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 |