Isolated Rat Atria Research Articles

Autonomic nervous control of cardiac frequency in the exercise-trained rat.

Autonomic nervous control of cardiac frequency in the exercise-trained rat.

Opposing anticholinergic and cardio-depressive effects of promazine and thioridazine in isolated rat atria.

Abstract: Acetylcholine (ACh) reduced both the rate of contraction and the contractile force in isolated rat atria, but these effects were less pronounced after the preparations had been treated with promazine or thioridazine. The anticholinergic activity of the phenothiazines was counteracted by their direct cardiodepressive effects. In electrically stimulated atria treated with promazine 5 × 10‐6M, the anticholinergic effect was dominant, the reduction in contractile force was less than that produced by ACh when acting alone. In the spontaneously beating atria promazine 5 × 10‐6M produced a depression of frequency which balanced the anticholinergic effect. The reduction in the work index produced by ACh was less in the presence of promazine 5 × 10‐6M because of the anticholinergic effect on the contractile force. The cardiodepressive effects of thioridazine 5 × 10‐6M and promazine 10‐5M and 2.5 × 10‐5M balanced or exceeded the anticholinergic effects; the reductions in cardiac performance were equal to, or greater than those produced by ACh when acting alone. It is suggested that the anticholinergic activity of phenothiazine derivatives is unspecific i.e. not due to receptor blockade, but to general membrane stabilizing effects, which counteract the changes in membrane permeability produced by ACh.

Effect of prolonged starvation on the functional status of the isolated rat atria.

SummaryStarvation results in a marked loss of body weight in rats, e.g., a 30% loss in 4 days after which the animals begin to die. By the sixth day only 5 of the 20 were still living. Despite thes...

The action of practolol on the isolated rat atrium.

The β‐receptor antagonism and the effects of practolol on the mechanical and electrical behaviour of isolated rat atria suspended in an organ bath have been investigated. Practolol produced a parallel shift to the right in the log. dose‐response curves of isoprenaline with no decrease in the maximal response, indicating that the antagonism is competitive. The drug was found to exert positive inotropic and chronotropic effects in doses between 10‐8M and 10‐5M. Practolol 10‐4M did not change the threshold for excitation and the threshold for experimentally induced atrial fibrillation to any extent, neither did it prolong the effective refractory period. The results show that practolol has β‐adrenergic receptor blocking properties as well as sympatomimetic properties. The results also indicate that practolol possesses no quinidine‐like or local anaesthetic activity.

In vitro effect of 6-hydroxydopamine on isolated rat atria.

In vitro treatment with 6-hydroxydopamine (6-OHDA), but not with oxidized 6-hydroxydopamine, caused transient, positive inotropic and chronotropic responses in the isolated rat atria. In the presence of rat blood plasma, the excitatory effect of 6-hydroxydopamine persisted unless the drug was washed out by fresh medium. 6-Hydroxydopamine failed to elicit the excitative response in the atria obtained from reserpinized rats or rats treated with 6-hydroxydopamine in vivo. In vitro treatment with 6-hydroxydopamine did not cause the development of supersensitivity to noradrenaline. Cocaine and desipramine, but not bretylium, inhibited the excitative action of 6-hydroxydopamine. No tachyphylaxis developed after repeated exposure to 6-hydroxydopamine in vitro. Propranolol, but not phentolamine, blocked the excitatory effect of 6-hydroxydopamine. It is thus concluded that in vitro treatment with 6-hydroxydopamine may cause atrial stimulation by an indirect action involving the release of catecholamines as a result of its displacement at the nerve ending.

The action of promazine and thioridazine in isolated rat atria. 3. effects of varying concentrations of calcium and different frequencies and strengths of stimulation on contractile force and excitability

The effects of promazine and thioridazine on electrically stimulated left rat atria were studied in the presence of varying concentrations of calcium and at different frequencies and strengths of stimulation. An increase of the calcium concentration, [Ca 2+] O, in the Ringer solution increased the force of contraction of the preparations. A slight decrease in excitability was found at [Ca 2+] O above 4.0 meq/1. Suprathreshold stimulation (50 mA) produced a considerable increase in contractile force when [Ca 2+] O was 2.0 meq/1, but on increasing the calcium concentration, this augmentation declined rapidly. On the basis of experiments with an adrenergic β-blocker, practolol, and atropine sulphate, it is concluded that suprathreshold stimulation releases noradrenaline as well as acetylcholine. The decrease in contractile force caused by promazine, 2.5 × 10 −5 M, and thioridazine, 2.5 × 10 −5 M, was, to a certain extent, antagonized by increasing the concentration of Ca 2+. In atria stimulated at suprathreshold values, the results indicate that some sort of competition between Ca 2+ and the phenothiazine derivatives may exist, and it is assumed that the drugs interfere with the exchangeability of calcium available for contraction. The decrease in excitability caused by promazine, 2.5 × 10 −5 M, seemed to be independent of varying [Ca 2+ O. An increase in the frequency of contractions increased the threshold for electrical stimulation and reduced the contractile force (‘negative staircase’). Promazine, 2.5 × 10 −5 M, enhanced these effects. It is concluded that the degree of the phenothiazine-induced reduction in contractile force of isolated rat atria depends upon the calcium concentration of the Ringer solution and also on the frequency and strength of stimulation.

Hemodynamic effects of hypertonic sodium chloride

ARTICLESHemodynamic effects of hypertonic sodium chlorideG. G. Rowe, D. H. McKenna, R. J. Corliss, and S. SialerG. G. Rowe, D. H. McKenna, R. J. Corliss, and S. SialerPublished Online:01 Feb 1972https://doi.org/10.1152/jappl.1972.32.2.182MoreSectionsPDF (718 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByInfusion of hypertonic saline (7.5% NaCl) causes minor immunological changes in normovolaemic womenActa Anaesthesiologica Scandinavica, Vol. 48, No. 2Effect of Intravenous Infusion of a 7.2% Hypertonic Saline Solution on Serum Electrolytes and Osmotic Pressure in Healthy Beagles.Journal of Veterinary Medical Science, Vol. 61, No. 6Effect of a 7.2% Hypertonic Saline Solution Infusion on Arterial Blood Pressure, Serum Sodium Concentration and Osmotic Pressure in Normovolemic Heifers.Journal of Veterinary Medical Science, Vol. 60, No. 7Hypertonic Saline Activates Protein Tyrosine Kinases and Mitogen-activated Protein Kinase p38 in T-cellsThe Journal of Trauma: Injury, Infection, and Critical Care, Vol. 42, No. 3New concepts in shock managementAir Medical Journal, Vol. 15, No. 2Effects of hypertonic saline on myocardial function and metabolism in nonischemic and ischemic isolated working rat heartsCritical Care Medicine, Vol. 23, No. 11Lesion of the anteroventral third ventricle region impairs the recovery of arterial pressure induced by hypertonic saline in rats submitted to hemorrhagic shockBrain Research, Vol. 587, No. 1Use of Hypertonic-Hyperoncotic Fluids for Resuscitation of Trauma Patients1 July 1992 | Journal of Intensive Care Medicine, Vol. 7, No. 4Pharmacology of Colloids and CrystalloidsCritical Care Clinics, Vol. 8, No. 2Intravenous Fluid Therapy in Neurologic InjuryCritical Care Clinics, Vol. 8, No. 2Reduced responsiveness to noradrenaline in isolated rat atria exposed to hyperosmotic solutionsGeneral Pharmacology: The Vascular System, Vol. 22, No. 1Instantaneous restoration of regional organ blood flow after severe hemorrhage: Effect of small-volume resuscitation with hypertonic-hyperoncotic solutionsJournal of Surgical Research, Vol. 49, No. 6Hypertonic saline-dextran solutions for the prehospital management of traumatic hypotensionThe American Journal of Surgery, Vol. 157, No. 5Hypertonic saline resuscitates dogs in endotoxin shockJournal of Surgical Research, Vol. 43, No. 1 More from this issue > Volume 32Issue 2February 1972Pages 182-184 Copyright & PermissionsCopyright © 1972 the American Physiological Societyhttps://doi.org/10.1152/jappl.1972.32.2.182PubMed5007866History Published online 1 February 1972 Published in print 1 February 1972 Metrics

The action of promazine and thioridazine in isolated rat atria.2. Effects of varying concentrations of potassium and sodium on automaticity, mechanical performance, refractoriness and excitability

Isolated rat atria were suspended in a water-jacketed organ bath. An increase in the potassium concentrations, [K +] o, of the Ringer solution from 1.325 to 10.6 meq/1 had little effect on the spontaneous rate of atrial contractions, whereas the mechanical performance (work index) was depressed when [K +] o was raised above 5.3 meq/l. The threshold for electrical stimulation increased at potassium levels above 5.3 meq/l; the effective refractory period increased at potassium levels above 7.95 meq/l. Promazine, 2.5 × 10 −5M, and thioridazine, 5 × 10 −5M, reduced the rate and the work index, and these effects wer the threshold values and in effective refractory period caused by the two drugs were enhanced when [K +] o was raised. Replacement of 59.2 mM/l NaCl with equinolar concentrations of choline chloride did not change the spontaneous atrial rate nor the work index. The threshold values and effective refractory period were, however, increased. The decrease in atrial rate and work index caused by thioridazine, 5 × 10 −5M, was not influenced by a reduction in [Na +] o. The drug induceded increase in the threshold for electrical stimulation and in the effective refractory period was potentiated in the presence of low [Na +] o. The results show that the effects of the phenothiazine derivatives on the electrical activity of isolated rat atria is accentuated by a decrease in [Na +] o and a rise in [K +] o, and conversely, counteracted by low [K +] o.

Evidence for the Existence of Alpha Adrenergic Receptor in Isolated Rat Atria

It has been generally accepted that only beta adrenergic receptors are present in myocardial tissue, however, there are many reports of the existence of both alpha and beta receptors in mammal’s hearts (1–4). In our laboratory also, existence of alpha adrenergic receptors was certified in rat atria (5): dose response curve of positive inotropic action of phenylephrine (PHE) shifted to the left after 6-propyl-2-thiouracil (PTU) treatment and depressed profoundly by phentolamine.

The mechanism of the negative inotropic effect of methoxyflurane on isolated rat atria.

The mechanism of the negative inotropic effect of methoxyflurane on isolated rat atria.

Endogenous lipids as energy source for contractile activity of isolated rat atria.

Endogenous lipids as energy source for contractile activity of isolated rat atria.

Changes in rat atrial action potentials induced by promazine and thioridazine.

The action potentials of electrically stimulated left rat atria were studied in an organ‐bath continuously supplied with a Ringer solution. Action potentials derived from single myocardial cells were displayed on a Tektronix dual‐beam oscilloscope by means of fine glass capillary electrodes and photographed. Promazine 10‐5 M and thioridazine 5 × 10‐5 M reduced the maximum rate of rise (dv/dt) and the overshoot of the action potential, without significantly altering the resting membrane potential. The drugs also caused a slight reduction in the rate of repolarization. The decrease in the rate of the depolarization due to promazine was minimized when the external potassium concentration was reduced from 5.3 to 1.325 meq./1, a procedure which increased the resting membrane potential. An increase in the potassium concentration from 5.3 to 7.95 meq./1 reduced the resting membrane potential and augmented the effect of the drug on the rate of depolarization. It is suggested that the findings described in this study may explain the phenothiazine induced alterations in electrocardiogram of isolated rat hearts as well as the changes in excitability and refractoriness of isolated rat atria.

The positive ionotropic effect of dibutyryl-3',5'-AMP on isolated rat atria

1. In isolated electrically driven (frequency 2 Hz) rat left atria the N6-2′-O-dibutyryl derivative of cyclic 3′,5′-AMP (DB-AMP; monosodium salt) produced a concentration-dependent and reversible positive inotropic effect. In normal Tyrode solution (1.8 mM Ca++, the threshold concentration was 5×10−5 M; the peak concentration (10−3 M) increased contractile force to 203% of control values. Negative inotropic responses were not observed in these experiments even with supramaximal DB-AMP concentrations (Fig. 1). 2. The positive inotropic effect of DB-AMP developed gradualy (Fig. 2). It began 0.3–7.7 min after addition of the drug and was maximal within 3.5–28.3 min (Tab. 2). Once established, the effect was prolonged and decreased only slightly within 60 min (Fig. 2). 3. The positive inotropic effect of DB-AMP was due to an increase in the rate of tension development. The time to peak tension and the duration of contraction remained unchanged (Tab. 3). 4. At high concentrations (10−3–5×10−3M) DB-AMP caused contractures in some experiments (Tab. 1). 5. The time course and the magnitude of the inotropic effects of DB-AMP were influenced by the [Ca]e. The increment in myocardial contractility caused by 10−3M DB-AMP developed faster at high than at low [Ca]e (Tab. 4; Fig. 5). On the other hand, the positive inotropic effect of 10−3M DB-AMP was most evident at normal (1.8 mM) and reduced (0.45; 0.9 mM) [Ca]e, less pronounced at 3.6 mM Ca++ and was insignificant at 7.2 mM Ca++ (Fig.3). 6. Sodium butyrate (10−4–10−2M) did not alter the contractile behaviour of isolated rat atria. 7. In isolated electrically driven (frequency 3 Hz) left guinea-pig atria no positive inotropic effects could be demonstrated with DB-AMP at concentrations up to 10−3M.

Some pharmacological properties of the venom of the scorpionfish Scorpaena guttata—I

California scorpionfish venom has a primary muscarinic action on the isolated rat atria and a secondary beta adrenergic stimulating action. The initial effect can be blocked with atropine and inhibited by hemicholinium. The secondary effect is inhibited by pretreatment with reserpine or a beta adrenergic blocking agent. The muscarinic activity is associated with labile components which cause the release of endogenous acetylcholine. The adrenergic effect is due to fractions which release endogenous catecholamines. The venom has little effect on the guinea pig phrenic nerve-diaphragm preparation. Although the venom possesses a mild in vitro direct hemolytic activity no changes were produced in the blood clotting systems studied.

Marine toxins from the Pacific—IX: Some effects of ciguatoxin on isolated mammalian atria

Ciguatoxin produced an initial negative inotropic and chronotropic effect which was followed by a positive inotropic and chronotropic effect on the isolated rat atria. The initial depression could be effectively blocked by atropine (1 × 10 −7 g per ml), and partially blocked by hexamethonium or hemicholinium-3 (2 × 10 −5 g per ml). The positive inotropic and chronotropic action of ciguatoxin was reduced by pretreating the atria with MJ-1999 (1 × 10 −6 g per ml) or guanethidine (1 × 10 −6 g per ml). Abolition of the response to ciguatoxin could also be accomplished with a single dose of 2 mg per kg of reserpine given to the rat 24 hr before isolating the heart. It is not yet possible to correlate inotropic and chronotropic effects of the toxin with the release of catecholamines, but it seems likely that excitatory effect of the toxin may be elicited by a release of catecholamines from their stores.

The action of promazine and thioridazine in isolated rat atria. 1. Effects on automaticity, mechanical performance, refractoriness and excitability

The contractile force of spontaneously beating rat atria was recorded isometrically. Promazine (5 × 10 −6 M to 5 × 10 −5 M) and thioridazine (5 × 10 −6 M to 10 −4 M) produced a dose and time dependent decrease in the rate of contractions and work index; atrial arrest was observed in some experiments with the highest drug concentrations. Promazine and thioridazine increased the threshold current required to drive the atria and prolonged the effective refractory period since the maximum following frequency (m.f.f.) at which the atria could respond to stimulation was reduced. The drugs increased the threshold for experimentally induced atrial fibrillation. Promazine was in every respect the more potent compound. It is concluded that the changes in automaticity, refractoriness, conduction velocity and excitability caused by promazine and thioridazine can explain the anti-arrhythmic property of these phenothiazine derivatives.

Nature of endogenous substrates used to support contractility of isolated rat atria.

SummaryIn the absence of exogenous substrate, bicarbonate-free medium produced a marked depressant effect on the force of contraction of isolated rat atria which was not reversed by 20 mM glucose. Since the negative inotropic effects of bicarbonate-free medium are due to an inhibition of phosphofructokinase (PFK) this indicates that endogenous substrate above the PFK step, probably glycogen, is very important for the contractile process, at least in the absence of exogenously supplied substrate. Citrate, another inhibitor of PFK, also produced a marked depressant action on the force of contraction in the absence of exogenous substrate. The nature of its inhibitory effect was different from that produced by bicarbonatefree medium since depression by citrate was partially overcome with 20 mM glucose. Since bicarbonate-free medium did not completely suppress the contractility of the atria, endogenous substrates below the PFK step, probably lipid and/or lactate, besides glycogen, can serve as a source of fuel...

Effect of starvation on contractile response of isolated rat atria to citrate and bicarbonate-free medium.

SummaryIsolated atria from 24-hr starved rats show a smaller rate of decline of contractility with time, when incubated in the absence of exogenous substrate than atria from fed rats. During starvation, endogenous substrate apparently accumulates and can be used by the heart to maintain contractility in vitro. The nature of this endogenous substrate was elucidated by the use of bicarbonate-free medium and 1.5 mM citrate. These agents apparently depress contractility by an inhibition of the phosphofructokinase (PFK) reaction in the glycolytic cycle. Both inhibitors produced marked, but not complete, contractile depression of atria from starved or fed rats incubated in the absence of exogenous substrate. This depression is likely due to an interference with the utilization of endogenous substrate, probably glycogen, normally metabolized via PFK. The maintenance of some degree of contractility in the presence of these inhibitors indicates that endogenous substrates, not metabolized via PFK, are utilized. Add...

Effect of Strontium on Transmembrane Potentials of the Rabbit Sino‐Atrial Node Deprived of Calcium

HomeCirculation ResearchVol. 28, No. 5Effect of Strontium on Transmembrane Potentials of the Rabbit Sino‐Atrial Node Deprived of Calcium Free AccessResearch ArticlePDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBEffect of Strontium on Transmembrane Potentials of the Rabbit Sino‐Atrial Node Deprived of Calcium NOBORU TODA NOBORU TODANOBORU TODA Department of Pharmacology, Faculty of Medicine, Kyoto University Kyoto, Japan Search for more papers by this author Originally published1 May 1971https://doi.org/10.1161/01.RES.28.5.545Circulation Research. 1971;28:545–553AbstractTransmembrane potentials were recorded from S-A nodal pacemaker and nonpacemaker fibers of the rabbit right atrium. Sr2+ (2.2 mM) prolonged the pacemaker action potentials but did not influence other parameters of the membrane potential. In Ca2+-free solution, maximal diastolic potential, threshold potential, and overshoot were reduced, and the action potential and rise time were prolonged; these changes were enhanced by previous treatment with EGTA (ethyleneglycol bis (β-aminoethylether)-N,N'-tetraacetic acid). In some preparations, pacemaker action potentials disappeared and subthreshold oscillations were observed; Sr2+ and norepinephrine restored action potentials. Addition of Sr2+ to the Ca2+-free solution slowed the pacemaker rate in association with an increase in maximal diastolic potential, threshold potential, overshoot, and action potential duration. In fibers of the right atrium, Sr2+ restored the magnitudes of resting potential and overshoot which had been markedly reduced by zero [Ca2+]o; an ectopic pacemaker was induced. The ability of norepinephrine to induce ectopic automaticity was not increased by Sr2+ at normal [Ca2+]o but was increased at zero [Ca2+]o, Sr2+ partly restored the positive chronotropic effect of sympathetic nerve stimulation which was abolished by removal of Ca2+, but Sr2+ did not correct the reduced susceptibility of the S-A node to exogenous norepinephrine in Ca2+-deficient solutions. It seems likely that Sr2+ can substitute for Ca2+ in maintaining the diastolic membrane potential and overshoot and decreases membrane conductance to K+, which would induce ectopic pacemakers. Previous Back to top Next FiguresReferencesRelatedDetailsCited By Watson B, Woodrough R and March N (1976) The effect of temperature on canine papillary muscle, Biophysics of Structure and Mechanism, 10.1007/BF00863703, 2:2, (99-104), . Refsum H and Landmark K (2009) The Effect of a Calcium-antagonistic Drug, Nifedipine, on the Mechanical and Electrical Activity of the Isolated Rat Atrium, Acta Pharmacologica et Toxicologica, 10.1111/j.1600-0773.1975.tb00855.x, 37:5, (369-376) TODA N (1972) Contractile Responses of Isolated Rabbit Aortae to Transmural Stimulation as Affected by Calcium, Strontium, Sodium and Ouabain, Japanese Journal of Pharmacology, 10.1016/S0021-5198(19)31669-5, 22:3, (347-357), . May 1, 1971Vol 28, Issue 5 Advertisement Article InformationMetrics Copyright copyright 1971 by the American Heart Association, Inc.https://doi.org/10.1161/01.RES.28.5.545 Manuscript receivedDecember 21, 1970Manuscript acceptedMarch 4, 1971Originally publishedMay 1, 1971 Keywordscontractilityright atriumnorepinephrinesympathetic nerve stimulationectopic automaticityPDF download Advertisement

Effects of monosaccharides, pyruvate, acetate, and butyrate on the developed tension and ATP levels on hypodynamic isolated rat atria.

SummaryThe effects of several substrates on the developed tension (DT) of isolated rat atria, made hypodynamic by the removal of glucose, were investigated. The addition of pyruvate, acetate, or bu...