Muscarinic and ganglionic blocking properties of atropine compounds in vivo and in vitro: time dependence and heart rate effects.
High doses (3 mg/kg) of methylatropine nitrate have been used in vivo to produce long-lasting muscarinic blockade during physiologic experiments. At these levels, the possibility exists that ganglionic blockade may also be responsible for some heart rate effects. Therefore, the effects of methylatropine nitrate (0.0012-2.4 mg.kg(-1)) and atropine sulfate (0.0036 - 0.060 mg.kg(1)) were evaluated in vivo using conscious dogs and in vitro using canine right atria and isolated stellate ganglia. The lowest doses of either agent given in vivo caused bradycardia, while intermediate doses induced excess tachycardia. High doses of methylatropine nitrate transiently decreased the heart rate, followed by slow recovery. In vitro using the canine right atria, neither drug caused pacemaker shifts nor directly altered the atrial rate, but postvagal tachycardia occurred with acetylcholine challenge and was prevented by metoprolol or 6-hydroxydopamine. In vitro studies using the canine stellate ganglia indicate that both agents depressed postganglionic compound action potentials at high doses. In conclusion, with high-dose methylatropine nitrate, ganglionic blockade yields the mechanism for a reduction of excess tachycardia as well as a likely explanation for opposing chronotropic effects in conscious and anesthetized dogs. In experimental studies where high doses of atropine compounds are used for long-term muscarinic blockade, it is possible that ganglionic blocking effects may also be produced.
Vicenzi
M N
MN
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Woehlck
H J
HJ
Boban
M
M
McCallum
B
B
Atlee
J L
JL
Bosnjak
Z J
ZJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D001286:Atropine Derivatives / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005730:Ganglionic Blockers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D013233:Stellate Ganglion / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D013997:Time Factors
D001286:Atropine Derivatives; D005730:Ganglionic Blockers; D018727:Muscarinic Antagonists; D001285:Atropine; C006649:methylatropine