Blood-perfused Sinoatrial Node Research Articles

Sphingosine 1-phosphate induces sinus tachycardia and coronary vasoconstriction in the canine heart.

Sphingosine 1-phosphate is a naturally occurring biologically active lysophospholipid. Recent studies suggested that sphingosine 1-phosphate is released into the blood flow from activated platelets upon stimulation to exert multiple biological phenomenon. The purpose of this study was to assess the effects of sphingosine 1-phosphate on sinus automaticity, ventricular contraction and coronary blood flow. The canine isolated, blood-perfused sinoatrial node and papillary muscle preparations were used. Sphingosine 1-phosphate increased the sinoatrial rate, while it decreased the coronary blood flow, which was followed by a weak negative inotropic effect. These positive chronotropic and coronary vasoconstrictor effects were not attenuated by the beta- and alpha-adrenoceptor antagonists atenolol and prazosin, respectively. Furthermore, sphingosine 1-phosphate did not affect the adenylate cyclase activity of the membrane preparations made from the canine right atrium and right ventricle, indicating the involvement of a novel signaling pathway in sphingosine 1-phosphate-induced cardiac effects. These results may provide a clue to better understanding the physiological as well as the pathophysiological regulation of sphingosine 1-phosphate in the heart.

Direct Cardiac Effects of a Novel Vesamicol Receptor Ligand, m-Iodobenzyl-Trozamicol, Assessed in the Canine Isolated, Blood-Perfused Heart Preparations

MIBT, m-(iodobenzyl)trozamicol, is a recently discovered vesamicol analogue that can be used as a functional marker of cholinergic activity in the heart as well as the brain. The purpose of this study was to assess the effects of MIBT on sinus node automaticity, ventricular contraction, and coronary blood flow in addition to the action-potential duration of the ventricle by using canine isolated, blood-perfused sinoatrial node and papillary muscle preparations. Intracoronary administration of MIBT (1-300 microg) exerted negative chronotropic, inotropic, and coronary vasodilator effects in a dose-related manner. Pretreatment of the preparations with the muscarinic receptor antagonist atropine did not change these effects of MIBT. Moreover, MIBT had little effect on the repolarization phase of the ventricular action potential. Because the doses of MIBT needed for imaging cardiac cholinergic function were much lower than those affecting the cardiovascular system, MIBT may be used safely in future clinical applications.

Chronotropic and inotropic effects of kampo extracts in the canine isolated, blood-perfused heart preparations.

Cardiac effects of drugs used for circulatory disorders in traditional Japanese medicine based on ancient Chinese medicine (Kampo Medicine): Saikoka-ryukotsu-borei-to, Oren-gedoku-to, Toki-shakuyaku-san, Shimbu-to, Moku-boi-to, Ryo-kei-jutsu-kan-to, Sha-kanzo-to, Keishi-ninjin-to, Toki-to and Ryo-kan-kyo-mi-shin-ge-nin-to were investigated using canine isolated, blood-perfused sinoatrial node and papillary muscle preparations. Single injections of small doses of Oren-gedoku-to, Moku-boi-to and Ryo-kan-kyo-mi-shin-ge-nin-to (0.1 to 3 mg) dose-dependently increased the sinoatrial rate and the developed tension of papillary muscle, while other drugs showed almost no effect on these parameters. All the drugs had almost no effect on the blood flow through the nutrient arteries of each preparation. The positive chronotropic and inotropic effects induced by Oren-gedoku-to, Moku-boi-to and Ryo-kan-kyo-mi-shin-ge-nin-to did not show tachyphylaxis and were not affected after pharmacological denervation by tetrodotoxin treatment or by reserpine pretreatment, but were significantly suppressed by atenolol. These results indicate that these three drugs act as beta-adrenoceptor agonists to produce clinically useful cardiac effects.

Chronotropic and Inotropic Effects of Kampo Extracts in the Canine Isolated, Blood-Perfused Heart Preparations

Cardiac effects of drugs used for circulatory disorders in traditional Japanese medicine based on ancient Chinese medicine (Kampo Medicine): Saiko-ka-ryukotsu-borei-to, Oren-gedoku-to, Toki-shakuyaku-san, Shimbu-to, Moku-boi-to, Ryo-kei-jutsu-kan-to, Sha-kanzo-to, Keishi-ninjin-to, Toki-to and Ryo-kan-kyo-mi-shin-ge-nin-to were investigated using canine isolated, blood-perfused sinoatrial node and papillary muscle preparations. Single injections of small doses of Oren-gedoku-to, Moku-boi-to and Ryo-kan-kyo-mi-shin-ge-nin-to (0.1 to 3 mg) dose-deoendently increased the sinoatrial rate and the developed tension of papillary muscle, while other drugs showed almost no effect on these parameters. All the drugs had almost no effect on the blood flow through the nutrient arteries of each preparation The positive chronotropic and inotropic effects induced by Oren-gedoku-to, Moku-boi-to and Ryo-kan-kyo-mi-shin-ge-nin-to did not show tachyphylaxis and were not affected after pharmacological denervation by tetrodo-toxin treatment or by reserpine pretreatment. but were significantly suppressed by atenolol. These results indicate that these three drugs act as beta-adrenoceptor agonists to produce clinically useful cardiac effects.

Differential effects of Bay k 8644, a presumed calcium channel activator, on sinoatrial nodal and ventricular automaticity of the dog heart.

Bay k 8644 is suggested to increase calcium influx through the voltage-dependent calcium channel. In isolated, blood-perfused sinoatrial node preparations of the dog. Bay k 8644 injected intra-arterially increased sinus rate as isoprenaline did. In isolated, blood-perfused papillary muscle preparations of the dog isoprenaline injected intra-arterially increased both the force of contraction of the papillary muscle and its spontaneous beating rate. In these preparations, however, Bay k 8644 failed to increase the beating rate, although it increased the force of contraction. These results are consistent with the concept that the slow inward current plays a role in sinoatrial nodal automaticity but not in automaticity of Purkinje fibres which was reflected as ventricular automaticity of the papillary muscle preparations used here.

PHARMACOLOGICAL PROFILE OF A NEW CORONARY VASODILATOR DRUG, 2-NICOTINAMIDOETHYL NITRATE (SG-75)

1. In anaesthetized, open-chest dogs, 2-nicotinamidoethyl nitrate (SG-75) administered intravenously (0.3-1 mg/kg) or intraduodenally (3 mg/kg) produced decrease in systemic blood pressure, coronary resistance, heart rate and an increase in coronary sinus outflow, but virtually no change in myocardial oxygen consumption and atrioventricular conduction. The effects of SG-75 administered intraduodenally emerged within a few minutes after dosing and lasted over about 1 h. 2. In isolated, blood-perfused sino-atrial node preparations of the dog SG-75 administered into the sinus node artery decreased slightly sinus rate at the dose which doubled blood flow through the artery. 3. In isolated, blood-perfused atrioventricular node preparations of the dog SG-75 administered into the atrioventricular node artery did not impair atrioventricular conduction even in doses which increased blood flow through the artery to more than twice the basal level. 4. In isolated, blood-perfused papillary muscle preparations of the dog SG-75 administered into the anterior septal artery scarely affected force of contraction of the papillary muscle at the dose which doubled blood flow through the artery, although in further large doses it produced a transient decrease in the force of contraction. In extremely large doses it produced ventricular fibrillation. 5. In anaesthetized, open-chest dogs in which cardiac input was kept constant SG-75 (0.01-1 mg/kg) administered into the ascending aorta increased venous return without changing systemic output. 6. 2-Nicotinamidoethyl alcohol, a denitrated compound of SG-75, had no vasodilator action in doses comparable to those of the parent compound. 7. These results indicate SG-75 to be a potential antianginal drug having no cardiodepressant actions but having properties uncharacteristic of the nitrates.

Excitation of autonomic nerves by 4-aminopyridine in the isolated, blood-perfused sino-atrial node preparation of the dog

4-Aminopyridine injected into the sinus node artery produced a long-lasting decrease in sinus rate preceded by a transient increase. With a large dose, a long-lasting increase in sinus rate was superimposed on the long-lasting decrease phase. The long-lasting decrease and increase in sinus rate were abolished by 1-hyoscyamine and propranolol respectively, and both were reduced by tetrodotoxin. These results can be interpreted as being due to excitation of autonomic nerves by 4-aminopyridine.

129) - Effects of 4-aminopyridine on the isolated, blood-perfused sino-atrial node preparation of the dog

129) - Effects of 4-aminopyridine on the isolated, blood-perfused sino-atrial node preparation of the dog

Chronotropic effects of coronary vasodilators as assessed in the isolated, blood-perfused sino-atrial node preparation of the dog.

Chronotropic effects of 6 coronary vasodilators, carbochromen, dilazep, diltiazem, dipyridamole, nifedipine and verapamil, were compared by close-arterial administration to the isolated, blood-perfused sino-atrial node preparation of the dog. All drugs produced a dose-related decrease in sinus rate, and the order of negative chronotropic potency determined on a weight basis was as follows: (formula: see text). Higher doses of these drugs except dipyridamole caused atrial standstill. The order of potency causing atrial standstill determined on a weight basis was as follows: (formula: see text). Dipyridamole in lower doses produced a negative chronotropic effect alone, but with higher doses a positive chronotropic effect preceded a negative one. Carbochromen in a wide range of doses produced a triphasic response consisting of initial brief positive, succeeding main negative and final gradually-developing slight positive components.

Effects of fusaric acid and its derivative on the cardiovascular system

The cardiovascular effects of fusaric acid, a dopamine-beta-hydroxylase (DBH) inhibitor and a hypotensive agent, and 5-(4'-chlorobutyl) picolinic acid, one of the most potent DBH inhibitors in fusaric acid derivatives, were investigated in anesthetized dogs. Fusaric acid (10-30 mg/kg) given intravenously caused immediately and dose-dependently a fall in blood pressure, an increase in heart rate, a stimulation of respiration, a marked increase in the rate of superior mesenteric arterial flow, and a decrease in the rate of femoral arterial flow. Fusaric acid (0.3-3 mg) given close-arterially caused a dose-dependent decrease in the sinus rate and in the developed tension in isolated blood-perfused sinoatrial node and papillary muscle preparations, respectively. For the superior mesenteric, renal, and femoral circulations which were perfused with blood, a close-arterial injection of fusaric acid (10-30 mg) increased in the rates of flow in a dose-dependent manner. 5-(4'-Chlorobutyl) picolinic acid showed similar responses as fusaric acid quantitatively or qualitatively. These results indicate that hypotension induced rapidly after intravenous administration of fusaric acid or 5-(4'-chlorobutyl) picolinic acid is not due to the enzyme inhibition, but rather to the direct depression of cardiac function and decrease in peripheral vascular resistance.