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(Circulation. 2004;110:II-174 – II-179.)
© 2004 American Heart Association, Inc.

Cardiac Transplantation and Surgery for Congestive Heart Failure

Atrial Natriuretic Peptide Helps Prevent Late Remodeling After Left Ventricular Aneurysm Repair

Hiroshi Tsuneyoshi, MD; Takeshi Nishina, MD; Takuya Nomoto, MD PhD; Hideo Kanemitsu, MD; Rika Kawakami, MD; Oriyanhan Unimonh, MD; Kazunobu Nishimura, MD PhD; Masashi Komeda, MD PhD

From Department of Cardiovascular Surgery (H.T., T.N., T.No., H.K., O.U., K.N., M.K.), Graduate School of Medicine, Kyoto University, Japan; Department of Medicine and Clinical Science (R.K.), Graduate School of Medicine, Kyoto University, Japan.

Correspondence to Masashi Komeda, Department of Cardiovascular Surgery, Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan 606-8507. E-mail masakom{at}kuhp.kyoto-u.ac.jp

Background— 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.

Methods and Results— 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 µg/h of carperitide, recombinant -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/µL). 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 ß1 inducing fibrosis significantly decreased in LV myocardium in LVR+A group. Histologically, myocardial fibrosis was significantly reduced in LVR+A group.

Conclusions— 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.

Key Words: remodeling • natriuretic peptides • surgery • fibrosis • myocardial infarction • cardiomyopathy