Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock

Cardiopulmonary performance, oxygen transport and tissue inflammation

Dongmei Wu, Jiansong Qi, Hui Dai, Henri Doods, William M. Abraham

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The aim of the present study was to examine the effects of inhibition of the Na+/H+ exchanger (NHE-1) on cardiopulmonary performance, oxygen carrying capacity and tissue inflammation in a pig model of traumatic haemorrhage-resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low-volume fluid resuscitation with either Hextend (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE-1 inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the beginning of resuscitation. 3. Compared with vehicle-treated controls, the addition of NHE-1 inhibition with BIIB513 significantly improved the left ventricle stroke work index and attenuated increases in pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment significantly increased the oxygenated haemoglobin ratio, blood oxygen content and mixed venous blood oxygen saturation and improved blood oxygen delivery. In addition, BIIB513 treatment reduced lung tissue levels of interleukin-6 by 80%, tumour necrosis factor-α by 37% and myeloperoxidase activity by 38%. Nuclear factor-κB DNA binding activity in the lung was also slightly and significantly attenuated following BIIB513 treatment. 4. In conclusion, the present study shows that NHE-1 inhibition facilitates the response to fluid resuscitation after traumatic haemorrhage by improving cardiac function, pulmonary vascular function and oxygen carrying capacity, which results in reduced tissue inflammatory injury.

Original languageEnglish
Pages (from-to)337-342
Number of pages6
JournalClinical and Experimental Pharmacology and Physiology
Volume37
Issue number3
DOIs
StatePublished - Mar 1 2010
Externally publishedYes

Fingerprint

Traumatic Shock
Sodium-Hydrogen Antiporter
Hemorrhagic Shock
Resuscitation
Oxygen
Inflammation
Hemorrhage
Lung
Conservation of Natural Resources
Swine
Lakes
Tibia
Tears
Vascular Resistance
Peroxidase
Heart Ventricles
Blood Vessels
Interleukin-6
Arterial Pressure
Hemoglobins

Keywords

  • Myeloperoxidase
  • Oxygen saturation
  • Oxygenated haemoglobin
  • Pigs
  • Pulmonary vascular resistance

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

Cite this

Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock : Cardiopulmonary performance, oxygen transport and tissue inflammation. / Wu, Dongmei; Qi, Jiansong; Dai, Hui; Doods, Henri; Abraham, William M.

In: Clinical and Experimental Pharmacology and Physiology, Vol. 37, No. 3, 01.03.2010, p. 337-342.

Research output: Contribution to journalArticle

@article{69f54b78fe83444187fe2d67b00b6a39,
title = "Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock: Cardiopulmonary performance, oxygen transport and tissue inflammation",
abstract = "The aim of the present study was to examine the effects of inhibition of the Na+/H+ exchanger (NHE-1) on cardiopulmonary performance, oxygen carrying capacity and tissue inflammation in a pig model of traumatic haemorrhage-resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low-volume fluid resuscitation with either Hextend (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE-1 inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the beginning of resuscitation. 3. Compared with vehicle-treated controls, the addition of NHE-1 inhibition with BIIB513 significantly improved the left ventricle stroke work index and attenuated increases in pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment significantly increased the oxygenated haemoglobin ratio, blood oxygen content and mixed venous blood oxygen saturation and improved blood oxygen delivery. In addition, BIIB513 treatment reduced lung tissue levels of interleukin-6 by 80{\%}, tumour necrosis factor-α by 37{\%} and myeloperoxidase activity by 38{\%}. Nuclear factor-κB DNA binding activity in the lung was also slightly and significantly attenuated following BIIB513 treatment. 4. In conclusion, the present study shows that NHE-1 inhibition facilitates the response to fluid resuscitation after traumatic haemorrhage by improving cardiac function, pulmonary vascular function and oxygen carrying capacity, which results in reduced tissue inflammatory injury.",
keywords = "Myeloperoxidase, Oxygen saturation, Oxygenated haemoglobin, Pigs, Pulmonary vascular resistance",
author = "Dongmei Wu and Jiansong Qi and Hui Dai and Henri Doods and Abraham, {William M.}",
year = "2010",
month = "3",
day = "1",
doi = "10.1111/j.1440-1681.2009.05296.x",
language = "English",
volume = "37",
pages = "337--342",
journal = "Clinical and Experimental Pharmacology and Physiology",
issn = "0305-1870",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock

T2 - Cardiopulmonary performance, oxygen transport and tissue inflammation

AU - Wu, Dongmei

AU - Qi, Jiansong

AU - Dai, Hui

AU - Doods, Henri

AU - Abraham, William M.

PY - 2010/3/1

Y1 - 2010/3/1

N2 - The aim of the present study was to examine the effects of inhibition of the Na+/H+ exchanger (NHE-1) on cardiopulmonary performance, oxygen carrying capacity and tissue inflammation in a pig model of traumatic haemorrhage-resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low-volume fluid resuscitation with either Hextend (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE-1 inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the beginning of resuscitation. 3. Compared with vehicle-treated controls, the addition of NHE-1 inhibition with BIIB513 significantly improved the left ventricle stroke work index and attenuated increases in pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment significantly increased the oxygenated haemoglobin ratio, blood oxygen content and mixed venous blood oxygen saturation and improved blood oxygen delivery. In addition, BIIB513 treatment reduced lung tissue levels of interleukin-6 by 80%, tumour necrosis factor-α by 37% and myeloperoxidase activity by 38%. Nuclear factor-κB DNA binding activity in the lung was also slightly and significantly attenuated following BIIB513 treatment. 4. In conclusion, the present study shows that NHE-1 inhibition facilitates the response to fluid resuscitation after traumatic haemorrhage by improving cardiac function, pulmonary vascular function and oxygen carrying capacity, which results in reduced tissue inflammatory injury.

AB - The aim of the present study was to examine the effects of inhibition of the Na+/H+ exchanger (NHE-1) on cardiopulmonary performance, oxygen carrying capacity and tissue inflammation in a pig model of traumatic haemorrhage-resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low-volume fluid resuscitation with either Hextend (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE-1 inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the beginning of resuscitation. 3. Compared with vehicle-treated controls, the addition of NHE-1 inhibition with BIIB513 significantly improved the left ventricle stroke work index and attenuated increases in pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment significantly increased the oxygenated haemoglobin ratio, blood oxygen content and mixed venous blood oxygen saturation and improved blood oxygen delivery. In addition, BIIB513 treatment reduced lung tissue levels of interleukin-6 by 80%, tumour necrosis factor-α by 37% and myeloperoxidase activity by 38%. Nuclear factor-κB DNA binding activity in the lung was also slightly and significantly attenuated following BIIB513 treatment. 4. In conclusion, the present study shows that NHE-1 inhibition facilitates the response to fluid resuscitation after traumatic haemorrhage by improving cardiac function, pulmonary vascular function and oxygen carrying capacity, which results in reduced tissue inflammatory injury.

KW - Myeloperoxidase

KW - Oxygen saturation

KW - Oxygenated haemoglobin

KW - Pigs

KW - Pulmonary vascular resistance

UR - http://www.scopus.com/inward/record.url?scp=77649087367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77649087367&partnerID=8YFLogxK

U2 - 10.1111/j.1440-1681.2009.05296.x

DO - 10.1111/j.1440-1681.2009.05296.x

M3 - Article

VL - 37

SP - 337

EP - 342

JO - Clinical and Experimental Pharmacology and Physiology

JF - Clinical and Experimental Pharmacology and Physiology

SN - 0305-1870

IS - 3

ER -