目的观察治疗浓度的硝酸甘油、地尔硫艹卓、尼可地尔以及腺苷对离体大鼠心肌缺血再灌注损伤的影响,探讨四种药物发挥心肌保护作用的不同机制以及各个药物的相对优劣。方法66只大鼠随机分为六组:正常对照组(N组)、缺血再灌注组(I-R组)、硝酸甘油组、地尔硫艹卓组、尼可地尔组、腺苷组。N组持续灌流Krebs-Henseleit液(K-H液)150 min;I-R组稳定灌流K-H液30 min后,结扎前降支30 min,继以K-H液再灌注90 min;药物后处理组分别在再灌注即刻给予硝酸甘油(10-8mol/L)、地尔硫艹卓(5μmo/L)、尼可地尔(200μmo/L)以及腺苷(100μmo/L)再灌注15 min,继以K-H液灌流75 min。记录并分析各组左心室发展压(left ventricular developed pressure,LVDP)、左心室内压力最大上升/下降速率(±dp/dtmax)、再灌注心律失常(RA)评分以及心肌梗死面积(myocardial infarct size)。结果 (1)I-R组再灌注30 min及45 min时LVDP均低于各药物后处理组(均P〈0.05)。在药物后处理组,再灌注30 min地尔硫艹卓组LVDP[(92.68±5.09)mm Hg比(84.26±3.02)mm Hg比(83.35±2.88)mm Hg]、尼可地尔组LVDP[(88.95±1.75)mm Hg比(84.26±3.02)mm Hg比(83.35±2.88)mm Hg],再灌注45 min地尔硫艹卓组LVDP[(90.39±4.29)mm Hg比(82.09±4.24)mm Hg比(80.98±3.89)mm Hg]、尼可地尔组LVDP[(86.13±2.38)mm Hg比(82.09±4.24)mm Hg比(80.98±3.89)mm Hg]均高于硝酸甘油组与腺苷组,且地尔硫艹卓组高于尼可地尔组,差异均有统计学意义(均P〈0.05),但硝酸甘油组与腺苷组比较,差异均无统计学意义(均P〉0.05)。(2)I-R组再灌注30 min及45 min的±dp/dtmax均低于各药物后处理组(均P〈0.05)。地尔硫艹卓组、尼可地尔组再灌注30 min及45 min的±dp/dtmax均高于硝酸甘油组、腺苷组,且地尔硫艹卓组高于尼可地尔组,差异均有统计学意义(均P〈0.05)。但硝酸甘油组?
Objective To observe and compare the effects of nitroglycerin,diltiazem,nicorandil and adenosin on isolated rat myocardial ischemia reperfusion injury modles,and to investigate the protective effect and related mechanisms of respective agents. Methods Sixty-six Wistar rats were randomly divided into six groups: normal group( N Group),ischemia-reperfusion group( I-R group),nitroglycerin +ischemia-reperfusion group,diltiazem + ischemia-reperfusion group,adenosine + ischemia-reperfusion group,nicorandil + ischemia-reperfusion group. The normal group( N group) was given continued perfusion of normal liquid for 150 min; the I-R group was given stable perfusion for 30 min followed by ligating the LAD for 30 min and subsequent reperfusion for 90 min. For the drug post-conditioning groups,the models were given reperfusion with nitroglycerin( 10- 8mol / L),diltiazem( 5 μmo / L),nicorandil( 200 μmo / L) and adenosine( 100 μmo / L) for 15 min respectively,and then perfused with K-H liquid for 75 min. Observed and recorded reperfusion arrhythmia( RA),Left ventricular developed pressure( LVDP),± dp / dtmax by Taimeng( Chengdu) BL-420 s system and calculated myocardial infarct size. Results( 1) LVDP was lowest in the I-R group compared with the other groups after 30 min and 45 min of reperfusion( P 0. 05). In the drug post-conditioning groups after 30 min reperfusion,LVDP in the diltiazem group [( 92. 68 ± 5. 09)mm Hg vs.( 84. 26 ± 3. 02) mm Hg vs.( 83. 35 ± 2. 88) mm Hg] and in the nicorandil group [( 88. 95 ±1. 75) mm Hg vs.( 84. 26 ± 3. 02) mm Hg vs.( 83. 35 ± 2. 88) mm Hg] was higher than the nitroglycerine and the adenosine treated group. LVDP after 45 min reperfusion in the diltiazem group [( 90. 39 ± 4. 29)mm Hg vs.( 82. 09 ± 4. 24) mm Hg vs.( 80. 98 ± 3. 89) mm Hg] and in the nicorandil group [( 86. 13 ±2. 38) mm Hg vs.( 82. 09 ± 4. 24) mm Hg vs.( 80. 98 ± 3. 89) mm Hg]was higher than the nitroglyce