Background
It was reported that cardioprotective effect of lipid emulsion (LE) in local anesthetic systemic toxicity is via glycogen synthase kinase (GSK)-3β phosphorylation and inhibition of mitochondrial permeability transition pore (mPTP) opening. Opioid receptors and ATP-sensitive K+ channels are important modulators of GSK-3β phosphorylation. Lipid emulsion also have a cardioprotective effect in calcium channel blocker (CCB) toxicity, thus we presumed it may be related with (GSK)-3β phosphorylation and also be through Opioid receptor and ATP-sensitive K+ channel activation.
So, we pretreated nonspecific opioid receptor antagonist (naloxne) and ATP-sensitive K+ channel blocker (glibenclamide) before lipid emulsion infusion and examined its effect on hemodynamics after CCB toxicity.

Method
We used 8week-old male rats. We divided the rats in 4 groups randomly. In all group, hemodynamics (heart rate, systolic, mean and diastolic blood pressure) and rate pressure product was recorded in carotid artery. In group 3 (n=8), naloxone 5mg/kg is administered, 5mins later, intralipid (0.17ml/kg/min continuous infusion after 3ml/kg bolus) was administered followed by high dose verapamil (5mg/kg/hr) for 7 mins. In group 2(n=6), normal saline 1ml/kg is injected, and lipid emulsion infusion, verapamil was administered in the same fashion. In group 1 (n=6), normal saline 1ml/kg injected and 5mins later, normal saline administered 3ml/kg bolus and 0.17ml/kg/min continuously for 5mins. And then verapamil was applied 5mg/kg/hr continuously for 7 mins. In group 4 (n=8), glibenclamide 0.5mg/kg was administered and lipid emulsion and verapamil was also administered in the same way.

Results
Group 2 showed higher than group 1 in systolic and mean blood after 7 min-verapamil infusion (SBP 35.3, 63.6%, p<0.05, MBP 31.7%, 56.9%, p<0.05). In group 3, systolic and mean blood pressure at the end point was lower than group 2 (SBP 63.6%, 48.3%, p<0.05, MBP 43.2%, 56.9%, p<0.05). Group 4 also showed lower systolic and mean blood pressure than group 2(SBP 25.9%, 42.5%, p<0.05, MBP 38.2%,24.2%, p<0.05).
Conclusion
The cardioprotective effect of lipid emulsion against calcium channel blocker is related with opioid receptors and ATP-sensitive potassium channels activation.

02 / Involvement of Opioid Receptors and ATP-sensitive Potassium Channels in the Action of Lipid Emulsion against calcium channel blocker toxicity