One of the leading causes of death in the United States is ventricular fibrillation, an uncoordinated movement of the individual cells in the heart which results in complete disruption of the circulation. The only known treatment for this fatal arrhythmia is electric countershock; however, the overall success rate is disappointingly low, only about 30%-50% in most clinical settings. Experimental studies have suggested that this low rate of success is due in part to immediate post-shock refibrillation which shows itself as a failure to defibrillate. Previous work in this laboratory has shown that this dysfunction is related to a shock induced prolonged depolarization of the myocardial cell membrane lasting several seconds to several minutes. This work suggested that the ionic mechanism which produces this prolonged depolarization differs from that producing activation and that it may result from a nonspecific redistribution of ions across the membrane during the shock. However the specific ionic mechanisms underlying this dysfunction and the factors which potentiate or ameliorate it are largely unknown. The goal of this research is to determine whether the prolonged depolarization takes place due to a nonspecific redistribution of ions through microlesions in the cell membrane during the shock, to determine the size of the lesions, and the effect of biphasic waveforms to decrease them. This work will use intracellular microelectrode techniques and fluorescent microcinematography to examine the dysfunction which occurs in """"""""adult-type"""""""" cultured myocardial cells during high intensity electric field stimulation. The results are expected to suggest specific modifications in countershock procedures and to yield insight into the processes through which myocardial cells respond to a discrete stress leading to membrane depolarization, in this case, the short high-intensity electric shock.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL026924-05
Application #
3338810
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1981-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Jones, J L; Jones, R E (1989) Improved safety factor for triphasic defibrillator waveforms. Circ Res 64:1172-7
Jones, J L; Jones, R E; Balasky, G (1987) Microlesion formation in myocardial cells by high-intensity electric field stimulation. Am J Physiol 253:H480-6
Jones, J L; Jones, R E; Balasky, G (1987) Improved cardiac cell excitation with symmetrical biphasic defibrillator waveforms. Am J Physiol 253:H1418-24