ALTERATIONS OF MYOCARDIAL SYMPATHETIC INNERVATION IN RESPONSE TO HYPOXIA

The effects of altitude hypoxia on myocardial sympathetic nerve functi on were assessed in rats using metaiodobenzylguanidine (MIBG). Methods : To estimate the change in uptake-1 function induced by hypoxia, thre e 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 mu Ci of I-123-MIBG. Four hours later, the rats were killed and I-123 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 I-123-MIBG administration. Myocardial perfusion was evaluated in 5-day hypoxic rats and controls by Tl-201 i njection. Results: Myocardial I-123-MIBG activity was 0.253% +/- 0.036 % kg dose/g(-1) in controls and was decreased (0.188% +/- 0.029% kg do se/g(-1), p = 0.001) in 5-day hypoxic rats. This decrease was not rela ted to a change in cardiac perfusion. The decrease in MIBG uptake exis ted before the appearance of cardiac hypertrophy. Desipramine decrease d MIBG uptake by 48% in controls and 17% in hypoxic rats, suggesting t hat the decrease predominantly affected MIBG uptake by the NE transpor ter. Conclusion: Chronic hypoxia leads to a decrease in myocardial NE uptake-1 function. This finding suggests that altered tissue oxygen su pply could play a role in the decreased cardiac MIBG uptake reported i n human cardiomyopathies.