Experimental and clinical research proposed in Project 4 is directed at developing and validating improved electrocardiographic methods for measuring repolarization, particularly its dynamics and spatial disparity. Although methods exist for studying repolarization in the laboratory, e.g., refractory period, action potential duration or MAP measurements, these are invasive, difficult to asses over large cardiac regions and often impossible to assess on a beat-to-beat basis or over long periods of time. The ultimate goal of the project is to determine simple measures of ventricular recovery which accurately reflect dynamics and distribution of repolarization. The common hypothesis driving the three projects is that existing electrocardiographic measures of repolarization are inadequate and that new methods can be developed which will be more robust and better reflect repolarization dynamics and disparity. A specific hypothesis is that Activation-Recovery Intervals (ARIs) and QRST integrals measured from the body surface, better reflect ventricular repolarization dynamics and disparity than do indices derived from QT interval measurements. The three projects focus on comparing existing and new measures of repolarization in both clinical and laboratory settings as well as for normal and abnormal myocardium. Project 4.1 is retrospective study of body surface maps on normal subjects and patients who underwent PTCA and will address comparison of ARIs, QRST integrals and QT intervals as measures of repolarization. Project 4.2 is an experimental study using isolated canine hearts suspended in an electrolytic tank and aimed at validating """"""""body surface"""""""" measures of repolarization in comparison to those directly measured from the cardiac surface. Project 4.3 is a clinical study in which post infarction patients will be studied using old and new repolarization measures for purposes of assessing ability of the indices to detect patients at risk to ventricular arrhythmias and sudden death. Significance of these studies lies in the likelihood that validation of these methods will provide improved detection of disease and assessment of therapeutic interventions in patients at risk.
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