January 1, 2006Thrombosis and Haemostasis
Effect of nitric oxide synthase (NOS) inhibition on macro- and microcirculation in a model of rat endotoxic shock
Key result
Selective iNOS inhibition with 1400W stabilized blood pressure (88 vs 67 mmHg, P<0.05) without aggravating lactate acidosis or deteriorating mucosal oxygenation in a rat model of endotoxic shock.
Why the study?
Does selective iNOS inhibition improve hemodynamics and microcirculation compared to non-selective NOS inhibition or norepinephrine in a rat model of endotoxic shock?
Population
Male Wistar rats in a model of endotoxic shock, n=24.
Comparison
Selective iNOS inhibitor 1400W, non-selective… vs Saline.
Design
Preclinical, Randomized into four different groups
Follow-up
60 minutes after infusion
Authors
Discussion
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Implication
Stabilizes hemodynamics without microcirculatory harm in rats; hypothesis-generating and should not change practice in human sepsis.
Study Design
Type
RCT (n=24)
Randomization
randomized
Structured PICO
Does selective iNOS inhibition improve hemodynamics and microcirculation compared to non-selective NOS inhibition or norepinephrine in a rat model of endotoxic shock?
P
Population
24 male Wistar rats with LPS-induced endotoxic shock randomized to receive saline, norepinephrine, L-NMMA, or 1400W.
I
Intervention
Selective iNOS inhibitor 1400W, non-selective NOS inhibitor L-NMMA, or norepinephrine.
C
Comparator
Saline.
O
Outcome
Hemodynamics (blood pressure) and microcirculation (tissue oxygenation in ileum mucosal layer, lactate formation).surrogate
Main Result
Absolute Event Rate: 88% vs 67%
p-value: p=<0.05
In a rat model of endotoxic shock, selective iNOS inhibition with 1400W stabilized blood pressure without the deleterious microcirculatory effects seen with norepinephrine or non-selective NOS inhibition.
Cite This Study
Pullamsetti et al. (2006) conducted an RCT in Endotoxic shock (n=24). 1400W (selective iNOS inhibitor) vs. Saline (hypotensive baseline) and norepinephrine was evaluated on Blood pressure at 60 minutes after injection (p=<0.05). Selective iNOS inhibition with 1400W stabilized blood pressure (88 vs 67 mmHg, P<0.05) without aggravating lactate acidosis or deteriorating mucosal oxygenation in a rat model of endotoxic shock.