The sympathetic nervous system plays an important role in the genesis of serious ventricular arrhythmias, particularly during myocardial ischemia or after myocardial infarction. In animal models of experimental myocardial infarction, the proposed research will seek: 1) to noninvasively map the distribution of myocardial sympathetic nerves and the distribution of viable perfused myocardium using radionuclide scintigraphy and functional images; 2) to compare the scintigraphic patterns to the regional morphology of sympathetic nerves determined by catecholamine fluorescence microscopy, and to the regional catecholamine content, beta receptor density, and adenylcyclase activity, determined biochemically; 3) to determine the effects of alterations in sympathetic innervation on the electrical stability of the myocardium using programmed stimulation techniques. The results of these experiments may provide important new insights into mechanisms of ventricular arrhythmias in ischemic heart disease, and also may improve identification of patients who are at risk for these lethal ventricular arrhythmias.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL038105-05
Application #
3470904
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1988-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1994-03-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Dae, M W; Lee, R J; Ursell, P C et al. (1997) Heterogeneous sympathetic innervation in German shepherd dogs with inherited ventricular arrhythmia and sudden cardiac death. Circulation 96:1337-42
Dae, M W; O'Connell, J W; Botvinick, E H et al. (1995) Acute and chronic effects of transient myocardial ischemia on sympathetic nerve activity, density, and norepinephrine content. Cardiovasc Res 30:270-80
De Marco, T; Dae, M; Yuen-Green, M S et al. (1995) Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation. J Am Coll Cardiol 25:927-31
Lee, M A; Dae, M W; Langberg, J J et al. (1994) Effects of long-term right ventricular apical pacing on left ventricular perfusion, innervation, function and histology. J Am Coll Cardiol 24:225-32
Newman, D; Munoz, L; Chin, M et al. (1993) Effects of canine myocardial infarction on sympathetic efferent neuronal function: scintigraphic and electrophysiologic correlates. Am Heart J 126:1106-12
Dae, M W; De Marco, T; Botvinick, E H et al. (1992) Scintigraphic assessment of MIBG uptake in globally denervated human and canine hearts--implications for clinical studies. J Nucl Med 33:1444-50
Dae, M W; Herre, J M; O'Connell, J W et al. (1991) Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction. J Am Coll Cardiol 17:1416-23
Dae, M W; O'Connell, J W; Botvinick, E H et al. (1989) Scintigraphic assessment of regional cardiac adrenergic innervation. Circulation 79:634-44