We will test the hypothesis that in heart failure and sudden death, heterogeneity and/or mismatch of pre- and post-synaptic regional cardiac SNS function are specific indicators of the extent and mechanisms of the diseases. Specifically, we hypothesize that the role of the cardiac SNS can be tested by in vivo quantitative measures of regional pre- and post-synaptic function. There is substantial evidence to support the concept that aberrations in cardiac SNS function contribute to and may be primarily responsible for the morbidity and mortality associated with sudden cardiac death (SCD) and congestive heart failure (CHF), two illnesses that are major public health problems.
Aim 1 will demonstrate that pre- and post-synaptic cardiac function can be quantified over a wide range of neuronal function using physiologically realistic blood-tissue exchange models that are directly applicable to PET imaging studies. These experiments will be performed in isolated perfused hearts and in vivo canine hearts.
Aim 2 a is a pilot human study to test the hypothesis that quantitation of regional SNS dysfunction, using physiologically realistic models, will differentiate patients with recurrent SCD from those experiencing only a single episode and that the new analysis methods for both pre-and post-synaptic function are more definitive than are qualitative methods for evaluating SNS function.
Aim 2 b is a pilot human study to test the hypothesis that modulation of cardiac sympathetic function by central inhibition of the SNS in patients with CHF can be demonstrated by quantitation of regional pre-and post synaptic function. When related to changes in regional myocardial flow and metabolism, this quantitative approach provides a tool for understanding mechanisms of CHF and for evaluating new therapeutic strategies.
| Bassingthwaighte, James B; Butterworth, Erik; Jardine, Bartholomew et al. (2012) Compartmental modeling in the analysis of biological systems. Methods Mol Biol 929:391-438 |
| Dash, Ranjan K; Bassingthwaighte, James B (2010) Erratum to: Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 38:1683-701 |
| Bassingthwaighte, James B; Raymond, Gary M; Butterworth, Erik et al. (2010) Multiscale modeling of metabolism, flows, and exchanges in heterogeneous organs. Ann N Y Acad Sci 1188:111-20 |
| Dash, Ranjan K; Bassingthwaighte, James B (2006) Simultaneous blood-tissue exchange of oxygen, carbon dioxide, bicarbonate, and hydrogen ion. Ann Biomed Eng 34:1129-48 |
| Dash, Ranjan K; Bassingthwaighte, James B (2004) Blood HbO2 and HbCO2 dissociation curves at varied O2, CO2, pH, 2,3-DPG and temperature levels. Ann Biomed Eng 32:1676-93 |
| Kellen, Michael R; Bassingthwaighte, James B (2003) Transient transcapillary exchange of water driven by osmotic forces in the heart. Am J Physiol Heart Circ Physiol 285:H1317-31 |
| Kellen, Michael R; Bassingthwaighte, James B (2003) An integrative model of coupled water and solute exchange in the heart. Am J Physiol Heart Circ Physiol 285:H1303-16 |
| Wang, C Y; Bassingthwaighte, J B (2001) Capillary supply regions. Math Biosci 173:103-14 |
| Swanson, K R; True, L D; Lin, D W et al. (2001) A quantitative model for the dynamics of serum prostate-specific antigen as a marker for cancerous growth: an explanation for a medical anomaly. Am J Pathol 158:2195-9 |
| Swanson, K R; Alvord Jr, E C; Murray, J D (2000) A quantitative model for differential motility of gliomas in grey and white matter. Cell Prolif 33:317-29 |
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