HMGB1 Release From Hemorrhagic Shock Patients

Evidence for SIRT1 Mediated HMGB1 Release From Kidney Cells in the Early Stages of Hemorrhagic Shock

It is reported that high mobility group box 1 (HMGB1), a non-histone nuclear protein, can serve as an alarmin with damage associated molecular patterns to activate immune responses in the early stages of hemorrhagic shock (HS). However, the origin of HMGB1 and how it is released following HS is poorly understood. In this study, we teased out this mechanism. We try to record the concentration of serum HMGB1 protein following HS in clinical patients.

Study Overview

• Status: Completed
• Conditions: Hemorrhagic Shock; Intensive Care Unit; Adult Disease

Detailed Description

The study was approved by the First People's Hospital of Chenzhou, Hunan, P.R. China. Consent was obtained from patients in their hospital course. Eighteen patients were enrolled for each group. In addition, Acute Physiological and Chronic Health Evaluation II (APACHE II) score was used to evaluate the severity and morbidity of HS patients Serial blood samples were collected at indicated time points on hospital admission for HS patients (0, 2, 4, 8, 24, and 72 h following HS). Levels of HMGB1 were detected by ELISA according to the kit manufacturer's instructions.

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• China
  • Hunan
    • Chenzhou, Hunan, China, 450003
      • The First Hospital of Chenzhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Healthy volunteers OR Hemorrhagic shock (HS) patients enrolled in ICU

Description

Inclusion Criteria:

Hemorrhagic shock (HS) was defined as out-of-hospital systolic blood pressure (SBP) of 70 mmHg or less or SBP ranging 71 to 90 mmHg with a heart rate of 108 beats/min or more.

Exclusion Criteria:

pregnancy, <18 years old, more than 2,000 mL of intravenous fluids or blood before enrollment, hypothermia, drowning, asphyxia, burns, isolated penetrating head injury, time of call received by dispatch to study intervention longer than 4 h, known prisoners, and transfer from another hospital

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
voluteer group; No treatment, only blood sample collection
hemorrhagic shock group; HS was defined as out-of-hospital systolic blood pressure (SBP) of 70 mmHg or less or SBP ranging 71 to 90 mmHg with a heart rate of 108 beats/min or more. Exclusion criteria were pregnancy, <15 years old, more than 2,000 mL of intravenous fluids or blood before enrollment, hypothermia, drowning, asphyxia, burns, isolated penetrating head injury, time of call received by dispatch to study intervention longer than 4 h, known prisoners, and transfer from another hospital

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum HMGB1 concentration	the concentration of serum HMGB1 were progressively increased following Hemorrhagic shock	24 hours following hemorrhagic shock

Collaborators and Investigators

• Sponsor: Xingui Dai

Publications and helpful links

General Publications

• Rickenbacher A, Jang JH, Limani P, Ungethum U, Lehmann K, Oberkofler CE, Weber A, Graf R, Humar B, Clavien PA. Fasting protects liver from ischemic injury through Sirt1-mediated downregulation of circulating HMGB1 in mice. J Hepatol. 2014 Aug;61(2):301-8. doi: 10.1016/j.jhep.2014.04.010. Epub 2014 Apr 18.
• Rabadi MM, Xavier S, Vasko R, Kaur K, Goligorksy MS, Ratliff BB. High-mobility group box 1 is a novel deacetylation target of Sirtuin1. Kidney Int. 2015 Jan;87(1):95-108. doi: 10.1038/ki.2014.217. Epub 2014 Jun 18.
• Hwang JS, Lee WJ, Kang ES, Ham SA, Yoo T, Paek KS, Lim DS, Do JT, Seo HG. Ligand-activated peroxisome proliferator-activated receptor-delta and -gamma inhibit lipopolysaccharide-primed release of high mobility group box 1 through upregulation of SIRT1. Cell Death Dis. 2014 Oct 2;5(10):e1432. doi: 10.1038/cddis.2014.406.
• Hwang JS, Choi HS, Ham SA, Yoo T, Lee WJ, Paek KS, Seo HG. Deacetylation-mediated interaction of SIRT1-HMGB1 improves survival in a mouse model of endotoxemia. Sci Rep. 2015 Nov 2;5:15971. doi: 10.1038/srep15971.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2017
• Primary Completion (Actual): April 11, 2018
• Study Completion (Actual): May 11, 2018

Study Registration Dates

• First Submitted: May 11, 2018
• First Submitted That Met QC Criteria: May 14, 2018
• First Posted (Actual): May 24, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2018
• Last Update Submitted That Met QC Criteria: May 14, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: HMGB1; hemorrhagic shock
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Shock; Shock, Hemorrhagic
• Other Study ID Numbers: HSHMGB12018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Hemorrhagic shock (HS) is a pathologic process caused by insufficient perfusion in multiple organs, and usually initiates a systemic post-traumatic inflammation response. The resulting increased inflammation response may accelerate the multiple organ dysfunctions . Extracellular high-mobility group box 1 (HMGB1) was found to mediate inflammation during sterile and infectious injury and contributes significantly to disease pathogenesis. However, the exact role of HMGB1-mediated inflammation in HS is not fully understood.

In this study, we first test the serum HMGB1 concentration in clinical HS patients and then we explored the underlying mechanism in HS animal model. An unexpected mechanism of HMGB1 released from multiple organs (especially in kidney) was found.

• IPD Sharing Time Frame: 72 hours following hemorrhagic shock
• IPD Sharing Access Criteria: HS was defined as out-of-hospital systolic blood pressure (SBP) of 70 mmHg or less or SBP ranging 71 to 90 mmHg with a heart rate of 108 beats/min or more. Exclusion criteria were pregnancy, <18 years old, more than 2,000 mL of intravenous fluids or blood before enrollment, hypothermia, drowning, asphyxia, burns, isolated penetrating head injury, time of call received by dispatch to study intervention longer than 4 h, known prisoners, and transfer from another hospital

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No