Molar Sodium Lactate Attenuates the Severity of Postcardiac Arrest Syndrome: A Preclinical Study

Abstract

To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure.DESIGN: Randomized blinded study (animal model). SETTING: University animal research facility.SUBJECTS: Twenty-four adult male "New Zealand White" rabbits. INTERVENTIONS:Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period. MEASUREMENTS AND MAIN RESULTS:Pupillary reactivity (primary outcome), levels of S100β protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100β protein levels (189 ± 42 vs 412 ± 63 pg/mL, p < 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p > 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ± 2 vs 29 ± 3 mm Hg; p < 0.05], higher cardiac output [108 ± 4 vs 58 ± 9 mL/min; p < 0.05], higher left ventricle surface shortening fraction [38% ± 3% vs 19% ± 3%; p < 0.05], and lower left ventricular end-diastolic pressure [3 ± 1 vs 8 ± 2 mm Hg; p < 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ± 3 mL/kg; p < 0.01) due to lower diuresis. CONCLUSIONS: Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest.

Hypertonic sodium lactate infusion reduces vasopressor requirements and biomarkers of brain and cardiac injury after experimental cardiac arrest

“…Our findings are in line with those from a study by Stevin et al [ 17 ], which showed that the infusion of molar HSL for 120 min in rabbits after ROSC increased the proportion of animals with pupillary reactivity at 2 h, reduced biomarkers of brain injury (astrocyte lysis marker S100β), improved hemodynamics (MAP, cardiac output, and left ventricular surface shortening fraction), and improved brain mitochondrial function. Similar to our results, HSL influenced lactatemia, natremia, and kalemia, and pH increased in HSL-treated animals [ 17 ].…”

“…Our findings are in line with those from a study by Stevin et al [ 17 ], which showed that the infusion of molar HSL for 120 min in rabbits after ROSC increased the proportion of animals with pupillary reactivity at 2 h, reduced biomarkers of brain injury (astrocyte lysis marker S100β), improved hemodynamics (MAP, cardiac output, and left ventricular surface shortening fraction), and improved brain mitochondrial function. Similar to our results, HSL influenced lactatemia, natremia, and kalemia, and pH increased in HSL-treated animals [ 17 ]. However, the rabbits in the study by Stevin et al [ 17 ] were treated with a higher HSL dose than that used in the present study (i.e., 80 µmol/Kg/min vs. 30 µmol/Kg/min) for a shorter period of time (i.e., 2 vs. 12 h), and the origin of CA (i.e., asphyxial vs. electrical) and CPR techniques differed.…”

“…Similar to our results, HSL influenced lactatemia, natremia, and kalemia, and pH increased in HSL-treated animals [ 17 ]. However, the rabbits in the study by Stevin et al [ 17 ] were treated with a higher HSL dose than that used in the present study (i.e., 80 µmol/Kg/min vs. 30 µmol/Kg/min) for a shorter period of time (i.e., 2 vs. 12 h), and the origin of CA (i.e., asphyxial vs. electrical) and CPR techniques differed. Furthermore, animals were not resuscitated to a minimal target MAP threshold and no targeted temperature management was used: By implementing these two factors, we limited the possible confounding effects of a different CPP and coronary perfusion pressure across groups when interpreting the organ damage.…”

“…HSL administration has only been studied in one rabbit model of CA, in which it increased mean arterial pressure, improved cardiac function, improved cerebral mitochondrial function, and reduced brain injury as assessed by reduced plasma levels of the protein S100ß [ 17 ]. Large animal models are better suited for research in CA, enabling use of mechanical CPR, frequent blood sampling, and invasive monitoring devices.…”

Reassessment of mitochondrial cyclophilin D as a target for improving cardiac arrest outcomes in the era of therapeutic hypothermia

“…Nevertheless, inhibition of CypD-dependent PTP opening might increase the rate of ROSC and short-term survival through mechanisms that remains to be determined. Thus, researchers should better investigate other therapeutic approaches (eg, molar sodium lactate 35 ) than trying to optimize pharmacological PTP inhibition for improving outcomes of patients admitted alive to hospital after CA. The increase in the rate of ROSC in CypD À/is a very important finding, because, for many decades, epinephrine has been the only pharmacological option to help to "restart" the heart.…”