Under certain conditions (presence of catecholamines, high calcium), a period of fast drive of cardiac tissues can induce repetitive activity (""""""""overdrive excitation"""""""") both in vivo and in vitro. The events underlying overdrive excitation are incompletely understood.
The aim of the proposed project is to investigate several facets of the problem in pacemaker tissues of the heart perfused in vitro. The membrane potentials will be recorded by means of a microelectrode technique, membrane currents by a voltage clamp, force by a force transducer and intracellular ion activity by means of ion-sensitive electrodes. The problems under investigation will include the following: The relationship of different catecholamines and different receptors to overdrive excitation; the influence of different factors on overdrive excitation; the relationship between overdrive suppression and overdrive excitation; the electrical events leading to overdrive excitation; the ions involved in overdrive excitation; the intracellular activity of calcium and sodium when overdrive excitation occurs; overdrive excitation of slow responses; the characteristics of the current underlying overdrive excitation; the ionic nature of such current; the mode of action of antiarrhythmic agents in suppressing overdrive excitation. Some of these experiments will be conducted also in muscle tissues and in vivo. The different questions will be studied using the appropriate techniques which have been in use in this laboratory and by different experimental manipulations based on current knowledge. The results of different experiments will be correlated to provide integrated information about the cellular events which lead to the onset of repetitive activity following a period of overdrive. These experiments should provide information which may be relevant to some of the arrhythmias induced clinically by pacing the heart or occurring spontaneously.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL027038-05
Application #
3338906
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1981-04-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1987-03-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Suny Downstate Medical Center
Department
Type
Schools of Medicine
DUNS #
068552207
City
Brooklyn
State
NY
Country
United States
Zip Code
11203
Song, Y; Liu, Q Y; Vassalle, M (1996) On the antiarrhythmic actions of magnesium in single guinea-pig ventricular myocytes. Clin Exp Pharmacol Physiol 23:830-8
Shen, J B; Vassalle, M (1996) Barium-induced diastolic depolarization and controlling mechanisms in guinea pig ventricular muscle. J Cardiovasc Pharmacol 28:385-96
Sohn, H G; Vassalle, M (1995) Cesium effects on dual pacemaker mechanisms in guinea pig sinoatrial node. J Mol Cell Cardiol 27:563-77
Spiegler, P A; Vassalle, M (1995) Role of voltage oscillations in the automaticity of sheep cardiac Purkinje fibers. Can J Physiol Pharmacol 73:1165-80
Vassalle, M; Yu, H; Cohen, I S (1995) The pacemaker current in cardiac Purkinje myocytes. J Gen Physiol 106:559-78
Liu, Q Y; Vassalle, M (1994) Mechanisms underlying the modulation of arrhythmogenic events by components of ischemia in guinea pig cardiac myocytes. Can J Physiol Pharmacol 72:382-93
Shen, J B; Vassalle, M (1994) Cesium abolishes the barium-induced pacemaker potential and current in guinea pig ventricular myocytes. J Cardiovasc Electrophysiol 5:1031-44
Iacono, G; Vassalle, M (1994) Effects of caffeine on intracellular sodium activity in cardiac Purkinje fibres: relation to force. Br J Pharmacol 113:289-95
Vassalle, M; Kotake, H; Lin, C I (1992) Pacemaker current, membrane resistance, and K+ in sheep cardiac Purkinje fibres. Cardiovasc Res 26:383-91
Liu, Q Y; Vassalle, M (1991) On the mechanism by which doxorubicin abolishes the oscillatory events induced by Ca overload in single cardiac myocytes. J Cardiovasc Pharmacol 18:711-20

Showing the most recent 10 out of 31 publications