CR03 - Cardiac Muscle & Mechanics

What is the sarcomere?

The basic contractile unit of cardiac muscle.

What are T-tubules?

Invaginations of the cell membrane at the Z-line.

What is the function of T-tubules in cardiac muscle?

Carry action potentials into the interior of the cell.

What structures do T-tubules form with the sarcoplasmic reticulum?

Dyads.

What is the sarcoplasmic reticulum (SR)?

An intracellular membrane network close to contractile elements that stores Ca+ for action potentials.

• The ER of muscle cells

What is the role of the sarcoplasmic reticulum in cardiac muscle?

Storage and release of Ca²⁺ for excitation-contraction coupling.

What determines the magnitude of tension developed by cardiac muscle?

Intracellular calcium concentration.

What are the phases of exitation-contraction coupling in cardiac muscle?

Cardiac action potential → Ca2+ enters cell during plateau phase → Ca2+ induced Ca2+ release from SR → Ca2+ binds to troponin C → Cross-bridge cycling → tension

What happens during cardiac muscle relaxation?

Ca2+ is pumped out of the cell via Na/Ca exchangers and pumped back into the SR by SERCA

What two main factors determine the force of cardiac muscle contraction?

Sarcomere length and excitation–contraction coupling.

How does increased ventricular filling affect contraction strength?

Increased filling (stretch) increases contraction strength.

What is end-diastolic volume (EDV)?

The volume of blood in the ventricle at the end of diastole.

Why does increased EDV increase force of contraction?

It stretches sarcomeres to a more optimal length.

How does sarcomere stretch affect actin-myosin interaction?

Improves overlap and increases cross-bridge formation, creating greater force.

What does the length–tension relationship describe?

The degree of actin-myosin filament overlap correlates to tension. Lmax = 2.2 um (maximal tension)

What determines the force of cardiac contraction?

Excitation-contraction coupling and initial myocardial cell length.

What is preload?

The blood volume in the ventricle during diastole (EDV).

How does preload affect cardiac muscle?

Causes myocardial stretch; establishes the length-tension relationship.

What factors lead to increased ventricular filling (preload)?

• Increased atrial contractility

• Increased HR

• Increased ventricular compliance

• Increased aortic pressure

• Increased central venous pressure

What does increased ventricular compliance cause?

Increased ventricular filling (preload) and dilated cardiomyopathy

What does decreased venous compliance cause?

Vasoconstriction of veins → increased central venous pressure → increased ventricular filling (preload)

What does increased thoracic venous blood volume cause?

Increased total blood volume → increased venous return → increased central venous pressure → increased ventricular filling

How does increased aortic pressure affect preload?

Increases afterload, reduces stroke volume by raising end-systolic volume, and secondarily increases preload.

What is afterload?

The resistance the ventricle must overcome to eject blood.

During which phase of the cardiac cycle does afterload act?

Systole.

What determines left ventricular afterload?

Systemic vascular resistance and aortic pressure.

What determines right ventricular afterload?

Pulmonary pressure.

How do stenotic aortic and pulmonary valves affect afterload?

Increase outflow resistance and afterload.

What does the Frank–Starling mechanism state?

The strength of the heart’s contraction is directly proportional to the volume of blood filling the heart (EDV).

How does preload affect contractility via Frank–Starling?

Increased preload increases contraction strength.

What cellular mechanism underlies Frank–Starling?

Optimal actin-myosin overlap due to fiber stretch for powerful contractions.

What is the functional purpose of the Frank–Starling mechanism?

Matches cardiac output to venous return.

What is the clinical implication of the Frank-Starling mechanism?

It is an adaptive response that allows the heart to ajust output based on lood volume. Essential during physiological demands like exercise.

How does contractility affect stroke volume and cardiac output?

Increased contractility → increased SV → increased CO

Decreased contractility → decreased SV → decreased CO

What is cardiac contractility?

Intrinsic ability of cardiac muscle to generate force at a given length.

What ion is contractility primarily related to?

Intracellular Ca²⁺.

What cellular factors determine contractility?

Amount of trigger Ca²⁺, amount of SR Ca²⁺ release, and sensitivity of contractile proteins to Ca2+

What is max dP/dt?

Maximum rate of pressure rise in the left ventricle during systole; it is an important hemodynamic parameter used to assess contractility in the heart.

Which drugs act as beta-agonists increasing contractility?

Dopamine, dobutamine, epinephrine, isoproterenol.

What are the effects of calcium channel blocker drugs?

Decrease contractility (negative ionotropy), decrease HR, decrease conduction velocity, smooth muscle relaxation (vasodilation)

What are cardiac glycosides?

Drugs that increase contractility indirectly by inhibiting the Na/K pump. Less Na pumped out → Ca/Na exchanger stops functioning → more Ca in the cell → increased contractions

Which drugs are cardiac glycosides?

Digitalis, digoxin, ouabain

What are positive inotropes?

Agents that increase myocardial contraction force.

How do β-agonists increase contractility?

Via β1-receptor activation and increased intracellular Ca²⁺.

What signaling pathway do β1 receptors activate?

Gs → adenylyl cyclase → cAMP → PKA → phosphorylates L-type Ca channels → increased Ca → increased contractility

How does PKA increase contractility?

Phosphorylates L-type Ca²⁺ channels, allowing Ca influx.

How does increased heart rate increase contractility?

More action potentials occur per unit time ➔ increase in trigger Ca2 ➔ more Ca2+ is released from the SR ➔ Ca2+ can’t be removed as quickly ➔ new equilibrium ➔ increased contractility

How do cardiac glycosides increase contractility?

Inhibit the Na+/K+ ATPase ➔ increase in intracellular Na+➔ decreases Na+/Ca2+ exchange ➔ intracellular Ca2+ increases ➔ increases contractility

What are negative inotropes?

Agents that decrease myocardial contraction force.

Which drugs act as negative inotropes?

β-blockers, parasympathetic stimulation, calcium channel blockers.

How does parasympathetic stimulation reduce contractility?

Via ACh acting on M2 receptors.

How do calcium channel blockers (CCB) reduce contractility?

Block L-type Ca²⁺ channels

What vascular effect do calcium channel blockers cause?

Arterial vasodilation.

What myocardial effects do calcium channel blockers cause?

Negative chronotropic, inotropic, and dromotropic effects.

What are dihydropyridine CCBs?

Potent vasodilators (e.g., nifedipine, amlodipine).

What are nondihydropyridine CCBs?

Potent myocardial depressants (e.g., verapamil).

What characterizes left-sided heart failure?

Pulmonary congestion, pulmonary hypertension, and dyspnea.

(Blood gets trapped in the lungs)

What characterizes right-sided heart failure?

Systemic venous congestion and peripheral edema. (Blood gets trapped in the periphery)

What is systolic dysfunction in heart failure?

Inadequate ventricular emptying during systole.

What is diastolic dysfunction in heart failure?

Impaired ventricular filling during diastole.

How do diuretics affect ocular health?

Cause dry eye by reducing tear production.

What visual effects can digoxin cause?

Blurred vision, color vision changes, photophobia.

What causes periorbital edema in heart failure?

Fluid retention or medication side effects.

How does Frank–Starling apply to chronic heart failure (HF)?

Increased preload and afterload reduce effective cardiac output. This leads to systemic congestion.

How does HF contribute to ocular vascular changes?

Systemic congestion leads to edema and vascular alterations.

How can amlodipine cause ocular side effects?

Amlodipine is a CCB that causes vasodilation → increased capillary permeability around the eyes → eyelid edema and conjunctival hyperemia

What ocular management strategies are important in HF patients?

Use preservative-free lubricants for dry eyes and monitor medication effects.

Why is cardiology coordination important for eye care?

To safely manage dilation and stress in cardiac patients.

What patient education is important for ocular/cardiac management?

Teach about recognizing signs of digoxin toxicity (blurred vision, halos) and importance of regular eye exams.