Increases in coronary collateral blood flow produced by sevoflurane are mediated by calcium-activated potassium (BKCa) channels in vivo.
BACKGROUND
Sevoflurane enhances coronary collateral blood flow independent of adenosine triphosphate-regulated potassium channels. The authors tested the hypothesis that this volatile anesthetic increases coronary collateral blood flow by either opening calcium-activated potassium channels or by directly stimulating nitric oxide synthesis in the canine coronary collateral circulation.


METHODS
Twelve weeks after left anterior descending coronary artery ameroid constrictor implantation, barbiturate-anesthetized dogs (n = 22) were instrumented for measurement of hemodynamics and retrograde coronary flow. Dogs received sevoflurane ([0.5 and 1.0 minimum alveolar concentration [MAC]) during intracoronary infusions of drug vehicle (0.9% saline), the calcium-activated potassium channel antagonist iberiotoxin (13 microg/min), or the nitric oxide synthase inhibitor -nitro-l-arginine methyl ester (l-NAME, 300 microg/min). Retrograde coronary collateral blood flow was measured under baseline conditions, during and after administration of sevoflurane, and during intracoronary infusion of bradykinin. Data are mean +/- SEM.


RESULTS
Sevoflurane increased (* < 0.05) retrograde coronary collateral blood flow (from 65 +/- 11 during control to 67 +/- 12* and 71 +/- 12* ml/min during 0.5 and 1.0 MAC, respectively). Iberiotoxin but not l-NAME attenuated these sevoflurane-induced increases in retrograde flow (6 +/- 1*, 7 +/- 2*, and 3 +/- 2 ml/min during vehicle, l-NAME, and iberiotoxin, respectively). After discontinuation of sevoflurane, retrograde flow returned to baseline values in each group. Bradykinin increased retrograde flow in vehicle- (63 +/- 12 to 69 +/- 12* ml/min) but not in iberiotoxin- (61 +/- 7 to 62 +/- 5 ml/min) or l-NAME-treated dogs (64 +/- 11 to 63 +/- 10 ml/min).


CONCLUSIONS
The results demonstrate that sevoflurane increases coronary collateral blood flow, in part, through activation of calcium-activated potassium channels. This action occurs independent of nitric oxide synthesis.
Kehl
Franz
F
Department of Anesthesiology, the Medical College of Wisconsin and the Zablocki VA Medical Center, Milwaukee 53226, USA.
Krolikowski
John G
JG
Tessmer
John P
JP
Pagel
Paul S
PS
Warltier
David C
DC
Kersten
Judy R
JR
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003097:Collateral Circulation / Q000187:drug effects*; D003251:Constriction, Pathologic / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008738:Methyl Ethers / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000502:physiology*; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D024681:Potassium Channels, Calcium-Activated; D000077149:Sevoflurane; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester