Effects Of Sufentanil Postconditioning On Myocardial Ischemia-reperfusion Injury In Rats In Vivo

Objective Restoration of blood flow through the occluded artery is the mainstay of treatment for myocardial ischemia.While reperfusion may also result in a complex group of pathological phenomenon.It has been reported that brief intermittent repetitive ischemic or pharmacological interruptions at the time of early reperfusion can reduce ischemia-reperfusion injury.Sufentanil,a selectiveμ-opioid agonist which is often used in clinical practice, can protect myocardium against ischemia-reperfusion injury either in the rats or rabbits when administered before ischemia.Whether it can mimic the effect of ischemic postconditioning remain to be investigated. So the purpose of this study is to investigate whether sufentanil postconditioning (SpostC) would protect the heart against ischemia-reperfusion injury and the optimal dose for rat and its mechanisms.Methods Forty-eight male SD rats weighing 230-330g were anesthetized with intraperitoneal 5% pentobarbital 40 mg/kg,tracheostomized and mechanically ventilated.Right carotid artery and jugular vein were cannulated for BP monitoring and drug administration.Electrocardilgram (ECG),mean arterial blood pressure (MAP),and heart rate (HR) were monitored continuously. A 6-0 proline ligature was placed under the left anterior descending (LAD) coronary artery and threaded through a small plastic tube to form a snare for reversible LAD artery occlusion.The body temperature was maintained constantly between 37℃～38℃by a heating pad. The animals were then randomized into 8 groups:â… Rats received no occlusion or reperfusion(group Sham);â…¡Rats were subjected to 30 min ischemia and 120 min reperfusion,for a negative control group, normal saline 1 ml was infused at the 25 min of ischemia (group CON);â…¢ Immediately at the onset of reperfusion,rats underwent 3 intermittent cycles of 10s reperfusion alternating with 10s ischemia (group IpostC);â…£-â…§Rats received at random an intravenous infusion of sufentanil diluted with normal saline to 1 ml of either dosage (0.1,0.3,1,3,10μg/kg) at the 25 min of ischemia (group 0.1SpostC -group 10SpostC).MAP,HR and rate-pressure product (RPP) were recorded after a 30 min stabilization (T₀),at the end of ischemia (T₁),at the end of postconditioning (T₂) and at the end of reperfusion (T₃).The infact size (IS) and the area at risk (AAR) were measured by 2,3,5-triphenyltetrazolium staining (TTC). Serum malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity were determined in group Sham,group CON,group IpostC and group optimal sufentanil postconditioning at the end of 120 min reperfusion.Results MAP, HR and RPP did not differ between groups at baseline.Compared with group Sham, group CON, 3SpostC and 10SpostC has the lower MAP and HR was reduced in group CON, IpostC and 10SpostC,RPP was also reduced in all groups except group 0.3SpostC and 1SpostC (P < 0.05);While 1 ug/kg of sufentanil increased RPP and 10SpostC reduced compared with group CON (P < 0.05).RPP and MAP was lower in group CON, IpostC,3SpostC and 10SpostC ,and similar to HR in group CON and 10SpostC during the experiment course with respect to the baseline (P < 0.05) IS/AAR was significantly decreased in the treatment groups except group 0.1SpostC compared with group CON and group 1SpostC has the optimal protective effect in the sufentanil postconditioning groups (P < 0.05).The sigmoidal equation of the dose-effect curve was Y=0.374 9+0.487 2/(1+10¹.502-X),ED50 was 0.0317 4μg/kg.The serum MDA concentration was significantly increased in group CON, IpostC and 1SpostC and the serum SOD activity significantly decreased in the three groups as compared with group Sham (P < 0.05). group IpostC and 1SpostC attenuated the I/R-induced increase in serum MDA concentration and decrease in SOD activity as compared with group CON (P < 0.05). Conclusion Sufentanil postconditioning can protect myocardium against I/R injury in rat hearts in vivo and the effect is dosage-dependent. 1μg/kg has the optimal protection.The cardioprotective effect of postconditioning may be induced by reduction of lipid peroxidation reaction and the superoxide anion.