The overall objective of this study is to determine the factors responsible for the rate-dependent conduction slowing induced by ischemia, the effect of drugs on the rate-dependent slowing and the effects of ischemia on the rate or use-dependent effects of the antiarrhythmic drugs. This study, which employes a model of low flow ischemia in the pig, continues ongoing studies in the Program Project evaluating the influence of drugs on ischemia and the influence of ischemia on the effects of drugs. This study is related to the central goal of the program in that it addresses the pathophysiology of the conduction slowing known to be a part of the ischemic process and the influence of drugs on this process. The study deals with the four interacting themes of the Program Project, namely; 1) the electrophysiology underlying sudden cardiac death, 2) the study of the ionic-electrical correlations in ischemia using ion selective electrodes, 3) the effects of rate on electrophysiologic properties and 4) the effects of cardio-active drugs. It specifically interacts with the other studies in group A which address the ionic and electrical interactions in acute ischemia, the single fiber studies in group B which address many of the same questions proposed in this project using microelectrode techniques, and the studies in group C dealing with the prospective identification of patients at risk for sudden cardiac death and their treatment with antiarrhythmic drugs. The project will utilize all core facilities, particularly the animal/electrode core and the computer core.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL027430-13
Application #
3736282
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Cole, R T; Lucas, C L; Cascio, W E et al. (2005) A LabVIEW model incorporating an open-loop arterial impedance and a closed-loop circulatory system. Ann Biomed Eng 33:1555-73
Cascio, Wayne E; Yang, Hua; Muller-Borer, Barbara J et al. (2005) Ischemia-induced arrhythmia: the role of connexins, gap junctions, and attendant changes in impulse propagation. J Electrocardiol 38:55-9
Xu, Le; Meissner, Gerhard (2004) Mechanism of calmodulin inhibition of cardiac sarcoplasmic reticulum Ca2+ release channel (ryanodine receptor). Biophys J 86:797-804
Kim, Chang-Soo; Ufer, Stefan; Seagle, Christopher M et al. (2004) Use of micromachined probes for the recording of cardiac electrograms in isolated heart tissues. Biosens Bioelectron 19:1109-16
Graff, Ronald D; Kelley, Scott S; Lee, Greta M (2003) Role of pericellular matrix in development of a mechanically functional neocartilage. Biotechnol Bioeng 82:457-64
Stange, Mirko; Xu, Le; Balshaw, David et al. (2003) Characterization of recombinant skeletal muscle (Ser-2843) and cardiac muscle (Ser-2809) ryanodine receptor phosphorylation mutants. J Biol Chem 278:51693-702
Bidasee, Keshore R; Xu, Le; Meissner, Gerhard et al. (2003) Diketopyridylryanodine has three concentration-dependent effects on the cardiac calcium-release channel/ryanodine receptor. J Biol Chem 278:14237-48
Sun, Junhui; Xu, Le; Eu, Jerry P et al. (2003) Nitric oxide, NOC-12, and S-nitrosoglutathione modulate the skeletal muscle calcium release channel/ryanodine receptor by different mechanisms. An allosteric function for O2 in S-nitrosylation of the channel. J Biol Chem 278:8184-9
Yamaguchi, Naohiro; Xu, Le; Pasek, Daniel A et al. (2003) Molecular basis of calmodulin binding to cardiac muscle Ca(2+) release channel (ryanodine receptor). J Biol Chem 278:23480-6
Lemasters, John J; Qian, Ting; He, Lihua et al. (2002) Role of mitochondrial inner membrane permeabilization in necrotic cell death, apoptosis, and autophagy. Antioxid Redox Signal 4:769-81

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