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Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock
Published on: June 6, 2011
Transformation of neutrophils as indicator of irreversibility in hemorrhagic shock
J Barroso-Aranda1, G W Schmid-Schönbein
1Department of Applied Mechanics and Engineering Sciences, University of California, San Diego, La Jolla 92093.
Abstract:
Recent evidence shows that the presence of circulating neutrophils (PMNs) influences the lethal course and extent of ischemic injury associated with hemorrhagic shock. The objective of this study was to use the Wiggers shock model to investigate the correlation between the appearance of activated circulating PMNs as measured by the spontaneous reduction of nitro blue tetrazolium [(NBT)-positive PMNs] and survival rate. Rats were maintained at 35-mmHg arterial pressure for 90 min and then observed over 24 h for survival. This protocol resulted in 50% mortality. In all animals in which levels of circulating NBT-positive PMNs before bleeding were greater than 225 cells/mm3, the experimental procedure was lethal. Animals that initially had low numbers of NBT-positive PMNs (to approximately 135 cells/mm3) and maintained low counts during the hypotensive period consistently survived. Animals, which before bleeding had low NBT-positive PMN counts but during the course of hypotension significantly elevated their circulating count, have low probability for survival. In those cases in which high NBT-positive PMN counts occurred only later in the course of the hypotensive period, the rats survived. These results suggest that the number of circulating NBT-positive PMNs is a singular index for the trend toward irreversibility in this shock model.
Insights
Activated neutrophils (PMNs) impact hemorrhagic shock outcomes. Measuring nitro blue tetrazolium-positive PMNs in circulation can predict survival rates in shock models, serving as a key indicator of injury severity.
Area of Science:
- Physiology
- Immunology
- Pathophysiology
Background:
- Circulating neutrophils (PMNs) are implicated in the severity of ischemic injury during hemorrhagic shock.
- Understanding the role of PMNs in shock progression is crucial for predicting patient outcomes.
Purpose of the Study:
- To investigate the correlation between activated circulating PMNs and survival rates in a rat hemorrhagic shock model.
- To assess the predictive value of nitro blue tetrazolium-positive PMNs for shock irreversibility.
Main Methods:
- Utilized the Wiggers shock model in rats, inducing hypotension at 35 mmHg for 90 minutes.
- Monitored survival rates over 24 hours post-hypotension.
- Quantified circulating nitro blue tetrazolium-positive PMNs (NBT-positive PMNs) before and during the hypotensive period.
Main Results:
- A 50% mortality rate was observed under the experimental conditions.
- Pre-bleeding NBT-positive PMN counts above 225 cells/mm³ were associated with lethality.
- Consistently low NBT-positive PMN counts (<135 cells/mm³) throughout hypotension correlated with survival.
- A significant increase in NBT-positive PMNs during hypotension, regardless of initial levels, reduced survival probability.
- Delayed increases in NBT-positive PMNs after the hypotensive period were observed in surviving rats.
Conclusions:
- Circulating NBT-positive PMN count serves as a singular index for predicting the trend toward irreversibility in hemorrhagic shock.
- Early detection of elevated NBT-positive PMNs may indicate a poorer prognosis in shock.
- The timing and magnitude of PMN activation are critical determinants of survival in hemorrhagic shock.

