Lactate improves cardiac efficiency after hemorrhagic shock.
This study was undertaken to examine the role of lactate on cardiac function and metabolism after severe acute hemorrhagic shock. Anesthetized, nonheparinized rats were bled to a mean arterial pressure of 25-30 mm Hg for 1 h; controls were not bled. Their hearts were removed, and cardiac work and efficiency (work/oxygen consumption) were measured in the isolated working heart mode for 60 min. The hearts were perfused with one of five substrate combinations: 1) glucose (11 mM), 2) glucose + 0.4 mM palmitate, 3) glucose + 0.4 mM palmitate + 8.0 mM lactate, 4) glucose + 1.2 mM palmitate, or 5) glucose + 1.2 mM palmitate + 8.0 mM lactate. After perfusion, hearts were freeze-clamped, and tissue contents of free coenzyme-A (CoA), acetyl CoA, and succinyl CoA were measured, as was myocardial pyruvate dehydrogenase (PDH) activity. The addition of 8.0 mM lactate significantly improved cardiac work in shocked hearts perfused with 0.4 mM palmitate and increased cardiac efficiency in the presence of either 0.4 mM or 1.2 mM palmitate. Compared to control hearts, shocked hearts exhibited a 20-30% decrease in PDH activity. Shocked hearts perfused with lactate demonstrated no increase in acetyl CoA content but did have a significant increase in tissue succinyl CoA compared to control hearts perfused with lactate or shocked hearts perfused without lactate. In the heart recovering from severe hemorrhagic shock, lactate improves cardiac efficiency in the presence of free fatty acids, possibly by a anaplerosis of the tricarboxylic acid cycle.
Kline
J A
JA
Department of Emergency Medicine, Carolinas Medical Center, Charlotte, North Carolina 28232-2861, USA.
Thornton
L R
LR
Lopaschuk
G D
GD
Barbee
R W
RW
Watts
J A
JA
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002952:Citric Acid Cycle / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006334:Heart Function Tests; D019344:Lactic Acid / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid / Q000378:metabolism / Q000494:pharmacology; D010477:Perfusion; D011768:Pyruvate Dehydrogenase Complex / Q000187:drug effects; D051381:Rats; D012771:Shock, Hemorrhagic / Q000097:blood / Q000150:complications / Q000503:physiopathology*
D000214:Acyl Coenzyme A; D011768:Pyruvate Dehydrogenase Complex; D019308:Palmitic Acid; D019344:Lactic Acid; D000105:Acetyl Coenzyme A; C012046:succinyl-coenzyme A; D005947:Glucose