Mechanisms of Volatile Anesthetic-Induced Coronary
Vasodilation
Volatile anesthetics produce direct coronary artery relaxation
by affecting intracellular Ca2+
regulation at several locations in the
vascular smooth muscle cell.[236]
Volatile agents
inhibit Ca2+
influx through voltage-operated[235]
and receptor-operated[227]
[228]
[232]
[233]
[264]
Ca2+
channels in coronary vascular smooth muscle. Volatile agents also
reduce Ca2+
accumulation in, and release by, the coronary vascular smooth
muscle SR,[265]
inhibit G proteins linked to phospholipase
C,[264]
and decrease formation of the second messenger
inositol triphosphate.[266]
The coronary vasodilating actions of volatile agents probably
are not related to the production or release of nitric oxide (i.e., endothelium-dependent
relaxing factor). Investigations conducted in isolated coronary[234]
and aortic[265]
[267]
[268]
[269]
vascular
preparations and in the intact canine coronary circulation[253]
demonstrated that volatile anesthetic-induced coronary vasodilation occurs independent
of nitric oxide. However, some experimental evidence suggests that the direct coronary
vasodilator effects of isoflurane may be mediated by the vascular endothelium.[227]
[270]
Other data indicate that halothane, enflurane,
and isoflurane may adversely affect the release or action of nitric oxide.[267]
[268]
[269]
[271]
[272]
Although nitric oxide-induced formation of
cyclic guanylate monophosphate (cGMP) may be attenuated to some degree by halothane,
[273]
several studies indicate that volatile anesthetics
do not affect vasodilation produced by the nitric oxide donors sodium nitroprusside
or nitroglycerin.[268]
[272]
[274]
[275]
Volatile
anesthetics may also reduce the stability of nitric oxide by generating oxygen-derived
free radicals[275]
while leaving nitric oxide release
and its action on vascular smooth muscle unaffected.[271]
Whether the results of these later studies conducted in isolated aortic preparations
are applicable to the coronary circulation requires further evaluation, but these
investigations provide important information about the potential effects of volatile
agents on the coronary vasculature.
Halothane and isoflurane cause coronary vasodilation by activation
of adenosine triphosphate (ATP)-sensitive potassium (KATP
) channels.[276]
[277]
Increases in coronary blood flow in response
to halothane and isoflurane were attenuated by the KATP
channel antagonist
glyburide in isolated rat hearts and anesthetized pigs, respectively.[276]
[277]
Glyburide also partially blocked increases
in coronary blood flow during intracoronary administration of volatile anesthetic-equilibrated
blood in canine hearts in situ.[278]
Isoflurane-induced
reductions in coronary vascular resistance were attenuated by the selective adenosine1
(A1
)-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX).[279]
These data suggest that coronary vasodilation produced by isoflurane may partially
occur as a result of stimulation of A1
receptors coupled to KATP
channels.[279]
[280]
