AJP - Heart and Circulatory Physiology, Vol 248, Issue 3 324-H330, Copyright © 1985 by American Physiological Society
Negative chronotropic and parasympatholytic effects of alinidine on canine sinus node and AV junction
G. R. Hageman, B. H. Neely, F. Urthaler and T. N. James
The direct effects of alinidine (N-allyl-clonidine) on the sinus node and
atrioventricular (AV) junction were studied in 18 anesthetized dogs.
Stimulus frequency-response curves to right stellate ganglion and right
cervical vagus stimulations as well as responses to norepinephrine or
acetylcholine were determined before and after selective perfusion of
alinidine into the sinus node artery. Alinidine (1 microgram/ml) had no
effect on spontaneous sinus rate [148 +/- 5 (SE) beats/min]. However,
alinidine concentrations of 5, 10, and 25 micrograms/ml produced
significant (P less than 0.05) sinus slowing to 138, 127, and 121
beats/min, respectively. Recovery to control rate was dose dependent and
took from 4 to 33 min. Sinus rate increases with right stellate
stimulations were not affected by alinidine. However, sinus rate decreases
with right vagal stimulations were significantly (P less than 0.01)
attenuated by alinidine. The negative chronotropic effects of acetylcholine
were not influenced by alinidine. Alinidine (1-100 micrograms/ml into AV
node artery) had no effect on the A-H interval of the His bundle
electrogram. However, alinidine (10 and 25 micrograms/ml) diminished the AV
block produced by stimulation of the left vagus in electrically paced
hearts but not the negative dromotropic actions of directly administered
acetylcholine. Thus alinidine has direct negative chronotropic effects, no
effect on sinus node responses to sympathetic stimulation, ability to
diminish sinus node and AV junctional responses to vagal stimulations
without interference at the cholinergic muscarinic receptor, and 4) no
effect on AV nodal conduction.
