No: 1994

Atrial Natriuretic Peptide(ANP) Helps Prevent Late Remodeling after Left Ventricular Aneurysm Repair


Keywords: Cardiomyoplasty, Ventricular remodeling, Natriuretic peptides, atrial

Author Block: Hiroshi Tsuneyoshi, Takeshi Nishina, Takuya Nomoto, Hideo Kanemitsu, Kazunobu Nishimura, Masashi Komeda; Dept of CV Surg, Kyoto Univ, Kyoto, Japan


LV aneurysm repair (LVR) reduces LV wall stress and improves LV function. However, as we reported, the initial improvement did not last long because of LV remodeling, but it lasted better by using ACE-inhibitor postoperatively. ANP has been used to treat patients with heart failure by natriuretic and vasodilatory actions. Recent reports suggested that ANP inhibits the rennin-angiotensin system. In this study, the effects of intravenous administration of ANP after LVR were evaluated.

Methods: Rats developed LV aneurysm 4 weeks after LAD ligation, underwent LVR by plicating LV aneurysm, and were randomized into two groups: ANP group were intravenously administrated with 0.5µg/kg/min of Carperitide, recombinant α hANP, by osmotic mini-pump for 4 weeks, Control group with normal-saline. LV dimensions, hemodynamics, myocardial fibrosis and mRNA expressions by RT-PCR were evaluated.

Results: Administration of ANP decreased arterial pressure only at 1 week (ANP group 106 vs. Control group 122 mmHg; p<0.03), but not since 2 weeks after administration. Echocardiography revealed better LV remodeling and function in ANP group than in Control group. Cardiac catheterization showed that the treatment with ANP significantly reduced LV end-diastolic pressure (LVEDP), and increased end-systolic pressure-volume relationship (E-max), and decreased time constant of LV isovolumic pressure fall (Tau). In ANP group, mRNA expressions of BNP and TGF-β1 inducing fibrosis significantly decreased in LV myocardium. The levels of SERCA2 mRNA showed no difference between two groups. In histology, interstitial fibrosis of myocardium around plication was significantly reduced in ANP group.

Conclusions: Intravenous administration of ANP had beneficial effects on LV remodeling, function and fibrosis after LVR. ANP could be a useful i.v. infusion drug for postoperative management after LV repair surgery.

Echocardiograph and Catheterization
 
Pre VRS
1 week
2 week
3 week
4 week
LVEDA
(cm2)
ANP
Control
0.75±0.09
0.78±0.07
0.49±0.04*
0.59±0.09
0.51±0.04*
0.64±0.1
0.59±0.04*
0.70±0.1
0.61±0.03*
0.73±0.11
FAC
(%)
ANP
Control
28±3.5
30±5.6
45±3.2
45±3.9
42±1.8*
36±3.8
40±3.2
35±7.1
41±4.4*
36±4.8
LVEDP
(mmHg)
ANP
Control
 
 
 
 
8.7±3.2*
18.8±5.7
E-max
(mmHg/μL)
ANP
Control
 
 
 
 
0.43±0.25*
0.21±0.12
Tau
(sec)
ANP
Control
 
 
 
 
11.9±2.4*
17.4±2.6
 *=p<0.05 vs. control
  LVEDA: LV end-diastolic area, FAC: Fractional area change