Unit 4 Mechanical Function of the Heart

Excitation-contraction coupling

Describes how the electrical activity leads to mechanical contraction of the heart.

Electrical events

Occur on the surface (sarcolemma) and must stimulate elements located throughout the myocardial cell.

Spatial relationship of sarcolemma, T-tubules, and sarcoplasmic reticulum

facilitates excitation-contraction coupling.

T tubules

Invaginations in the sarcolemma, signal propagates down them.

Terminal cisternae & longitudinal tubules

Ca+ storage pools.

Step 1-2: Ca+ induced Ca+ release

E-C coupling is mediated by changes in sarcoplasmic Ca+ levels.

Long acting Ca+ channel during phase of the ventricular action potential

Ca+ binds to ryanodine receptor and causes more release of Ca+

Cytosolic Ca+ concentration

Major determinant of the force of contraction (intropy); more intracellular Ca+ = stronger contraction.

Resting state of tropomyosin

Tropomyosin wraps around the actin filament blocking myosin binding sites and prevents actin-myosin interaction during resting state.

Cardiac troponin (cTn) complex

regulates tropomyosin's position & inhibitory function

Step 3: ventricular contraction

- when Ca+ enters the sarcoplasm & binds to cardiac troponin C, a morphologic change to the troponin complex pulls the tropomyosin to the side exposing the myosin binding site

- once the myosin binds to actin (cross bridge), myosin releases phosphate and creates a power strike resulting in myocardial contraction

cTn I

Inhibits myosin binding.

cTn C

Binds calcium.

cTn T

Binds tropomyosin.

Step 4: ventricular relaxation

Goal is to get Ca+ out of the sarcoplasm; no calcium = no contraction.

Resequestration of Ca+ into SR. or pumping of Ca+ out of cell.

Sarcoplasmic reticulum calcium ATPase (SERCA)

Active: sympathetic stimulation of B1 receptors; Inactive: parasympathetic stimulation of muscarinic receptors.

Resequesters Ca+ into SR.

Gated by phospholamban.

Phospholamban (PL)

SERCA's gatekeeper; regulates SERCA and opens gate when phosphorylated.

Pumping Ca+ out of the cell

Involves Na-Ca exchanger and Ca-ATPase pump, both having minor roles.

Strength of ventricular contraction & relaxation

Mediated by autonomic signals & medications.

During systole

Increased contractility due to sympathetic stimulation and positive inotropes; decreased contractility due to parasympathetic stimulation and negative inotropes.

During diastole

Increased relaxation due to sympathetic stimulation and positive lusitropes; decreased relaxation due to parasympathetic stimulation and negative lusitropes.

Mitral valve

- Open when LA pressure > LV pressure: atrial contraction, early rapid ventricular filling and diastasis (slow filling)

- Closed when LV pressure > LA pressure: isovolumic contraction, ejection and isovolumic relaxation

Aortic valve

-Open when LV pressure > Aorta pressure: During ejection

-Closed when Aorta pressure > LV pressure: during all other stages

Systole

The phase of the heartbeat when the heart muscle contracts and pumps blood.

Isovolumic contraction

Ventricles are contracting and the ventricular pressure increases but all the valves remain closed and the blood volume in the ventricles remain unchanged.

Ventricular pressure > Atrial pressure. AV valve closes.

Aortic valve also closed.

Ejection

Ventricular pressures exceed aortic pressure; Aortic valve opens and blood is ejected into the artery.

Initially, both ventricular & aortic pressures continue to increase as ventricle continues to contract & pump more blood into the aorta.

2nd half of ejection, following ventricular repolarization, the pressures in the ventricle and aorta gradually reduce until the ventricular pressures fall below the aortic pressure and the aortic valve closes.

As ventricles are contracting,

Atria are filling with blood.

S1 'Lub' heart sound

Occurs at the time of MV closure & marks start of systole.

S2 'Dub' heart sound

Occurs at time of AoV closure & marks end of systole.

Systolic dysfunction diseases

Characterized by reduced pumping function and progressive heart dilation & can have varied underlying causes.

Primary heart Dz or secondary to other diseases.

Dilated cardiomyopathy (DCM)

Results in myocyte atrophy, degeneration, and death that appears as attenuated wavy fibers and fibrosis

Stroke volume

The amount of blood pumped by the left ventricle of the heart in one contraction.

Determined by preload, afterload, and contracility (inotropy).

Preload

Ventricular wall tension at end of diastole; Estimated by End diastolic volume or pressure.

Afterload

Ventricular wall tension during contraction; Systolic BP is used as an estimate.

Contractility (inotropy)

Strength of contraction modulated by drug or autonomic influences.

Ejection fraction percentage (EF%)

Represents the percent change in left ventricular volume before and after contraction of the ventricle; Normal > 50%; Systolic dysfunction < 50%.

Fractional shortening percentage (FS%)

Represents the percent change in the width of the left ventricular chamber between systole and diastole; Normal > 30%; Systolic dysfunction < 30%.

Pathophysiology of dilated cardiomyopathy (DCM)

Genetic disease of the myocardium results in atrophy, degeneration, death of myocytes and replacement fibrosis leading to myocardial dysfunction.

Decreased contractility --> decreased SV --> decreased CO --> decreased BP

- More blood remains in the ventricle due to decreased SV (increased end systolic volume) --> progressive ventricular dilation --> fibrosis and dilation

Compensatory increase in HR

Directing at increasing CO improving the BP - baroreceptor reflex.

Treatment for DCM

Positive inotrope (pimobendan - vetmedin).

What occurs during isovolumic relaxation in diastole?

The ventricular pressure falls, causing the aortic valve to close, while the volume of blood in the ventricles remains unchanged due to all valves being closed.

What happens during early rapid ventricular filling?

The pressure in the ventricle is less than in the atrium, causing the mitral valve to open and the ventricle to rapidly fill with blood due to a large pressure difference.

What is diastasis in the cardiac cycle?

A phase where the atrium empties and the ventricle fills, leading to nearly equilibrated pressures in each chamber and less rapid ventricular filling.

What is the 'atrial kick'?

The last 20% of blood is emptied into the ventricle during atrial contraction (following atrial depolarization), resulting in a small increase in pressure in both the atria and ventricle.

What does ventricular compliance describe?

The stiffness of the ventricle, indicating how easily it can distend to accommodate end diastolic volume.

What characterizes normal to increased ventricular compliance?

The ventricle easily distends to accommodate end diastolic volume with a relatively small increase in interventricular pressure.

What is decreased ventricular compliance?

A condition where a stiff ventricle does not relax well, requiring a larger increase in pressure for the same end diastolic volume.

What is the S3 heart sound and when does it occur?

The S3 heart sound occurs during early rapid filling in patients with dilated hearts and is caused by oscillation of hemodynamic structures in a poorly compliant ventricle.

What does the presence of an S3 heart sound signify?

It signifies heart disease with ventricular dilation and poor compliance, commonly seen in dilated cardiomyopathy (DCM).

What is the S4 heart sound and when does it occur?

The S4 heart sound occurs late in diastole during atrial contraction in patients with thickened hearts and is caused by the atrium trying to fill a hypertrophied ventricle.

What does the presence of an S4 heart sound indicate?

It indicates heart disease with ventricular hypertrophy and poor compliance, often associated with hypertrophic cardiomyopathy (HCM).

What is hypertrophic cardiomyopathy (HCM)?

A condition characterized by left ventricular myocardium thickening, leading to decreased compliance, relaxation, and audible S4 heart sound during diastole.

What are the consequences of incomplete ventricular filling in HCM?

It results in decreased preload, backup of blood into the atrium, progressive dilation of the atrium, potential blood stasis, clot formation, and backup of fluid to the lungs (pulmonary edema or pleural effusion).

What is the relationship between atrial contraction and ventricular compliance in HCM?

Atrial contraction in a poorly compliant ventricle results in an audible S4 heart sound and incomplete ventricular filling.

What is the significance of the S4 gallop in patients with HCM?

It indicates the presence of a stiff ventricle due to hypertrophy, leading to impaired filling and increased pressure during atrial contraction.

What is preload in cardiac physiology?

Preload is the volume filling the ventricle, specifically the end-diastolic volume (EDV).

How do volume overload diseases affect preload?

Volume overload diseases increase preload, often seen in conditions like mitral or tricuspid valve regurgitation.

What is the result of volume overload on cardiac structure?

Volume overload causes eccentric hypertrophy, characterized by normal wall thickness with a dilated chamber.

Define afterload in the context of cardiac function.

Afterload is the pressure needed to pump blood out of the ventricle, typically represented by arterial blood pressure.

What diseases increase afterload?

Pressure overload diseases such as arterial vasoconstriction, stenosis of the aortic or pulmonary valves, and arterial hypertension increase afterload.

What type of hypertrophy results from pressure overload?

Pressure overload causes concentric hypertrophy, which is characterized by increased wall thickness and a smaller chamber.

What is degenerative mitral valve disease?

Degenerative mitral valve disease is a volume overload condition where mitral regurgitation leads to increased volume in the left atrium, causing dilation. During diastole there is increased volume in LA which is delivered to the LV causing LV Dilation.

How does chronic mitral regurgitation affect blood pressure?

Chronic mitral regurgitation results in less blood pumped into the aorta, leading to reduced blood pressure and activation of the RAAS system to increase BP by volume retention in the kidneys and vasoconstriction.

Explain the Frank-Starling mechanism.

The Frank-Starling mechanism states that as preload increases, the force of contraction increases due to

-Increased cTn C affinity for Ca+ release when stretched

-Increased action-myosin interaction when stretched

What is the pathophysiology of volume overload disease?

Volume overload disease results in excess volume in atrial and ventricular chambers, leading to dilation, increased wall tension, and compensatory eccentric hypertrophy.

CO is reduced and RAAS system provides long term compensatory mechanism to maintain BP.

What are the consequences of moderate to severe atrial dilation?

Moderate to severe atrial dilation can lead to fluid backup, resulting in congestive heart failure, with left-sided failure causing pulmonary edema and right-sided failure causing cavitary effusions.

What is systemic hypertension in relation to cardiac health?

Systemic hypertension is a pressure overload disease that leads to left ventricular concentric hypertrophy.

What does the Law of LaPlace state regarding ventricular hypertrophy?

The Law of LaPlace states that ventricular hypertrophy reduces wall tension, with tension calculated as Pressure x Radius/wall thickness.

What is the pathophysiology of pressure overload disease?

Pressure overload disease results from high afterload requiring the ventricle to generate higher pressure during systole, leading to concentric hypertrophy and poor ventricular compliance. Poor compliance leads to poor relaxation.

What complications arise from poor relaxation in hypertrophied ventricles?

Poor relaxation leads to inadequate atrial emptying, progressive atrial dilation, blood stasis, clot formation, and can result in congestive heart failure.

How does poor relaxation affect coronary perfusion?

Poor relaxation results in poor coronary perfusion of cardiac muscle, leading to ischemia and myocardial fibrosis, which can predispose patients to arrhythmias.

P wave

Represents atrial depolarization and is followed by atrial contraction; S4 sound is associated.

QRS complex

Represents ventricular depolarization and is followed by ventricular contraction; S1 sound.

T wave

Represents ventricular repolarization and is followed by ventricular relaxation; S2 sound and early rapid filling; S3 sound.

Isovolumic contraction

No volume change on wiggers on diagram.

Ejection

Volume reduces as it is ejected from ventricle into aorta.

Isovolumic relaxation

No volume change.

Early rapid filling

Volume increases fast as ventricle fills.

Diastasis

Pressure gradient reduced and filling slows.

Atrial contraction

Small pressure increase due to atrial kick; last blood enters ventricle.