The effect of an angiotensin converting enzyme inhibitor (ACEI) on right ventricular remodeling

血管紧张素转换酶抑制剂（ACEI）对右心室重构的影响

• 批准号: 13660329
• 负责人: WAKAO Yoshito
• 金额: $ 1.79万
• 依托单位: Azabu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13660329/
• 关键词: Ventricular remodeling; ACEI; PA Banding; Dog

In this study, we prepared a PS model that is commonly found in dogs, and examined the inhibitory effect of ACEI on myocardial remodeling. The effect was examined following administration of ACEI by monitoring clinical conditions and various laboratory test parameters, as well as by measuring enzyme activity in cardiac muscle, fibrous tissue and cardiomyocyte diameter.In this 60-day experiment, laboratory tests revealed a time-dependent decrease in flow rate in the pulmonary artery in the ACEI group. However, exacerbation of the clinical conditions caused by administration of ACEI was not observed. The cause of the decrease in flow rate in the pulmonary artery in the ACEI group is unknown, and it is therefore considered necessary to determine the influence of this decrease by carrying out long-term observation. Although ACEI inhibited ACE activity in circulating blood, no significant inhibition of ACE activity was observed in the right ventricular muscle. In addition, histological examinations revealed an increase in the thickness of the right ventricular wall, an increase in fibrous tissue and an increase in cardiomyocyte diameter in both the PS and ACEI groups. As such, inhibition of myocardial remodeling by ACEI was not observed. It was suggested that this is because more ANG II is produced by chymase than by ACE in dogs. In fact, in the Sham group, chymase activity was greater than ACE activity in the right ventricle. It is considered necessary in the future to examine the usefulness of ANG II receptor blockers against PS, which can control ANG II formation that involves chymase.

在本研究中，我们制备了狗常见的PS模型，并检测了ACEI对心肌重构的抑制作用。通过监测临床情况和各种实验室测试参数，以及测量心肌、纤维组织和心肌细胞直径的酶活性，来检查ACEI给药后的效果。在这个为期60天的实验中，实验室测试显示ACEI组肺动脉流速随时间而降低。然而，没有观察到服用ACEI引起的临床病情恶化。ACEI组肺动脉流速下降的原因尚不清楚，因此认为有必要通过长期观察来确定这种下降的影响。虽然ACEI抑制循环血液中ACE活性，但在右心室肌中未观察到明显的ACE活性抑制。此外，组织学检查显示，PS组和ACEI组右心室壁厚度增加，纤维组织增加，心肌细胞直径增加。因此，未观察到ACEI对心肌重构的抑制作用。有人认为，这是因为狗的乳糜酶比ACE产生更多的ANG II。事实上，假手术组右心室乳糜酶活性大于ACE活性。未来有必要研究ANG II受体阻滞剂对PS的有效性，它可以控制涉及糖化酶的ANG II的形成。