Lactic acidosis: effect of treatment on intracellular pH and energetics in living rat heart.
Systemic acidemia may impair cardiac contractility and predispose to arrhythmias. Moreover, bicarbonate treatment may further depress cardiac performance and increase mortality. Whether changes in myocardial intracellular pH or energy metabolism underlie this diminished performance has not been clarified in the in vivo setting. Thus we investigated the effect of lactic acidosis and two proposed treatments on myocardial energetics and intracellular pH in anesthetized living rats. A previously validated 31P-labeled nuclear magnetic resonance (31P-NMR) spectroscopic technique using saturating pulses was used to follow myocardial intracellular pH, phosphocreatine (PCr), ATP, and inorganic phosphate (Pi). After obtaining baseline values, we infused lactic acid to achieve a level greater than 5 mM. We then added an infusion of either bicarbonate (n = 7) or saline (n = 5). During lactic acid infusion, arterial pH declined (from 7.27 to 7.07, P less than 0.0001), but myocardial intracellular pH did not change (7.13 vs. 7.07, P not significant). The ratio of PCr to Pi, however, decreased with acidemia (from 3.13 to 2.24, P = 0.004), suggesting impaired energy metabolism. Compared with saline, bicarbonate infusion restored systemic pH (from 7.08 to 7.29), but myocardial pH was unaltered. In addition, PCr/Pi declined further following bicarbonate treatment (1.41 vs. 2.42, P = 0.08) but not following saline. Thus, despite reversal of systemic acidemia, bicarbonate treatment was associated with more severe impairment of energy metabolism than saline. This suggests a mechanism for previously reported adverse cardiac effects of bicarbonate treatment.
Zahler
R
R
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Barrett
E
E
Majumdar
S
S
Greene
R
R
Gore
J C
JC
D000140:Acidosis, Lactic / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000627:therapeutic use; D004734:Energy Metabolism / Q000187:drug effects; D006439:Hemodynamics; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D007773:Lactates / Q000627:therapeutic use; D019344:Lactic Acid; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D001639:Bicarbonates; D007773:Lactates; D010710:Phosphates; D019344:Lactic Acid; D006859:Hydrogen