Shigetoshi Chiba

Muscarinic suppression of the nicotinic action of acetylcholine on the isolated, blood-perfused atrium of the dog

Summary1.The isolated canine right atrium perfused through the sinus node artery at a constant pressure of 100 mm Hg with blood led from a support dog was suspended in a bath filled with blood and kept at constant temperature. This preparation maintained its constant tension development and rate over 5 hrs in all 5 control experiments.2.A relatively small amount of acetylcholine (ACh) induced a negative inotropic effect at 0.01 μg and a negative chronotropic effect at 0.1 μg.3.A relatively large dose of ACh induced a biphasic inotropic response, i.e., initially a negative inotropic response and secondarily a long-lasting positive one (LPIR) in a spontaneously beating preparation and even in the paced preparation.4.The LPIR to ACh was not inhibited by propranolol, tetrodotoxin or hexamethonium. However, the LPIR disappeared after treatment with physostigmine.5.In atropine-treated preparations, ACh caused a rapid positive chronotropic and inotropic response. These positive chronotropic and inotropic responses were abolished by propranolol, hexamethonium or tetrodotoxin.6.In the papillary muscle and atrial muscle preparations isolated from one canine heart, ACh caused negative and positive inotropic effect in both paced papillary and atrial muscle preparations. In contrast to the results obtained with atria, the positive inotropic response of the papillary muscle preparation was completely blocked by treatment with propranolol or tetrodotoxin.7.From these results, it is suggested that in the canine atrium muscarinic mechanisms predominate over nicotinic ones. This may well be due to the known inhibition of nicotinic responses by stimulation of muscarinic receptors.

Comparison of β-adrenergic blocking activity of eight blockers in the excised and blood-perfused canine sino-atrial node preparation

Mit neu ausgebauter Methode sind 8 ältere und neuere β-Blocker auf ihre Eigenwirkung und ihre Wirksamkeit als Noradrenalin-Antagonisten geprüft worden. Die abgestuften Wirksamkeitszahlen sind: Kö1366 (20)>Pindolol (10)>C-3 (5)>YB-2=Y-6124 (3)>Propranolol (1)>Practolol (2/3)>Sotalol (1/3).

Inhibition of the negative chronotropic action of adenosine by caffeine in the dog.

Abstract The sinus node artery was perfused in situ in 15 dogs. Injection of adenosine into the sinus node artery induced a negative chronotropic effect at doses of 1, 3 and 10 μg. The negative chronotropic response to adenosine was blocked by 300 μg to of caffeine given into the same artery. On the contrarym, the negative chronotropic response to ACh was not inhibited but rather enhanced by caffeine, so that the atrial fibrillation threshold to ACh was lowered. Neither norepinephrine nor calcium when injected into the sinus node artery inhibited the deceleration response to adenosine.

Beta-adrenergic blocking effect of dichloroisoprenaline (DCI), (H 56/28, I.C.I. 50172, LB 46), methoxamine (MJ 1999) and propranolol on the sinus node activity of the dog heart

Der Hemmungseffekt siebenΒ-adrenergischer Blockierungsmittel auf positive chronotrope Wirkung bei zunehmender Dosierung von Isoprenalin wurde durch Verabreichung in die Sinusknotenarterie vergleichend untersucht. Reihenfolge der Wirksamkeit: LB 46, H 56/28, Propranolol>I.C.I. 50172, DCI>MJ 1999>Methoxamin.

Effects of catecholamines on the AV nodal pacemaker in situ after destroying the SA node

Abstract Perfusion of the AV node artery in 15 dogs was performed in situ. After destroying the SA node by selective injection of ethanol into the sinus node artery, administration of catecholamines (dopamine, norepinephrine, epinephrine and isoproterenol) into the sinus node artery produced an acceleration of AV nodal rhythm. During the course of recovery, a sudden deceleration or oscillatory change in the AV nodal rhythm was usually observed. This change was not influenced by treatment with atropine, tetrodotoxin or phenoxybenzamine, while both the acceleration and the postaccelerator change were completely blocked by propranolol. These results suggest that postaccelerator changes, i.e., deceleration or oscillation of the AV nodal rhythm, are characteristics of the AV nodal pacemaker itself.

Pharmacological analysis of chronotropic responses of the S-A node to caffeine

Abstract The sinus node artery was perfused in situ in 12 dogs. Selective administration of caffeine into the sinus node artery produced double peaked positive chronotropic responses, i.e., initial rapid acceleration of the sinus rhythm followed by slow but long-lasting acceleration. The initial positive chronotropic response to caffeine was not suppressed by treatment with a β-adrenergic blocking agent, propranolol or H 56/28, or by treatment with tetrodotoxin whereas these substances effectively blocked the secondary positive chronotropic response. It is suggested that the initial positive chronotropic response to caffeine is a direct effect on the S-A node and the secondary positive response is due to catecholamine release from adrenergic nerve terminals by excitation of nerve fibers.

Blocking effect of McN-A-343 on cardiac slowing produced by vagal stimulation

The effect of McN-A-343 was studied by direct administration into the sinus node artery of dogs vagotomized at the mid-cervical level. McN-A-343 blocked sinus bradycardia caused by electrical stimulation of the right vagus, while bradycardia induced by administration of acetylcholine or nicotine into the sinus node artery was not modified.