What question did this study set out to answer?

To investigate the specific role of inducible nitric oxide synthase (NOS2) in vivo during endotoxin-induced myocardial systolic and diastolic dysfunction.

September 19, 2000CirculationOpen Access

Congenital Deficiency of Nitric Oxide Synthase 2 Protects Against Endotoxin-Induced Myocardial Dysfunction in Mice

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Why the study?

Does NOS2 deficiency or inhibition prevent endotoxin-induced myocardial dysfunction in mice?

Population

Wild-type and NOS2-deficient mice subjected to endotoxin challenge

Comparison

NOS2 deficiency or pharmacological inhibition… vs Wild-type mice or saline challenge

Design

Preclinical

Follow-up

Up to 24 hours after endotoxin challenge

Authors

RURoman UllrichVienna General Hospital MSMarielle Scherrer‐CrosbieCardiac Imaging KBKenneth D. BlochHarvard University

Discussion

Member takes

Implication

Hypothesis-generating for NOS2 inhibition in septic cardiomyopathy; should not change practice pending human trials.

Key Points

To investigate the specific role of inducible nitric oxide synthase (NOS2) in vivo during endotoxin-induced myocardial systolic and diastolic dysfunction.
Wild-type and NOS2-deficient mice received an endotoxin challenge or saline control.
Serial echocardiographic measurements were taken at baseline and at 4, 7, 16, and 24 hours post-challenge, alongside invasive hemodynamic assessments of left ventricular pressures, dP/dt, Slope(LVESPD), and tau at 7 hours.
Wild-type mice were treated with the NOS2 inhibitor L-N:(6)-(1-iminoethyl)lysine hydrochloride at 3 hours or 7 hours following endotoxin administration.
Endotoxin challenge impaired systolic and diastolic parameters in wild-type mice, reducing fractional shortening, dP/dt(max), and Slope(LVESPD) while increasing ventricular NOS2 expression and cGMP concentrations.
NOS2-deficient mice exhibited preserved systolic performance (higher fractional shortening, dP/dt(max), and Slope(LVESPD)) and maintained diastolic function (preserved dP/dt(min) and relaxation time constant tau) compared to endotoxin-challenged wild-type mice.
Pharmacological inhibition of NOS2 at 3 hours post-challenge prevented myocardial dysfunction in wild-type mice, whereas intervention at 7 hours failed to reverse existing cardiac impairment.

Structured PICO

Does NOS2 deficiency or inhibition prevent endotoxin-induced myocardial dysfunction in mice?

Population

Wild-type and NOS2-deficient mice subjected to endotoxin challenge

Intervention

NOS2 deficiency (genetic) or pharmacological inhibition with L-N:(6)-(1-iminoethyl)lysine hydrochloride

Comparator

Wild-type mice or saline challenge

Outcome

Myocardial function (echocardiographic parameters, systemic and left ventricular pressures, dP/dt, Slope(LVESPD), and time constant of isovolumic relaxation tau)surrogate

NOS2 is required for the development of systolic and diastolic dysfunction in murine sepsis, and early inhibition can prevent this dysfunction.

Cite This Study

Ullrich et al. (2000) studied this question.

synapsesocial.com/papers/6a8907fd888d86b74818bb85 https://doi.org/10.1161/01.cir.102.12.1440

Topics

Echocardiography Cardiomyopathy

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Congenital Deficiency of Nitric Oxide Synthase 2 Protects Against Endotoxin-Induced Myocardial Dysfunction in Mice

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Topics

Congenital Deficiency of Nitric Oxide Synthase 2 Protects Against Endotoxin-Induced Myocardial Dysfunction in Mice

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Topics

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