摘要
目的 :研究阿芬太尼对缺血再灌注心肌功能的保护作用及其作用机制。方法 :采用Langendorff离体大鼠心脏模型 ,以停灌的方式造成全心缺血2 5min ,然后复灌 30min ,药物于缺血前 10min给予并持续到复灌末。观察 5 0 μg·L- 1和 10 0 μg·L- 1阿芬太尼及其与纳洛酮和L NAME合用时对缺血前及再灌注期间左心功能的影响 ,并测定再灌注末时心肌组织ATP和NOS的含量。结果 :(1)在非缺血情况下 ,10 0 μg·L- 1阿芬太尼能使HR减慢 ,对LVEDP、LVDP、±dp/dtmax 和CF无明显影响 ;(2 )5 0 μg·L- 1和 10 0 μg·L- 1阿芬太尼均能明显促进再灌期间左心功能和冠脉流量的恢复 ,且 10 0 μg·L- 1阿芬太尼比 5 0 μg·L- 1阿芬太尼作用更明显 ;(3)2 0 0 μg·L- 1纳洛酮和 10 0 μmol·L- 1L NAME均削弱了阿芬太尼对缺血再灌注心肌功能恢复的有利作用。结论 :阿芬太尼对离体大鼠的心肌功能影响轻微且能促进缺血再灌注后心肌功能的恢复 ,其作用机制可能与阿片受体和内皮细胞释放的一氧化氮有关。
AIM:?To?investigate?if?alfentanil?protects?the?isolated?rat?heart?against?myocardial?reperfusion?injury?and?if?the?mechanism?of?this?protection?is?mediated?via?opioid?receptors?and?NO-dependent?pathways. METHODS: Langendorff rat hearts were perfused at constant pressure with Kreb-Henseleit(K-H) buffer for 20 min?and?then?were?perfused?with?test?solution:?K-H?buffer?or?K-H?buffer?containing?alfentanil? 50 μg·L -1,?alfentanil? 100 μg·L -1, naloxone 200 μg·L -1, alfentanil 100 μg·L -1+naloxone 200 μg·L -1, L-NAME 100 μmol·L -1 and alfentanil 100 μg·L -1+L-NAME 100 μmol·L -1. After 10 min of this, the hearts were subjected to 25 min normothermic( 37 ℃) global ischemia followed by 30 min reperfusion with the same test solution as before. To evaluate myocardial function, LVEDP, LVDP, ±dp/dt max, HR and CF were measured at the 20th, 25 and 30th minute of perfusion and the 1st, 3rd, 5th, 10th, 20th and 30th minute of reperfusion. After experiment, the NOS and ATP content of myocardium were assessed. RESULTS: Before ischemia, alfentanil 100 μg·L -1 decreased the HR at the 30th minute compared with the 20th minute(P< 0.05). Treatment with 50 μg·L -1 alfentanil and alfentanil 100 μg·L -1 improved post-ischemic mechanical function assessed by LVEDP, LVDP and ±dp/dt max compared with controls after 30 min of reperfusion(P< 0.05 or P< 0.01). Furthermore, 100 μg·L -1 alfentanil improved post-ischemic mechanical function better than 50 μg·L -1 alfentanil indicated by lower LVEDP and higher -dp/dt max(P< 0.05). These effects were attenuated by 200 μg·L -1 naloxone and 100 μmol·L -1 L-NAME. CONCLUSION: Alfentanil have few inhibitive effects on the mechanical function of the non-ischemic hearts and have dose-depended protective effects against myocardial reperfusion injury by a mechanism mediated via opioid receptors and NO-dependent pathways in rats.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2002年第2期119-123,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
