Effects of bupivacaine on mitochondrial energy metabolism in heart of rats following exposure to chronic hypoxia.
BACKGROUND
Adaptation to chronic exposure to hypoxia alters energy metabolism in the heart, particularly in the left ventricle, which undergoes a loss in oxidative capacity. Highly lipophilic local anesthetics interfere with mitochondrial energy metabolism. The purpose of this study was to compare the effects of bupivacaine on mitochondrial energy metabolism in heart of rats subjected to normoxic or hypoxic environments.


METHODS
Male Wistar rats (n = 10) were subjected to hypobaric hypoxia (simulated altitude = 5,000 m, 380 mmHg) for 2 weeks. Control rats (n = 10) were maintained in an ambient normoxic environment. Mitochondrial metabolism (oxygen consumption and adenosine triphosphate synthesis) was assessed using saponin-skinned ventricular fibers. Bupivacaine (0-5 mM) was tested on both left and right ventricles of normoxic or hypoxic heart.


RESULTS
In animals exposed to hypobaric hypoxia for 14 days, cardiac mass significantly increased, and the right-to-left ventricular ratio was approximately twofold (0.48 +/- 0.11 vs. 0.22 +/- 0.04, P < 0.05). Oxygen consumption and adenosine triphosphate synthesis were significantly lower in the hypoxic left ventricles but not in the right ones. The uncoupling effect of bupivacaine was more pronounced in the left ventricle from hypoxic heart than in the right ventricle; the bupivacaine-induced decrease in the adenosine triphosphate synthesis rate and in the adenosine triphosphate-to-oxygen ratio was significantly greater in the hypoxic left ventricle than in the normoxic one.


CONCLUSIONS
Chronic hypoxia impairs cardiac energy metabolism in left ventricles and enhances the depressant effects of bupivacaine on mitochondrial functions.
Nouette-Gaulain
Karine
K
Laboratoire d'Anesthésiologie (INSERM EMI 9929), Université Victor Segalen Bordeaux 2, F-33076 Bordeaux Cedex, France.
Forestier
François
F
Malgat
Monique
M
Marthan
Roger
R
Mazat
Jean-Pierre
JP
Sztark
François
F
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar
D000779:Anesthetics, Local; D002045:Bupivacaine