A low probability for successful resuscitation (about 50%), postshock arrhythmias including shock-induced refibrillation, S-T segment changes, and other signs of dysfunction are often observed following clinical defibrillation. This dysfunction, which is dependent on the waveform and intensity of the shock, is caused in part, by a shock-induced, prolonged depolarization of the myocardial cell membrane. The probability for successful resuscitation in animal models is predicted by the """"""""safety factor"""""""" (ratio between dysfunction-producing intensities and excitation or defibrillation threshold shock intensities) of the defibrillating waveform. This study examines mechanisms underlying defibrillation and postshock dysfunction at the cellular level. Its goals are to confirm the safety factor concept, which is based on the hypothesis that mechanisms underlying defibrillation and shock-induced dysfunction differ, and to develop a triphasic waveform to increase safety factor. This waveform, which consists of a """"""""conditioning prepulse"""""""", a """"""""defibrillating pulse"""""""", and a """"""""healing postpulse"""""""" is expected to increase safety factor by 300% over present clinical waveforms. Initial studies will be carried out in cultured myocardial cells using photocell mechanograms, and intracellular microelectrode techniques, as well as optical techniques for measurement of membrane potential distribution and intracellular calcium. Results from experimental studies will be incorporated into theoretical models to explain defibrillation mechanisms in terms of dynamic membrane characteristics and electromagnetic field theory. The triphasic waveform developed in these studies will be tested using the dog model for transthoracic defibrillation. The results of these experiments will suggest specific modifications to defibrillation procedures which are based on a firm physiological understanding of the actions of the strong electric field on the myocardial cell. In addition to yielding information of potentialy significant clinical interest, these studies also will increase our understanding of the fundamental mechanisms underlying interactions of external electric field with biological systems.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL024606-11
Application #
3337776
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1987-05-16
Project End
1994-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Georgetown University
Department
Type
School of Medicine & Dentistry
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Tovar, Oscar H; Snyder, David E; Jones, Janice L (2004) Immediate termination of fibrillation at 50% probability of overall success correlates with defibrillation dose-response curve width. J Cardiovasc Electrophysiol 15:1207-11
Zhang, Yi; Davies, Loyd R; Coddington, William J et al. (2003) Open-chest epicardial ""surgical"" defibrillation: biphasic versus monophasic waveform shocks. Pacing Clin Electrophysiol 26:711-8
Zhang, Yi; Ramabadran, R S; Boddicker, Kimberly A et al. (2003) Triphasic waveforms are superior to biphasic waveforms for transthoracic defibrillation: experimental studies. J Am Coll Cardiol 42:568-75
Tovar, O H; Jones, J L (2000) Electrophysiologic deterioration after one-minute fibrillation increases relative biphasic defibrillation efficacy. J Cardiovasc Electrophysiol 11:645-51
Tovar, O H; Jones, J L (2000) Electrophysiological deterioration during long-duration ventricular fibrillation. Circulation 102:2886-91
Jones, J L; Tovar, O H (2000) Electrophysiology of ventricular fibrillation and defibrillation. Crit Care Med 28:N219-21
Jones, J; Noe, W; Tovar, O et al. (1998) Can shocks timed to action potentials in low-gradient regions improve both internal and out-of-hospital defibrillation? J Electrocardiol 31 Suppl:41-4
Walcott, G P; Melnick, S B; Chapman, F W et al. (1998) Relative efficacy of monophasic and biphasic waveforms for transthoracic defibrillation after short and long durations of ventricular fibrillation. Circulation 98:2210-5
Tovar, O H; Bransford, P P; Jones, J L (1998) Probability of induction and stabilization of ventricular fibrillation with epinephrine. J Mol Cell Cardiol 30:373-82
Hsu, W; Lin, Y; Lang, D J et al. (1998) Shock timing lowers transvenous defibrillation energy requirement. J Electrocardiol 31 Suppl:35-40

Showing the most recent 10 out of 24 publications