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Increased platelet microvesicle formation is associated with mortality in a porcine model of endotoxemia
M Eriksson1, D Nelson, A Nordgren
1Department of Anesthesiology & Intensive Care, University Hospital, Uppsala, Sweden.
Background:
Gram-negative sepsis in humans and endotoxemia in pigs induce the formation of platelet microvesicles. These microvesicles are active in homeostasis and may thus contribute to the outcome in patients with activated coagulation and fibrinolysis. We decided to prospectively evaluate the effects of endotoxemia on microvesicle formation and some common physiologic variables against survival in a porcine model.
Methods:
Nineteen included pigs were anesthetized, monitored and subjected to an infusion of E. coli endotoxin. Microvesicle formation was determined by flow cytometry.
Results:
The formation of microvesicles was significantly increased in the 6 pigs that died during endotoxin exposure. This increased formation became significant from the 3rd hour of endotoxemia. Microvesicle formation did not increase in surviving endotoxemic pigs. Cardiac index, mean arterial blood pressure, base excess and systemic vascular resistance index were distinctly reduced in the animals that died as compared to those surviving the endotoxemic period.
Conclusion:
The increased formation of platelet microvesicles seems to be associated with poor prognosis in porcine endotoxemia. Since microvesicles are active in coagulation, they may contribute to the derangement of the coagulation system caused by endotoxemia. Different degrees of microvesicle formation may reflect inter-individual responses to a given challenge.
Insights
Increased platelet microvesicle formation during endotoxemia in pigs is linked to a higher risk of death. This finding suggests microvesicles may play a role in sepsis outcomes.
Area of Science:
- Sepsis research
- Hemostasis and thrombosis
Background:
- Gram-negative sepsis and endotoxemia trigger platelet microvesicle formation.
- Platelet microvesicles are involved in hemostasis and may influence outcomes in activated coagulation and fibrinolysis.
Purpose of the Study:
- To prospectively evaluate the impact of endotoxemia on microvesicle formation.
- To assess the relationship between microvesicle formation, physiological variables, and survival in a porcine model.
Main Methods:
- Nineteen pigs were anesthetized and monitored.
- An infusion of E. coli endotoxin was administered.
- Microvesicle formation was quantified using flow cytometry.
Main Results:
- Pigs that died during endotoxin exposure showed significantly increased microvesicle formation starting from hour 3.
- Surviving pigs did not exhibit increased microvesicle formation.
- Died animals displayed reduced cardiac index, mean arterial blood pressure, base excess, and systemic vascular resistance index compared to survivors.
Conclusions:
- Elevated platelet microvesicle formation appears to correlate with a poor prognosis in porcine endotoxemia.
- Microvesicles may contribute to coagulation system derangements in endotoxemia.
- Variations in microvesicle formation could indicate differing individual responses to endotoxin challenge.