Exogenous nitric oxide prevents cardiovascular collapse during hemorrhagic shock

Resuscitation 82 (2011) 607–613

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Resuscitation
journal homepage: www.elsevier.com/locate/resuscitation

Experimental paper

Exogenous nitric oxide prevents cardiovascular collapse during hemorrhagic shock
Parimala Nachuraju a , Adam J. Friedman b , Joel M. Friedman a , Pedro Cabrales c,∗
a

Department of Physiology and Biophysics, AlbertEinstein College of Medicine, Bronx, NY, United States Division of Dermatology, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, United States c Department of Bioengineering, 0412, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0412, United States
b

a r t i c l e
Article history:

i n f o

a b s t r a c t
This study investigated thesystemic and microvascular hemodynamic changes related to increased nitric oxide (NO) availability following significant hemorrhage, made available by administration of NO releasing nanoparticles (NO-nps). Hemodynamic responses to hemorrhagic shock were studied in the hamster window chamber. Acute hemorrhage was induced by arterial controlled bleeding of 50% of blood volume, and the resulting hemodynamicparameters were followed over 90 min. Exogenous NO was administered in the form of NO-nps (5 mg/kg suspended in 50 l saline) 10 min following induced hemorrhage. Control groups received equal dose of NO free nanoparticles (Control-nps) and Vehicle solution. Animals treated with NO-nps partially maintained systemic and microvascular function during hypovolemic shock compared to animals treatedwith Control-nps or the Vehicle (50 l saline). The continuous NO released by the NO-nps reverted arteriolar vasoconstriction, partially recovered both functional capillary density and microvascular blood flows. Additionally, NO supplementation post hemorrhage prevented cardiac decompensation, and thereby maintained and stabilized the heart rate. Paradoxically, the peripheral vasodilation induced bythe NO-nps did not decrease blood pressure, and combined with NO’s effects on vascular resistance, NO-nps promoted intravascular pressure redistribution and blood flow, avoiding tissue ischemia. Therefore, by increasing NO availability with NO-nps during hypovolemic shock, it is possible that cardiac stability and microvascular perfusion can be preserved, ultimately increasing survivability andlocal tissue viability, and reducing hemorrhagic shock sequelae. The relevance, stability, and efficacy of exogenous NO therapy in the form of NO-nps will potentially facilitate the intended use in battlefield and trauma situations. © 2011 Elsevier Ireland Ltd. All rights reserved.

Keywords: Microcirculation Hemorrhage Glutathione Nitrosoglutathione Functional capillary density

1. IntroductionHemorrhagic shock accounts for about 50% of battlefield deaths in conventional warfare.1 Early, aggressive, high volume resuscitation was widely accepted and most practiced during the Vietnam War.2 However, metabolic benefits of this approach were only demonstrated in controlled hemorrhage animal models, and when implemented in humans, showed severe deleterious effects including pulmonary failureand re-bleeding.3,4 Small volume resuscitation can be considered a model to improve the efficiency of fluid therapy by changing the composition and infusion regimens.5 Even following trauma, blood transfusion produces

A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2010.12.025. ∗ Corresponding author. Tel.:+1 858 534 5847; fax: +1 858 822 4830. E-mail address: pcabrales@ucsd.edu (P. Cabrales). 0300-9572/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.resuscitation.2010.12.025

inflammatory responses, potentially causing more morbidity than the original insult.6 Nitric oxide (NO) plays several major roles in human physiology. NO is a neurotransmitter, a...