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ANESTHETIC PHARMACOLOGY

The Dose-Dependent Effects of Fentanyl on Rat Skeletal Muscle Microcirculation In Vivo

Section of Surgical and Anesthetic Sciences, Division of Clinical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kingdom

Address correspondence and reprint requests to Charles S. Reilly, MD, Section of Surgical and Anesthetic Sciences, Division of Clinical Sciences, University of Sheffield, Royal Hallamshire Hospital, Sheffield S10 2JF, UK. Address e-mail to c.s.reilly{at}sheffield.ac.uk

Determining the effects of analgesia on the microcirculation is difficult because the surgery needed to allow in vivo observation often requires anesthesia. In this study, we used the dorsal microcirculatory chamber (DMC) to determine the effects of large (LF) and small (SF) dose IV fentanyl on the microcirculation compared with a conscious control. Male Wistar rats (130 g, n = 5) were implanted with the DMC to enclose a single layer of striated muscle. Animals were allowed 3 wk to recover from surgery and then, over the following 2 wk (1 infusion/wk) using intravital microscopy, the microcirculation was viewed in conscious animals (t = 0–30 min), followed by an induction bolus dose (t = 40–45 min), then a "step-up" maintenance infusion of one of the following, LF (40–90 µg · kg^-1 · h^-1), SF (10–60 µg · kg^-1 · h^-1), or saline (5–10 µg · kg^-1 · h^-1) (t = 45–105 min). Small arterioles (<30 µm) dilated (23.6% ± 7.1%) after induction with LF, but constricted (-21.3% ± 7.1%) with SF (P < 0.05). During maintenance, constriction increased with increasing dose of LF (-21.9% ± 4.0%) and SF (-16.7% ± 9.1%) (t = 105 min, P < 0.05). Similar patterns were observed in all arterioles (10–120 µm) and venules (15–250 µm). We conclude that the DMC provides an excellent technique for observing microcirculatory responses to fentanyl, and in rat skeletal muscle in vivo, an IV infusion of fentanyl produces significant constriction of arterioles.

IMPLICATIONS: Fentanyl is used as a pain killing drug during surgery, but its effects on small blood vessels are uncertain. We implanted chambers into a skin flap in rats to study skeletal muscle microcirculation. Fentanyl caused a decrease in blood vessel diameter that could potentially reduce blood flow to tissues during surgery.

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