Supernormal Supernormal ConductionConduction

Dr. VIKAS MEDEPDr. VIKAS MEDEP

Membrane potentialMembrane potential (also (also transmembrane potentialtransmembrane potential or or membrane voltagemembrane voltage) is the difference in ) is the difference in electric potentialelectric potential between the interior and the exterior of between the interior and the exterior of a biological cell. a biological cell.

With respect to the exterior of the cell, typical values of With respect to the exterior of the cell, typical values of membrane potential range from –40 mV to –80 mV.membrane potential range from –40 mV to –80 mV.

All animal cells are surrounded by a membrane All animal cells are surrounded by a membrane composed of a lipid bilayer with proteins embedded in it. composed of a lipid bilayer with proteins embedded in it.

The membrane serves as both an insulator and a The membrane serves as both an insulator and a

diffusion barrier to the movement of ions.diffusion barrier to the movement of ions.

Ion transporter/pumpIon transporter/pump are electrically equivalent to a set of batteries and are electrically equivalent to a set of batteries and

resistors inserted in the membrane, and therefore create resistors inserted in the membrane, and therefore create a voltage difference between the two sides of the a voltage difference between the two sides of the membrane.membrane.

All eukaryotic cells maintain a non-zero transmembrane All eukaryotic cells maintain a non-zero transmembrane potential, with a negative voltage in the cell interior as potential, with a negative voltage in the cell interior as compared to the cell exterior ranging from –40 mV to –compared to the cell exterior ranging from –40 mV to –80 mV.80 mV.

The membrane potential has two basic functions. The membrane potential has two basic functions. First, it allows a cell to function as a battery, providing First, it allows a cell to function as a battery, providing

power to operate a variety of "molecular devices" power to operate a variety of "molecular devices" embedded in the membrane. embedded in the membrane.

Second, in electrically excitable cells such as neurons Second, in electrically excitable cells such as neurons and muscle cells, it is used for transmitting signals and muscle cells, it is used for transmitting signals between different parts of a cell between different parts of a cell

In non-excitable cells, and in excitable cells in their In non-excitable cells, and in excitable cells in their baseline states, the membrane potential is held at a baseline states, the membrane potential is held at a relatively stable value, called the relatively stable value, called the resting potentialresting potential

For neurons, typical values of the resting potential range For neurons, typical values of the resting potential range from –70 to –80 millivolts.from –70 to –80 millivolts.

The opening and closing of ion channels can induce a The opening and closing of ion channels can induce a departure from the resting potential. departure from the resting potential.

This is called a This is called a depolarizationdepolarization if the interior voltage if the interior voltage becomes more positive (say from –70 mV to –60 mV), becomes more positive (say from –70 mV to –60 mV),

Or a Or a hyperpolarizationhyperpolarization if the interior voltage becomes if the interior voltage becomes

more negative (say from –70 mV to –80 mV).more negative (say from –70 mV to –80 mV).

In excitable cells, a sufficiently large depolarization can In excitable cells, a sufficiently large depolarization can evoke an evoke an action potentialaction potential, in which the membrane , in which the membrane potential changes rapidly and significantly for a short potential changes rapidly and significantly for a short time often reversing its polarity.time often reversing its polarity.

Action potentials are generated by the activation of Action potentials are generated by the activation of certain voltage-gated ion channelscertain voltage-gated ion channels

The The threshold potentialthreshold potential is the critical level to which the is the critical level to which the membrane potential must be depolarized in order to membrane potential must be depolarized in order to initiate an action potential initiate an action potential

Supernormal Conduction

DEFINITION Supernormal conduction implies conduction that is better than Supernormal conduction implies conduction that is better than

anticipated or conduction that occurs when block is expected. anticipated or conduction that occurs when block is expected. It should be emphasized that most of the cases of so-called It should be emphasized that most of the cases of so-called

supernormal conduction described in humans have been supernormal conduction described in humans have been associated with baseline disturbances of A–V conduction. associated with baseline disturbances of A–V conduction.

Therefore, the term Therefore, the term supernormal has been referred to supernormal has been referred to improved conduction but not to conduction that is better improved conduction but not to conduction that is better than normalthan normal

Mackenzie‘ in1913. 1925,Lewis, Mackenzie‘ in1913. 1925,Lewis, In man, "supernormal"conduction is recorded only in In man, "supernormal"conduction is recorded only in

abnormally functioning cardiac tissue.abnormally functioning cardiac tissue.

Effects of Membrane Potential on Supernormal Excitability and Conduction.

In 1955,Weidmann demonstrated the relationship In 1955,Weidmann demonstrated the relationship between the amplitude and voltage time Course of between the amplitude and voltage time Course of Purkinje fiber actionpotentials evoked at different levels Purkinje fiber actionpotentials evoked at different levels of membrane potential by means of premature of membrane potential by means of premature stimulation.stimulation.

Impulses resulting from premature stimulation were Impulses resulting from premature stimulation were thought to propagate at reduced velocity until they thought to propagate at reduced velocity until they encountered fully repolarized tissue, at which time encountered fully repolarized tissue, at which time conduction velocity was thought to return to normal.conduction velocity was thought to return to normal.

Impulses elicited by stimuli applied immediately after the Impulses elicited by stimuli applied immediately after the end of repolarization, and thus at the maximum level of end of repolarization, and thus at the maximum level of membrane potential, display a greater rate Of rise and membrane potential, display a greater rate Of rise and amplitude of the actionpotential amplitude of the actionpotential

Propagate more rapidly than those initiated later at a Propagate more rapidly than those initiated later at a somewhat lower level of membrane potential.somewhat lower level of membrane potential.

Premature beats evoked early during the repo-larization Premature beats evoked early during the repo-larization phase of the action potential often reached the more phase of the action potential often reached the more distant electrode earlier than did later responses evoked distant electrode earlier than did later responses evoked at membrane potentials closer to maximum resting at membrane potentials closer to maximum resting potentials.potentials.

The apparent conduction time between two recording The apparent conduction time between two recording electrodes often decreased with increasing prematuity,.electrodes often decreased with increasing prematuity,.

Purkinje fibers exhibit supernormal conduction and Purkinje fibers exhibit supernormal conduction and supernormal excitability while His-bundle and ventricular supernormal excitability while His-bundle and ventricular muscle fibers do not.muscle fibers do not.

In an experiment where 3 microelectrodes were In an experiment where 3 microelectrodes were simultaneously impaled along a canine Purkinje fiber.simultaneously impaled along a canine Purkinje fiber.

Weidmann found that the Period of supemormal Weidmann found that the Period of supemormal excitability was due to the rapid recovery of excitabilityexcitability was due to the rapid recovery of excitability

The time Course of two The time Course of two simultaneously recorded simultaneously recorded Purkinje Transmembrane AP Purkinje Transmembrane AP are displayed together with the are displayed together with the threshold current required to threshold current required to Evoke a conducted response.Evoke a conducted response.

The graph at the right Of the The graph at the right Of the transmembrane potentials transmembrane potentials displays the threshold current displays the threshold current required to evoke conducted required to evoke conducted responses During the responses During the repolarization phase.repolarization phase.

It can be noted that there is a It can be noted that there is a decreased current requirement decreased current requirement associated with repolarization associated with repolarization in Purkinje fibersin Purkinje fibers

During this During this supemormal supemormal phase of phase of excitability, there excitability, there also is a also is a corresponding corresponding decrease in decrease in conduction timeconduction time

The supernormal phase of conduction has several The supernormal phase of conduction has several outstanding features;outstanding features;

A pro-longed refractory period, either in the His–Purkinje A pro-longed refractory period, either in the His–Purkinje system or AV accessory pathways, appears to be one of system or AV accessory pathways, appears to be one of the prerequisite requirements for its occurrence.the prerequisite requirements for its occurrence.

According to Levi et al., SNC occurs at a relatively According to Levi et al., SNC occurs at a relatively constant position within the cardiac cycle, constant position within the cardiac cycle,

Namely close to the end of the T wave. Namely close to the end of the T wave. However, it occurs earlier at faster heart rates (i.e., However, it occurs earlier at faster heart rates (i.e.,

shorter cycle lengths) and later in longer cycle shorter cycle lengths) and later in longer cycle lengths/slower heart rates.lengths/slower heart rates.

Physiologic mechanisms explaining apparent explaining apparent supernormal conduction includesupernormal conduction include

1.1. Supernormal excitability in phase 3Supernormal excitability in phase 3

2. Diastolic Phase4 Depolarization

3.3. The gap phenomenon.The gap phenomenon.

4.4. Dual A–V nodal pathways.Dual A–V nodal pathways.

5.5. Peeling back refractorinessPeeling back refractoriness

6.6. The shortening of refractoriness by changing the The shortening of refractoriness by changing the

preceding CLpreceding CL..

Supernormal Conduction

7. The Wenckebach phenomenon in the bundle 7. The Wenckebach phenomenon in the bundle branches.branches.

8. Summation of sub threshold impulses.8. Summation of sub threshold impulses.

9. Wendensky facilitation.9. Wendensky facilitation.

10. Bradycardia-dependent blocks10. Bradycardia-dependent blocks..

1. Supernormal excitability During the super normal During the super normal

period excitation is period excitation is possible in otherwise possible in otherwise subthreshold stimulus .subthreshold stimulus .

Possible explanations are Possible explanations are 1.1. Availability of fast Na Availability of fast Na

channelschannels2.2. Proximity of membrane Proximity of membrane

potential to threshold potential to threshold potentialpotential

2. Diastolic Phase 4 Depolarization The presence of diastolic depolarization (phase4depolar-The presence of diastolic depolarization (phase4depolar-

ization) can also lead to apparent supernormal ization) can also lead to apparent supernormal excitability and conduction.excitability and conduction.

Premature beats that arrive early when the Premature beats that arrive early when the membranepotential Is within the potential range of the membranepotential Is within the potential range of the supernormal period of excitability will conduct more supernormal period of excitability will conduct more rapidly than earlier or later premature beats.rapidly than earlier or later premature beats.

The term gap in A–V conduction was originally used by The term gap in A–V conduction was originally used by Moe and his associates to define a zone in the cardiac Moe and his associates to define a zone in the cardiac cycle during which PAC failed to evoke ventricular cycle during which PAC failed to evoke ventricular responses, while PAC of greater and lesser prematurity responses, while PAC of greater and lesser prematurity conducted to the ventricles. conducted to the ventricles.

The gap phenomenon was attributed to functional The gap phenomenon was attributed to functional differences of conduction and/or refractoriness in two or differences of conduction and/or refractoriness in two or more regions of the conducting system.more regions of the conducting system.

3. The Gap Phenomenon

The physiologic basis of gap phenomenon in most The physiologic basis of gap phenomenon in most instances depended on a distal area with a long instances depended on a distal area with a long refractory period and a proximal site with a shorter refractory period and a proximal site with a shorter refractory period refractory period

During the gap phenomenon, initial block occurs distally. During the gap phenomenon, initial block occurs distally. With earlier impulses, proximal delay is encountered, With earlier impulses, proximal delay is encountered, which allows the distal site of early block to recover which allows the distal site of early block to recover excitability and resume conduction.excitability and resume conduction.

When the A V node is excited early by conduction from When the A V node is excited early by conduction from the PAC , prepotential occurs, preceding the all-or-none the PAC , prepotential occurs, preceding the all-or-none AV N actionpotential.AV N actionpotential.

The AVN pre-potential results in a delay in conduction The AVN pre-potential results in a delay in conduction through the A V node ,allowing the BB actionpotential to through the A V node ,allowing the BB actionpotential to recover to a potential closer to the RMP.recover to a potential closer to the RMP.

Accordingly, the BB can be excited and a Propagated Accordingly, the BB can be excited and a Propagated response to the ventriclesresponse to the ventricles

Premature A response develops later ,allowing Premature A response develops later ,allowing conduction to reach the A V node when it is excitable.conduction to reach the A V node when it is excitable.

The all-or- none AVN AP results in conduction to BB fiber The all-or- none AVN AP results in conduction to BB fiber when the BB has not repolarized to a sufficient when the BB has not repolarized to a sufficient membranepotential to permit an all-or-none response .membranepotential to permit an all-or-none response .

Conduction to the ventricles fails.Conduction to the ventricles fails. Is the most accepted theoryIs the most accepted theory

4. Dual A–V nodal pathways Dual A V pathways can also allow earlier PAC to Dual A V pathways can also allow earlier PAC to

propagate over the slower A V pathway, resulting in early propagate over the slower A V pathway, resulting in early PAC being propagated to ventricles. PAC being propagated to ventricles.

Later PAC that propagate over the fast A V pathway are Later PAC that propagate over the fast A V pathway are blocked since they reach the A V nodal cells when they blocked since they reach the A V nodal cells when they are still refractory .are still refractory .

This demonstration of fast This demonstration of fast pathway conduction during pathway conduction during slow pathway conduction slow pathway conduction adds strong evidence for the adds strong evidence for the existence of dual A-V nodal existence of dual A-V nodal pathways.pathways.

Pre-excitation of the AV node by a ventricular or junctional beat shortens the Pre-excitation of the AV node by a ventricular or junctional beat shortens the absolute refractory period of the AV or the His-purkinje system and allows absolute refractory period of the AV or the His-purkinje system and allows conduction of a supraventricular impulseconduction of a supraventricular impulse

5. Peeling back refractoriness

The duration of refractory period is directly proportional The duration of refractory period is directly proportional to length of preceding R-R interval.to length of preceding R-R interval.

6. The shortening of refractoriness by changing the preceding CL.

480ms

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270ms

7. The wenckebach phenomenon in the bundle branches

8. Summation of Subthreshold Responses

If the controlled If the controlled subthreshold stimulus is subthreshold stimulus is applied intracellularly at applied intracellularly at times A or C excitation did times A or C excitation did not cause depolarization.not cause depolarization.

However, if that same However, if that same Stimulus was delivered at Stimulus was delivered at time B depolarization time B depolarization occuredoccured

These experiments demonstrated that Summation of two subthreshold events in Purkinje fibers can elicit Propagated responses

9. WENDENSKY FACILITATION Depressed segment of PF / Mus fibersDepressed segment of PF / Mus fibers

Keep the impulses reaching this site blocked at this siteKeep the impulses reaching this site blocked at this site

Block is overcome Block is overcome

Multiple stimuli reach the distal siteMultiple stimuli reach the distal site

Suprathreshold stimulus resultsSuprathreshold stimulus results

ConductionConduction

BRADYCARDIA-DEPENDENT,

Occurrence of impaired intraventricular conduction after Occurrence of impaired intraventricular conduction after long pauses or slowing of the heart to a critical rate long pauses or slowing of the heart to a critical rate

Due to a gradual loss transmembrane resting potential Due to a gradual loss transmembrane resting potential during a prolonged diastole with excitation from a less during a prolonged diastole with excitation from a less negative take-off potenial negative take-off potenial

In patients with bradycardia dependent aberrancy, the In patients with bradycardia dependent aberrancy, the beat at the end of a lengthened cycle is aberrated. beat at the end of a lengthened cycle is aberrated.

It is generally unexpected since there should be It is generally unexpected since there should be sufficient time for the bundles to recover and conduction sufficient time for the bundles to recover and conduction to be normal after a long cycle. to be normal after a long cycle.

One explanation for its occurrence is that the bundles One explanation for its occurrence is that the bundles are serving as pacemaker tissue and manifest are serving as pacemaker tissue and manifest spontaneous phase 4 depolarization. spontaneous phase 4 depolarization.

This pacemaker tissue is no longer suppressed by This pacemaker tissue is no longer suppressed by stimuli from upper pacemakers when the cycle length is stimuli from upper pacemakers when the cycle length is very prolonged, leading to generation of an impulse very prolonged, leading to generation of an impulse which will be conducted via the bundle and hence which will be conducted via the bundle and hence aberrantly.aberrantly.