新型选择性强效磷酸二酯酶V型抑制剂E4021对麻醉开胸犬顿抑心肌的影响  

Effects of E4021, A Novel Selective and Potent Phosphodiesterase Type V Inhibitor, on Stunned Myocardium in Anesthetized Open-chest Dogs

作　　者：常天辉[1] 陈磊[1] 儿玉耕太郎 足立秀之[2] 

机构地区：[1]中国医科大学基础医学院临床药理教研室,沈阳110001 [2]日本エ-ザイ研究开发本部筑波研究所心血管疾病研究室

出　　处：《中国医科大学学报》2000年第4期254-256,共3页Journal of China Medical University

摘　　要：目的 :观察新型选择性磷酸二酯酶 V型强效抑制剂 E40 2 1,对顿抑心肌局部收缩功能的影响。方法 :闭塞麻醉开胸犬左冠状动脉前降枝 (L AD) 15 min伴 3 h再灌注 ,闭塞前 15 m in连续静脉给药 ,30 m in滴完 ;用心内膜下植入超声波微晶体法测局部心肌活动。结果 :E40 2 110μg· kg- 1 · min- 1 对心率 ,平均血压 ,二项乘积 ,左室最大上升速率 (L V dp/ dtmax)无明显经时影响 ,但使闭塞 L AD所致缺血区的心肌节段收缩率从 (17.3± 1.4) %减为 (1.0± 1.7) % ,再灌流后立即恢复 ,3 h后达到原来的 (11.1± 1.8) % ,并略高于溶媒组 (P <0 .0 5 )。结论 :E40 2 1在不影响实验性麻醉犬心脏血流动力学的剂量下 ,对顿抑心肌有改善或保护倾向。Objective: To examine the effects of E4021, a novel selective and potent phosphodiesterase type V inhibitor, on regional dysfunction of stunned myocardium in anesthetized open-chest dogs. Methods: An intravenous infusion of E4021 was administered at 30 min intervals to six anesthetized open-chest dogs subjected to a 15 min occlusion of the LAD followed by a 3 h reperfusion. Cardiohemodynamic parameters and segment lengths of left ventricular wall were measured with polygraph system and ultrasonic dimension crystals, respectively. Results: E4021 at the dosage of 10 μg·kg -1 ·min -1 did not change HR, MAP, DP, and LV dp/d tmax during the whole ischemic reperfusion. It ameliorated the LAD-regional dysfunction of stunned myocardium and restored the % of segment shortening immediately after reperfusion,and reached to(11.1±1.8)% of the baseline value (P<0.05 vs control) 3 h after reperfusion which was a slight higher than that of the control. Conclusion: E4021 showed a tendency to improve the stunned myocardium.

关 键 词：cGMP-PDE抑制剂 抗心绞痛药 顿抑心肌 心肌保护 

分 类 号：R972[医药卫生—药品]