B P7 C62 Mechanisms of Cardiac Arrhythmias Flashcards
Cardiac cells normally have a negative intracellular resting potential, which for most of the heart (working atrial and ventricular muscle, specialized His-Purkinje conducting system) is about __________
−80 to −90 mV
RMP of sinoatrial (SA) and central AV (AV) node regions
−50 and −65 mV
The cardiac AP is by convention divided into four phases, the_____.
Phase 0: AP-upstroke, which depolarizes the cell from its negative resting potential to a potential positive to 0 mV;
Phase 1: the initial rapid repolarization phase;
Phase 2: the so-called plateau, in which the AP voltage changes relatively slowly;
Phase 3: the final rapid repolarization phase, which brings the cell back to its resting potential
Phase 4: Resting potential
Phase 0 happens when there is a rapid increase in membrane permeability to _______ , and K + permeability falls, making Na + the dominant conductance
Na+
At the peak of phase 0 (the “overshoot”), the cell moves close to the Na + equilibrium potential, which is quite positive because in contrast to K+ , Na + is more concentrated outside the cell than inside and the Na + chemical force makes it move into the cell, making the interior more positive.
Phase ____ is carried by a transient, rapid exit of K +from the cell.
Phase 1
____________ is the portion of the AP during which Ca 2+ enters the cell and causes a large secondary release of Ca 2+ from the sarcoplasmic reticulum (SR), the main cellular Ca2+ -storage organelle. The SR Ca2+ -release rapidly increases free intracellular [Ca2+ ], which causes cellular contraction and mediates electromechanical coupling.
Phase 2
During phase 2, the transmembrane potential is governed by balanced permeabilities to Ca 2+and K+,
Phase ______, a rapid increase in K + permeability offsets the decreasing Ca 2+ conductance and repolarizes the cell.
Phase 3
Finally, phase 3 (carried by a rapid egress of K+ ) brings the cell back to its negative resting potential. Because the cell cannot be activated by normal means at voltages positive to −60 mV, from when the cell reaches −60 mV during phase 0 until the time that it repolarizes to −60 mV during phase 3 the cell cannot be fired and is “refractory” to activation.Thus, the timing of phase 3 sets the refractory period (RP)
Finally, phase 3 (carried by a rapid egress of K+) brings the cell back to its negative resting poten- tial.
Because the cell cannot be activated by normal means at voltages positive to −60 mV, from when the cell reaches −60 mV during phase 0 until the time that it repolarizes to −60 mV during phase 3 the cell cannot be fired and is “refractory” to activation. Thus,the timing of phase 3 sets the _____ period
Refractory period (RP)
The _____ ions are the major charge carriers, and their movement across the cell membrane through channel pores creates a flow of current that generates excitation and signals in cardiac myocytes
Sodium, potassium, calcium, and chloride (Na+, K+, Ca2+, and Cl−)
Functions of the Cardiac Electrical System
To initiate rhythmic contraction at a rate appropriate to the needs of the body
To ensure appropriate timing of contraction for each cardiac chamber
To prevent heart rates that are excessively slow or rapid for the body’s needs
Equilibrium is created when the chemical force tending to push K+ out of the cell is balanced by an equal and opposite electrical force created by the net intracellular negative charge tending to pull the K+ back into the cell. The voltage at which these forces balance is called the _____
Equilibrium potential
In the case of K+, the equilibrium potential is given by the Nernst equation _____, where R is the universal gas constant, T = absolute temperature, F = Faraday’s constant, and [K+o], [K+i] = extracellular and intracellular K+ concentration, respectively.
This value, designated “EK” for K+ equilibrium potential, is about −__ mV
(E = RT/F·ln([K+o]/[K+i])
-95 mV
The _____ ratio is commonly used to define a channel’s ionic selectivity, defined as the ratio of the permeability of one ion type to that of the main permeant ion type.
Permeability ratio
Spindle-shaped structure composed of a fibrous tissue matrix containing closely packed cells. In man, it is 10 to 20 mm long and 2 to 3 mm wide, narrowing caudally toward the inferior vena cava (IVC).
SA node
The SA node is superficial, lying less than 1 mm from the epicardial surface, laterally in the RA sulcus terminalis at the junction of the superior vena cava (SVC) and right atrium
Resting potential (mV)
SA node: -50 to -60
AV nodal cell: -60 to -70
Atrial myocyte: -80 to -90
His Purkinje cell: -90 to -95
Ventricular myocyte: -80 to -90
_____ are the proteins that form the intercellular channels of gap junctions.
Connexins
_____, a 43-kDa polypeptide, is the most abundant cardiac connexin in heart cells, with connexins 40 and 45 being found in smaller amounts
Connexin 43
Ventricular muscle expresses connexins _____, whereas atrial muscle and the specialized conduction system express connexins _____.
Ventricular muscle: 43 and 45
Atrial muscle/specialized conduction system: 40, 43, 45
Alterations in the distribution and function of cardiac gap junctions are associated with increased susceptibility to arrhythmias.
Conduction slowing and arrhythmogenesis have been associated with redistribution of connexin 43 (Cx43) gap junctions from the end of cardiomyocytes to the _____ borders and with decreased phosphorylation of Cx43 in a dog model of nonischemic dilated cardiomyopathy
Lateral borders
Artery supplying the SA node in 55-60% of cases
RCA
The artery supplying the SAN branches from the right (55% to 60% of the time) or the left (40% to 45%) circumflex coronary artery and approaches the node around the junction of the SVC and right atrium
The artery supplying the SAN branches from the _____ and approaches the node around the junction of the SVC and right atrium
RCA (55% to 60%)
or
LCx (40% to 45%)
The proximity to the _____ nerve is an important consideration when catheter ablation or modification of the sinoatrial node (SAN) is contemplated.
Right phrenic nerve
Sinoatrial node (SAN) artery variations in the arterial supply of the sinus node.
The SAN blood supply originates from a single coronary artery in __% of cases and from both coronary arteries in __%
Single CA: 96%
Both CA: 4%
R anterior atrial artery: 64%
L anterior atrial artery: 22%
L lateral atrial artery: 8%
R lateral atrial artery: 2%
If the origin is from the _____coronary artery, the nodal artery crosses the roof or the anterior wall of the left atrium.
Left coronary artery
Anatomic landmarks of the triangle of Koch
Superior: Tendon of Todaro
Inferior: Attachment of the septal leaflet of the TV
Base: mouth of the coronary sinus
The normal AV junctional area is composed of multiple distinct structures, including transitional tissue, inferior nodal extension (INE), compact portion, penetrating bundle, His bundle, atrial and ventricular muscle, central fibrous body, tendon of Todaro, and valves
At the level of the AV junction, the tract of nodal tissue is divided into two major components, the ______ and the ____________
INE
Penetrating bundle
The ________ is continuous with the penetrating bundle, which penetrates the fibrous tissue separating the atria and ventricles and emerges in the ventricles as the bundle of His. Both structures are covered by connective tissue and are therefore enclosed.
INE
The ____________ is a superficial structure lying just beneath the right atrial endocardium, anterior to the ostium of the coronary sinus, and directly above the insertion of the septal leaflet of the tricuspid valve.
It is at the apex of a triangle formed by the tricuspid annulus and the tendon of Todaro, which originates in the central fibrous body and passes posteriorly through the atrial septum to continue with the Eustachian valve.
Compact portion of the AV node
In 85% to 90% of human hearts, the arterial supply to the AV node is derived from a branch of the _______________ that originates at the posterior intersection of the AV and interventricular grooves (crux). A branch of the circumflex coronary artery provides the arterial supply to the AV node in the remaining hearts
RCA
This structure is the continuation of the penetrating bundle on the ventricular side of the AV junction before it divides to form the left and right bundles
Bundle of His
Branches from the anterior and posterior descending coronary arteries supply the upper muscular interventricular septum with blood, which makes the conduction system at this site more impervious to ischemic damage unless the ischemia is extensive.
Branches from the _____coronary arteries supply the upper muscular interventricular septum with blood, which makes the conduction system at this site more impervious to ischemic damage unless the ischemia is extensive.
Anterior and posterior descending coronary arteries
The bundle branches begin at the superior margin of the muscular interventricular septum, immediately beneath the membranous septum, with cells of the ______ bundle branch cascading downward as a continuous sheet onto the septum beneath the noncoronary aortic cusp
Left bundle branch (LBB)
The _______________ continues intamyocardially as an unbranched extension of the AV bundle down the right side of the interventricular septum to the apex of the right ventricle
Right bundle branch
The __________________ connect with the ends of the bundle branches to form interweaving networks on the endocardial surface of both ventricles and transmit the cardiac impulse almost simultaneously to the right and left ventricular endocardium.
Purkinje fibers
APs propagate within the thin Purkinje fiber bundles from the base to the apex before activating surrounding myocytes.
Purkinje myocytes have less well-developed transverse tubules which reduces membrane capacitance and thus accelerates AP propagation.
In humans, Purkinje fibers penetrate only the _____of the endocardium, whereas in pigs, they almost reach to the epicardium
Inner third
Although conduction of cardiac impulses is their principal function, large free-running Purkinje fibers composed of many Purkinje cells, often called _____, are capable of contraction
False tendons
APs propagate within the thin Purkinje fiber bundles from the _____ before activating surrounding myocytes.
Base to apex
Purkinje fiber coupling relies on connexins _____.
Connexins 40 and 45
In general, autonomic neural input to the heart exhibits some degree of “sidedness,” with the right sympathetic and vagal nerves affecting the __________ and the left sympathetic and vagal nerves affecting the __________ more than the SA node.
Right - SA node
Left - AV node
Stimulation of the right stellate ganglion produces sinus tachycardia with less effect on AV nodal conduction, whereas stimulation of the left stellate ganglion generally shifts the sinus pacemaker to an ectopic site and consistently shortens AV nodal conduction time and refractoriness. Left stellate stimulation produces variable and usually smaller degrees of SAN acceleration. Stimulation of the right cervical vagus nerve primarily slows the SA nodal discharge rate, whereas stimulation of the left vagus primarily prolongs AV nodal conduction time and refractoriness. Neither sympathetic nor vagal stimulation affects normal conduction in the His bundle.
Most efferent sympathetic impulses reach the canine ventricles over the ansae subclavia, branches from the stellate ganglia.
Sympathetic nerves then synapse primarily in the caudal cervical ganglia and form individual cardiac nerves that innervate relatively localized parts of the ventricles.
The major route to the heart is the _____ nerve on the right side and the _____ nerve on the left.
Right: recurrent cardiac nerve
Left: ventrolateral cardiac nerve
Identify the mechanism
A patient with persistent sinus tachycardia at rest or sinus bradycardia during exertion exhibits inappropriate SAN rates, but the underlying ionic mechanisms responsible can still be basically normal, with changes in the kinetics or magnitude of relevant currents underlying the abnormal rate.
Normal automaticity
The discharge rate of a latent pacemaker can accelerate inappropriately and usurp control of cardiac rhythm from the SA node, as may occur with a premature ventricular complex (PVC) or a burst of ventricular tachycardia (VT)
Normal automaticity
Such disorders of impulse formation can be caused by alteration in a normal pacemaker mechanism (e.g., phase 4 diastolic depolarization that is physiologically normal for SA node or for ectopic site such as a Purkinje fiber, but occurs inappropriately fast or slow) or by a physiologically abnormal pacemaker mechanism.
Identify mechanism
Slow atrial, junctional, or ventricular escape rhythms; certain types of atrial tachycardias (ATs) (e.g., those produced by digitalis or perhaps those coming from PVs); accelerated junctional (nonparoxysmal junctional tachycardia) and idioventricular rhythms
Abnormal automaticity
Abnormal automaticity can arise from cells that have reduced maximum diastolic potentials, often at membrane potentials positive to −50 mV, in the activation range of both I Kand ICaL. Automaticity at membrane potentials more negative than −70 mV may be caused by If
Partial depolarization and failure to reach normal maximal diastolic potential can induce automatic discharges in most if not all cardiac fibers.
Identify the mechanism
Arrhythmias precipitated by digitalis, spontaneous atrial ectopic beats, CPVT
Delayed afterdepolarization
Identify the mechanism
Acquired and congenital LQTS
Early afterdepolarization
Identify the mechanism
Sinoatrial block, AV block, bundle branch block
Bidirectional or unidirectional without reentry
Identify the mechanism
AVNRT
VT caused by Bundle branch block reentry
Reciprocating tachycardia in WPW
Unidirectional block with reentry
In _____ reentry, there is a discrete anatomical barrier separating alternate conduction pathways, and allowing reentry to be initiated and maintained.
Anatomic reentry
Figure 62.18A Premature beat arriving during the RP of the fast pathway (here designated Pathway 1) but after the shorter-RP pathway (Pathway 2) has recovered excitability.
The impulse then travels antegradely down Pathway 2 to the His bundle entrance, conducting via the His bundle to the ventricles (Fig. 62.18B). If the distal end of Pathway 1 has now had time to recover, the impulse will propagate retrogradely up Pathway 1 (Fig 62.18C). If the circuit time (the time to leave each point in the circuit and get back to the initial point of reference) is longer than the RP of Pathway 2, it will now be reexcited in the antegrade direction and the process can continue indefinitely (Fig 62.18D) if the conditions are right.
