Tsuneyoshi Hiroshi, Nishina Takeshi, Nomoto Takuya, Kanemitsu Hideo, Kawakami Rika, Unimonh Oriyanhan, Nishimura Kazunobu, Komeda Masashi
Department of Cardiovascular Surgery, Graduate School of Medicine, Kyoto University, Japan.
Circulation. 2004 Sep 14;110(11 Suppl 1):II174-9. doi: 10.1161/01.CIR.0000138348.77856.ef.
Left ventricular aneurysm repair (LVR) reduces LV wall stress and improves LV function. However, as we reported previously, the initial improvement of LVR was short-term because of LV remodeling but could be maintained longer with postoperative use of an angiotensin-converting enzyme (ACE) inhibitor. Atrial natriuretic peptide (ANP) has been used to treat patients with heart failure by natriuretic and vasodilatory actions. Recent reports have suggested that ANP inhibits the rennin-angiotensin system. In this study, the effects of ANP after LVR were evaluated.
Rats that had an LV aneurysm 4 weeks after left anterior descending artery ligation underwent LVR by plicating the LV aneurysm and were randomized into 2 groups: LVR+A group was intravenously administrated with 10 microg/h of carperitide, recombinant alpha-hANP, by osmotic-pump for 4 weeks, and the LVR group was given normal saline. Echocardiography revealed better LV remodeling and function in LVR+A group than in LVR group. Four weeks after LVR, left ventricular end diastolic pressure (LVEDP) and Tau were significantly lower in LVR+A group (LVEDP: 10+/-4 in LVR+A group versus 18+/-6 mm Hg in LVR group, Tau: 13+/-2 versus 17+/-2ms). End-systolic elastance (Ees) was higher in LVR+A group (Ees: 0.34+/-0.2 versus 0.19+/-0.11 mm Hg/microL). The levels of myocardial ACE activity in LVR+A group was significantly lower than in LVR group. The mRNA expressions of brain natriuretic peptide and transforming growth factor beta1 inducing fibrosis significantly decreased in LV myocardium in LVR+A group. Histologically, myocardial fibrosis was significantly reduced in LVR+A group.
Intravenous administration of ANP had beneficial effects on LV remodeling, function, and fibrosis after LVR. ANP could be a useful intravenous infusion drug for postoperative management after LV repair surgery.
左心室动脉瘤修复术（LVR）可降低左心室壁应力并改善左心室功能。然而，正如我们之前所报道的，由于左心室重塑，LVR术后的最初改善是短期的，但术后使用血管紧张素转换酶（ACE）抑制剂可使改善维持更长时间。心房利钠肽（ANP）已被用于通过利钠和血管舒张作用治疗心力衰竭患者。最近的报告表明，ANP可抑制肾素-血管紧张素系统。在本研究中，评估了LVR术后ANP的作用。
在左前降支动脉结扎4周后出现左心室动脉瘤的大鼠接受了通过折叠左心室动脉瘤进行的LVR，并随机分为2组：LVR+A组通过渗透泵静脉注射10μg/h卡培立肽（重组α-hANP），持续4周，LVR组给予生理盐水。超声心动图显示，LVR+A组的左心室重塑和功能优于LVR组。LVR术后4周，LVR+A组的左心室舒张末期压力（LVEDP）和Tau显著降低（LVR+A组：10±4，LVR组：18±6mmHg；Tau：LVR+A组：13±2，LVR组：17±2ms）。LVR+A组的收缩末期弹性（Ees）更高（Ees：0.34±0.2，LVR组：0.19±0.11mmHg/μL）。LVR+A组的心肌ACE活性水平显著低于LVR组。LVR+A组左心室心肌中脑利钠肽和诱导纤维化的转化生长因子β1的mRNA表达显著降低。组织学检查显示，LVR+A组的心肌纤维化显著减轻。
静脉注射ANP对LVR术后的左心室重塑、功能和纤维化有有益作用。ANP可能是左心室修复手术后术后管理的一种有用的静脉输注药物。
