title: Efficient extra- and intracellular alkalinization improves cardiovascular functions in severe lactic acidosis induced by hemorrhagic shock.
abstract: BACKGROUND
  Lactic acidosis is associated with cardiovascular failure. Buffering with sodium bicarbonate is proposed in severe lactic acidosis. Bicarbonate induces carbon dioxide generation and hypocalcemia, both cardiovascular depressant factors. The authors thus investigated the cardiovascular and metabolic effects of an adapted sodium bicarbonate therapy, including prevention of carbon dioxide increase with hyperventilation and ionized calcium decrease with calcium administration.
  
  
  METHODS
  Lactic acidosis was induced by hemorrhagic shock. Twenty animals were randomized into five groups: (1) standard resuscitation with blood retransfusion and norepinephrine (2) adapted sodium bicarbonate therapy (3) nonadapted sodium bicarbonate therapy (4) standard resuscitation plus calcium administration (5) hyperventilation. Evaluation was focused in vivo on extracellular pH, on intracellular pH estimated by P nuclear magnetic resonance and on myocardial contractility by conductance catheter. Aortic rings and mesenteric arteries were isolated and mounted in a myograph, after which arterial contractility was measured.
  
  
  RESULTS
  All animals in the hyperventilation group died prematurely and were not included in the statistical analysis. When compared with sham rats, shock induced extracellular (median, 7.13; interquartile range, [0.10] vs. 7.30 [0.01]; P = 0.0007) and intracellular acidosis (7.26 [0.18] vs. 7.05 [0.13]; P = 0.0001), hyperlactatemia (7.30 [0.01] vs. 7.13 [0.10]; P = 0.0008), depressed myocardial elastance (2.87 [1.31] vs. 0.5 [0.53] mmHg/μl; P = 0.0001), and vascular hyporesponsiveness to vasoconstrictors. Compared with nonadapted therapy, adapted bicarbonate therapy normalized extracellular pH (7.03 [0.12] vs. 7.36 [0.04]; P < 0.05), increased intracellular pH to supraphysiological values, improved myocardial elastance (1.68 [0.41] vs. 0.72 [0.44] mmHg/μl; P < 0.05), and improved aortic and mesenteric vasoreactivity.
  
  
  CONCLUSIONS
  A therapeutic strategy based on alkalinization with sodium bicarbonate along with hyperventilation and calcium administration increases pH and improves cardiovascular function.
authors.affiliation: From the CHU Nancy, Service de Réanimation Médicale Brabois, Pole Cardiovasculaire et Réanimation Médicale, Hôpital Brabois, Vandoeuvre les Nancy, France; Institut National de la Santé Et de la Recherche Médicale (INSERM) U1116, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France; Université de Lorraine, Nancy, France (A.K., N.D., and B.L.); INSERM U1116, Equipe 2, Faculté de Médecine, Vandoeuvre les Nancy, France; Université de Lorraine, Nancy, France (N.S., K.I., and C.S.); and Critallographie, Résonnance Magnétique et Modélisation (CRM2), Unité Médicale de Recherche (UMR), Centre National de la Recherche Scientifique (CNRS), Institut Jean Barriol, Faculté des Sciences et Technologies, Vandoeuvre les Nancy, France; Université de Lorraine, Nancy, France (J.-M.E. and S.L.).
authors.forename: Antoine
authors.initials: A
authors.lastname: Kimmoun
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ducrocq
authors.forename: Nacira
authors.initials: N
authors.lastname: Sennoun
authors.forename: Khodr
authors.initials: K
authors.lastname: Issa
authors.forename: Charlène
authors.initials: C
authors.lastname: Strub
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Escanyé
authors.forename: Sébastien
authors.initials: S
authors.lastname: Leclerc
authors.forename: Bruno
authors.initials: B
authors.lastname: Levy
mesh_terms: D000140:Acidosis, Lactic / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage; D000818:Animals; D001803:Blood Transfusion / Q000379:methods; D002118:Calcium / Q000008:administration & dosage; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006985:Hyperventilation / Q000628:therapy; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D012771:Shock, Hemorrhagic / Q000150:complications* / Q000503:physiopathology; D017693:Sodium Bicarbonate / Q000627:therapeutic use*
chemical_list: D000316:Adrenergic alpha-Agonists; D017693:Sodium Bicarbonate; D002118:Calcium; D009638:Norepinephrine