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.
Endothelium-dependent relaxation is resistant to inhibition of nitric oxide synthesis, but sensitive to blockade of calcium-activated potassium channels in essential hypertension
