The long term goal of these studies is to obtain information that will provide better understanding of the electrophysiological mechanisms that sensitize the ischemic heart, or the heart damaged by infarction, to ventricular fibrillation and to learn the manner and extent to which antiarrhythmic drugs can influence this outcome. The overall objective is to reduce the incidence of sudden cardiac death. One group of experiments will be conducted on single ventricular myocytes isolated from canine or guinea pig heart and studied with voltage-clamp methods to identify specific effects of various classes of antiarrhythmic drugs and related compounds that will have predictable effects on impulse conduction in ischemic regions of the canine ventricle. The drugs will be administered to chronically instrumented dogs, with and without prior infarction, in which transient coronary occlusion can be made and in which electrograms can be recorded from the ischemic myocardium. The objective of these experiments is to determine what drug effects consistently modify impulse propagation in ischemic muscle to alter the incidence of ventricular fibrillation. Other experiments will be conducted on isolated preparations of canine cardiac muscle to develop rules for interpretation of the complex electrograms recorded from the heart during local ischemia. This information will aid in the interpretation of data obtained from the in situ heart.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL008508-25
Application #
3485255
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1976-01-01
Project End
1990-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
25
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
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Yao, J A; Tseng, G N (1994) Modulation of 4-AP block of a mammalian A-type K channel clone by channel gating and membrane voltage. Biophys J 67:130-42
Hoffman, B F; Ren, X L (1994) Reversibility of electrophysiological abnormalities in subacute ischemia. Pacing Clin Electrophysiol 17:2095-9
Tseng-Crank, J; Yao, J A; Berman, M F et al. (1993) Functional role of the NH2-terminal cytoplasmic domain of a mammalian A-type K channel. J Gen Physiol 102:1057-83
Sorota, S (1992) Swelling-induced chloride-sensitive current in canine atrial cells revealed by whole-cell patch-clamp method. Circ Res 70:679-87
Spinelli, W; Sorota, S; Siegal, M et al. (1991) Antiarrhythmic actions of the ATP-regulated K+ current activated by pinacidil. Circ Res 68:1127-37
Tseng, G N; Hoffman, B F (1990) Actions of pinacidil on membrane currents in canine ventricular myocytes and their modulation by intracellular ATP and cAMP. Pflugers Arch 415:414-24
Tseng, G N; Boyden, P A (1989) Multiple types of Ca2+ currents in single canine Purkinje cells. Circ Res 65:1735-50
Tseng, G N; Hoffman, B F (1989) Two components of transient outward current in canine ventricular myocytes. Circ Res 64:633-47
Tseng, G N (1988) Calcium current restitution in mammalian ventricular myocytes is modulated by intracellular calcium. Circ Res 63:468-82

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