Functional and metabolic responses of isolated hearts to acidosis: effects of sodium bicarbonate and Carbicarb.
To investigate the mechanisms by which acidosis depresses cardiac function, a Langendorff isolated, perfused rat heart preparation was studied using 31P-magnetic resonance spectroscopy. Isolated hearts were subjected to normal perfusion conditions or moderate or severe metabolic acidosis. Acidosis resulted in dose-dependent decreases in O2 consumption (VO2), rate of developed ventricular pressure (dP/dt), intracellular pH (pHi), and the tissue concentration of creatine phosphate (PCr) after 30 min. Acidosis did not affect ATP concentration but resulted in significant increases in the concentrations of total and monovalent inorganic phosphate (Pi and Pim). When metabolic determinants of the change in dP/dt with acidosis were examined, changes in pHi, extracellular pH, and tissue concentrations of Pi and Pim all correlated significantly with the change in dP/dt. In a second set of experiments using the severe acidosis model, normal saline, 1 M sodium bicarbonate, and the experimental buffer Carbicarb (1 ml/kg body wt) were infused in a crossover manner at 20-min intervals. None had significant effects on tissue concentrations of ATP, PCr, Pi, or PCr/Pi. Administration of bicarbonate resulted in an increase in VO2 without significant effects on pHi or dP/dt. In contrast, Carbicarb effected little change in VO2 but resulted in sustained increases in pHi and decreases in Pim and marked increases in dP/dt. These data suggest that the decrease in cardiac function that occurs during acidosis may be related to the metabolic consequences of reductions in pHi and that a buffer that causes intracellular alkalinization may cause functional improvement in this model.
Shapiro
J I
JI
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.
D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology*; D000468:Alkalies / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D002254:Carbonates / Q000494:pharmacology*; D004338:Drug Combinations / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012044:Regression Analysis; D012964:Sodium / Q000494:pharmacology*; D017693:Sodium Bicarbonate
D000468:Alkalies; D001639:Bicarbonates; D002254:Carbonates; D004338:Drug Combinations; C046283:sodium bicarbonate, sodium carbonate drug combination; D017693:Sodium Bicarbonate; D012964:Sodium