Comparison of the chronotropic responses to local anesthetics (procaine, lidocaine, prilocaine, mepivacaine and bupivacaine) of the canine sinus node in situ.

Satoh, Hiroyuki

doi:10.1254/jjp.31.85

Cited by 10 publications

(3 citation statements)

References 16 publications

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“…For lidocaine the concentrations could be increased up to 100 µM until the cells stopped beating. In accordance with literature data, application of lidocaine did not result in an increase of frequency but rather in a decrease [64,65].…”

Section: Nasupporting

confidence: 92%

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Goßmann

Frotscher

Linder³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.

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Section: Nasupporting

confidence: 92%

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Goßmann

Frotscher

Linder³

et al. 2016

Cell Physiol Biochem

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“…In the atrium-isolated preparation cocaine decreases the rate of contractibility in a monoamine-independent manner (Trendelenburg, 1968). Similarly, procaine decreases heart rate when delivered directly at the sinoatrial node through the sinus node artery (Satoh, 1981). The negative chronotropic effect of procaine on sinoatrial cells is a combination of blockade of sodium and potassium conductances (Satoh and Hashimoto, 1986).…”

Section: Discussionmentioning

confidence: 99%

Ventral tegmental area neurons are either excited or inhibited by cocaine's actions in the peripheral nervous system

Mejías-Aponte

Kiyatkin

2012

Neuroscience

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Cocaine’s multiple pharmacological substrates are ubiquitously present in the peripheral and central nervous system. Thus, upon its administration, cocaine acts in the periphery before directly acting in the brain. We determined whether cocaine alters ventral tegmental area (VTA) neuronal activity via peripheral actions, and whether this precedes its central actions. In urethane-anesthetized rats, we recorded VTA neurons responses to intravenous injections of two cocaine analogs: cocaine-hydrochloride (HCl, 0.25 mg/kg) that readily cross the blood-brain barrier (BBB) and cocaine-methiodide (MI, 0.33 mg/kg) that does not cross the BBB. Both cocaine analogs produced sustained changes in discharge rates that began 5s after the initiation of a 10s drug infusion. Within the first 90s post-injection the magnitudes of neuronal responsive of both cocaine analogs were comparable, but later in time the effects of cocaine-HCl were stronger and persisted longer than those of cocaine-MI. The proportion of neurons responsive to cocaine-HCl was twice to that of cocaine-MI (74% and 35% respectively). Both analogs also differed in the response onsets. Cocaine-MI rarely evoked responses after 1 min whereas cocaine-HCl continued to evoke responses within 3 min post-injection. VTA neurons were either excited or inhibited by both cocaine analogs. Most units responsive to cocaine-MI, regardless of excitation or inhibition, had electrophysiological characteristics of putative DA neurons. Units inhibited by cocaine-HCl also had characteristic of DA neurons whereas excited neurons had widely varying action potential durations and discharge rates. Cocaine-MI and cocaine-HCl each produced changes in VTA neuron activity under full DA receptor blockade. However, the duration of inhibition was shortened, the number of excitations increased, and they occurred with an earlier onset during DA receptor blockade. These findings indicate that cocaine acts peripherally with a short latency and alters the activity of VTA neurons prior to its well-known direct actions in the brain.

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“…Equivalent concentrations impair slow AP conduction through depolarized canine Purkinje fibres (Lamanna et al, 1982). Higher concentrations of lidocaine (2 x 10-4 M) depress the electrical activity that depends on slow inward currents, as in rabbit sinus node cells (Satoh & Hashimoto, 1984) and in canine nodal cells (Satoh, 1981). On the other hand, it has been shown that lidocaine suppresses depressed fast responses, but has little or no effect on slow APs on canine Purkinje fibres (Brennan et al, 1978) and on guineapig atrial muscle (Hashimoto et al, 1979).…”

Section: Comparison With Verapamilmentioning

confidence: 99%

Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts

Neto

Sperelakis

1985

British J Pharmacology

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The effects of lidocaine, procaine, procainamide and quinidine were studied on organ‐cultured embryonic chick (2–3 day‐old) ventricular cells. Lidocaine (10−5 − 10−4 M), in a dose‐dependent manner, reduced the rate of pacemaker discharge, the action potential amplitude (APA), the maximum rate of rise (Vmax) of the upstroke of the action potential and the action potential duration at 50% repolarization (APD50). These changes occurred without alterations in the maximum diastolic potential (MDP). Extracellular electrical field stimulation could still evoke action potentials in cells arrested by 10−4 M lidocaine, but 10−3 M lidocaine completely abolished electrical activity. Procaine, procainamide and quinidine, at 5 × 10−5 M to 10−3 M, depolarized the cells to around − 30 mV and reduced APA and Vmax. Procaine and procainamide increased APD50, but quinidine shortened it. All the effects described disappeared completely in about 40 min of superfusion with drug‐free Tyrode solution. Isoprenaline (5 × 10−7 M) and adrenaline (10−6 M) restored spontaneous firing of preparations arrested by any of the antiarrhythmic agents and repolarized ventricular cells depolarized by procaine, procainamide or quinidine. Propranolol (5 × 10−7 M) did not affect the depolarization produced by procaine (5 × 10−4 M), but antagonized its reversal by isoprenaline. In contrast, isoprenaline (10−6 M) did not produce recovery of automaticity of preparations arrested by verapamil (10−5 M). Histamine (10−5 M) or strontium (10 mM) were not able to restore rhythmic activity in cells arrested procaine. Application of long (10–15 s duration) hyperpolarizing currents did not reverse the blocking effect of procaine, procainamide and quinidine. The input resistance increased during the procaine‐induced depolarization. It is suggested that the four agents studied block the slow Na+ channels responsible for the upstroke of the action potential in young chick heart cells. A drug‐induced decrease in PK may occur in those cells arrested at low levels of membrane potential.

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Comparison of the chronotropic responses to local anesthetics (procaine, lidocaine, prilocaine, mepivacaine and bupivacaine) of the canine sinus node in situ.

Cited by 10 publications

References 16 publications

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Mechano-Pharmacological Characterization of Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells

Ventral tegmental area neurons are either excited or inhibited by cocaine's actions in the peripheral nervous system

Effects of lidocaine, procaine, procainamide and quinidine on electrophysiological properties of cultured embryonic chick hearts

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