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

Abstract

1. 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 filed 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 mug and a negative chronotropic effect at 0.1 mug. 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 tropic 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.

Chronotropic responses to large doses of adenosine and ATP in dog isolated atria.

“…Therefore, it was difficult to detect drug-induced changes in heart rate in his study (1,2). In the present experiments, the volume of injection was made small (0.01-0.03 ml) so that the chronotropic effects of adenosine and ATP could be investigated in the isolated and blood perfused atrial preparation developed by Chiba et al (4,5). The perfusion pressure was fixed at 100 mm Hg by means of a constant perfusion pressure system con sisting of a Starling resistance and a pump.…”

“…The details of the preparation are described in previous papers (4,5 brief phase of the positive chronotropic effect followed by a little longer phase (Fig. 1).…”

Cardiovascular effects of dobutamine, dopamine and isoproterenol on the whole animal and isolated cross-perfused atrium in dogs.

“…Atrial rate and isometric tension development of the isolated atrium and systemic blood pressure and heart rate of the donor dog were simultaneously measured during the experiments. The details of the preparation are described in previous papers (4,5).…”

“…However, no report is available concerning the effect of dobutamine assessed in isolated dog heart preparations. Thus, in the present study, we attempted to compare chronotropic and inotropic effects of dobutamine, dopamine and isoproterenol using the isolated dog atrial preparation which was perfused with the arterial blood of the donor dog (4,5). We administered these three catecholamines intravenously to the donor dog or intraarterially to the isolated atrium to observe their direct cardiac chrono tropic and inotropic effects and probable modification of these effects by extracardiac factors.…”

Effect of Diltiazem on the Membrane Potential of Uterine Smooth Muscle

“…However, even in the in situ SA node preparations, a complete isolation from extracardiac factors which may influence pacemaker activity of the SA node via neurogenic reflexes is most difficult to attain. Recently Chiba et al (5,6) developed a completely isolated, blood…”