Lesson 8: Contractility and Excitation Coupling

Contractility and Excitation Coupling

  • Definition of Contractility: Ability of myocardial sarcomeres to shorten and produce force; independent of preload and afterload.

  • Increased Contractility (Positive Inotropy):

    • Factors: SNS stimulation, catecholamines, digitalis, PDE inhibitors.

    • Results in greater ventricular output for a given end-diastolic volume.

  • Decreased Contractility (Myocardial Depression):

    • Factors: Myocardial ischemia, severe hypoxia, acidosis, hypercapnia, hyperkalemia, hypocalcemia, volatile anesthetics, propofol, beta-blockers, calcium channel blockers.

    • Results in lower ventricular output for a given end-diastolic volume.

  • Hyperkalemia Effect: Locks voltage-gated sodium channels in closed-inactive state, impairing depolarization.

  • Ventricular Output Components:

    • CO (Cardiac Output)

    • SV (Stroke Volume)

    • LVSW (Left Ventricular Stroke Work)

    • RVSW (Right Ventricular Stroke Work)

  • Filling Pressures:

    • CVP (Central Venous Pressure)

    • PAD (Pulmonary Artery Diastolic pressure)

    • RVEDV (Right Ventricular End-Diastolic Volume)

    • LVEDV (Left Ventricular End-Diastolic Volume)

    • PAOP (Pulmonary Artery Occlusion Pressure)

    • LAP (Left Atrial Pressure)

    • LVEDP (Left Ventricular End-Diastolic Pressure)

  • Inotropy Factors: Chemicals significantly influence contractility, mainly through calcium availability or sensitivity.

    • Positive: SNS stimulation, catecholamines, calcium, digitalis, phosphodiesterase inhibitors.

    • Negative: Myocardial ischemia, severe hypoxia, acidosis, hypercapnia, and others.

  • Beta-1 Stimulation Mechanism:

    1. Activates adenylate cyclase, converting ATP to cAMP.

    2. cAMP increases PKA activity:

    • More L-type Ca²⁺ channels activated.

    • Ryanodine receptors stimulate calcium release.

    • SERCA2 activity increased for faster calcium uptake.

    1. Overall effect: Enhanced contraction and relaxation (positive inotropy and lusitropy).

  • Calcium Role in Myocardium:

    1. Action potential leads to Ca²⁺ entry via L-type channels.

    2. Activates RyR2 causing further Ca²⁺ release from sarcoplasmic reticulum (calcium-induced calcium release).

    3. Ca²⁺ binds to troponin C, facilitating contraction.

    4. Ca²⁺ unbinds from troponin C, leading to relaxation.

    5. Most Ca²⁺ is returned to the SR via SERCA2; some is removed via NCX.

    6. Na/K-ATPase restores resting membrane potential.