Elsevier

Resuscitation

Volume 83, Issue 6, June 2012, Pages 715-720
Resuscitation

Clinical paper
Perturbation of the endothelial glycocalyx in post cardiac arrest syndrome

https://doi.org/10.1016/j.resuscitation.2012.01.028Get rights and content

Abstract

Background

The prognosis of immediate survivors of cardiac arrest remains poor, as the majority of these patients develops an inflammatory disorder known as the post-cardiac arrest syndrome (PCAS). Recently, the endothelial glycocalyx has been shown to be a key modulator of vascular permeability and inflammation, but its role in PCAS remains unknown.

Methods

Plasma levels of the glycocalyx components syndecan-1, heparan sulfate and hyaluronic acid were measured in 25 patients after immediate survival of cardiac arrest during different phases of PCAS. Twelve hemodynamically stable patients with acute coronary syndrome served as controls.

Results

Cardiac arrest resulted in a significant increase in syndecan-1, heparan sulfate and hyaluronic acid levels compared to controls, indicating a shedding of the endothelial glycocalyx as a pathophysiological component of the post cardiac arrest syndrome. The time course differed between the individual glycocalyx components, with a higher increase of syndecan-1 in the early phase of PCAS (2.8-fold increase vs. controls) and a later peak of heparan sulfate (1.7-fold increase) and hyaluronic acid (2-fold increase) in the intermediate phase. Only the plasma levels of syndecan-1 correlated positively with the duration of CPR and negatively with the glycocalyx-protective protease inhibitor antithrombin III. Plasma levels of both syndecan-1 and heparan sulfate were higher in eventual non-survivors than in survivors of cardiac arrest.

Conclusion

Our data for the first time demonstrates a perturbation of the endothelial glycocalyx in immediate survivors of cardiac arrest and indicate a potential important role of this endothelial surface layer in the development of post-cardiac arrest syndrome.

Introduction

Morbidity and mortality following initial survival of cardiac arrest remain high despite great efforts to improve resuscitation techniques and post-resuscitation care.1 Approximately 70% of patients admitted to the intensive care unit after out of hospital cardiac arrest die before discharge. Among the survivors, only 68% of adults and 58% of children had a good neurological outcome, defined as a cerebral performance category score of 1 (good cerebral performance) or 2 (moderate cerebral disability).2 This high mortality rate of patients with an initial return of spontaneous circulation (ROSC) is in part due to a specific pathophysiological process known as the post-cardiac arrest syndrome (PCAS). This term basically describes a global ischemia-reperfusion injury in response to whole-body ischemia and successful resuscitation. The four major clinical manifestations of PCAS are (1) neurological injury, (2) myocardial dysfunction, (3) the systemic ischemia-reperfusion response that can evolve into multiple organ failure and (4) the persistent precipitating pathology, which is aggravated by the concomitant PCAS.2 On a pathophysiological level, these injuries involve microcirculatory dysfunction,3 vascular leakage with edema formation and an increase in platelet and leukocyte adhesion to the endothelium, resulting in a sepsis-like inflammatory response,2, 4, 5 that can determine the patients outcome.

Recently, the endothelial glycocalyx has been implicated as a key modulator of these processes.6, 7 This endothelial surface layer is a negatively charged mesh of proteoglycans, glycosaminoglycans and glycoproteins that lines the inner surface of all blood vessels and can extend up to several micrometer from the endothelial cell membrane.8 The glycosaminoglycans heparan sulfate and hyaluronic acid constitute two of the major components of the glycocalyx of endothelial cells and syndecan-1 represents the most prevalent proteoglycan.9 These structures are important modulators of vascular permeability, leukocyte adhesion, mechanotransduction and the endothelial inflammatory response.10 The thickness of the glycocalyx layer is dependent on the balance of biosynthesis and rapid shedding in response to multiple stressors such as ischemia, redox stress, hyperglycemia and alterations in shear forces.9

Since cardiac arrest and resuscitations induces both glycocalyx degrading stressors and potentially glycocalyx-dependent endothelial responses,4 we here investigated the shedding of the three glycocalyx components heparan sulfate, hyaluronic acid and syndecan-1 during the early and the intermediate phase of post-cardiac arrest syndrome. We provide the first evidence of glycocalyx perturbation as a potential pathologic component after cardiac arrest and describe how the extent of glycocalyx damage relates to clinical parameters and survival.

Section snippets

Patient recruitment

The study was approved by the ethics committee of our institution and confirms to the tenets of the declaration of Helsinki. 25 patients admitted to our intensive care unit at the University Hospital of Freiburg, Germany after successful resuscitation following out of hospital cardiac arrest were included. Patients admitted after traumatic injury and patients younger than 18 years were excluded.

Informed consent was obtained from the next of kin or retrospectively from the patients that survived

Patient characteristics

The mean age of the CPR patients was 66.2 years (±14.2 years) and there were 72% males. Mean age of the control patients with acute coronary syndrome was not significantly different (68.3 ± 9.4 years), with 75% males (Table 1).

Ventricular fibrillation or ventricular tachycardia were the most common initially detected cardiac rhythms in the CPR patients (n = 18, 72%), whereas 28% suffered from aystole or pulseless electrical activity. The mean estimated time of no-responsiveness (“down time”) before

Discussion

We provide evidence of an increased endothelial glycocalyx perturbation in immediate survivors of cardiac arrest and describe a differential time course of plasma levels for three major glycocalyx components. Our observations for the first time directly implicate the endothelial surface layer as a potential pathophysiological factor in the development of post cardiac arrest syndrome.

The existence of an endothelial surface layer, coating the luminal face of blood vessels was first postulated

Conflict of interest statement

No conflict of interest to declare.

Acknowledgments

The authors thank the staff of the intensive care units I and II of the University Hospital Freiburg for their help in sample and data collection.

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  • Cited by (0)

    A Spanish translated version of the abstract of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2012.01.028.

    a

    These authors contributed equally to the study.

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