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J C Bailey

Publications and source records attributed to J C Bailey.

At least 37 records · Page 2Linked to original sources
PubMed1983

Direct effects of cholinergic stimulation on ventricular automaticity in guinea pig myocardium.

The purpose of these experiments was to determine whether muscarinic cholinergic agonists exerted a negative chronotropic effect in the absence of endogenous norepinephrine in isolated guinea pig ventricular myocardial strips. The chronotropic response to physostigmine (10(-6) M) in control, reserpine-pretreated animals, and in the presence of increased norepinephrine release induced by superfusion of tyramine (10(-5) M), was studied. The control rates in the control, reserpine-pretreated, and tyramine-treated groups were 106 +/- 40, 93 +/- 31, 109 +/- 28/min, respectively. Propranolol (10(-6) M) produced a 23% slowing in rate in control animals and an 8% slowing in reserpine pretreated animals (P less than 0.01), suggesting basal secretion of norepinephrine. Tyramine (10(-5) M) produced a 28% increase in rate in control animals (P less than 0.05) and tyramine (10(-4) M) produced no increase in reserpine-pretreated animals. Physostigmine produced similar negative chronotropic response in control, reserpine-pretreated, and tyramine-treated groups of 45, 49, and 28%, respectively. Physostigmine produced no change in measured Purkinje fiber action potential characteristics, except for a decreased rate of spontaneous diastolic depolarization. Our results demonstrate that physostigmine slows the spontaneous rate in control, reserpine-pretreated and tyramine-treated groups, indicating that muscarinic cholinergic agonists exert a direct negative chronotropic effect at postjunctional cell surface receptors, independent of the presence or level of adrenergic tone.

Action Potentials↗
PubMed1983

Time course of the electrophysiological effects of quinidine on canine cardiac Purkinje fibers: concentration dependence and comparison with lidocaine and disopyramide.

We used standard microelectrode techniques to observe the time course of the appearance and disappearance of the cellular electrophysiologic effects of antiarrhythmic drugs during drug infusion and after washout. The slopes of phases 0 (Vmax), 2(V2) and 3(V3) of the action potential of canine Purkinje fibers were followed during 30 min of infusion of quinidine (0.2 - 1 x 10(-5) M), disopyramide (1 x 10(-5) M) or lidocaine (1 x 10(-5) M) and then during 60 min of washout with drug-free Tyrode's solution. All three drugs significantly reduced V3 and increased V2; quinidine and disopyramide also significantly reduced Vmax. The onset of the effects of quinidine and disopyramide on Vmax, V2 and V3 occurred at similar rates. Both the onset and disappearance of the effects of lidocaine were more rapid than those of quinidine and disopyramide. This may have been related to the greater lipid solubility of lidocaine with a heptane: water partition coefficient of 0.85 for lidocaine compared with 0.16 for disopyramide and 0.06 for quinidine. The effects of quinidine (1 x 10(-5) M) on V3 reversed much more slowly upon washout (T1/257 +/- 12 min, mean +/- S.E.) than the effects of quinidine on Vmax (T1/218 +/- 3 min, P less than .01) and V2 (T1/215 +/- 3 min, P less than .01). Concentration-response data showed that the time course of washout of the effects of quinidine was independent of drug concentration. These data suggest that rapidity of antiarrhythmic drug action is related to lipophilicity and that the effect of quinidine on V3 is due to action at a different cellular site from its effects on Vmax and V2.

Action Potentials↗
PubMed1982

Potential biochemical mechanisms for regulation of the slow inward current: theoretical basis for drug action.

Regulation of the slow inward current appears to be an important mechanism by which the autonomic nervous system modifies cardiac function. Beta-adrenergic stimulation augments the slow inward current by increasing the number of functional slow inward current channels. This effect is mediated by cyclic adenosine monophosphate (cyclic AMP) and presumably involves phosphorylation of membrane proteins associated with the slow channels. Beta antagonists (propranolol) act by inhibiting beta-adrenergic activation of adenylate cyclase and thereby prevent increases in cyclic AMP. The calcium channel antagonists (verapamil) act directly at the level of the slow channels to inhibit the slow inward current independent of changes in cyclic AMP. Cholinergic stimulation attenuates beta-adrenergic stimulation of the slow inward current by one or both of two potential mechanisms: reduction in cyclic AMP formation and antagonism of the distal effects of cyclic AMP.

Adenylyl Cyclase Inhibitors↗
PubMed1982

Effects of extracellular calcium ions, verapamil, and lanthanum on active and passive properties of canine cardiac purkinje fibers.

The effects of alteration of extracellular calcium ion concentration ([Ca++]o) were studied in isolated false tendons using microelectrode techniques. Several determinants of cellular excitability and conduction velocity were affected by extracellular calcium. Increasing [Ca++]o from 2 to 8 mM resulted in: (1) a progressive decrease in interelectrode conduction velocity (2) a 7-mV shift of the maximum upstroke velocity-membrane potential relation toward less negative potential, (3) an increase in rheobasic current, (4) a 14-mV shift of the voltage threshold for all-or-none depolarization to less negative potentials, (5) a 52% increase in internal longitudinal resistance per unit length, and (6) a 27% decrease in the capacitance filled by the foot of the action potential from 4.90 to 3.56 microF/cm2. Blockade of the slow inward current by Mn++ or verapamil did not alter the [Ca++]o-induced effects on the maximum upstroke velocity-membrane potential relation. Cable properties were determined during alteration of [Ca++]o in the presence of verapamil (3 X 10(-6) and 1 X 10(-5) M) or in the presence of La+++ (0.2 mM). Verapamil increased membrane resistance X unit length but did not affect internal longitudinal resistance per unit length. La+++ had no effects on either membrane resistance X unit length or internal longitudinal resistance per unit length. Verapamil did not block the increase in ri induced by elevation of [Ca++]o. However, no change in ri occurred during an increase of [Ca++]o when La+++ was present. The results suggest that [Ca++]o-induced changes in internal longitudinal resistance may occur by the influx of calcium ions through the Na+/Ca++ exchange mechanism.

Action Potentials↗
PubMed1981

pH-dependent electrophysiological effects of quinidine and lidocaine on canine cardiac purkinje fibers.

We used standard microelectrode techniques to evaluate the effects of lidocaine and quinidine on canine Purkinje fibers at normal pH (7.3) and in the presence of acidosis (pH 6.9). Acidosis alone reduced resting potential, action potential amplitude, and Vmax, while increasing APD90 and conduction time. Lidocaine concentrations of 6 x 10(-6) to 1.5 x 10(-5) M had minimal effect on resting potential, action potential amplitude, and Vmax at pH 7.3. At pH 6.9, the same lidocaine concentrations significantly reduced resting potential (3-10%), action potential amplitude (3-8%) and Vmax (14-22%). Quinidine (6 x 10(-6) to 1.5 x 10(-5) M) reduced resting potential (3-5%), action potential amplitude (4-9%), and Vmax (19-34%) at pH 7.3. At pH 6.9, quinidine produced significantly greater reductions in resting potential (4-15%), action potential amplitude (5-18%), and Vmax (22-49%). These changes were associated with much more quinidine- and lidocaine-induced prolongation of interelectrode conduction time at acidic than at normal pH. Inexcitability occurred at pH 6.9 in four of 14 experiments with 1.5 x 10(-5) M quinidine and in two of 10 with 1.5 x 10(-5) M lidocaine, and was reversed at the same drug concentration by normalizing pH. Acidosis did not alter the Vmax-resting potential relationship in either the absence or presence of antiarrhythmic agents. Furthermore, changes in ionization did not account for the alterations in electrophysiological effects of quinidine and lidocaine produced by acidosis. Our data suggest that extracellular pH changes may modify importantly the effects of antiarrhythmic agents.

Acidosis↗
PubMed1981

Electrophysiological effects of the optical isomers of disopyramide and quinidine in the dog. Dependence on stereochemistry.

We studied the electrophysiological effects of the optical isomers of disopyramide and quinidine on canine cardiac Purkinje fibers. Conventional microelectrode techniques were employed to study the effects of racemic disopyramide, (+)-disopyramide, (-)-disopyramide, quinidine, and quinine. Racemic disopyramide, (+)-disopyramide, and quinidine prolonged action potential duration (APD) measured at 90% repolarization. In contrast, (-)-disopyramide and quinine shortened APD. These directionally opposite effects on repolarization were observed throughout 60 minutes exposure to drug and were concentration-dependent. All five components reduced dV/dt of phase 0, increased conduction time, and increased the current requirement for all-or-none depolarization. The effects of all five compounds on dV/dt, conduction time, and current requirements were time- and concentration-dependent. Our results indicate that the stereochemical configurations of disopyramide and quinidine determine their effects on repolarization of cardiac Purkinje fibers.

Action Potentials↗
PubMed1981

Electrophysiological effects of hypertonic sucrose solutions on canine cardiac Purkinje fibers.

Microelectrode techniques were used to study the electrophysiological effects of hypertonic solutions on canine cardiac Purkinje fibers. Tyrode's solution was rendered hyperosmotic by the addition of sucrose to produce 320, 350, 400, and 500 mOsm solutions. Hyperosmotic solutions produced sucrose concentration-dependent hyperpolarization, increased the current required to effect all-or-none depolarization, slowed transmission, and prolonged action potential duration. The action potential prolongation was reversed or prevented by lidocaine (10-5 M). Treatment of potassium-depolarized Purkinje fibers with hypertonic solutions produced hyperpolarization, increased Vmax phase 0, decreased the current required to evoke all-or-none depolarization, increased action potential duration, and increased transmission speed. The potent electrophysiological actions of hypertonic sucrose solutions probably derive from their osmotic effects rather than from selective actions at specific membrane sites or hormone receptors.

Action Potentials↗
PubMed1980

Intravenous leiomyomatosis of the uterus with extension into the heart.

A 42 year old woman presented with impaired filling of the right atrium and right ventricle two years after removal of uterine leiomyomas. At the time of hysterectomy, intravenous leiomyomatosis was noted, with extension of the tumor into the inferior vena cava. The tumor subsequently extended into the right atrium and coronary sinus, and protruded through the tricuspid orifice. It was successfully removed from the heart, and proved to be histologically benign.

Adult↗
PubMed1980

Vaginal chemoprophylaxis in the reduction of reinfection in women with gonorrhoea. Clinical evaluation of the effectiveness of a vaginal contraceptive.

A clinical investigation was undertaken to determine if chemoprophylaxis in the form of a contraceptive pessary would reduce the rate of reinfection with gonorrhoea in 1245 female patients attending a venereal disease clinic. After the introduction of the pessary the reinfection rate over a 16-week period was 19% compared with 40% in the control clinic patients. It was also found that women could be motivated to use a pessary; 65% of women used pessaries before sexual intercourse at least some of the time. High reinfection rates in venereal disease clinic patients emphasise the need for improved methods of preventing reinfection. Vaginal chemoprophylaxis appears to be an alternative means of reducing gonorrhoea morbidity.

Contraceptive Agents, Female↗
PubMed1980

Anticholinergic effects of disopyramide and quinidine on guinea pig myocardium. Mediation by direct muscarinic receptor blockade.

We studied the interaction of disopyramide, quinidine, and procainamide with cardiac muscarinic receptors. In electrophysiological experiments, the effects of disopyramide, quinidine, procainamide, and atropine were determined on spontaneously depolarizing guinea pig right atria (GPRA) both in the presence and absence of pharmacologically induced (physostigmine) cholinergic stimulation. All four agents demonstrated a concentration-dependent antagonism of the negative chronotropic effects of physostigmine. The order of anticholinergic potency was atropine greater than disopyramide greater than quinidine greater than procainamide. The ability of disopyramide to antagonize the physostigmine induced slowing was stereoselective, (+)disopyramide greater than (-)disopyramide. In contrast, the ability of quinidine to antagonize the negative chronotropic effects of physostigmine was non-stereoselective, quinidine = quinine. In parallel experiments, we studied the ability of disopyramide, quinidine, procainamide, and atropine to compete with the radiolabeled muscarinic receptor antagonist [3H] quinuclidinyl benzilate ([3H]QNB) for binding to muscarinic receptors in crude homogenates of GPRA and membrane vesicles from canine ventricular myocardium. All four agents inhibited [3H]QNB binding to muscarinic receptors. The order of anticholinergic potency determined by the receptor binding studies was identical to that determined by the physiological studies. The interaction of disopyramide with muscarinic receptors was stereoselective, (+)disopyramide > (-)disopyramide. Quinidine was only slightly more potent than quinine in inhibiting [3H]QNB binding to muscarinic receptors. Interaction of antiarrhythmic drugs with muscarinic receptors satisfied criteria for a competitive interaction. The data from this study localize the anticholinergic effects of disopyramide and quinidine to the muscarinic receptor.

Animals↗
PubMed1979

Acetylcholine antagonism of the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers.

The purpose of these experiments was to determine whether or not acetylcholine modulated the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers. Conventional microelectrode techniques were used. Predictably, isoproterenol produced shortening of action potential duration; acetylcholine significantly blunted this effect of isoproterenol. Isoproterenol restored excitability to fibers exposed to 22 mM potassium solutions, and acetylcholine abolished this isoproterenol-restored excitability. Both of these antagonistic effects of acetylcholine were blocked by atropine. Acetylcholine alone did not affect action potential duration in polarized fibers or excitability in potassium-depolarized fibers. Furthermore, acetylcholine had no effect on the decrease in action potential duration induced by premature electrical stimulation or by acetylstrophanthidin administration, or on excitability of fibers exposed to a zero sodium, high calcium superfusant. These data demonstrate a direct cellular basis for cholinergic antagonism of the electrophysiological effects of beta-adrenergic stimulation of canine cardiac specialized intraventricular conducting tissue.

Acetylcholine↗
PubMed1979

Dissociation between the electrophysiological properties and total tissue cyclic guanosine monophosphate content of guinea pig atria.

The purpose of this study was to investigate the role of cyclic guanosine monophosphate (cyclic GMP) in mediating the direct electrophysiological effects of acetylcholine in guinea pig atria. Acetylcholine significantly diminished spontaneous rate of right atria without increasing cyclic GMP content. Reductions in rate following acetylcholine were augmented by pretreatment with physostigmine, but cyclic GMP levels remained unchanged. In left atria, acetylcholine significantly shortened action potential duration within 5 seconds (both with and without physostigmine pretreatment), but cyclic GMP content was not significantly elevated. Cyclic GMP levels in right atria were significantly increased in response to acetylcholine when the Ca2+ content of the buffer was elevated from 1.25 mM TO 2.5 MM; however, reductions in automaticity in the right atria were not augmented in the high Ca2+ buffer. Marked increases in cyclic GMP content were produced by Na nitroprusside superfusion without changing automaticity of right atria or action potential duration of left atria. Finally, both right and left atria were superfused with cyclic GMP analogs (8-bromo cyclic GMP and dibutyryl cyclic GMP) at high concentrations (10(-4)) for 15 minutes without producing significant effects on spontaneous rate or action potential duration. These results failed to show a correlation between total tissue cyclic GMP content and the electrophysiological effects of acetylcholine on guinea pig atria. The reasons for this are either that cyclic GMP does not mediate directly the electrophysiological effects of acetylcholine, or that small changes in cyclic GMP concentrations, undetectable when total tissue nucleotide levels are measured, occur in discrete effector pools of the cardiac cell to mediate the intracellular effects of the choline ester.

Acetylcholine↗
PubMed1978

Slow-channel depolarization: mechanism and control of arrhythmias.

The secondary inward current that flows through the slow channel is probably carried primarily by calcium ions. This current is responsible, in part, for the plateau phase of the cardiac action potential. Inward calcium current through the slow channel is essential to excitation-contraction coupling, and enhancement of this current exerts a positive inotropic effect. Transmembrane electrical potentials generated as a consequence of this slow inward current, so-called slow-channel depolarizations or slow responses, have been useful models in recent studies of cardiac autonomic interactions. The significance of the slow response in ventricular arrhythmias remains controversial and awaits more definitive experiments. The role of slow-channel depolarization as a basis for SA and AV nodal electrical activity is suggested by the electrophysiological similarities between these tissues and slow responses produced in vitro. This hypothesis is supported by the responses of these nodal tissues to interventions that augment of impede the slow inward current. More direct evidence in support of this notion may not be obtainable in the near future, since the critical voltage-clamp studies of ionic currents in SA and AV nodes are not technically feasible at this time.

Action Potentials↗
PubMed1978

Effects of aprindine HCl on slow channel action potentials and transient depolarizations in canine Purkinje fibers.

The electrophysiologic effects of aprindine hydrochloride were studied on normal Purkinje fibers, on Purkinje fibers superfused with Tyrode's solution containing 22 mM KCl and isoproterenol (1 X 10(-5) M) and on transient depolarizations induced by exposure to acetylstrophanthidin (1.7--2 X 10(-7) M). Aprindine (3 X 10(-6) M) significantly reduces the action potential amplitude and dV/dtmax and shortens the action potential duration but does not alter the resting membrane potential. Transient depolarizations were suppressed by aprindine at a dose of 2 X 10(-6) M. Isoproterenol (1 X 10(-5) M) failed to restore the transient depolarizations after suppression with aprindine. Slow responses induced in K-depolarized, isoproterenol-treated fibers were unchanged by aprindine (3 X 10(-6)-1 X 10(-5) M) in the presence as well as in the absence of acetylstrophanthidin. These experiments suggest that aprindine does not have slow channel blocking properties and that an inward current through the slow channel cannot be considered as the sole basis of the digitalis-induced transient depolarization.

Action Potentials↗
PubMed1977

Lack of electrical interaction between proximal bundle branches and subjacent muscle.

Microelectrode techniques were used to assess the importance of subthreshold electrotonic interactions between the canine proximal bundle branches and adjacent septal myocardium, and vice versa. Bundle branch action potential duration, maximal rising velocity of phase O, current threshold requirements for all-or-none depolarization, transmembrane voltage, and spontaneous frequency were not altered by adjacent septal muscle activation. Activation of the proximal bundle branches did not change the transmembrane voltage of immediately subjacent muscle cells; likewise, all-or-none activation of ventricular septal muscle did not effect a voltage change in the overlying proximal bundle branches. We conclude that a high ohmic resistance barrier between proximal bundle branch and subjacent muscle precludes significant electrotonic interactions between these neighboring structures.

Action Potentials↗