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Biomedical subjects

M N Levy

Publications and source records attributed to M N Levy.

At least 19 recordsLinked to original sources
PubMed1992

Analysis of vagally induced sinus arrhythmias.

Vagal stimulation at precise times in successive cardiac cycles can elicit sinus arrhythmias. Two mechanisms have been identified that can, but do not necessarily, cause these vagally induced sinus arrhythmias. First, changes in cycle length elicited by a given concentration of acetylcholine (ACh) depend on the phase of the pacemaker cell action potential when the ACh binds to muscarinic receptors. Second, acetylcholinesterase degrades ACh rapidly enough for the mean concentration of ACh per cardiac cycle to vary from cycle to cycle. We used a mathematical model of the underlying cellular physiology, to examine whether these mechanisms are responsible for arrhythmogenesis. Computer simulation showed that both mechanisms contribute to the vagally induced sinus arrhythmias.

Arrhythmias, Cardiac↗
PubMed1992

Synergism between cAMP and ATP in signal transduction in cardiac myocytes.

ATP transiently increases the intracellular Ca2+ concentration in cardiac myocyte suspensions. Pretreatment with norepinephrine (NE) greatly potentiates the ATP response. We performed experiments on adult rat myocyte suspensions loaded with fura-2 to investigate the mechanism of NE potentiation. We found that forskolin (an activator of adenylate cyclase), 3-isobutyl-1-methylxanthine (an inhibitor of phosphodiesterase), and permeative adenosine 3',5'-cyclic monophosphate (cAMP) analogues potentiate the increase in cytosolic Ca2+ concentration induced by ATP. NE, forskolin, and 8-(4-chlorophenylthio)-cAMP all increase Vmax of the Ca2+ response curve of ATP. Measurement of cAMP by radioimmunoassay confirmed that the changes in the ATP response were accompanied by an increase in cAMP. These results suggest that the noradrenergic potentiation of the ATP-induced Ca2+ mobilization involves cAMP as a second messenger. Patch-clamp studies of isolated myocytes showed that neither NE nor forskolin alters the inward current elicited by ATP, but rather they increase the duration of secondary slow action potentials elicited by ATP. NE also increases the Ca2+ current through L-type Ca2+ channels in the myocytes. We conclude that NE potentiates the ATP-induced Ca2+ transient by increasing cAMP levels and that one of the early events is the increase of the inward Ca2+ current during the action potential.

Adenosine Triphosphate↗
PubMed1992

Ca2+ mobilization by extracellular ATP in rat cardiac myocytes: regulation by protein kinase C and A.

Activation of protein kinase C (PKC) modulates the mobilization of intracellular Ca2+ induced by extracellular ATP in rat ventricular myocytes. Pretreatment of myocytes with PKC activators attenuated both the ATP-induced Ca2+ transient and the noradrenergic potentiation of the Ca2+ response. Various PKC activators decreased both the basal cAMP level and the cAMP levels that had been elevated by norepinephrine, forskolin, or 3-isobutyl-1-methylxanthine. The inhibitory effects of PKC activators were reversed by the PKC inhibitor staurosporine. The ATP-induced Ca2+ response is an integrated response resulting from ATP eliciting an inward cation current (IATP), cellular depolarization, Ca2+ influx through Ca2+ channels, and Ca2+ release from the sarcoplasmic reticulum. We used the whole cell voltage-clamp technique to investigate which steps of this integrated response are affected by PKC. PKC activators did not significantly affect the IATP. In contrast, PKC activators decreased the basal Ca2+ current (ICa) or Ba2+ current and the beta-adrenergic-stimulated ICa. These results suggest that PKC-induced suppression of the ATP-induced Ca2+ response and the beta-adrenergic-potentiated Ca2+ response is achieved at least partially by decreasing the intracellular cAMP level and ICa.

Adenosine Triphosphate↗
PubMed1979

Concealed extrasystoles due to Wenckebach conduction delay within the reentry loop.

Long electrocardiographic strips were analyzed from an aged patient whose heart rhythm had periods of unifocal ventricular extrasystoles with fixed coupling intervals. Periods of gradual prolongation of the coupling interval finally led to omission of a ventricular premature beat. This sequence was repetitive and is considered to be the results of reentrant extrasystoles with a 3:2 Wenckebach type of conduction delay within the reentry loop. The mechanism of concealed conduction due to overlong propagation within the reentry loop is discussed.

Aged↗
PubMed1979

Concealed quadrigeminy and quintageminy.

Electrocardiographic rhythm strips were analyzed from three patients who had frequent unifocal extrasystoles. Parasystole was excluded in all three cases. Analysis of the distributions of the numbers (S) of conducted sinus beats between extrasystoles revealed that the distributions conformed to two variants of concealed quadrigeminy (namely, the "S = 4n" and "S = 4n - 2" variants) and to one variant of concealed quintageminy (namely, the "S = 5n - 2" variant). The binomial theorem was used to test the likelihoods that these patterns of distribution of extrasystoles could occur on the basis of chance alone; the probabilities were all extremely small.

Adult↗
PubMed1979

Autonomic control of right atrial contractile strength in the dog.

The combined effects of parasympathetic and sympathetic stimulation on right atrial contractile strength were assessed in open-chest, pentobarbital-anesthesized dogs. A factorial experimental design was employed to quantify the percent changes in atrial contractile strength in spontaneously beating and paced hearts as a function of the frequencies of vagal and stellate ganglion stimulation. In 7 of 10 dogs, there was a substantial interaction between the two autonomic divisions; the sympathetically mediated inotropic effect became less pronounced as the background level of vagal stimulation increased. The relationship between stimulation frequencies and atrial contractile strength was not significnatly altered by pacing the hearts.

Animals↗
PubMed1979

Effects of repetitive bursts of vagal activity on atrioventricular junctional rate in dogs.

A stable atrioventricular (AV) junctional rhythm was produced in open-chest dogs by injecting pentobarbital into the sinus node artery. When the cervical vagus nerves were stimulated repetitively, the junctional pacemaker cells tended to become synchronized with the vagal activity. During such synchronization, the junctional rate varied directly rather than inversely with the frequency of vagal stimulation. The magnitude of the chronotropic response depended on the timing of the vagal stimuli within the cardiac cycle. In 9 dogs, when the mean heart periods were plotted as a function of the R-st intervals (i.e., the time from the beginning of ventricular depolarization to the beginning of the stimulus burst), the mean heart periods varied from a maximum of 1,815 ms to a minimum of 1,160 ms, depending on the R-st interval. A small change in the R-st interval was capable of evoking a relatively large change in cycle length. Therefore, the impulses from various efferent vagal fibers to the AV junction must arrive almost synchronously, the released acetylcholine must be removed rapidly, and the sensitivity of the pacemaker cells to acetylcholine must change rapidly at some critical time during the cardiac cycle.

Acetylcholine↗
PubMed1979

The effects of cocaine and metanephrine on the cardiac responses to sympathetic nerve stimulation in dogs.

The effects of infusions of cocaine (COC) and metanephrine (MET) on the inotropic and chronotropic responses to cardiac sympathetic nerve stimulation were studied in open-chest, anesthetized dogs. COC blocks the neuronal uptake of norepinephrine (NE), whereas MET blocks the extraneuronal uptake. Both blocking agents slightly enhanced the inotropic but not the chronotropic responses. COC prolonged the cardiac responses significantly, particularly the chronotropic responses, whereas MET had no appreciable effect on the durations of these responses. Hence, it appears that the neuronal uptake mechanism plays a major role in the dissipation of neurally released NE in the heart, but that the extra-neuronal uptake mechanism plays only a minor role in its dissipation. In contrast to the results in certain other tissues, the combined effects of COC and MET on the cardiac responses were no greater or more prolonged than the sum of the effects produced by each agent acting alone.

Analysis of Variance↗
PubMed1978

The influence of cocaine and desipramine on the cardiac responses to exogenous and endogenous norepinephrine.

In open-chest, anesthetized dogs, cocaine and desipramine potentiated the pressor, chronotropic, inotropic and coronary sinus blood flow responses to norepinephrine (NE) infusions. The chronotropic and inotropic responses were also prolonged, the former more markedly than the later and the extraction of exogenous NE from the coronary blood stream was diminished. Cocaine and desipramine also potentiated the pressor and coronary sinus blood flow responses, but not the chronotropic or inotropic responses, to stimulation of the left ansa subclavia. The inotropic response was slightly prolonged, however, and the chronotropic response was markedly prolonged. The overflow of NE into the coronary sinus blood was not increased by either neuronal uptake blocking agent. It is proposed that cocaine and desipramine, at the doses employed, diminish the release of NE from the cardiac nerve endings at the same time that they inhibit reuptake of the neurotransmitter. Their mechanisms of action and their side effects on the circulatory system do not appear to differ significantly.

Animals↗
PubMed1978

Concealed atrial bigeminy and trigeminy.

Patterns indicative of concealed atrial extrasystoles were observed in two patients with frequent premature atrial depolarizations. In the first patient, the predominant pattern was such that most of the numbers (S) of sinus P waves between atrial extrasystoles satisfied the equation S = 3n-1, where n is any positive integer. This pattern is characteristic of concealed trigeminy. Over a sequence of 49 interectopic intervals, this patient vacillated between concealed atrial trigeminy and bigeminy. A second patient displayed a pattern characteristic of the "even number" variant of concealed bigeminy. The numbers of sinus P waves in consecutive interectopic intervals were predominantly even. These various patterns of concealed atrial extrasystoles closely resemble previously reported patterns of concealed ventricular extrasystoles.

Aged↗
PubMed1978

Autonomic control of pacemaker activity in the atrioventricular junction of the dog.

A stable atrioventricular (AV) junctional rhythm was induced in open-chest, anesthetized dogs by injecting pentobarbital into the sinus node artery. A factorial experimental design was used to quantify the changes in AV junctional rate as a function of the frequency of cardiac sympathetic and parasympathetic stimulation. The AV junctional pacemaker cells were more responsive to autonomic neural stimulation, but the vagal-sympathetic interactions were less pronounced than had previously been observed for the SA nodal pacemaker cells. In a group of seven animals, sympathetic stimulation at a frequency of 1.4 Hz increased the AV junctional rate by 102% from a control rate of 54 beats/min. In the same animals, vagal stimulation at a frequency of 8.4 Hz reduced the AV junctional rate by 56%. In three other animals, the AV junction was even more responsive; equivalent chronotropic effects were achieved with stimulation frequencies that were only about one-third of those cited above. There was a moderate, but significant, autonomic interaction: in the group of seven animals, the positive chronotropic effect of sympathetic stimulation at 1.4 Hz was 72% greater at the low level (0 Hz) than at the high level (8.4 Hz) of vagal activity.

Animals↗
PubMed1978

The effect of changing interpulse intervals on the negative chronotropic response to repetitive bursts of vagal stimuli in the dog.

The chronotropic responses to repetitive bursts of vagal stimulation were determined in open-chest, anesthetized dogs. Either 5 or 10 electrical pulses were included in each stimulus burst, and the interpulse interval (deltat) was varied over the range of 5 to 150 msec. As the frequency of the stimulus bursts was progressively changed, the sinoatrial (SA) nodal pacemaker cells became synchronized with the repetitive bursts of stimuli over a certain range of burst frequencies. The magnitude of this frequency range varied with deltat. For 5 and 10 pulses/burst, the values of deltat that produced the greatest magnitude of this frequency range were 30.2 and 24.3 msec, respectively. Also, over the range of values of deltat from 5 to 50 msec, the magnitude of the negative chronotropic effect of the vagal stimulus burst varied directly with deltat. It is likely that, as the interpulse interval is increased within the range of values, either more acetylcholine is released from the vagal nerve endings per pulse or there is less saturation of the receptors on the pacemaker cell membranes during each burst.

Action Potentials↗
PubMed1977

Two variants of concealed trigeminy.

Long rhythm strips were analyzed from three patients with frequent unifocal ventricular extrasystoles. The predominant rhythm in each patient was concealed trigeminy; i.w., the number of conducted sinus beats, S, between extrasystoles satisfied the equation S = 3n --1, where n is any positive integer. In one of these patients, about one-fourth of the values of S did not satisfy this equation; however, all such exceptional values of S satisfied the equation S = 3n. In the other two patients, very few of the exceptional values of S fit the equation S = 3n, but they did conform to the equation S = 3n --2. It is proposed that in all forms of concealed trigeminy, there is a characteristic 3:1 block in the re-entry loop that is responsible for the extrasystoles. Furthermore, it is postulated that immediately after each manifest extrasystole, the 3:1 block is converted transiently to a 4:1 or 2:1 block in the "3n" and "3n--2" variants, respectively. After the first penetration of the block site after a manifest extrasystole, if the re-entrant impulse is concealed, the 3:1 ratio is resumed in both variants until the next manifest extrasystole appears.

Adult↗
PubMed1977

A subvariant of concealed bigeminy.

A subvariant of the "even variant" of concealed bigeminy was studied in two patients. The typical pattern consisted of two types of sequences of conducted sinus beats between extrasystoles. One pattern was bigeminal, i.e., alternating sinus beats and extrasystoles. Between bigeminal sequences were intervals in which there were more than one conducted sinus beat between extrasystoles. In such longer sequences, the numbers of sinus beats were almost invariably even. In the bigeminal sequences, the coupling intervals progressively diminished for each successive extrasystole in the sequence. The proposed explanation for the subvariant was based on a reentry loop in which there were three sites of block: proximal, intermediate, and distal. Block was postulated to take place at the proximal site after those extrasystoles with the shortest coupling intervals, at the intermediate site after odd-numbered conducted sinus beats in the non-bigeminal sequences, and at the distal site ("concealment") after the even-numbered sinus beats in these longer sequences.

Aged↗
PubMed1977

Correlation of the mechanical responses of the heart with the norepinephrine overflow during cardiac sympathetic neural stimulation in the dog.

The changes in heart rate and right ventricular contractile force were measured in anaesthetised dogs during stimulation of each ansa subclavia, and the responses were correlated with the overflow or norepinephrine (NE) into the coronary sinus blood. The increase in heart rate was considerably greater during stimulation of the right than of the left ansa subclavia. Conversely, left ansa stimulation had a slightly greater effect on right ventricular contractile force than did right-sided stimulation. The changes in norepinephrine overflow into the coronary sinus blood paralleled the alterations in contractile force; during stimulation at 2 and 4 Hz, the rates of norepinephrine overflow were 50 and 34% greater, respectively, with left-sided than with right-sided stimulation. On both the right and left sides, stimulation of the anterior limb of the ansa subclavia produced greater increments in heart rate and contractile force than did stimulation of the posterior limb. Similarly, the rates of norepinephrine overflow during anterior ansal stimulation were 100 and 75% greater than during posterior ansal stimulation for the right and left sides, respectively. Thus, both limbs of the two ansae subclaviae innervate the myocardial regions drained by the coronary sinus, but the greatest innervation arises from the anterior limb on the left side.

Animals↗