Abstract

Background: After severe injury, optical measures of microvascular blood flow (MBF) decrease and do not normalize with resuscitation to normal blood pressure. These changes are associated with organ dysfunction, coagulopathy, and death. However, the pathophysiology is not well understood. Several possible pathways could also contribute to the development of trauma-induced coagulopathy (TIC). A small-animal model of trauma-related MBF derangement that persists after resuscitation and includes TIC would facilitate further study. Parametric contrast-enhanced ultrasound (CEUS) is particularly advantageous in this setting, because it noninvasively assesses MBF in large, deep vascular beds. We sought to develop such a model, measuring MBF with CEUS. Methods: Sixteen male Sprague-Dawley rats were anesthetized, ventilated, and cannulated. Rats were subjected to either no injury (sham group) or a standardized polytrauma and pressure-targeted arterial catheter hemorrhage with subsequent whole blood resuscitation (trauma group). At prespecified time points, CEUS measurements of uninjured quadriceps muscle, viscoelastic blood clot strength, and complete blood counts were taken. Results: After resuscitation, blood pressure normalized, but MBF decreased and remained low for the rest of the protocol. This was primarily driven by a decrease in blood volume with a relative sparing of blood velocity. Viscoelastic blood clot strength and platelet count also decreased and remained low throughout the protocol. Conclusion: We present a rat model of MBF derangement in uninjured skeletal muscle and coagulopathy after polytrauma that persists after resuscitation with whole blood to normal macrohemodynamics. Parametric CEUS analysis shows that this change is primarily due to microvascular obstruction. This platform can be used to develop a deeper understanding of this important process.

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