BMS 204: Cardiac Properties Part 2

BMS 204: Cardiac Properties Part 2

• The lecture covers the spread of excitation waves, AV node characteristics, excitation-contraction coupling, and factors affecting cardiac muscle inotropy.
• Students should be able to describe the spread of excitation waves and its importance.
• Students should be able to describe the characteristics of the AV node.
• Students should be able to explain excitation-contraction coupling.
• Students should be able to identify the factors affecting cardiac muscle inotropy.

3) Conductivity

• All cardiac muscle cells are conductive, but at differing rates.
• Vagal stimulation decreases conduction rate, while sympathetic stimulation increases it.
• SAN (Sinoatrial node) conduction is very slow (0.05 m/sec). This slow conduction prevents ectopic foci from depolarizing and maintains the normal pacemaker as the primary.

2. Atrial Conduction of Excitation Wave (EW)

• EWs rapidly spread through the atria, converging on the AV node (atrioventricular node) within 0.1 seconds.
• Specialized atrial pathways (internodal pathways) facilitate rapid conduction (1 m/sec) from the SA node to other atrial regions and the AV node.

3. AVN Conduction

• The AV node has the slowest conduction rate in the heart (0.02-0.05 m/sec.).
• It has three functional zones: A-N zone (maximum delay due to long path length), N zone (slowest conduction velocity), and N-H zone.
• A-V nodal delay (100-150 msec) occurs between the atria and ventricles. This delay helps prevent ventricular overload.
• A-V nodal block (refractoriness) protects ventricles from high atrial rhythms, allowing only 180-200 bpm to pass. This prevents rapid atrial rhythms from overwhelming the ventricle.
• The AV node's decreased chance of retrograde conduction safeguards the sinoatrial node (SAN) from ventricular ectopic foci.

4. Ventricular Conduction

• Ventricular conduction involves the A-V bundle, bundle branches, and Purkinje fibers.
• The A-V bundle branches into right and left bundle branches, with conduction rates of 1-2 m/sec.
• Purkinje fibers exhibit high conduction velocities (4-5 m/sec), synchronizing ventricular activation.
• The final Purkinje fiber ramifications reach about 2/3 of the ventricular muscle thickness.

5. Ventricular Myocardial Conduction

• Ventricular muscle activation begins in the mid-portion of the septum on the left ventricle
• Activation spreads through the left and right ventricular walls.
• The last part to be activated is the epicardial surface of the left ventricle.

4th Cardiac Property is Contractility

• Contractility is the heart's inherent ability to contract and generate force in response to stimulation.
• This capability is independent of muscle length.

Sources of Ca++ for Contraction

• Depolarizing Ca++ enters the cell during the plateau phase.
• SR Ca++ is released by the depolarizing Ca++.

Mechanism of Muscle Contraction

• Ca++ binds to troponin C, leading to conformational changes in the troponin-tropomyosin complex.
• Myosin binding sites on the actin molecules are exposed.
• Cross-bridge cycles between actin and myosin occur (binding, bending, detaching).
• Sliding of actin over myosin produces muscle contraction.

Mechanism of Cardiac Muscle Relaxation

• Ca++ is pumped back into the sarcoplasmic reticulum (SR) by Ca++ pumps.
• Ca++ is extruded outside the cell by membrane Ca++ pumps and Na+-Ca++ exchangers.
• The release of Ca++ from troponin C stops, and tropomyosin moves back to cover actin binding sites.
• Muscle relaxation (diastole) occurs when actin and myosin interactions cease.

3] The Duration of Contraction

• The duration of contraction directly correlates to the intracellular Ca++ concentration and is directly proportionate.
• Higher intracellular Ca++ concentrations lead to prolonged contractions because of the increased time needed by the Ca++ pump to remove Ca++.

Regulation of Relaxation

• Catecholamines (E, NE) increase sarcoplasmic reticulum Ca++-ATPase pump activity and reuptake of Ca++.
• This accelerates relaxation, particularly important during rapid heart rates like exercise.

4] The Most Important Physiological Factor

• Sympathetic stimulation enhances relaxation by accelerating Ca++ reuptake into the sarcoplasmic reticulum via a beta-adrenergic mechanism that is mediated by cAMP.
• Important during exercise or increased heart rates.
• The pathological implications for relaxation in ischemia heart disease.

Time Relations & Characteristics Of The Contractile Response

• Contraction begins 20 msec after action potential onset.
• Peak tension is reached during the plateau of the action potential.

3 - The Cardiac Muscle cannot be tetanized

• The long absolute refractory period (ARP) prevents tetanus.
• Ventricular relaxation is necessary for adequate filling.

4 - The Contractile Response is all- or none

• Cardiac muscle contractions are all-or-none, not graded.
• Each atrial and ventricular muscle sheet functions as a single unit (functional syncytium).

Factors Affecting Myocardial Force Of Contraction

• Intrinsic factors (Determinants): Initial length (preload), frequency of stimulation, contractility
• Extrinsic factors (Inotropic Factors): Nervous (sympathetic, parasympathetic), neurohormonal (epinephrine, norepinephrine, acetylcholine), ECF ions , drugs.

EC coupling as target of contractility regulation

• Parasympathetic NS reduces heart rate and contractile force.
• Sympathetic NS increases heart rate and contractile force.

Extrinsic Factors Affecting Myocardial Contraction Force

• Sympathetic stimulation increases Ca++ entry and release from the SR.
• There are multiple mechanisms for increasing intracellular Ca++ including the mechanisms of the frequency of action potentials and the relationship between Ca++ and force of contraction.
• Sympathetic stimulation increases the rate of relaxation.

Neurohormones

• Epinephrine and norepinephrine act as positive inotropic factors.
• Acetylcholine acts as a negative inotropic factor, opposing sympathetic effects.

ECF Ions

• Ca++ infusion can cause heart stoppage (Ca++ rigor).
• Insufficient extracellular Ca++ has a negative inotropic effect.
• High K+ (hyperkalemia) depresses contractility and can stop the heart in diastole.

Drugs

• Ca++ entry blockers are negative inotropic agents (e.g., nifedipine).
• Drugs that increase intracellular Ca++ are positive inotropic agents(e.g., cardiac glycosides).
• Digitalis inhibits Na+-K+-ATPase, leading to Na+ accumulation, activating the Na+-Ca+ exchange mechanism, and increasing intracellular Ca++.

1) Initial Length (Preload)

• Preload is the degree of passive stretch exerted by blood volume in the ventricle before contraction.
• End-diastolic volume (EDV) is used instead of muscle length.
• A direct relationship between preload and contraction strength up to a point. Beyond that point further increases in preload reduce contractility.

2) Afterload

• Afterload is the resistance the heart must overcome to eject blood.
• Isometric contractions result in increased tension without ventricular volume change.
• In isotonic contraction, the tension developed allows muscle shortening.
• Increased afterload (e.g., high blood pressure) reduces the velocity of shortening of the cardiac muscle.

The relation between afterload & Velocity (Force-Velocity relationship)

• Heavier loads are lifted slower.
• Lighter loads result in higher velocities until the maximum velocity is reached at zero load.
• The maximum velocity is independent of preload.
• Increased preload allows the muscle to overcome larger afterloads, however this does not change Vmax which is related to contractility.

3) Frequency of Stimulation

• Increased rates of stimulation result in progressively greater contraction forces.
• This phenomenon is known as the frequency-force relationship and is caused by changes in intracellular Ca++ concentration during repeated stimulation.

Examples & Explanations

• Increased heart rate leads to greater contractility (more Ca++ triggers).
• Vagus nerve stimulation decreases contractility through decreased heart rate.

2] Stair-case phenomenon (= Treppe = Bodwitch effect)

• Increased stimulation frequency leads to stepwise increases in the force of each contraction until a plateau is reached.
• This occurs because the SR cannot remove all Ca++ quickly enough before the next action potential.

Summary of Cardiac Muscle Contraction

• The troponin-tropomyosin complex prevents actin-myosin interactions at rest.
• Increased intracellular Ca++ causes conformational changes in troponin, allowing actin-myosin interactions.
• The binding, bending, and detachment of actin-myosin cross-bridges cause muscle shortening.
• ATP is needed for detachment.
• The cycle repeats.

Sources of Ca+2

• Ca++ comes from the extracellular and intracellular compartments; the SR at the T-Tubules.
• Extracellular Ca++ plays an important role in contraction and is regulated by numerous intrinsic and extrinsic factors.

To Sum up: Myocardial Contractility

• The intrinsic ability of the cardiac muscle to generate force at a constant length.
• Myocardial contractility depends on the integrity of the muscle elements.
• Contractility changes are related to sarcoplasmic Ca++ concentration.
• Factors raising intracellular Ca++ are positive inotropic agents.
• Factors decreasing intracellular Ca++ are negative inotropic agents.

Ca2+ signaling in cardiac muscle

• Numerous intrinsic and extrinsic factors affect Ca2+ signaling in the heart.
• This signaling process underlies myocardial contractility and relaxation.
• Several sources of Ca2+ contribute to the needed Ca2+ for contraction.

References.

• Ganong's Review of Medical Physiology, Kim E. Barrett, 2019
• Guyton and Hall textbook of Medical Physiology
• Fox, Stuart Ira.