Detrimental Hemodynamic Effects of Nitric Oxide Synthase Inhibition in Septic Shock

doi:10.1001/archsurg.1994.01420260045005

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Vol. 129 No. 2, February 1994

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Detrimental Hemodynamic Effects of Nitric Oxide Synthase Inhibition in Septic Shock

Frank M. Robertson, MD; Patrick J. Offner, MD, MPH; David P. Ciceri, MD; William K. Becker, MD; Basil A. Pruitt, Jr, MD

Arch Surg. 1994;129(2):149-156.

Abstract

Objective
To investigate the physiologic effects of nitric oxide synthaseinhibition with N-nitro-L-arginine methyl ester in an acuteresuscitated model of porcine septic shock.

Design
Randomized control trial.

Setting
Animal research facility.

Study Subjects
Domestic Yorkshire swine.

Interventions
Twenty-four animals were randomly divided into one of four treatmentgroups as follows: normal saline resuscitation (NSR) (controlgroup); NSR plus 200 µg/kg of lipopolysaccharide (LPS)at 1 hour after baseline (LPS group); NSR, LPS, and a continuousinfusion of 50 µg/kg per minute of N-nitro-L-argininemethyl ester (NAME) at 1 hour after baseline (LPS/NAME group);and NSR and NAME (NAME group). All animals received NSR at 1mL/kg per minute starting at baseline.

Main Outcome Measures
Mean arterial pressure (MAP), systemic vascular resistance index(SVRI), mean pulmonary arterial pressure (MPAP), and pulmonaryvascular resistance index (PVRI) were measured at baseline andhourly for 4 hours. Values at baseline and 3 hours are givenbelow as mean (±SE).

Results
All variables remained unchanged in the control group. The administrationof LPS produced a systemic hyperdynamic response characterizedby a decrease in MAP and SVRI from 66.0±3.9 to 55.0±2.8mm Hg (P<.05) and from 422.0±22.0 to 272.0±29.0mm Hg.min.kg/L (P<.05), respectively. The administrationof LPS produced an increase in MPAP and PVRI from 16.3±0.8to 30.0±1.3 mm Hg (P<.05) and from 37.0±5.3to 119.0±13.0 mm Hg.min.kg/L (P<.05), respectively.In the LPS/NAME group, NAME infusion normalized MAP and increasedSVRI from 506.0±40.0 to 642.0±72.0 mm Hg.min.kg/L(P<.05). Infusion of NAME potentiated LPS-induced pulmonaryhypertension, increasing MPAP and PVRI from 16.8±0.6to 36.0±2.8 mm Hg (P<.05) and from 59.0±3.5to 319.0±64.0 mm Hg.min.kg/L (P<.05), respectively.Infusion of NAME alone increased MAP from 74.0±1.3 to100.0±4.1 mm Hg (P<.05) and had no significant effecton MPAP and PVRI.

Conclusions
The potentiation of LPS-induced pulmonary hypertension followingNAME infusion suggests that inhibition of nitric oxide synthasemay have a limited role in the treatment of septic shock.

(Arch Surg. 1994;129:149-156)

Author Affiliations

From the Department of Surgery, Critical Care Service, Brooke Army Medical Center (Drs Robertson, Offner, and Ciceri) and the US Army Institute of Surgical Research (Drs Becker and Pruitt), Fort Sam Houston, Tex.; Dr Robertson is now with the Division of Pediatric Surgery, New England Medical Center, Boston, Mass.

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