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Biomedical subjects

P F Cranefield

Publications and source records attributed to P F Cranefield.

16 recordsLinked to original sources
PubMed1991

Torsades de pointes and early afterdepolarizations.

It is suggested that torsades de pointes may be only one of a group of arrhythmias that are characterized by being pause induced or bradycardia induced. A distinction is made between the cause of the "twisting of the points" and the cause of the action potentials that initiate and sustain the tachycardia. It is pointed out that torsades de pointes and other pause-induced arrhythmias share many features with rhythmic activity arising from early afterdepolarizations. Both are seen after pauses or at low rates, both are seen in quinidine intoxication, and both are seen in hypokalemia. The short-long-short sequence that is seen in torsades de pointes and certain other pause- or bradycardia-induced arrhythmias can be fully explained by the behavior of rhythmic activity initiated and sustained by early afterdepolarizations, as can the abrupt onset and termination of pause-induced arrhythmias and their tendency to show initial warming up and terminal slowing down.

Animals↗
PubMed1988

Torsade de pointes and other pause-induced ventricular tachycardias: the short-long-short sequence and early afterdepolarizations.

The early afterdepolarization, which is an interruption of repolarization, can evoke a second upstroke or a salvo of action potentials. It is suggested that the electrophysiological characteristics of the early afterdepolarization can produce a lengthening of the QT interval and that the second upstroke and salvo of activity that may follow, it can explain many features of torsade de pointes and of certain other ventricular tachycardias. The early afterdepolarization, torsade de pointes, and repetitive monomorphic idiopathic ventricular tachycardia are all induced by bradycardia or by a preceding long RR interal. The R-on-T phenomenon is also discussed.

Animals↗
PubMed1979

Direct measurement of changes in sodium pump current in canine cardiac Purkinje fibers.

Purkinje fibers from dog hearts may have either a "high" resting potential of about -90 mV or a "low" resting potential of about -40 mV when immersed in low-Cl(-) solution containing 4 mM K(+). Brief exposure of Purkinje fibers at the low level of resting potential to K(+)-free fluid causes further depolarization, and return to K(+)-containing solution elicits a transient hyperpolarization which reaches a peak within a few seconds and then declines within a few minutes. Repeating these changes in K(+) concentration after clamping the membrane potential at its steady resting level in K(+)-containing fluid allows the changes in net membrane current presumably underlying the depolarization and transient hyperpolarization to be measured. Net inward current is recorded when the fiber is exposed to K(+)-free solution, and a transient net outward current arises when it is returned to K(+)-containing solution. The transient net outward current reflects a temporary increase in the rate of electrogenic Na(+) extrusion caused by the rise in intracellular Na(+) concentration that occurs while the sodium pump is slowed in K(+)-free fluid. Sodium extrusion remains enhanced, presumably until the internal Na(+) concentration has been brought back to its resting level. The transient outward current is completely abolished by the cardiac steroid acetylstrophanthidin, and its amplitude is increased as the prior exposure to K(+)-free fluid is prolonged. The decay of the transient outward current and the decline in intracellular Na(+) concentration both appear to follow first-order kinetics.

Animals↗
PubMed1979

Electrogenic sodium extrusion in cardiac Purkinje fibers.

Thin canine cardiac Purkinje fibers in a fast flow chamber were exposed to K-free fluid for 15 s to 6 min to initiate "sodium loading," then returned to K-containing fluid to stimulate the sodium pump. The electrophysiological effects of enhanced pump activity may result from extracellular K depletion caused by enhanced cellular uptake of K or from an increase in the current generated as a result of unequal pumped movements of Na and K, or from both. The effects of pump stimulation were therefore studied under three conditions in which lowering the external K concentration ([K]0) causes changes opposite to those expected from an increase in pump current. First, the resting potential of Purkinje fibers may have either a "high" value of a "low" (less negative) value: at the low level of potential, experimental reduction of [K]0 causes depolarization, whereas an increase in pump current should cause hyperpolarization. Second, in regularly stimulated Purkinje fibers, lowering [K]0 prolongs the action potential, whereas an increase in outward pump current should shorten it. Finally, lowering [K]0 enhances spontaneous "pacemaker" activity in Purkinje fibers, whereas an increase in outward pump current should reduce or abolish spontaneous activity. Under all three conditions, we find that the effects of temporary stimulation of the sodium pump are those expected from a transient increase in outward pump current, not those expected from K depletion.

Action Potentials↗
PubMed1978

Reentrant excitation as a cause of cardiac arrhythmias.

Mechanisms that cause reentry were defined in rings of tissue cut from jellyfish as early as 1906 by Mayer. The concepts were developed by Mines and Garrey during the next 10 years. Lewis then tried to demonstrate that reentry caused atrial flutter. Lewis, Garrey, and later Moe also proposed that atrial fibrillation was caused by reentry. Rosenblueth provided additional experimental evidence that reentry could cause atrial arrhythmias after crushing the intercaval bridge of atrial muscle. Recent studies by Allessie using microelectrodes have provided detailed evidence for reentry in atrial tissue. Mines in 1913 also proposed that reentry could occur in the AV node. Scherf then introduced the concept of functional longitudinal dissociation as a cause of return extrasystoles and this was later shown to happen in the node by Moe and his colleagues. Reentry can also occur between atria and ventricles utilizing accessory connecting pathways. Schmitt and Erlanger in 1913 were the first to do experiments which indicated that reentry can also occur in the ventricles. Subsequently it was shown that reentry can occur in Purkinje fiber bundles. Reentry in ventricular muscle may also cause some of the arrhythmias that occur after myocardial infarction.

Action Potentials↗
PubMed1978

The effects of acetylcholine on the electrical activity of canine cardiac Purkinje fibers.

We studied the effects of acetylcholine (ACh) on small bundles of canine cardiac Purkinje fibers exposed to normal, or low-chloride (isethionate) Tyrode's solution in a rapid superfusion system. In superfusate containing 4 mM K+, the resting potential of Purkinje fibers may be either "low," near -40 mV, or "high," near -90 mV. ACh, at 10(-6) to 10 (-5) M, increased the membrane potential from both the low and high resting levels and, in low-Cl solution, often induced a maintained shift in potential from the low to the high level. The increase in membrane potential caused by ACh was greater at the low than at the high level. ACh, at 10(-6) to 10(-5) M, reduced action potential duration in both normal and low-Cl Tyrode's solution, the effect being more marked in the latter. These effects of ACh were reversibly abolished by atropine (5 X 10(-5) M), indicating that they were mediated via muscarinic ACh receptors, and they probably result from an increase in membrane K+ conductance since 10(-5) M ACh reversibly reduced, by 13% on the average, the amplitudes of the steady changes in membrane potential evoked by applying small current pulses (-5 to -25 nA, 200 msec). ACh (10(-5) M) also diminished the rate of, or stopped, spontaneous activity arising from either level of membrane potential. The cessation of spontaneous slow response activity, arising from the low level, sometimes was accompanied by a maintained shift of the membrane potential to the high resting level. It is concluded that the action of ACh on Purkinje fibers is qualitatively similar to its action on sinoatrial nodal and atrial cells.

Acetylcholine↗
PubMed1978

Effects of lidocaine and on slow response and depressed fast response action potentials of canine cardiac Purkinje fibers.

Disease may decrease resting potential of cardiac fibers, thereby depressing the upstroke velocity of the action potential, causing slow conduction and reentry. A decrease in resting potential may also cause automaticity. We studied the effects of lidocaine (5 and 20 mg/l) on canine Purkinje fibers with reduced membrane potentials with either depressed Na+-dependent upstrokes (depressed fast responses) or with slow inward (Ca++) current-dependent upstrokes (slow responses). Depressed fast responses were produced by elevating [K+]0 in the perfusate, reducing membrane potential to around -60 mV, without abolishing excitability. Slow responses were produced by either perfusing fibers with a Na+-free, Ca++-rich solution, or by perfusing them with a high [K+]0 Tyrode's solution containing norepinephrine. Lidocaine had a marked depressant effect on depressed fast response action potentials. The drug markedly decreased Vmax and conduction velocity. It sometimes decreased action potential amplitude and caused conduction block. Resting potential was not changed. On the other hand, lidocaine had little effect on slow response action potentials. Resting potential, Vmax and action potential amplitude were not altered nor was conduction changed. The rate of spontaneous impulse initiation was slightly reduced by 5 mg/l of lidocaine but not by 20 mg/l. We conclude that lidocaine does not exert its antiarrhythmic effect by directly depressing the slow inward current but may be antiarrhythmic because it depresses an already depressed fast inward current and can cause conduction block.

Action Potentials↗
PubMed1977

Two levels of resting potential in cardiac Purkinje fibers.

In an appropriate ionic environment, the resting potential of canine cardiac purkinje fibers may have either of two value. By changing the external K concentration, [K](0), in small steps, it was shown that, in the low (1 mM) Cl, Na-containing solutions used in this study, the two levels of resting potential could be obtained only within a narrow range of [K](0) values; that range was usually found between 1 and 4 mM. Within the critical [K](0) range the resting potential could be shifted from either level to the other by the application of small current pulses. It was shown that under these conditions the steady-state current- voltage relationship was "N-shaped," and that a region of both negative slope, and negative chord conductance lay between the two stable zero-current potentials. The negative chord conductance was largely due to inward sodium current, only part of which was sensitive to tetrodotoxin (TTX). Under appropriate conditions, the negative chord conductance could be abolished by several experimental interventions and the membrane potential thereby shifted from the lower to the higher resting level: those interventions which were effective by presumably diminishing the steady-state inward current included reducing the external sodium concentration, adding TTX, or adding lidocaine; those which presumably increased the steady-state outward current included small increases in [K](0), brief depolarizations to around -20 mV, or the addition of acetylcholine chloride.

Action Potentials↗
PubMed1977

Action potentials, afterpotentials, and arrhythmias.

Triggered activity must be added to spontaneous activity and to circus movement as a cause for extrasystoles and tachycardias of either atrial or ventricular origin. The activity of a triggerable focus requires phase 4 depolarization caused by an afterpotential; this distinguishes it from the activity seen in circus movement. A triggerable focus becomes rhythmically active only if driven at a critical rate or by a critically timed premature impulse; this distinguishes it from a focus of spontaneous or automatic activity. The ease of triggering a triggerable focus increases in the presence of catecholamines; triggerable foci in the atrium become quiescent when exposed to acetylcholine. At the present time, fibers within the coronary sinus provide the most persuasive example of triggered activity as a possible cause of arrhythmias of clinical significance. It is possible that the coupled extrasystoles of digitalis toxicity may be triggered; there is every reason to believe that further examples of triggered arrhythmias of possible clinical significance will be discovered.

Action Potentials↗
PubMed1976

Triggered activity in cardiac muscle fibers of the simian mitral valve.

The action potential of cardiac fibers in the anterior mitral valve leaflet of the monkey heart is followed by an after-hyperpolarization. The addition of catecholamines causes a delayed after-depolarization to follow the after-hyperpolarization. The amplitude of the after-depolarization increases as the stimulus cycle length is decreased, or after premature stimulation, and as a result can reach threshold to yield nondriven, sustained rhythmic activity which we term triggered activity. This sustained rhythmic activity can be terminated by a single, appropriately timed, premature stimulus. The amplitude of the action potentials of mitral valve fibers is increased by catecholamines; the amplitude and rate of depolarization are depressed by verapamil. The amplitude of the action potentials is little affected by tetrodotoxin (TTX) but the maximum rate of depolarization is reduced by TTX. The delayed after-depolarization induced by catecholamines is abolished by verapamil, as is triggered activity. These observations suggest that mitral valve fibers generate slow response action potentials, that triggerable sustained rhythmic activity may be a property of the slow response and that such activity may cause the types of cardiac arrhythmias that usually are attributed to reentry.

Action Potentials↗
PubMed1976

Two levels of resting potential in canine cardiac Purkinje fibers exposed to sodium-free solutions.

Canine cardiac Purkinje fibers exposed to sodium-free solutions containing 16 mM CaCl2, 20 mM tetraethylammonium chloride, 108 mM tetramethylammonium chloride, and 2.7 mM KCl may be quiescent at a resting potential of either -50 mV or -90 mV. The membrane potential of these fibers can be switched from -50 mV to -90 mV by a hyperpolarizing current pulse and from -90 mV to -50 mV by a depolarizing current pulse. The transition from -50 mV to -90 mV depends on a voltage-dependent increase in potassium conductance, that conductance being low at -50 mV and high at -90 mV. A reduction in potassium conductance causes the fiber to depolarize from -90 mV to -50 mV because of the presence of an inward current which apparently is carried mainly by Ca. Fibers that show a high resting potential cannot be excited except by depolarizing stimuli strong enough to move the membrane from -90 mV to a threshold potential of about -40 mV. Fibers that show a low resting potential are more easily excited and may show rhythmic activity sustained by afterpotentials that appear only if the low membrane potential is accompanied by a low potassium conductance. Slow changes in membrane potential also are seen; these changes may result from movements of chloride.

Action Potentials↗
PubMed1975

The effects of verapamil and paired-pulse stimulation on mammalian ventricle.

Postextrasystolic potentiation induced by paired-pulse stimulation was studied in mammalian ventricle muscle in the presence of verapamil (0.2-4.0 muM). Verapamil exerts a negative inotropic effect on the potentiated contraction, but the force of the potentiated contraction in the presence of verapamil is greater than that of the normal, unpotentiated contraction in the absence of verapamil. The positive inotropic effect of paired stimulation appears to result both from an additional calcium influx appearing as a calcium current during the plateau of the premature action potential and from some additional mechanism, tentatively identified as a Na: Ca exchange. Our results suggest that paired-pulse stimulation could be used clinically to counteract the negative inotropic effects of verapamil; moreover, the antiarrhythmic action of verapamil might counteract any arrhythmias caused by paired pacing.

Animals↗