The role of nitric oxide on the antiarrhythmic effects of ketamine/xylazine in a rat model of acute cardiac ischemia-reperfusion

The prevalence of ventricular arrhythmias during general anesthesia is about 70%. In experimental studies on the antiarrhythmic effects of different agents, using anesthetic drugs that do not have any protective properties are preferable. The present study was conducted to investigate molecular mechanisms involved in the antiarrhythmic effects of ketamine/xylazine (K/X). Sixty male rats were assigned to eight groups: K/X, L -NAME (25–35 mg/kg) with thiopental (TP), L-NAME (25–35 mg/kg) with ketamine/xylazine, L arginine (100 mg/kg) with thiopental, L-arginine (100 mg/kg) with ketamine/xylazine. After anesthetic induction using TP or K/X, the animals were subjected to 30 min of ischemia. Hemodynamic parameters, ventricular arrhythmias during ischemia, the incidence of ventricular tachycardia (VT), and ventricular fibrillation (VF) were measured. Additionally, in order to assess nitrite/nitrate ratio and LDH after ischemia, serum samples were collected and used. Our results showed that in the K/X group, the number of VT and VF, duration of VT (p = 0.006), the severity of arrhythmias (p = 0.0179). There was no VF incidence in this group. These protective effects were faded by administration of L-NAME with K/X. The combination of L- Arginine in the TP group decreased the number and duration of VT (p < 0.001, p = 0.0013) with no incidence of VF in comparison with TP. L-arginine with K/X groups increased the number and duration of VT (p < 0.0001, p < 0.001) compared to K/X and VF was seen (100%). However, there was no significant difference between TP and K/X groups in terms of this nitrite/nitrate ratio. These findings suggest that the antiarrhythmic effects of ketamine/xylazine might be partially relative to the nitric oxide synthesis pathway.