Effects of dichloroacetate following canine asphyxial arrest.
Sodium dichloroacetate (DCA) has been shown to lower elevated serum lactate levels produced by hypoxia, exercise, and phenformin. We conducted a study to investigate the effect of DCA treatment on lactic acidosis following resuscitation from asphyxial cardiac arrest. Conditioned dogs were anesthetized with pentobarbital (30 mg/kg), endotracheally intubated, and mechanically ventilated to maintain an arterial pCO2 of 30 to 40 mm Hg. Asphyxial cardiac arrest was produced by endotracheal tube occlusion for six to eight minutes. After five minutes of cardiac arrest, the endotracheal tube was unclamped and closed-chest CPR was begun. Six animals received DCA 100 mg/kg IV push after one minute of CPR. Control animals (n = 6) received an equal volume of saline. CPR was continued until the return of a spontaneous pulse, when mechanical ventilation was resumed. Arterial and venous blood gases, glucose, and lactate levels were obtained at baseline and 15, 30, 45, 60, 90, and 120 minutes after resuscitation. Mean arterial blood pressure, pulse, and glucose, and venous and arterial blood gases were similar in both groups throughout the study. By 45 minutes after resuscitation, the DCA-treated group showed a significantly faster rate of decline in lactate levels that continued to the final sampling period. By 90 minutes, arterial lactate in DCA animals was not significantly different from baseline (pre-arrest) values. DCA given during cardiac arrest will cause a more rapid normalization of arterial lactate after successful resuscitation. Further studies are needed to evaluate the effects of lowered lactic acid on survival and neurological outcome following cardiac arrest.
D000085:Acetates / Q000627:therapeutic use*; D000140:Acidosis, Lactic / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001237:Asphyxia / Q000150:complications / Q000628:therapy; D001786:Blood Glucose; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D003999:Dichloroacetic Acid / Q000627:therapeutic use*; D004285:Dogs; D006323:Heart Arrest / Q000150:complications / Q000628:therapy*; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000097:blood*; D011674:Pulse / Q000187:drug effects; D012151:Resuscitation
D000085:Acetates; D001786:Blood Glucose; D007773:Lactates; D002245:Carbon Dioxide; D003999:Dichloroacetic Acid