Alterations of myocardial sympathetic innervation in response to hypoxia.
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.


CONCLUSIONS
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.
Scherrer-Crosbie
M
M
Department of Medical Research, Service Hospitalier Frédéric Joliot, DSV-CEA, Orsay, France.
Mardon
K
K
Cayla
J
J
Syrota
A
A
Merlet
P
P
D019797:3-Iodobenzylguanidine; D018759:Adrenergic Uptake Inhibitors; D000532:Altitude Sickness / Q000000981:diagnostic imaging* / Q000378:metabolism; D000818:Animals; D006332:Cardiomegaly / Q000000981:diagnostic imaging* / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003891:Desipramine; D006321:Heart / Q000294:innervation*; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013565:Sympatholytics; D027981:Symporters
D018759:Adrenergic Uptake Inhibitors; D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D050484:Norepinephrine Plasma Membrane Transport Proteins; C493226:Slc6a2 protein, rat; D013565:Sympatholytics; D027981:Symporters; D019797:3-Iodobenzylguanidine; D003891:Desipramine; D009638:Norepinephrine