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Biomedical subjects

A L Wit

Publications and source records attributed to A L Wit.

At least 73 records · Page 4Linked to original sources
PubMed1983

The basis for the membrane potential of quiescent cells of the canine coronary sinus.

During prolonged periods of quiescence, the membrane potential of cells in the isolated canine coronary sinus, exposed to normal Tyrode solution containing 4 mM-K, declines to about -60 mV. The nature of the resting potential was investigated, in small strips of coronary sinus tissue mounted in a fast-flow system, by recording the membrane potential responses to sudden changes in the extracellular ionic environment. At extracellular K concentrations ([K]o) from 0 to 64 mM the resting potential was little affected by replacing all but 1 mM of external Cl ions with isethionate and methylsulphate ions. At [K]o levels from 4 to 150 mM the resting potential was reasonably well described by the Goldman-Hodgkin-Katz equation on the assumption that the intracellular K concentration ([K]i) was 155 mM and that the ratio of membrane permeability coefficients for Na and K, PNa/PK, was 0.07. In the presence of a high concentration of acetylcholine or carbachol (greater than or equal to 1 microM), the resting potentials at [K]o levels from 1 to 150 mM approximated K equilibrium potentials (EK) calculated on the assumption that [K]i was 155 mM. At [K]o levels less than or equal to 8 mM replacing most of the external Na with sucrose or Tris caused a substantial hyperpolarization, whereas application of 1-2 microM-tetrodotoxin caused only slight hyperpolarization. A transient hyperpolarization, due to enhanced electrogenic Na extrusion, was recorded on switching back to 4 mM-K following brief exposures to K-free solution; no transient hyperpolarization was recorded in the presence of 5 microM-acetylstrophanthidin. The acetylstrophanthidin itself caused a rapid depolarization of several millivolts. Preliminary conductance measurements made with two micro-electrodes in some smaller preparations indicate that the steady-state current-voltage relationship is N-shaped. We conclude that the low membrane potential of quiescent coronary sinus cells reflects not a low [K]i but rather a relatively high ratio PNa/PK, of about 0.07: the Na ions flow into the cells via predominantly TTX-insensitive pathways and are extruded by the electrogenic Na/K exchange pump, which thereby makes a substantial contribution to the resting potential.

Acetylcholine↗
PubMed1983

Recurrent sustained ventricular tachycardia: structure and ultrastructure of subendocardial regions in which tachycardia originates.

Surgical resection of the endocardium and subendocardium often abolishes chronic recurrent sustained ventricular tachycardia in patients with healed myocardial infarcts or ventricular aneurysms, presumably by interrupting the reentrant pathway. To define the morphologic characteristics of cells in the reentrant pathway, we studied the histology and ultrastructure of the endocardial resections of 23 patients who underwent this procedure. Bundles of apparently viable myocardial fibers embedded in dense fibrous tissue were identified throughout the endocardial resections from all patients. These bundles of cells were separated from one another by fibrous tissue but extended uninterrupted to the margins of the surgical resection. In 14 patients Purkinje fibers were identified beneath the thickened endocardium whereas the remaining bundles were composed of ventricular muscle. The Purkinje fibers appeared to have normal ultrastructure and ventricular cells with both normal and abnormal ultrastructures were present. The abnormal muscle cells were characterized by loss of contractile elements, aggregates of dilated sarcoplasmic reticulum, and osmiophilic dense bodies. The sarcolemma was intact and the nuclear chromatin was evenly dispersed suggesting that these cells were still viable. The abnormal structure and arrangement of the surviving cardiac fibers in the endocardium may cause the abnormal electrophysiologic function that results in ventricular tachycardia.

Adult↗
PubMed1982

Method for evaluating the effects of antiarrhythmic drugs on ventricular tachycardias with different electrophysiologic characteristics and different mechanisms in the infarcted canine heart.

In a canine model of myocardial infarction caused by coronary occlusion and reperfusion, ventricular tachycardia occurs spontaneously at 24 hours and has many of the characteristics of an accelerated idioventricular rhythm. It cannot be induced by premature or rapid stimulation of the ventricles; overdrive pacing during this tachycardia usually causes some transient overdrive suppression but occasionally there is overdrive acceleration. We suggest that this arrhythmia is caused mainly by enhanced automaticity. Ventricular tachycardia also can be induced by premature or rapid ventricular pacing 3 to 5 days after infarction, but it does not occur spontaneously. It can be stopped by overdrive pacing, suggesting that it is caused by reentry. Electrocardiographic features are identical to chronic, recurrent sustained ventricular tachycardia in human patients. Because the arrhythmias occurring at different times probably result from different mechanisms this canine model is useful for comparing the actions of drugs on different kinds of arrhythmias. Lidocaine and procainamide generally abolished tachycardia 24 hours after infarction, but only procainamide abolished tachycardia 3 to 5 days after infarction. Isoproterenol accelerated tachycardia at both times. Verapamil did not abolish tachycardia 3 to 5 days after infarction.

Animals↗
PubMed1982

Effects of left atrial enlargement on atrial transmembrane potentials and structure in dogs with mitral valve fibrosis.

The effects of left atrial enlargement on atrial cell electrophysiology and structure were studied in dogs with mitral valve fibrosis. Thirteen dogs (Groups I) had left atrial enlargement and intermittent atrial arrhythmias; 10 dogs (Group II) had left atrial enlargement and chronic atrial fibrillation. The resting and action potentials of cells in isolated preparations from the enlarged left atrium were found not to differ from those in the nonenlarged right atrium or in the atrium of control dogs. The resting and action potentials of cells in Group II atria did not differ significantly from those in Group I atria. Some cells (15 percent of the total studied) in the atria of dogs in Groups I and II were inexcitable, but either superfusion with acetylcholine or norepinephrine restored excitability. The structural studies showed that the left atrium of the dogs in Groups I and II had a reduced number of muscle cell layers spanning the wall with an unusually large amount of connective tissue between greatly hypertrophied cells. Very few degenerating cells were seen. Dramatic abnormalities of cell electrophysiology may not be involved in the genesis of arrhythmias in the enlarged canine atrium, and the altered morphologic features of the atrium in these dogs may be important in the genesis of persistent atrial arrhythmias.

Acetylcholine↗
PubMed1982

Electrophysiologic mapping to determine the mechanism of experimental ventricular tachycardia initiated by premature impulses. Experimental approach and initial results demonstrating reentrant excitation.

Epicardial activation patterns were determined during repetitive responses and nonsustained and sustained ventricular tachycardias induced by premature impulses in infarcted canine hearts. A multiplexing system enabled recordings to be obtained from up to 192 electrodes simultaneously either from the entire epicardial surface with a sock electrode array or only from the sheet of epicardial muscle that survives over the infarcts, with a plaque electrode array. In hearts with an infarct caused by permanent occlusion of the left anterior descending coronary artery, the earliest epicardial excitation during nonsustained tachycardias occurred on the anterior left ventricle at the border of the infarcted region and in epicardial muscle surviving over the infarcted region. Circuitous conduction patterns leading to reentry occurred in the epicardial muscle over the infarct and probably caused the arrhythmias. During sustained tachycardia in hearts with an infarct caused either by permanent or temporary occlusion of the left anterior descending coronary artery, the earliest epicardial excitation also occurred at the border of the infarcted region, but there was no evidence of reentry in the surviving epicardial muscle.

Animals↗
PubMed1981

Electrogenic sodium extrusion can stop triggered activity in the canine coronary sinus.

Soon after a burst of triggered activity in the canine coronary sinus begins, an initial fall in maximum diastolic potential and increase in rate gives way to an increase in maximum diastolic potential, reduction in rate, and eventual quiescence. This hyperpolarization, slowing, and subsequent quiescence might result from enhanced electrogenic sodium/potassium extrusion caused by the rise in intracellular sodium concentration ([Na+]i) associated with the high rate of firing. Triggered bursts can be terminated prematurely by a sudden increase in the rate of sodium extrusion, Brief exposure to K+- free fluid is known to cause [Na+]i to rise; reactivating the pump by switching back to K+-containing fluid causes immediate hyperpolarization, and within a few seconds, quiescence. Brief periods of overdrive, also thought to increase [Na+]i, are followed by hyperpolarization, slowing and, often, by premature termination of the burst. Inhibiting the sodium/potassium pump by exposure to 2 micrometer acetylstrophanthidin or to K+-free fluid (1) prevents or delays the hyperpolarization, (2) increases the rate of triggered activity and (3) prolongs bursts of activity when bursts last less than 2.5 minutes under control conditions. In the presence of 2 micrometer acetylstrophanthidine, neither brief exposures to K+- free fluid not overdrive causes sudden, premature termination of triggered bursts. Bursts do eventually stop in the presence of pump inhibitors; however, that termination is associated with an increase in rate and a decline in maximum diastolic potential and in action potential amplitude. We conclude that electrogenic Na+ extrusion plays an important role in the spontaneous termination of triggered activity.

Animals↗
PubMed1980

Coronary occlusion and reperfusion: effects on subendocardial cardiac fibers.

Coronary flow and transmembrane potentials of Purkinje and muscle fibers in reperfused infarcts and infarcts caused by permanent coronary occlusion were compared. Purkinje fibers in permanently occluded infarcts at 24 h had markedly reduced resting potentials. Action potential amplitudes, and Vmax were reduced and duration markedly prolonged. In reperfused infarcts, changes in Purkinje fiber transmembrane potentials were not as marked. Action potential duration in 3-day-old permanently occluded infarcts were longer than at 24 h, but in reperfused infarcts durations had returned to normal. Premature impulses conducted more rapidly in the reperfused infarct Purkinje system than in the permanently occluded. Other transmembrane potential parameters of Purkinje fibers in 3-day-old and 9- to 10-day-old reperfused and permanently occluded infarcts were not significantly different from each other. The ventricular muscle cells that survived in reperfused infarcts at all times also had reduced resting potentials and action potentials with decreased amplitudes, reduced Vmax, and prolonged durations. Almost no muscle cells survived in permanently occluded infarcts. Therefore, reperfusion salvages subendocardial fibers and prevents some but not all of the electrophysiological abnormalities.

Action Potentials↗
PubMed1979

Right atrial ultrastructure in congenital heart disease. II. Atrial septal defect: effects of volume overload.

Portions of operatively resected right atrium from 15 patients with atrial septal defect were studied ultrastructurally to determine whether the cell hypertrophy in the right atrium of patients with increased right atrial blood flow and increased right atrial pressure is caused by the increased blood flow. In 12 patients with normal right atrial mean pressure but increased right atrial blood flow the atrium was dilated but no atrial arrhythmias were noted clinically. Ultrastructurally, the atrial myocardial cells in these patients were normal, measuring 6 to 10 mu in diameter, and there was no evidence of cell hypertrophy or degeneration. The remaining three patients had elevated right atrial mean pressure and increased right atrial blood flow. Ultrastructurally, the atrial myocardial cells in all three patients were hypertrophied, and two patients had evidence of focal cell degeneration; the atrium was markedly dilated, but atrial arrhythmias were not noted. The lack of cell hypertrophy in the right atrium of the 12 patients with increased blood flow but normal mean pressure suggests that in congenital heart disease volume overload alone does not lead to cell hypertrophy of the right atrial myocardium.

Adult↗
PubMed1979

Time course of infarct growth toward the endocardium after coronary occlusion.

Transmembrane potentials and ultrastructure of subendocardial Purkinje and ventricular muscle fibers, isolated 1, 3, 5, 6, 14, and 24 h after coronary occlusion were investigated. Action potentials were recorded from progressively fewer layers of muscle cells as the age of the infarct increased. At 14 h little viable muscle remained. The decrease in the number of electrophysiologically viable muscle fibers correlated with structural evidence that the infarct moved with time toward the endocardial surface until only viable Purkinje fibers remained. Purkinje and surviving ventricular muscle fibers demonstrated a progressive decrease in resting potential, action potential amplitude, and Vmax and a progressive increase in action potential duration. Spontaneous diastolic depolarizations were found in Purkinje fibers only in 24-h infarcts and occasionally in cells deep to the endocardial surface, which may have been muscle cells. We hypothesize that during the first 24 h after coronary occlusion arrhythmias originate near the interface of infarcted and ischemic myocardium. As this interface moves toward the endocardium, this site of origin of arrhythmias moves with it until the Purkinje network is reached.

Animals↗
PubMed1979

Protracted ventricular tachcardia induced by premature stimulation of the canine heart after coronary artery occlusion and reperfusion.

The effects of premature ventricular stimuli were studied in two groups of dogs with infarcts, one group subjected to permanent occlusion of the left anterior descending coronary artery and the other to temporary occlusion for 2 hours. In dogs with permanent occlusion, spontaneous ventricular arrhythmias occurred after 3-6 hours. In 13 dogs with temporary occlusion, ventricular arrhythmias occurred immediately after reperfusion and then persisted. In five dogs with temporary occlusion, ventricular arrhythmias did not occur spontaneously until 13-15 hours after occlusion. On days 2-9 after surgery, after sinus rhythm had returned, the ventricles of each awake dog were stimulated. After permanent occlusion, premature stimuli occurring on the T wave usually induced from one to 10 repetitive responses on days 2-4. Protracted ventricular tachycardia (lasting greater than 10 seconds) was induced in only two of 10 dogs. The response to premature stimuli was similar after temporary occlusion when ventricular arrhythmias did not occur spontaneously until 13-15 hours after occlusion. Protracted tachycardia was not induced. In the dogs with temporary occlusion, which initially had continuous arrhythmias, premature stimuli occurring on the T wave on days 3-5 after surgery induced both repetitive responses and protracted ventricular tachycardia. Stimuli applied to the ventricles during tachycardia terminated it. Histological studies on all infarcts showed that, after permanent occlusion, necrosis was uniform; after temporary occlusion, viable myocardium survived in the necrotic region. These salvaged myocardial fibers may provide reentrant pathways, causing long-lasting tachycardia.

Animals↗
PubMed1978

Right atrial ultrastructure in congenital heart disease. I. Comparison of ventricular septal defect and endocardial cushion defect.

Ultrastructural studies were performed on portions of the operatively resected right atrium from six patients with a ventricular septal defect and six patients with an endocardial cushion defect. The six patients with a ventricular septal defect had normal right atrial mean pressure and no evidence of right atrial volume overload. Ultrastructurally, the atrial muscle cells in these patients appeared normal and measured 6 to 12 mu in diameter. The six patients with an endocardial cushion defect had elevated right atrial mean pressure and evidence of right atrial volume overload. Ultrastructurally, the atrial muscle cells in these patients were generally larger than 12 mu in diameter. The cells were irregular and had multiple and occasionally widened intercalated discs. In addition, there were degenerative changes in two patients with markedly increased atrial pressure. These changes included extensive loss of contractile elements, aggregation of small irregular mitochondria and proliferation of tubules of the sarcoplasmic reticulum. The structural changes suggest that hypertrophy of the right atrium may be secondary to volume overload of the atrium, whereas degenerative changes may be secondary to increased right atrial pressure.

Basement Membrane↗
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↗