Plasma resuscitation restores damage to endothelial glycocalyx after hemorrhagic shock

Anesthesia & AnalgesiaJun 1 2011

Using plasma rather than standard resuscitation fluids seems to improve survival in trauma patients with massive blood loss. Now a new study in animals suggests that this benefit may result from plasma's ability to restore the "endothelial glycocalyx," a special layer lining the blood vessels, reports the June issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

Dr. Rosemary A. Kozar of University of Texas Health Science Center at Houston conducted a study in rats to find out how plasma resuscitation affects the endothelial glycocalyx—a coating that lines and protects the integrity of endothelial cells and blood flow within blood vessels. Recent studies have found the glycocalyx performs a number of important functions, including protecting the blood vessel wall from inflammation-promoting factors in blood.

Plasma Infusion Restores Damage to Glycocalyx Caused by Hemorrhagic Shock
In the experiments, rats were subjected to hemorrhagic shock, then resuscitated with electrolyte solutions or with plasma—the liquid portion of blood (ie, with the blood cells removed). Consistent with recent epidemiologic studies in human trauma patients, plasma appeared more effective than standard fluid in resuscitating the rats from hemorrhagic shock, and helped to reverse evidence of lung damage that accompanies shock.

The researchers took a close look at how the endothelial glycocalyx was affected during the experiments. Electron microscope images showed that hemorrhagic shock caused a sharp reduction in the thickness of the glycocalyx—it was basically stripped away. This damage was little affected by resuscitation with standard fluids.

However, in animals receiving plasma resuscitation, the damage to the glycocalyx was largely restored within a few hours. The plasma-resuscitation group also showed higher levels of messenger RNA for syndecan—a protein that forms the "backbone" of the glycocalyx.

"Taken together, our findings support the protective effects of plasma seen clinically, which may be due in part to its ability to restore the endothelial glycocalyx and preserve syndecan-1 after hemorrhagic shock," Dr. Kozar and coauthors conclude. Although the results of animal studies may not directly apply to the human situation, they provide an important clue as to how plasma resuscitation works to improve outcomes in trauma patients.

An accompanying editorial by Dr. Marie Csete of iFluidics and  the University of California, San Diego, sets the results in the context of the "Great Fluid Debate"—the ongoing controversy among anesthesiologists as to the best approach to fluid resuscitation in critically ill patients. While the study raises many new questions, "It does point to syndecan-1 and the glycocalyx as a whole as potential targets of therapies in shock patients," according to Dr. Csete.

"The rapid time course of reversal of the cellular pathologies by plasma resuscitation was particularly striking, but also may indicate a short therapeutic window for optimal resuscitation," Dr. Csete adds. She calls for further studies to see whether syndecan-1 (which coordinates signals from outside cells to the inside of cells) and other glycocalyx components could be used as markers of severity of injury, and potentially markers of the adequacy of resuscitation for patients with massive blood loss.