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Articles in PresS, published online ahead of print February 14, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00917.2001
Submitted on October 22, 2001
Accepted on February 6, 2002
1 Cardiovascular Institute, University of Pittsburgh, Pittsburgh, PA, USA
2 Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Higashi-ku, Fukuoka, Japan
* To whom correspondence should be addressed. E-mail: shustermanv{at}msx.upmc.edu.
Transgenic mice are widely used to study cardiac function but strain-dependent differences in autonomic nervous system activity (ANSA) have not been explored. To test the hypothesis that the homeostatic state of ANSA is strain-specific, we compared 1) short-term pharmacological responses of cardiac rhythm in FVB versus C57Black6/SV129 wild-type mice, and 2) long-term physiological dynamics of cardiac rhythm in TNF-
transgenic mice with heart failure on an FVB background (TNF- mice).
Methods and results. Ambulatory telemetry ECG recordings were examined in 10 FVB, 9 C57Black6/SV129, and 13 TNF- mice. Baseline heart rate (HR) was higher in FVB mice than in C57Black6/SV129 or TNF- mice. Changes in HR and HR variability have been examined after injection of saline, isoproterenol, propranolol, metoxamine, prazosin, carbocholine, and atropine. In FVB mice, HR did not change after injection of isoproterenol or atropine, but decreased after propranolol. In C57Black6/SV129 mice, HR did not change after propranolol but increased after injection of isoproterenol and atropine. Mean HR, but not the indices of HR variability, was an excellent predictor of response to autonomic agents. The proportion of surviving animals was higher in TNF- mice with heart failure on an FVB background than in TNF- mice on a mixed FVB/ C57Black6 background.
Conclusions. The homeostatic states of ANSA are strain-specific, which can explain the inter-strain differences in mean HR, pharmacological responses, and survival of animals with congestive heart failure. The lack of increased HR during the development of heart failure in TNF- mice on an FVB background may depend in part on the baseline high sympathetic activity in this strain. Strain-specific differences should be considered in selecting the strains of mice used for transgenic and gene-targeting experiments.
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