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CARDIOVASCULAR ANESTHESIA

Dilation by Isoflurane of Preconstricted, Very Small Arterioles from Human Right Atrium Is Mediated in Part by K+-ATP Channel Opening

Kyung W. Park, MD^*, Hai B. Dai, MD, Mark E. Comunale, MD^*, Alok Gopal, MD^*, and Frank W. Sellke, MD

Departments of *Anesthesia and Critical Care and Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Address correspondence and reprint requests to Kyung W. Park, MD, Department of Anesthesia & Critical Care, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215. Address e-mail to kpark{at}caregroup.harvard.edu

The adenosine triphosphate (ATP)-sensitive potassium channels (K⁺-ATP channels) are activated by decreases in intracellular ATP and help to match blood flow to tissue needs. Such metabolism-flow coupling occurs predominantly in the smallest arterioles measuring 50 µm or less in diameter. Previous studies demonstrated that isoflurane may activate the K⁺-ATP channels in larger arteries. We examined whether isoflurane also activates the channels in the smallest arterioles of ~50 µm. Microvessels of ~50 µm were dissected from right atrial appendages from patients undergoing coronary artery bypass surgery and were monitored in vitro for diameter changes by videomicroscopy. With or without preconstriction with the thromboxane analog U46619 1 µM, vessels were exposed to isoflurane 0%–3% either in the presence or absence of the K⁺-ATP channel blocker glibenclamide 1 µM. Without preconstriction, isoflurane neither dilated nor constricted the vessels significantly. After preconstriction, isoflurane had a concentration-dependent dilation of the small arterioles (39 ± 13% [mean ± SD] dilation at 3% isoflurane) (P < 0.001), and this effect was significantly attenuated by glibenclamide (18 ± 5% dilation at 3% isoflurane) (P < 0.01). In comparison, nitroprusside 10^-4 M produced 79 ± 6% dilation, and adenosine diphosphate 10^-4 M produced 29 ± 7% dilation. We conclude that isoflurane-mediated dilation of the smallest resistance arterioles may be in part based on activation of the K⁺-ATP channels when the arterioles are relatively constricted.

Implications: Vasodilation of very small coronary arterioles by isoflurane depends on preexisting tone and may in part be mediated by the K⁺-ATP channels.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999