La. Turner et al., A SUBTYPE OF ALPHA(1) ADRENOCEPTOR MEDIATES DEPRESSION OF CONDUCTION IN PURKINJE-FIBERS EXPOSED TO HALOTHANE, Anesthesiology, 82(6), 1995, pp. 1438-1446
Background: An action of epinephrine at or adrenoceptors has been repo
rted to slow conduction In Purkinje fibers exposed to halothane.In Pur
kinje fibers one pharmacologically distinguishable alpha(1)-adrenocept
or subtype (alpha(IB)) sensitive to the noncompetitive antagonist chlo
roethylclonidine mediates decreases in automaticity Another alpha(1) s
ubtype (alpha(1A)), sensitive to the competitive antagonist WB4101, in
creases spontaneous rate and action potential duration by a mechanism
thought to involve hydrolysis of membrane phosphoinositides by phospho
lipase C, This study examined the dose-response relation and receptor-
effector mechanisms underlying depression of conduction in canine Purk
inje fibers by epinephrine with halothane. Methods: Conduction velocit
y was determined in vitro by measuring the conduction time between act
ion potentials recorded from two Purkinje fibers located about 6 mm ap
art along the length of free running portions of the ventricular condu
ction system, the false tendons. Velocity was evaluated at 1-min inter
vals during trials of rapid exposure to different agonists in groups o
f 6-12 preparations. Results: Epinephrine (0.2-5.0 mu M) transiently d
ecreased Purkinje conduction velocity in a dose-related manner by as m
uch as 33% (at 5 mu M epinephrine with 0.86 mM (2.8%) halothane). Velo
city decreased by 5% (P less than or equal to 0.01) at an epinephrine
concentration similar to ''just-threshold'' dysrhythmogenic plasma epi
nephrine concentrations (0.2 mu M epinephrine with 0.46 mM halothane)
reported in halothane anesthetized dogs. The decreases of conduction v
elocity were blocked by prazosin but not by metoprolol, were produced
by phenylephrine but not by clonidine, and were antagonized by equimol
ar (0.5 mu M) concentrations of WB4101 more so (P less than or equal t
o 0.01) than by chloroethylclonidine. WB4101 (0.1 mu M) produced 87% i
nhibition of the response to 0.2 mu M epinephrine after chloroethylclo
nidine pretreatment, indicating mediation by the alpha(1A) subtype, Ot
her agonists linked to cardiac phospholipase C activation, including e
ndothelin 1 (40 nm) and the muscarinic agonist carbamylcholine (1 mM),
also decreased conduction velocity in fibers exposed to halothane. Co
nclusions: Clinically relevant concentrations of epinephrine transient
ly depress conduction in Purkinje fibers exposed to halothane by activ
ating cardiac alpha(1) adrenoceptors, largely but not exclusively the
WB4101-sensitive alpha(1A) subtype, reportedly coupled to stimulation
of phospholipase C and generation of the second messengers diacylglyce
rol and inositol trisphosphate. anesthetic potentiation of cardiac alp
ha(1)-adrenoceptor effects may contribute to the generation of halotha
ne-epinephrine dysrhythmias by abnormally slowing conduction and facil
itating reentry.