title: Sodium bicarbonate treatment during transient or sustained lactic acidemia in normoxic and normotensive rats.
abstract: BACKGROUND
  Lactic acidosis is a frequent cause of poor outcome in the intensive care settings. We set up an experimental model of lactic acid infusion in normoxic and normotensive rats to investigate the systemic effects of lactic acidemia per se without the confounding factor of an underlying organic cause of acidosis.
  
  
  METHODS
  Sprague Dawley rats underwent a primed endovenous infusion of L(+) lactic acid during general anesthesia. Normoxic and normotensive animals were then randomized to the following study groups (n = 8 per group): S) sustained infusion of lactic acid, S+B) sustained infusion+sodium bicarbonate, T) transient infusion, T+B transient infusion+sodium bicarbonate. Hemodynamic, respiratory and acid-base parameters were measured over time. Lactate pharmacokinetics and muscle phosphofructokinase enzyme's activity were also measured.
  
  
  RESULTS
  Following lactic acid infusion blood lactate rose (P<0.05), pH (P<0.05) and strong ion difference (P<0.05) drop. Some rats developed hemodynamic instability during the primed infusion of lactic acid. In the normoxic and normotensive animals bicarbonate treatment normalized pH during sustained infusion of lactic acid (from 7.22 ± 0.02 to 7.36 ± 0.04, P<0.05) while overshoot to alkalemic values when the infusion was transient (from 7.24 ± 0.01 to 7.53 ± 0.03, P<0.05). When acid load was interrupted bicarbonate infusion affected lactate wash-out kinetics (P<0.05) so that blood lactate was higher (2.9 ± 1 mmol/l vs. 1.0 ± 0.2, P<0.05, group T vs. T+B respectively). The activity of phosphofructokinase enzyme was correlated with blood pH (R2 = 0.475, P<0.05).
  
  
  CONCLUSIONS
  pH decreased with acid infusion and rose with bicarbonate administration but the effects of bicarbonate infusion on pH differed under a persistent or transient acid load. Alkalization affected the rate of lactate disposal during the transient acid load.
authors.affiliation: Dipartimento di Anestesia, Rianimazione e Terapia del Dolore, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. franco.valenza@unimi.it
authors.forename: Franco
authors.initials: F
authors.lastname: Valenza
authors.forename: Marta
authors.initials: M
authors.lastname: Pizzocri
authors.forename: Valentina
authors.initials: V
authors.lastname: Salice
authors.forename: Giorgio
authors.initials: G
authors.lastname: Chevallard
authors.forename: Tommaso
authors.initials: T
authors.lastname: Fossali
authors.forename: Silvia
authors.initials: S
authors.lastname: Coppola
authors.forename: Sara
authors.initials: S
authors.lastname: Froio
authors.forename: Federico
authors.initials: F
authors.lastname: Polli
authors.forename: Stefano
authors.initials: S
authors.lastname: Gatti
authors.forename: Francesco
authors.initials: F
authors.lastname: Fortunato
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
authors.forename: Luciano
authors.initials: L
authors.lastname: Gattinoni
mesh_terms: D000140:Acidosis, Lactic / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D019344:Lactic Acid / Q000097:blood; D025221:Phosphofructokinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D056152:Respiratory Rate / Q000187:drug effects; D017693:Sodium Bicarbonate / Q000627:therapeutic use*
chemical_list: D019344:Lactic Acid; D017693:Sodium Bicarbonate; D025221:Phosphofructokinases