Mechanism of impaired energy metabolism during acidosis: role of oxidative metabolism.
Isolated perfused rat hearts were used to study the effects of metabolic acidosis on energy metabolism. Hearts perfused with different substrates (glucose, pyruvate, and succinate) were subjected to metabolic acidosis. With all substrates, there were comparable decrements in oxygen consumption (approximately 35%), cardiac function (decrease in first derivative of pressure of 65%), and similar changes in high-energy phosphates (approximately 150% increases in inorganic phosphate and 25% decreases in phosphocreatine concentrations) with metabolic acidosis. To further investigate the metabolic effects of acidosis, isolated cardiac mitochondria were exposed to different incubation media pH conditions and given simple metabolites (glutamate/malate, succinate, or pyruvate) or fatty acids (octanoate). Reduction of incubation media pH to 6.0 did not significantly affect either coupled respiration rate or the respiratory control ratio (RCR) with any substrate. These data suggest that metabolic acidosis induces decreases in energy production in the isolated perfused heart by inhibiting mitochondrial substrate utilization and not by impairing glycolysis. However, this impairment of mitochondrial function is not a direct effect of acidosis itself but appears to occur secondarily to some other effects of acidosis which are, as yet, incompletely understood.
Suleymanlar
G
G
Giles Filley Laboratory, Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
Zhou
H Z
HZ
McCormack
M
M
Elkins
N
N
Kucera
R
R
Reiss
O K
OK
Shapiro
J I
JI
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D003326:Coronary Circulation; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D010477:Perfusion; D011312:Pressure; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D013997:Time Factors
D011773:Pyruvates; D013386:Succinates; D019289:Pyruvic Acid; D019802:Succinic Acid; D005947:Glucose