VENTRICULAR FIBRILLATION AND ITS ALTERATION BY PACING

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DESCRIPTION (Verbatim from Applicant's Abstract): Sudden cardiac arrest frequently is caused by ventricular fibrillation (VF). This application proposes to use cardiac mapping to answer important questions about the mechanisms of how VF is maintained and how VF can be altered and controlled by pacing in patients and animals. There are three specific aims. Specific Aim 1: Quantify VF organization in patients and determine which measures of organization predict spontaneous VF termination and the defibrillation threshold (DFT). The following hypotheses about VF will be tested in patients undergoing cardiac surgery or cardioverter/defibrillator implantation. (1) Epicardial reentry is uncommon and short-lived. (2) Conduction block is more frequent for activation fronts parallel rather than perpendicular to the long axis of myofibers. (3) A minimal length of block is necessary to initiate reentry. (4) While spared tissue around a myocardial infarct may be responsible for VF initiation, it does not contribute to VF maintenance. (5) Quantitative measures of activation front organization predict when VF will stop spontaneously. (6) A slightly different group of quantitative measures identifies patients with a low DFT. Specific Aim 2: Determine algorithms to maximize the capture of myocardium by pacing during VF in pigs. Optical and electrical mapping will be performed to test the following hypotheses. (1) Gradually increasing the pacing rate will increase the amount of tissue captured in some cardiac regions. (2) Gradually slowing the pacing rate will allow the capture of more tissue in other regions. (3) Alternately slowing and increasing the pacing rate will maximize the amount of tissue that is captured. (4) Pacing from two sites spaced appropriately apart will capture more than the sum of the tissue captured by pacing from each side alone. (5) Pacing from up to 16 sites simultaneously will halt VF. (6) Pacing from regions in which the defibrillation shock potential gradient is weakest will lower the DFT. (7) The epicardium can be divided into domains, each with a different activation rate. (8) Pacing from faster domains captures more tissue than pacing from slower domains. Specific Aim 3: Determine if it is possible to capture myocardium by pacing during VF in patients. The most successful pacing techniques and most of the hypotheses of Specific Aim 2 will be tested in patients.