The influences of Morphine or Ketamine pre-treatment on hemodynamic, acid-base status, biochemical markers of brain damage and early survival in rats after asphyxial cardiac arrest

Abstract

Background In different models of hypoxia, blockade of opioid or N-methyl-D-aspartate (NMDA) receptors shows cardio- and neuroprotective effects with a consequent increase in animal survival. The aim of the study was to investigate effects of pre-treatment with Morphine or Ketamine on hemodynamic, acid-base status, early survival, and biochemical markers of brain damage in a rat model of asphyxial cardiac arrest (ACA). Methods Under anaesthesia with Thiopental Sodium 60 mg/kg, i.p., Wistar rats (n=42) were tracheostomized and catheters were inserted in a femoral vein and artery. After randomization the rats were pre-treated with: Morphine 5 mg/kg i.v. (n=14); Ketamine 40 mg/kg iv (n=14); or equal volume of i.v. NaCl 0.9% as a Control (n=14). ACA was induced by corking of tracheal tube for 8 min, and defined as a mean arterial pressure (MAP) < 20 mmHg. Resuscitation was started at 5 min after cardiac arrest (CA). Invasive MAP was recorded during experiments. Arterial pH and blood gases were sampled at baseline (BL) and 10 min after CA. At the end of experiments, all surviving rats were euthanised, brain and blood samples for measurement of Neuron Specific Enolase (NSE), s100 calcium binding protein B (s100B) and Caspase-3 (CS-3) were retrieved. Results At BL no differences between groups were found in hemodynamic or acid-base status. After 3 min of asphyxia all animals had got cardiac arrest (MAP < 20 mm Hg). Return of spontaneous circulation (MAP > 60 mmHg) was achieved in all animals within 3 min after CA. At the end of the experiment, the Ketamine pre-treated group had significantly increased survival compared to Control; one rat had died in the Ketamine group while four and seven rats had died in the Morphine and Control groups, respectively. Conclusion In rats after ACA, pre-treatment with Morphine or Ketamine did not have any significant influence on hemodynamic and biochemical markers of brain damage. However, significantly better pH level and increased early survival were found in the Ketamine pre-treated group.