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ANESTHETIC PHARMACOLOGY

Isoflurane Pretreatment Supports Hemodynamics and Leukocyte Rolling Velocities in Rat Mesentery During Lipopolysaccharide-Induced Inflammation

Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia

Address correspondence and reprint requests to John K. Hayes, PhD, University of Virginia Health System, Department of Anesthesiology, PO Box 800710, Charlottesville, VA 22908-0710. Address e-mail to jkh2n{at}virginia.edu

We hypothesized that the protective effects of isoflurane (ISO) pretreatment on the vasculature may be attributed, in part, to altered leukocyte-endothelial interactions. Rats were anesthetized with pentobarbital and then randomized into four groups: control, ISO-control (pretreatment with 30 min of 1.4% ISO), lipopolysaccharide (LPS; 10 mg/kg IV), and ISO-LPS (ISO pretreatment and then LPS). The mesentery was prepared for intravital videomicroscopy. Mean arterial blood pressure (MAP), along with microcirculatory variables that included postcapillary venular and arteriolar blood flow velocity and leukocyte dynamics (number of rolling and adherent leukocytes and individual rolling leukocyte velocities), were measured hourly (baseline and at 0–4 h). In LPS rats, ISO pretreatment significantly (P < 0.05) attenuated the decrease in MAP at 2 and 4 h after LPS and increased leukocyte rolling velocities after 2–4 h. Four hours after LPS, leukocyte rolling velocities were >200% more rapid (63.7 ± 27.6 µm/s versus 19.8 ± 6.4 µm/s) in ISO-LPS versus LPS rats. In control rats, ISO pretreatment had no effect on MAP or leukocyte rolling velocities but increased the number of rolling leukocytes. ISO pretreatment had no effect on arteriolar and postcapillary venular blood flow velocity in LPS rats or leukocyte adherence in LPS or control rats. In conclusion, ISO pretreatment supported hemodynamics and increased leukocyte rolling velocities but did not alter the number of rolling or adherent leukocytes in the mesenteric microcirculation during LPS-induced inflammation.

IMPLICATIONS: Isoflurane pretreatment supported hemodynamics and increased leukocyte rolling velocities in the mesenteric microcirculation during lipopolysaccharide-induced inflammation. Faster rolling velocities may reduce the incidence of inflammation by decreasing leukocyte-endothelial interactions and cellular injury.

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