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Sevoflurane Decreases Expression of ICAM-1 Antigens on Polymorphonuclear Leukocytes in Rats
John K. Hayes, Ph.D.; Roman V. Plachinta, M.D.; Yonghua Zhang, M.D.; Bradford D. Hare, M.D., Ph.D.
Anesthesiology, University of Virginia, Charlottesville, Virginia, United States
The general cardiovascular effects of sevoflurane (SEVO) are well known. However, SEVO effects on the microcirculation and leukocyte dynamics (i.e., rolling and adherence phenomenon) are not well understood. Rolling and adherence of leukocytes are mediated through P-Selectin and intracellular adhesion molecule 1 (ICAM-1) [1, 2]. Accumulation of adherent leukocytes onto the endothelium may affect microcirculatory hemodynamics, flow characteristics and influence leukocyte dependent organ or immune system injury [3]. The purpose of this study was to determine whether exposing rats to 1.5 MAC SEVO for 3 hrs increased the expression of P-Selectin and ICAM-1 antigens on the surface of leukocytes.

Methods: After IACUC approval, rats (n=14, 293 ± 34 g) were induced with SEVO and oxygen in a closed chamber. Afterwhich, a tracheostomy tube was inserted for artificial ventilation (rate: 60-70 breaths/min, tidal volume: 1.0 ml/100 g body weight) and immediately a control blood sample (0.4 ml) was obtained from the carotid artery and labeled with antibodies (see below). The rat was maintained at 37 ± 1°C and ventilated with a mixture of 1.5 MAC SEVO and oxygen for 3 hrs. The expired gas concentration (oxygen, carbon dioxide and SEVO) was monitored continuously using an infrared multi-gas analyzer. After 3 hrs, the abdominal cavity was opened and 1 ml of blood was withdrawn from the inferior vena cava (IVC). The withdrawn blood (carotid and IVC) was labeled with fluorochrome conjugated-monoclonal and polyclonal antibodies that bind specifically to P-Selectin and ICAM-1 cell surface antigens. The treated whole blood was lysed to remove erythrocytes while preserving the leukocytes, then washed twice to remove excess antibody and debris. Polymorphonuclear (mono- and granulo-) leukocytes were then analyzed using flow cytometry.

Results: The percentage of gated leukocytes expressing ICAM-1 on their cell surface decreased significantly (P<0.05) following 3 hrs of SEVO anesthesia from 60.3 ± 9.0 to 36.3 ± 7.7 (-39.8%). This decrease was mostly due to a reduction in ICAM-1 expression on granulocytes. The percentage of gated leukocytes expressing P-Selectin was not significantly different after 3 hrs of SEVO when compared to polymorphonuclear leukocytes from control blood (27.7 ± 13.13 and 22.17 ± 20.73, respectively).

Conclusion: Rats exposed to 3 hrs of 1.5 MAC SEVO showed a decreased expression of ICAM-1 on the surface of their leukocytes. P-Selectin expression on leukocytes was unchanged from control blood. However, further studies are required to determine whether the decreased expression of ICAM-1 on leukocytes following SEVO administration is consistant with preserving blood flow and microcirculatory hemodynamics.


1. Morisaki H, et al. Anesthesiology 87:591-8, 1997.

2. Yoshia K, Okabe E. Aneshesiology 76:440-7, 1992.

3. Suzuki M, et al. Microvasc Res 42:125-38, 1991.

Anesthesiology 2001; 95:A641