两种血管紧张素转换酶抑制剂对冠状动脉侧支循环的影响

Effect of different angiotensin converting enzyme inhibitors on coronary collateral circulation

目的 建立狗急性心肌缺血模型 ,观察不同血管紧张素转换酶抑制剂 (ACEI)对血管紧张素转换酶 (ACE)活性、冠状动脉侧支循环形成的影响。方法 选健康杂种犬 2 4条随机分为卡托普利组、苯那普利组、对照组。结扎前降支近端 ,测量冠状动脉舒张压 (DCP)、侧支返流量 (Qret)及主动脉舒张压 (DAP)。术后给予不同药物干预 ,采血测定血浆ACE活性。第 2次手术后 ,将狗处死 ,提取标本 ,观察冠状动脉侧支循环形成情况以及组织ACE活性。结果 (1)卡托普利、苯那普利组用药前、用药后 10d及用药后 2 5d血浆ACE活性分别为 (5 7 6± 0 8)U/L、(2 4 1± 0 6 )U/L、(2 4 3±0 6 )U/L及 (5 9 5± 1 3)U/L、(2 4 4± 0 4 )U/L、(2 4 0± 0 5 )U/L ,用药后两组血浆ACE活性均明显降低 (P <0 0 1) ,但两组间差异无显著意义。对照组、卡托普利组、苯那普利组心脏组织ACE活性分别为 (13 0± 2 9)U·L-1·g-1、(7 9± 1 6 )U·L-1·g-1及 (1 83± 0 74 )U·L-1·g-1。卡托普利、苯那普利组ACE活性均明显低于对照组 (P <0 0 1) ,而苯那普利组ACE活性明显低于卡托普利组 (P <0 0 1)。 (2 )对照组、卡托普利组用药后DCP明显升高 [(3 4 5± 0 6 3)kPa及 (3 4 2± 0 5 9)kPa ,P <0 0 5 ]

Objective To observe the effects of different angiotensin converting enzyme inhibitors (ACEI) on coronary collateral circulation. Methods Twenty-four healthy dogs underwent measurement of distolic aortic pressure (DAP) and ligation of the left anterior descending coronary artery. The distolic coronary pressure (DCP) and retrograde blood flow (Qret) were measured. Five days after the operation the dogs were randomly divided into three groups of 8 dogs : benazepril group (benazepril 10 mg qd);captopril group (captopril 12.5 mg bid) and control group (starch tablet was given). Thirty days after the operation a reflux catheter was inserted to measure the DCP and Qret again. Then the dogs were killed and their hearts were taken out to examine the pathologic changes. The angiotensin converting enzyme (ACE) activity levels in plasma and myocardium were examined by FAPGG spectrophotometry. Results (1)In the captopril group the plasma ACE activity was (24.1±0.6) U/L 10 days after medication, and 24.3±0.6 U/L twenty-five days after medication, both significantly lower than that before medication [(57.6±0.8) U/L, both P <0.01];in benazepril group the plasma ACE activity was (24.4±0.4) U/L ten days after medication, and (24.0±0.5) U/L 25 days after medication, both significantly lower than that before medication [(59.5±1.3) U/L, both P <0.01]. The plasma ACE activity levels of captopril and benazepril groups, especially of the benazepril group, after medication were significantly lower than that of the control group. The tissue ACE activity levels of the captopril and benazepril groups were lower than that of the control group. (2)The values of DCP in the control and captopril group were higher after medication than before medication. A tendency of decrease of DCP was shown in the benazepril group, however, without statistical significance. (3)In the control group Qcol was (2.01±0.31) ml/min 25 days after medication, significantly than that before medication [(0.91±0.15) ml/min], the corresponding values in captopril group were (2.24±0.46) ml/min and (0.88±0.13) ml/min respectively in the captopril group and (3.18±0.27) ml/min and (0.89±0.11) ml/min respectively in the benazepril group with the value 25 days after in the benazepril group being the highest. (4)30 days after operation collateral circulation was established in the ischemic myocardium in all 3 groups. The microvessel density in the ischemic zone of myocardium was higher than that in the nonischemic zone in all 3 groups. The microvessel density in the ischemic zone of myocardium was greater in the benazepril group than in the captopril and control groups. There was no difference in microvessel density between the captopril group and control group. Conclusion Benazepril increases the microvessel density and collateral flow, promotes the creation of collateral circulation in ischemic area, but captopril has not such effects.