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In vivo myocardial electrical impedance during ischemia: phase shift as a marker of cellular uncoupling and predictor of fibrillation Eric Plourde1, Pierre LeGuyader2, Pascal Daleau3 and Pierre Savard1 1Institut de génie biomédical and Hôpital du Sacré Cœur de Montréal, 2Institut de cardiologie de Montréal and 3Institut de cardiologie de Québec Canadian Cardiovascular Congress, Halifax NS October 22, 2001 Plan • • • • • • Motivation and objectives Introduction Measurement system Experimental protocol Results Discussion et conclusions October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Motivation and objectives • Motivation – Cellular uncoupling during ischemia is related to cardiac arrhythmias1. • Objectives – Impedance and resistivity measurements in order to better understand the relation between ischemia, cellular uncoupling and arrhythmias : • Are resistivity measurements or impedance phase measurements able to reflect cellular uncoupling? • Is there a link between cellular uncoupling and fibrillation? 1Smith et al. Circulation 1995;92:3051-3060 October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Introduction Impedance Z = V / I = R + jX Impedance amplitude Z R X 2 2 arctg ( X / R ) Impedance phase I V time October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Introduction Cellular uncoupling Healthy region K+ Ca++ Na+ Na+ K+ Ca++ Na+ K+ Ca++ K+ Ca++ Na+ Ischemic region K+ Ca++ Na+ Na+ K+ Ca++ Gap junction October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Measurement system Impedance measurement The four-electrode technique f h g e October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Measurement system Resistivities determination • From impedance to intracellular and extracellular resistivities : The bidomain anisotropic model re extracellular Rm Cm rc intracellular October 22, 2001 Canadian Cardiovascular Congress, Halifax NS rgap rj Experimental protocol 1. n = 13 pigs in vivo 2. Electrode fixation on the heart • Orientation determination 3. LAD occlusion 4. Impedance measurements during 3 hours (12 Hz - 10 kHz) October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Results Impedance (n=1) Fibrillation October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Results Impedance (n=1) Fibrillation October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Results Bidomain parameters (n=1) Fibrillation October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Results Bidomain parameters (n=1) Fibrillation October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Discussion and conclusion • Are resistivity measurements or impedance phase measurements able to reflect cellular uncoupling? – The phase doesn’t mark cellular uncoupling in all experiments (2 / 4) – Cellular uncoupling was observed in all experiments with the use of the bidomaine anisotropic model including an intracellular capacitance (4 / 4) • Is there a link between cellular uncoupling and fibrillation? – Fibrillation follows cellular uncoupling in two experiments (2 / 4) October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Acknowledgments • Pr. Pierre Savard • Dr. Pierre Le Guyader • Personnel of the Research Center at the Sacré-Cœur Hospital – Ms Caroline Bouchard – Mr Michel Vermeulen – Mr Bruno Dubé • Supported in part by the Natural Science and Engineering Research Council of Canada (NSERC) and the Heart and Stroke Foundation of Canada October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Thank You Questions? October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Resistivity In a resistive environment: R = V/I = l / A = resistivity [m] l A October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Measurement system Impedance measurement The acquisition system October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Système de mesure La sonde: courant alternatif Courant direct Idc g e -1 Rm Courant alternatif g i -1 g e -1 Rm g i -1 October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Idc Signal treatment software Tension Bruit + Signal filtré Détecteu r RMS Z=V/I Phase + - Signal filtré Détecteu r RMS Courant Bruit October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Source: Pierre LeGuyader Measurement system Resistivities determination Measures Simulations V/I V/I + Error f f • longitudinal + transverse • frequencies (12Hz-10kHz) Parameters October 22, 2001 Minimisation of the error Canadian Cardiovascular Congress, Halifax NS Results Parameters (n=1) Fibrillation October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Résultats Conductivités (n=5) October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Résultats Conductivités (n=5) October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Discussion and conclusion October 22, 2001 Canadian Cardiovascular Congress, Halifax NS Ce que je dit dans l ’abstract • The most striking change was observed in the phase of the high frequency impedance, with a significant phase lag (4+/-1 degrees) that occurred rapidly (within about 5 minutes), 26 to 74 minutes after LAD occlusion, and was soon followed by fibrillation. • Preconditioning (which resulted from defibrillation in some animals) seemed to eliminate this abrupt phase lag • Questions: – Since a small inter-electrode distance was used (350 um), the current flowed only in the extracellular domain at low frequencies... Pourquoi? October 22, 2001 Canadian Cardiovascular Congress, Halifax NS