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Hypertonic Saline Solution Reduces Microcirculatory Dysfunction and Inflammation in a Rat Model of Brain Death

Correia, Cristiano de Jesus; Armstrong, Roberto Jr; Carvalho, Priscila Oliveira de; Simas, Rafael; Sanchez, Daniela Crisina Janolli; Breithaupt-Faloppa, Ana Cristina; Sannomiya, Paulina; Moreira, Luiz Felipe Pinho

doi: 10.1097/SHK.0000000000001169
Basic Science Aspects

Background: Brain death (BD) induces hemodynamic instability with microcirculatory hypoperfusion, leading to increased organ inflammation and dysfunction. This study investigated the effects of 7.5% hypertonic saline solution (HSS) on mesenteric microcirculatory dysfunction and inflammation in a rat model of BD.

Methods: Male Wistar rats were anesthetized and mechanically ventilated. BD was induced by rapidly inflating an intracranial balloon catheter. The rats were randomly divided into: SH, sham-operated rats subjected to trepanation; NS, rats treated with NaCl 0.9%, 4 mL/kg immediately after BD; T1, rats treated with HSS (NaCl 7.5%, 4 mL/kg) immediately or 60 min after BD, T60. All groups were analyzed 180 min after the start of the experiment.

Results: Rats in BD groups presented with a similar hypertensive peak, followed by hypotension. Proportion of perfused small vessels was decreased in the NS group (46%) compared with the SH group (74%, P = 0.0039). HSS restored the proportion of perfused vessels (T1 = 71%, P = 0.0018). The anti-endothelial nitric oxide synthase (eNOS) protein expression significantly increased in rats given HSS (T1, and T60, P = 0.0002). Similar results were observed regarding endothelin-1 (P < 0.0001). Increased numbers of rolling (P = 0.0015) and migrated (P = 0.0063) leukocytes were observed in the NS group compared with the SH group. Rats given HSS demonstrated an overall reduction in leukocyte–endothelial interactions. The ICAM-1 levels increased in the NS group compared with the SH group, and decreased in the HSS-treated groups (P = 0.0002).

Conclusions: HSS may improve the density of mesenteric perfused small vessels due to its effects on eNOS and endothelin-1 protein expression, and reduces inflammation by decreasing leukocyte adhesion and migration in a rat model of BD.

Laboratório Cirúrgico de Pesquisa Cardiovascular (LIM-11), Instituto do Coração (Incor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

Address reprint requests to Luiz Felipe Pinho Moreira, MD, PhD, Laboratory of Cardiovascular Surgery Research (LIM-11), University of São Paulo Medical School, Dr. Arnaldo 455 Ave, 2nd Level, Room 2146, São Paulo 01246-903, Brazil. E-mail:

Received 5 March, 2018

Revised 21 March, 2018

Accepted 17 April, 2018

Availability of data: “The dataset(s) supporting the conclusions of this article is(are) available in the [repository name] repository, [unique persistent identifier and hyperlink to dataset(s) in http://format].”

CdJC performed all experiments with the collaboration of RAJr and RS for microcirculation analysis, POdC performed RT-PCR analysis, ACB-F and DCJS performed the immunohistochemical analyzes. CdJC drafted the manuscript and was advised by PS and LFPM. All authors read and approved the final manuscript.

Financial Support: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-2012/19841-2.

The authors report no conflicts of interest.

© 2019 by the Shock Society