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Updated: Jul 6, 2026
In utero Measurement of Heart Rate in Mouse by Noninvasive M-mode Echocardiography
Published on: November 22, 2013
Congenital deficiency of nitric oxide synthase 2 protects against endotoxin-induced myocardial dysfunction in mice
R Ullrich1, M Scherrer-Crosbie, K D Bloch
1Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Background:
Sepsis can be complicated by severe myocardial dysfunction and is associated with increased nitric oxide (NO) production by inducible NO synthase (NOS2). To investigate the role of NOS2 in endotoxin-induced myocardial dysfunction in vivo, we studied wild-type and NOS2-deficient mice.
Methods And Results:
Serial echocardiographic parameters of myocardial function were measured before and at 4, 7, 16, and 24 hours after an endotoxin challenge. Seven hours after challenge with either endotoxin or saline, systemic and left ventricular pressures were measured, and the first derivative of left ventricular developed pressure (dP/dt), slope of the end-systolic pressure-dimension relationship (Slope(LVESPD)), and time constant of isovolumic relaxation (tau) were calculated. Endotoxin challenge in wild-type mice decreased left ventricular fractional shortening, velocity of circumferential shortening, dP/dt(max), Slope(LVESPD), and dP/dt(min) and increased time constant tau. Endotoxin-induced myocardial dysfunction was associated with increased ventricular NOS2 gene expression and cGMP concentrations. Seven hours after endotoxin challenge, NOS2-deficient mice had greater fractional shortening, dP/dt(max), and Slope(LVESPD) than did endotoxin-challenged wild-type mice. Measures of diastolic function, dP/dt(min) and time constant tau, were preserved in endotoxin-challenged NOS2-deficient mice. After endotoxin challenge in wild-type mice, early (3-hour) inhibition of NOS2 with L-N:(6)-(1-iminoethyl)lysine hydrochloride prevented, whereas later (7-hour) inhibition could not reverse, endotoxin-induced myocardial dysfunction.
Conclusions:
These results suggest that NOS2 is required for the development of systolic and diastolic dysfunction in murine sepsis.
Insights
Inducible nitric oxide synthase (NOS2) plays a critical role in sepsis-induced heart dysfunction. Blocking NOS2 early in sepsis prevents cardiac dysfunction, highlighting its importance in this condition.
Area of Science:
- Cardiology
- Immunology
- Molecular Biology
Background:
- Sepsis often leads to myocardial dysfunction.
- Increased nitric oxide (NO) production via inducible NO synthase (NOS2) is linked to sepsis complications.
Purpose of the Study:
- To investigate the role of NOS2 in endotoxin-induced myocardial dysfunction in vivo.
- To compare cardiac function in wild-type and NOS2-deficient mice following endotoxin challenge.
Main Methods:
- Serial echocardiography to assess myocardial function.
- Measurement of left ventricular pressures and derived parameters (dP/dt, Slope(LVESPD), tau).
- Analysis of NOS2 gene expression and cGMP levels in ventricular tissue.
- Pharmacological inhibition of NOS2 at different time points.
Main Results:
- Endotoxin challenge impaired systolic and diastolic function in wild-type mice, correlating with increased NOS2 expression and cGMP.
- NOS2-deficient mice exhibited preserved cardiac function after endotoxin challenge.
- Early NOS2 inhibition (3 hours) prevented, but later inhibition (7 hours) did not reverse, endotoxin-induced myocardial dysfunction.
Conclusions:
- NOS2 is essential for the development of both systolic and diastolic dysfunction in murine sepsis models.
- Targeting NOS2 early in sepsis may be a therapeutic strategy to prevent cardiac complications.
