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.