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Biomedical subjects

A L Wit

Publications and source records attributed to A L Wit.

At least 91 records · Page 5Linked to original sources
PubMed1978

Actions of lidocaine on transmembrane potentials of subendocardial Purkinje fibers surviving in infarcted canine hearts.

We compared the effects of lidocaine, 2 X 10(-5) M, on transmembrane resting and action potentials of Purkinje fibers on the endocardial surface of 24- to 72-hour-old myocardial infarcts in dogs with its actions and subendocardial Purkinje fibers in normal hearts. At both proximal (near the tip of the papillary muscle) and distal (toward the apex) recording sites in noninfarcted hearts, lidocaine had no significant effect on maximum diastolic potential (MDP) or Vmax. It shortened action potential duration (APD) only at the proximal site. In infarcted hearts, we arbitrarily divided Purkinje fibers at the infarcted distal site into two groups. Group I consisted of fibers which did not have a severely depressed MDP or Vmax but in which APD was markedly prolonged. Lidocaine had no effect on MDP of these fibers, significantly depressed Vmax, and shortened APD. Group II consisted of fibers in which MDP and Vmax were markedly reduced. Lidocaine also reduced Vmax of these fibers further (by 60%) without altering resting potential. In addition, lidocaine depressed pacemaker activity of Purkinje fibers in infarcts. The drug did not alter conduction of premature impulses in the subendocardial Purkinje network in normal hearts but increased the maximum delay of early premature impulses in Purkinje fibers in infarcted hearts and sometimes resulted in nondriven repetitive activity. Therefore, the effects of lidocaine on transmembrane potentials of Purkinje fibers in infarcts are different from its effects on fibers in normal hearts.

Action Potentials↗
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↗
PubMed1976

Structural basis of ventricular arrhythmias in human myocardial infarction: a hypothesis.

The present study was undertaken using light and electron microscopic techniques to determine whether Purkinje fibers survive in the subendocardial region of anteroseptal infarcts in humans. Tissue was obtained for this purpose from 11 patients with 12 documented infarctions at the time of autopsy; six patients died within 72 hours of the infarction and five had healed infarcts. Seven of the 11 patients had ventricular arrhythmias. Light microscopic study indicated that intact cells with a normal appearance remained on the subendocardial surface, although the underlying ventricular muscle either was necrotic or was replaced by fibrous tissue. Electron microscopy demonstrated that these intact surviving cells over the surface of the infarct had few randomly oriented myofibrils, abundant glycogen, and other characteristics of Purkinje fibers. These cells could be readily distinguished from normal or infarcted ventricular muscle cells. Purkinje fibers, the most peripheral part of the conduction system, survive in extensive anteroseptal infarcts and may be the site of origin of ventricular arrhythmias.

Animals↗
PubMed1976

Eelctrophysiologic and ultrastructural characteristics of the canine tricuspid valve.

Collagen extending from chordae tendineae sweeps into each tricuspid leaflet in a loose fanlike arrangement merging with the annulus. Each leaflet contains variable amounts of cardiac muscle in continuity with right atrial muscle; valve fibers are sparse, and scattered myofibers and/or bundles of myofibers usually extend only 2-3 mm into the leaflet body. Valve myofibers are structurally identical to working right atrial muscle but are 2-3 mum in diameter compared to 5-7 mum in working muscle. Electrical stimulation of the low right atrial wall often induces propagated activity in the leaflet. Transmembrane recordings obtained from isolated Tyrode superfused leaflets showed low maximum diastolic potential, action potential amplitude, and rate of depolarization; action potentials usually had prominent plateaus. Excitation of discrete regions in tricuspid leaflets did not excite atrial wall, but valve muscle fibers often developed spontaneous diastolic depolarization and automaticity after stretch or exposure to catecholamines Automaticity was suppressed by acetylcholine. Physiological and pathophysiological significance of tricuspid muscle may reside in its participation in valve closure during ventricular contraction and the fact that it is a site of abnormal impulse formation.

Acetylcholine↗
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↗
PubMed1975

Electrophysiology and pharmacology of cardiac arrhythmias. III. The causes and treatment of cardiac arrhythmias. Part B.

Studies on the electrophysiologic mechanisms responsible for disturbances of cardiac rate, rhythm, and conduction, and studies on the actions and mechanisms of action of antiarrhythmic and other drugs, permit the development of an apparently reasonable approach to treatment of cardiac arrhythmias. Some of the rules derived from an appreciation of cardiac electrophysiology are generally applicable. Others appear to require further testing. There are many discrepancies between what can be predicted or expected and what happens; these discrepancies result from many factors. It is likely that cardiac disease in humans has effects on the electrical activity of cardiac cells which have not been reproduced in the laboratory. It is likely, also, that disease modifies the response of cardiac cells to drugs in ways that have not yet been discovered. Nevertheless, some progress has been made and further experiment and thought may provide both better understanding and new and better therapeutic agents.

Arrhythmias, Cardiac↗
PubMed1975

Electrophysiology and pharmacology of cardiac arrhythmias. VIII. Cardiac effects of diphenylhydantoin. B.

DPH is highly effective against both atrial and ventricular arrhythmias resulting from digitalis toxicity and should be considered one of the primary antiarrhythmic drugs in this clinical situation. Clinical studies have indicated that DPH, for the most part, is effective against atrial arrhythmias and not markedly effective against ventricular arrhythmias associated with acute or chronic cardiac disease. For the latter ventricular arrhythmias, DPH is usually considered only after other antiarrhythmic drug therapy has failed. Studies on the mechanisms responsible for the antiarrhythmic effects of DPH are, as yet, inconclusive, There is good evidence that its actions differ from those of the commonly used drugs with local anesthetic effects. The extent to which it exerts direct effects on the heart which are therapeutically relevant remains to be demonstrated; further, there is solid evidence that its effects on the central nervous system may be of prime importance in its antiarrhythmic efficacy.

Action Potentials↗