Cardiac physiologyCardiac physiology11

Abeer elnakeraAbeer elnakera

20132013

Objectives Objectives

• Describe the Function and layout of the cardiovascular system

• Describe the Muscular wall and conductive system of the heart

• Demonstrate the Cardiac action potential,Initiation & Conduction of the Cardiac Impulse

• Describe the Excitation-contraction coupling• Enumerate the anesthetic effects on cardiac

electrical conduction and Excitation-contraction coupling

The heartThe heart

Muscular wall of the heartMuscular wall of the heart

• The self-excitatory nature of cardiac muscle cells and their unique organization allow the heart to function as a highly efficient pump. Serial low-resistance connections (intercalated disks) between individual myocardial cells allow the rapid and orderly spread of electrical activity in each pumping chamber.

Conductive systemConductive system

• The normal absence of direct connections between the atria and ventricles except through the atrioventricular (AV) node delays conduction and enables atrial contraction to prime the ventricle.

Cardiac action potentialsCardiac action potentials

• Electrical potential depends on– Selective membrane

permeability to ions– Different ionic

concentrations inside and outside the cell

Resting membrane potentialResting membrane potential

• An electrical potential is established across the cell membrane, with the inside of the cell negative with respect to the extracellular environment, because anions do not accompany K+. Thus, the resting membrane potential represents the balance between two opposing forces: the movement of K+ down its concentration gradient and the electrical attraction of the negatively charged intracellular space for the positively charged potassium ions.

Cardiac action potentialCardiac action potential

• The normal ventricular cell resting membrane potential is –80 to –90 mV. As depolarization develops, The action potential transiently raises the membrane potential of the myocardial cell to +20 mV.

Cardiac action potentialCardiac action potential

• In contrast to neuron,the spike in cardiac action potentials is followed by a plateau phase that lasts 0.2–0.3 s.

• Whereas the action potential for skeletal muscle and nerves is due to the abrupt opening of fast sodium channels in the cell membrane, in cardiac muscle it is due to the opening of both fast sodium channels (the spike) and slower calcium channels (the plateau).

Cardiac action potentialCardiac action potential

Cardiac fast response action Cardiac fast response action potentialpotential K+ permeability

Inactivation of Na+ channels

Normal permeabilityrestored

Refractory periodsRefractory periods

Slow response cardiac action Slow response cardiac action potentialpotential

• S.A. and A.V. nodes

Cardiac action potentialCardiac action potential

• Phases 1 and 2 are absent. no plateau.• Phase 4 - Pacemaker potential - The cell membrane

gradually depolarise from ~-60mV to a threshold of ~-40mV due to a slow continuous influx of Na+ ions and a decreased permeability to K+ ions. A Ca2+ current due to the opening of T-type completes the pacemaker potential.

• Phase 0 - Depolarisation - when the membrane potential reaches threshold potential (L-type_ calcium channels open, causing Ca2+ influx and an AP is generated.

• Phase 3 - Repolarisation - due to efflux of K+ .(normal permeability)

Refractory periodsRefractory periods

200msec 50msec

250 msec

Initiation & Conduction of the Initiation & Conduction of the Cardiac Impulse Cardiac Impulse

A-V insulationA-V insulation

Electromechanical CouplingElectromechanical Coupling

PR Interval: AV Node ConductionPR Interval: AV Node Conduction

QRS - Complex: QRS - Complex: Ventricular ContractionVentricular Contraction

Ventricular contractionVentricular contraction

Depolarization-repolarizationDepolarization-repolarization

Cardiac Cycle on the EKGCardiac Cycle on the EKG

Surface Electrode RecordingSurface Electrode RecordingElectrocardiogram (EKG)Electrocardiogram (EKG)

Anesthetic effectsAnesthetic effects

• Halothane, enflurane, and isoflurane depress SA node automaticity. These agents appear to have only modest direct effects on the AV node, prolonging conduction time and increasing refractoriness.

frequent occurrence of junctional tachycardia when an anticholinergic is

administered for sinus bradycardia during inhalation anesthesia; junctional

pacemakers are accelerated more than those in the SA node.

Anesthetic effectsAnesthetic effects

• Both antiarrhythmic and arrhythmogenic properties are described for volatile anesthetics

• The former may be due to direct depression of Ca2+ influxes, whereas the latter generally involves potentiation of catecholamines

Anesthetic effectsAnesthetic effects

• Intravenous induction agents have limited electrophysiological effects in usual clinical doses.

• Opioids, particularly fentanyl and sufentanil, can depress cardiac conduction

Anesthetic effectsAnesthetic effects

• Local anesthetics have important electrophysiological effects on the heart at blood concentrations that are generally associated with systemic toxicity.

• In the case of lidocaine, electrophysiological effects at low blood concentrations can be therapeutic

Anesthetic effectsAnesthetic effects

• At high blood concentrations, local anesthetics depress conduction by binding to fast sodium channels; at extremely high concentrations they also depress the SA node

• The most potent local anesthetics—bupivacaine and, to lesser degrees, etidocaine and ropivacaine—appear to have the greatest effects on the heart,

Anesthetic effectsAnesthetic effects

Bupivacaine binds inactivated fast sodium channels and

dissociates from them slowly. It can cause profound sinus

bradycardia and sinus node arrest as well as malignant

ventricular arrhythmias

Anesthetic effectsAnesthetic effects

• Calcium channel blockers are organic compounds that block calcium influx through L-type but not T-type channels

Excitation –contraction coupling

Excitation-contraction couplingExcitation-contraction coupling

• The quantity of calcium required to initiate contraction exceeds that entering the cell through slow channels during phase 2. The small amount that does enter through slow channels triggers the release of much larger amounts of calcium stored intracellularly (calcium-dependent calcium release) within cisterns in the sarcoplasmic reticulum

Excitation-contraction couplingExcitation-contraction coupling

• The force of contraction is directly dependent on the magnitude of the initial calcium influx

• During relaxation, when the slow channels close, a membrane-bound ATPase actively transports calcium back into the sarcoplasmic reticulum. Calcium is also extruded extracellularly by an exchange of intracellular calcium for extracellular sodium by an ATPase in the cell membrane. Thus, relaxation of the heart also requires ATP.

Excitation-contraction couplingExcitation-contraction coupling

• The quantity of intracellular Ca2+ available, its rate of delivery, and its rate of removal determine, respectively, the maximum tension developed, the rate of contraction, and the rate of relaxation

Excitation-contraction couplingExcitation-contraction coupling

• Sympathetic stimulation increases the force of contraction by raising intracellular calcium concentration via a 1-adrenergic receptor-mediated increase in intracellular cyclic adenosine monophosphate (cAMP). The increase in cAMP recruits additional open calcium channels. Moreover, adrenergic agonists enhance the rate of relaxation by enhancing calcium reuptake by the sarcoplasmic reticulum.

Excitation-contraction couplingExcitation-contraction coupling

• Phosphodiesterase inhibitors, such as theophylline, amrinone, and milrinone, produce similar effects by preventing the breakdown of intracellular cAMP

• Digitalis increases intracellular calcium concentration through inhibition of the membrane-bound Na+–K+-ATPase; the resulting small increase in intracellular Na+ allows for a greater influx of Ca2+ via the Na+–Ca2+ exchange mechanism.

Excitation-contraction couplingExcitation-contraction coupling

• Glucagon enhances contractility by increasing intracellular cAMP levels via activation of a specific nonadrenergic receptor.

• In contrast, release of acetylcholine following vagal stimulation depresses contractility through increased cyclic guanosine monophosphate (cGMP) levels and inhibition of adenylyl cyclase;

Excitation-contraction couplingExcitation-contraction coupling

• Acidosis blocks slow calcium channels and therefore also depresses cardiac contractility by unfavorably altering intracellular calcium kinetics.

Anesthetic effectsAnesthetic effects

• all volatile anesthetics depress cardiac contractility by decreasing the entry of Ca2+ into cells during depolarization (affecting T- and L-type calcium channels), and decreasing the sensitivity of contractile proteins to calcium

• Halothane………. More depressant

• Isoflurane……….less depressant

Anesthetic effects Anesthetic effects

• Anesthetic-induced cardiac depression is potentiated by hypocalcemia, -adrenergic blockade, and calcium channel blockers

• Nitrous oxide also produces dose-dependent decreases in contractility by reducing the availability of intracellular Ca2+ during contraction.

Anesthetic effectsAnesthetic effects

• Of all the major intravenous induction agents, ketamine appears to have the least direct depressant effect on contractility.

• Local anesthetic agents also depress cardiac contractility by reducing calcium influx and release in a dose-dependent fashion. Bupivacaine, tetracaine, and ropivacaine cause greater depression than lidocaine and chloroprocaine.

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Summary Summary

• Cardiac action potential is the communication tool between cardiac muscle cells

• Initiation & Conduction of the Cardiac Impulse

• Excitation-contraction coupling

• Anesthetic implications

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