Lecture 15 Regulation of Heart Function PDF

Regulation of heart function  Regulation of Heart Function Intrinsic regulation: results from normal functional characteristics, not on neural or hormonal regulation Starling’s law of the heart Extrinsic regulation: involves neural and hormonal control Parasympathetic stimulation...

Regulation of heart function  Regulation of Heart Function Intrinsic regulation: results from normal functional characteristics, not on neural or hormonal regulation Starling’s law of the heart Extrinsic regulation: involves neural and hormonal control Parasympathetic stimulation Supplied by the vagus nerve Decreases heart rate Acetylcholine secreted Sympathetic stimulation Supplied by cardiac nerves Increases heart rate and force of contraction Epinephrine and Norepinephrine released Cardiac innervation  Parasympathetic control on nodal cells → Gi ACh K+/ACh If LTCC m2AChR - - Gαi - + ↓cAMP - β g ↓PKA 1. ↓ If activity → ↓ Phase 4 slope → ↓ HR → (-) chronotropic 2. ↑ K+/ACh channel activity → hyperpolarizes ↓ HR ↓ Phase 4 slope 3. ↓ LTCC activity → ↓ Phase 0 (takes longer to depolarize) ↓ conduction velocity (-) dromotropic effect  Extrinsic regulation: Parasympathetic control Normal Parasympathetic stimulation 20 Membrane potential (mV) 0 −60 Hyperpolarized Slower depolarization 0.8 1.6 2.4 Time (sec)  Sympathetic control on nodal cells → Gs E, NE LTCC β1 AC If Gs + + + + cAMP + PKA 1. ↑ If activity → ↑ Phase 4 slope Reaches threshold (VT) faster → ↑ HR (SA node) (+) chronotropic 2. ↑ LTCC activity → ↑ Phase 0 slope ↑ conduction velocity (+) dromotropic (AV node)  Extrinsic regulation: Sympathetic control Normal Sympathetic stimulation 20 Membrane potential (mV) 0 −60 Depolarized More rapid depolarization 0.8 1.6 2.4 Time (sec) Types of effects: Chronotropic effect + Chronotropic effect →  HR - Chronotropic effect →  HR Types of effects: Dromotropic effect SA node Internodal pathways AV node AV bundle Bundle branches Purkinje fibers Types of effects: Dromotropic effect + Dromotropic effect →  conduction velocity - Dromotropic effect →  conduction velocity Sympathetic control on cardiac contractile cells → Gs E, NE LTCC β1 Gs AC - + + ATP Phospholamban (PLB): protein cAMP that inhibits the SERCA2 pump - SERCA-2 PLB + - RYR2 PKA SR LTCC + + ↑ RYR2 activity ↑ LTCC activity [Ca+2]cytosol →  contractility → (+) inotropic ↑SERCA-2 activity → ↑ [Ca+2]SR → ↓duration Types of effects: Ionotropic effect Contractility Inotropic agent → any chemical that affects contractility Function of Ca+2 interaction with contractile filaments – Epinephrine, Norepinephrine and digitalis have positive inotropic effects – Chemicals with negative inotropic effects decrease contractility Norepinephrine Stroke volume (mL) Control + Inotropic effect →  contractility - Inotropic effect →  contractility A Ventricular end-diastolic volume (mL) Types of effects Type of effect Location Sympathetic Parasympathetic Effect Chronotropic SA node + - HR Dromotropic AV node + - Conduction velocity Inotropic Cardiac contractile cells + NA Contractility STROKE VOLUME AND HEART RATE DETERMINE CARDIAC OUTPUT CARDIAC OUPTUT is a function of Heart rate Stroke volume determined by determined by Rate of depolarization Force of contraction in in autorhythmic cells ventricular myocardium is influenced by Decreases Increases increases Contractility End-diastolic volume Sympathetic Due to innervation and which varies with parasympathetic epinephrine innervation increases Venous constriction Venous return aided by Skeletal muscle Respiratory pump pump Wiggers diagram 0 100 200 Time (msec) 300 400 500 600 700 800 QRS QRS complex complex Electro- cardiogram T P P (ECG) 120 B 90 Dicrotic notch Pressure A (mm Hg) Left 60 ventricular pressure 30 Left atrial pressure D 0 C Heart sounds S1 S2 135 E Left ventricular volume (mL) 65 F Atrial Ventricular Ventricular Atrial systole systole diastole systole Atrial systole Isovolumic Ventricular Early Late Atrial systole ventricular systole ventricular ventricular contraction diastole diastole