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Alterations of myocardial sympathetic innervation in response to hypoxia
M Scherrer-Crosbie1, K Mardon, J Cayla
1Department of Medical Research, Service Hospitalier Frédéric Joliot, DSV-CEA, Orsay, France.
Unlabelled:
The effects of altitude hypoxia on myocardial sympathetic nerve function were assessed in rats using metaiodobenzylguanidine (MIBG).
Methods:
To estimate the change in uptake-1 function induced by hypoxia, three sets of rats were submitted to 5-, 7- and 21-day hypoxia (hypobaric chamber at 410 Torr) and one set of control rats was injected with 25 muCi of 123I-MIBG. Four hours later, the rats were killed and 123I activity was counted in both ventricles. The proportion of MIBG fixed in the myocardium through the norepinephrine (NE) transporter (uptake-1) was evaluated indirectly in 5-day hypoxic and controls rats by the injection of desipramine before 123I-MIBG administration. Myocardial perfusion was evaluated in 5-day hypoxic rats and controls by 201Tl injection.
Results:
Myocardial 123I-MIBG activity was 0.253% +/- 0.036% kg dose/g-1 in controls and was decreased (0.188% +/- 0.029% kg dose/g-1, p = 0.001) in 5-day hypoxic rats. This decrease was not related to a change in cardiac perfusion. The decrease in MIBG uptake existed before the appearance of cardiac hypertrophy. Desipramine decreased MIBG uptake by 48% in controls and 17% in hypoxic rats, suggesting that the decrease predominantly affected MIBG uptake by the NE transporter.
Conclusion:
Chronic hypoxia leads to a decrease in myocardial NE-uptake-1 function. This finding suggests that altered tissue oxygen supply could play a role in the decreased cardiac MIBG uptake reported in human cardiomyopathies.