Myocardial metabolism during hypoxia: maintained lactate oxidation during increased glycolysis.
In the intact animal, myocardial lactate utilization and oxidation during hypoxia are not well understood. Nine dogs were chronically instrumented with flow probes on the left anterior descending coronary artery and with a coronary sinus sampling catheter. [14C]lactate and [13C]glucose tracers, or [13C]lactate and [14C]glucose were administered to quantitate lactate and glucose oxidation, lactate conversion to glucose, and simultaneous lactate extraction and release. The animals were anesthetized and exposed to 90 minutes of severe hypoxia (PO2 = 25 +/- 4 torr). Hypoxia resulted in significant increases in heart rate, cardiac output and myocardial blood flow, but no significant change in myocardial oxygen consumption. The arterial/coronary sinus differences for glucose and lactate did not change from normoxia to hypoxia; however, the rate of glucose uptake increased significantly due to the increase in myocardial blood flow. Tracer-measured lactate extraction did not decrease with hypoxia, despite a 250% increase in lactate release. During hypoxia, 90% +/- 4% of the extracted 14C-lactate was accounted for by the appearance of 14CO2 in the coronary sinus, compared with 88% +/- 4% during normoxia. Thus, in addition to the expected increase in glucose uptake and lactate production, we observed an increase in lactate oxidation during hypoxia.
Mazer
C D
CD
Department of Medicine, University of California, San Francisco.
Stanley
W C
WC
Hickey
R F
RF
Neese
R A
RA
Cason
B A
BA
Demas
K A
KA
Wisneski
J A
JA
Gertz
E W
EW
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002250:Carbon Radioisotopes; D002302:Cardiac Output; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000502:physiology / Q000503:physiopathology; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007773:Lactates / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D011865:Radioisotope Dilution Technique
D000085:Acetates; D002250:Carbon Radioisotopes; D005230:Fatty Acids, Nonesterified; D007773:Lactates; D005947:Glucose