coronary artery that supplied it. In those experiments in which it was verified that the coronary branch did perfuse the EBZ, halothane produced extensive areas of complete conduction block in EBZ. Regions in which such block occurred were where in previous studies reentrant circuits were shown to occur. The regions of block in this study are predicted to prevent the occurrence of reentry. Therefore, the concept that gap junction uncoupling leads to conduction block in arrhythmogenic regions is de (...truncated)


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Cervantes, D., Coromilas, J., Wit, A.. P.1.8 Uncoupling myocardial gap junctions: A new antiarrhythmic drug mechanism, EP Europace, 2003, pp. A35, Volume 4, Issue Supplement_1, DOI: 10.1016/eupace/4.Supplement_1.A35-b