A. L. Marinica2, D. M. Liberati1, D. Edelman1, L. N. Diebel1 1Wayne State University,Surgery,Detroit, MI, USA 2Michigan State University,Surgery,Lansing, MI, USA
Introduction:
Morbidly obese patients have impaired responses to resuscitation following severe injury which may contribute to adverse outcomes. Obesity is associated with microvascular dysfunction and metabolic changes leading to altered hemorheological profiles. These include decreased red blood cell (RBC) deformity associated with impaired aggregation and adhesion. The importance of the glycocalyx layer of erythrocytes and the vascular endothelial cells (EC) on microvascular perfusion has been recently recognized. Degradation of either or both glycocalyx layers may impair microvascular perfusion. This was studied from blood obtained from obese patients and also with an in vitro microfluidic device to mimic the microvascular environment under normal and shock conditions.
Methods:
RBC were obtained from fresh whole blood of normal controls and obese patients (BMI 37.6-60.0). RBC glycocalyx degradation was assessed by fluorescent intensity and shedding of endothelial cell glycocalyx (ECG) components was measured by serum syndecan-1 (Syn-1) and hyaluronic acid (HLA). In a second set of experiments, human umbilical vein endothelial cell monolayers (HUVEC) were perfused with RBC suspension from control and obese patients. Then using a microfluidic device, RBC adherence under normoxic or shock conditions (hypoxia (Hyp) + epinephrine) was determined using confocal microscopy.
Results:
RBC glycocalyx thickness and ECG shedding for normal and obese patients are noted in Table 1. ECG thickness was found to be 265.3 ± 19.6 for HUVEC control and was reduced to 143.4 ± 18.5 for the HUVEC+Hyp+Epi group (<0.05). EC Syn-1 shedding was 27.5 ± 2.4 for HUVEC control and was increased to 100.5 ± 9.2 in HUVEC+Hyp+Epi group (p<0.05). EC HLA shedding was 14.8 ±.5 for control and was increased to 98.4 ± 8.2 in HUVEC+Hyp+Epi group (p<0.05). Increased ECG shedding and RBC adherence in the obese cohort are also noted in Table 1.
Conclusion:
Blood from obese patients has decreased RBC glycocalyx thickness accompanied by evidence of increased EC glycocalyx shedding. In vitro adhesion to endothelium was more pronounced with RBC from the obese patients and was significantly greater under “shock conditions” vs. controls. Hemorheological properties of RBC from obese patients may contribute to microvascular perfusion abnormalities under both control and shock conditions. This may account for the noted impaired response to resuscitation following injury in this patient population.
