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Permanent Ligation of the Left Anterior Descending Coronary Artery in Mice: A Model of Post-myocardial Infarction Remodelling and Heart Failure
Published on: December 2, 2014
Mice lacking inducible nitric oxide synthase have improved left ventricular contractile function and reduced
F Sam1, D B Sawyer, Z Xie
1Cardiovascular Medicine Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USA.
Abstract:
Nitric oxide produced by inducible nitric oxide synthase (NOS2) has been implicated in the pathophysiology of chronic myocardial remodeling and failure. We tested the role of NOS2 in left ventricular (LV) remodeling early (1 month) and late (4 months) after myocardial infarction (MI) in mice lacking NOS2. MI size measured 7 days, 1 month, and 4 months after MI was the same in NOS2 knockout (KO) and wild-type (WT) mice. The LV end-diastolic pressure-volume relationship measured by the isovolumic Langendorff technique showed a progressive rightward shift from 1 to 4 months after MI in WT mice. LV developed pressure measured over a range of LV volumes was reduced at 1 and 4 months after MI in WT mice (P<0.05 and P<0.01 versus shams, respectively). In KO mice, the rightward shift was similar to that in WT mice at 1 and 4 months after MI, as was peak LV developed pressure at 1 month after MI. In contrast, at 4 months after MI, peak LV developed pressure in KO mice was higher than in WT mice (P<0.05 versus WT) and similar to that in sham-operated mice. At 1 month after MI, the frequency of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive myocytes in the remote myocardium was increased to a similar extent in WT and KO mice. At 4 months after MI, the frequency of apoptotic myocytes was increased in WT mice but not in KO mice (P<0.05 versus WT). Improved contractile function and reduced apoptosis were associated with reduced mortality rate in KO mice at 4 months after MI. Thus, NOS2 does not play an important role in determining infarct size or early LV remodeling during the first month after MI. In contrast, during late (ie, 4 months after MI) remodeling, NOS2 in remote myocardium contributes to decreased contractile function, increased myocyte apoptosis in remote myocardium, and reduced survival.
Insights
Inducible nitric oxide synthase (NOS2) does not impact early heart attack remodeling. However, NOS2 contributes to reduced heart function and increased cell death in later stages, affecting survival after myocardial infarction.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pathophysiology
Background:
- Inducible nitric oxide synthase (NOS2) is linked to chronic myocardial remodeling and failure.
- Understanding NOS2's role in post-myocardial infarction (MI) cardiac remodeling is crucial.
Purpose of the Study:
- To investigate the role of NOS2 in left ventricular (LV) remodeling at early (1 month) and late (4 months) stages after MI.
- To determine the impact of NOS2 deficiency on cardiac function, apoptosis, and survival post-MI.
Main Methods:
- Utilized NOS2 knockout (KO) and wild-type (WT) mice subjected to myocardial infarction.
- Assessed infarct size, LV pressure-volume relationships, and myocyte apoptosis (TUNEL assay).
- Monitored survival rates in KO and WT mice post-MI.
Main Results:
- Infarct size and early LV remodeling (1 month) were similar between NOS2 KO and WT mice.
- Late remodeling (4 months) showed preserved LV developed pressure and reduced myocyte apoptosis in NOS2 KO mice compared to WT.
- NOS2 deficiency in the late phase was associated with improved cardiac function and reduced mortality.
Conclusions:
- NOS2 is not critical for infarct size determination or early LV remodeling post-MI.
- During late remodeling (4 months post-MI), NOS2 in remote myocardium impairs contractile function, increases myocyte apoptosis, and reduces survival.
