The applicant's long-term goal is to understand the neurocardiac mechanism underlying sudden cardiac death. The applicant states that neurocardiological approaches over the past two decades, in both animal and human studies, have clearly shown that psychosocial stressors, higher cerebral integrative-centers, and the autonomic nerves have important regulatory roles, perhaps even causal ones, in the process of lethal ventricular fibrillation (VF). The heart rate variability (HRV) is primarily regulated by the nervous system. An altered range, synchrony or pattern of HRV is predictive of risk in prospective clinical studies. Of these, the applicant believes the altered pattern of variability, represented by a reduction in the chaotic dimension of the heartbeats, seems to best predict VF, but this measure has only been studied in high-risk patient groups. The applicant now wishes to study this HRV measure, along with other promising stochastic and deterministic candidate-measures, in data collected during experimental ischemia in the conscious pig, a preparation in which the neurocardiac variables regulating vulnerability to VF can be systematically controlled. The applicant also wishes to integrate his studies of HRV with a mathematical theory of heartbeat generation and arrhythmogenesis. The applicant developed a strategy in which he can remap the variables of the theoretical model into the QT and RR-QT subintervals of each heartbeat. In support of this strategy the applicant has found 1) a predicted exclusion area of the QT vs RR-QT dynamics; 2) a breakdown of this exclusion area by neurocardiac variables known to increase risk of VF, and 3) evoked arrhythmias when the QT vs RR-QT dynamics enter the exclusion area. The applicant's final aim is to model these phenomena, using a mathematical simulation of an excitable medium that has T-waves.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS027745-08
Application #
2750842
Study Section
Special Emphasis Panel (ZRG4-CVA (03))
Program Officer
Broman, Sarah H
Project Start
1989-08-01
Project End
2000-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
8
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Delaware Water Gap Science Institute
Department
Type
DUNS #
City
Bangor
State
PA
Country
United States
Zip Code
18013
Skinner, J E; Molnar, M; Kowalik, Z J (2000) The role of the thalamic reticular neurons in alpha- and gamma-oscillations in neocortex: a mechanism for selective perception and stimulus binding. Acta Neurobiol Exp (Wars) 60:123-42
Skinner, J E; Nester, B A; Dalsey, W C (2000) Nonlinear dynamics of heart rate variability during experimental hemorrhage in ketamine-anesthetized rats. Am J Physiol Heart Circ Physiol 279:H1669-78
Skinner, J E; Molnar, M (1999) Event-related dimensional reductions in the primary auditory cortex of the conscious cat are revealed by new techniques for enhancing the non-linear dimensional algorithms. Int J Psychophysiol 34:21-35
Meyer, M; Rahmel, A; Marconi, C et al. (1998) Stability of heartbeat interval distributions in chronic high altitude hypoxia. Integr Physiol Behav Sci 33:344-62
Meyer, M; Rahmel, A; Marconi, C et al. (1998) Is the heart preadapted to hypoxia? Evidence from fractal dynamics of heartbeat interval fluctuations at high altitude (5,050 m). Integr Physiol Behav Sci 33:9-40
Skinner, J E; Wolf, S G; Kresh, J Y et al. (1996) Application of chaos theory to a model biological system: evidence of self-organization in the intrinsic cardiac nervous system. Integr Physiol Behav Sci 31:122-46
Meyer, M; Marconi, C; Ferretti, G et al. (1996) Heart rate variability in the human transplanted heart: nonlinear dynamics and QT vs RR-QT alterations during exercise suggest a return of neurocardiac regulation in long-term recovery. Integr Physiol Behav Sci 31:289-305
Skinner, J E; Molnar, M; Tomberg, C (1994) The point correlation dimension: performance with nonstationary surrogate data and noise. Integr Physiol Behav Sci 29:217-34
Skinner, J E (1994) The role of the central nervous system in sudden cardiac death: heartbeat dynamics in conscious pigs during coronary occlusion, psychologic stress and intracerebral propranolol. Integr Physiol Behav Sci 29:355-61
Skinner, J E; Pratt, C M; Vybiral, T (1993) A reduction in the correlation dimension of heartbeat intervals precedes imminent ventricular fibrillation in human subjects. Am Heart J 125:731-43

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