Cardiac Electro-Mechanical Coupling and Determinants of Function PDF

Cardiac Electro-Mechanical Coupling and Determinants of Function Lecture prepared by : Ricardo Rodriguez-Millan M.D. Harvey Mayrovitz PhD Assistant Professor Profe...

Cardiac Electro-Mechanical Coupling and Determinants of Function Lecture prepared by : Ricardo Rodriguez-Millan M.D. Harvey Mayrovitz PhD Assistant Professor Professor Department of Medical Education Department of Medical Education [email protected] [email protected]  Cardiac Muscle Electromechanical Coupling AP opens ECF voltage-gated Ca++ Ca-L channels Pumps & Exchangers Sarcolemma 20% 20% Free Trigger [Ca++] Contractile Ica-L Ca++ Machinery Ica-L Actin-Myosin causes 80% Calcium Ca-ATPase pump Induced Ca++ Ca++ Calcium Store Release Sarcoplasmic Reticulum (CICR) Cluster of Ca++- release channels open when LOCAL [Ca++] increases More Ica-L = more clusters opened! Typically, 50% of stores released. Dr HN Mayrovitz 2 of 30  Electrical-Mechanical Aspects: Preview R EKG T P Q +20 S K+ out f1 f2 K+ out 0 Ca++ in Ventricular Action Potential f0 Ventricular Pressure f3 (mv) Na+ in Threshold -65 -90 f4 0 f4 Absolute Refractory Period 250 ms Fast Na+ channels closed RRP Dr HN Mayrovitz 3 of 30 Introducing Cardiac Cycle Dynamics Cardiac Cycle Definitions S1: 1st heart sound S2: 2nd heart sound ABP: Aortic Blood Pressure LVP: Left Ventricle Pressure PHONO: phonocardiogram PEP: Pre-Ejection Period LVET: LV Ejection Time ED: Electromechanical Delay Dr HN Mayrovitz 4 of 30 IC: Isovolumic contraction  Contraction à Experimental Setup Slope = dL/dt Force (Tension) Length Papillary Time Stimulus Muscle High Afterload Afterload Force Time Load starts to move Preload Low Afterload Preload = Initial Stretch +Afterload à -Shortening Velocity Afterload = Load to Move Dr HN Mayrovitz 5 of 30  Contraction Force Determinants Contractility [Ca]++ and Preload Force increases with 2.0 µm Sarcomere Length Force Sarcomere at a given Ca++ 1.9 µm Length Force increases with 1.8 µm increasing [Ca++] at a fixed length Force Increases with +[Ca++] Contractility Force and Papillary +Sarcomere Frank-Starling Stimulus Muscle Given Length Afterload [Ca++] 2 5 10 20 50 100 Preload [Ca++] µM Dr HN Mayrovitz 6 of 30  Summary For any AFTERLOAD: Greater velocity with increasing preload: This is the basis of the FRANK-STARLING mechanism For any PRELOAD (PL): Reduced velocity with increasing AFTERLOAD Vmax Velocity converges to a common Vmax as Afterload approaches zero Vmax is a plausible surrogate for contractility since it is independent of preload and afterload Velocity of shortening (mm/s) For any AFTERLOAD and PRELOAD an increase in CONTRACTILITY will Fixed Afterload increase velocity of shortening Increasing preload (pre-activation stretch) PL 1 PL 2 Afterload à Dr HN Mayrovitz 7 of 30  Ectopic Timing à Mechanical Impact Peripheral Arterial Pulses Measured on the Index Finger A. Early Ectopic Normal beat would occur here R-R = 1.15 sec: HR = 52 Pulse Ratio = 4.4/5.6 =78% B. Earlier Ectopic Normal beat would occur here R-R = 1.12 sec: HR = 54 Pulse Ratio = 3/5 = 60% Dr HN Mayrovitz 8 of 30 Determinants of Cardiac Function Dr HN Mayrovitz 9 of 30 Muscle Fiber Mechanics à Cardiac Pump Function B Force/SV A B Velocity Pressure Contractility A of B > A Preload Afterload EDV Wall Stress (next slide) EDP TPR CVP Aortic/Ventricle Pressure EDP = EDV / CLV Dr HN Mayrovitz 10 of 30  Cardiac Muscle : Stress as Afterload EDV Elastic Tissue Myocyte “spring-like” Myocardium Muscle contracts (systole) To shorten … myocyte must Outward force due to P TM overcome tension (Wall Stress) Inward force due to wall T AFTERLOAD Equal and opposite at equilibrium Inward radial force increases (F 2) Chamber Radius decreases (r) LV Pressure increases Blood is ejected (Stroke Volume) Dr HN Mayrovitz 11 of 30  Determinants of Cardiac Output CO = SV x HR Frank-Starling ~ preload Sympathetic Sympathetic ~ contractility Vagus Afterload ~ pressure Frank-Starling: +SV if +preload +Sympathetic: +HR Sympathetic: +Contractility = +SV +Vagus: -HR Afterload: - SV if +Afterload Dr HN Mayrovitz 12 of 30 Ventricular Pressure: Isovolumic and Stimulated Aortic Pressure A) Clamped aorta with ventricle A contracting à isovolumic contraction C B) Developed ventricular pressure is LV Pressure maximum for its state of activation B C) Further sympathetic stimulation à Increased contractility à + Pressure) Contraction force and rate increased Peak isovolumic pressure determined with due to increased sympathetic traffic isolated heart-lung preparation with aorta (positive inotropic effect) outflow clamped Dr HN Mayrovitz 13 of 30 Closer Look: Frank-Starling “Law” of the Heart Contraction force increases as EDV increases Translates to increased SV as EDV increases Peak Isovolumic Pressures Isolated Heart LV Pressure achievable increases directly Ejection prevented with increases in preload Contractions Active are isovolumic Max-Systolic Developed P-V Curve Pressure Contraction Isovolumic Onset of systole EDP 1 2 3 Passive Filling LV Volume Dr HN Mayrovitz 14 of 30  Effects of Contractility on PIP Line Increased contractility increases PIP line slope Translates to increased SV as contractility increases Increased Contractility Stroke Volume Same SV for 100 ml Less preload Contraction Isovolumic Passive EDV Filling LV Volume Dr HN Mayrovitz 15 of 30  Frank-Starling vs. Contractility Movement ON a Increased CFC is due to F-S contractility Cardiac Stroke Volume (ml) Function Curves (CFC) Movement BETWEEN Increasing contractility CFC at a fixed (+ inotropy) results in a preload is due greater SV at equalto preloads. contractility changes Decreased Decreasing contractility contractility Increased contractility (+ inotropy) results in a reduced SV Fixed à Increased SV at equal preloads at equal preloads Preload Opposite for decreased contractility 0 5 10 15 20 LVEDP (mmHg) Dr HN Mayrovitz 16 of 30 Some Indicators of Cardiac Function Dr HN Mayrovitz 17 of 30 Ventricular Muscle’s Load and Energy Demand Ejection Ventricular Pressure Isovolumic curve contraction Lower wall High wall stress s stress r/w s P P less r r F Ejecting Afterload à s = P (r / w) Dr HN Mayrovitz Energy Need 〜 Stress x Time Large O2 demand during isovolumic contraction (large P and large r) Increased in conditions with elevated P (Aortic stenosis or Hypertension) O2 demand during ejection also increased in conditions with elevated P 18 of 30  Measures of Ventricle Energy Demand Area under the P – T curve Increased P Increased duration Tension Time Integral (TTI) ∫s(t) = ∫[P(t) x r(t) /w(t)] 160 Contractility of B > A > C (dP/dt)max B LV Pressure (mmHg) 120 Double product (MAP X HR) A Clinically Measurable 80 Clinically Useful C 40 0 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 Time (sec) Dr HN Mayrovitz 19 of 30 Respiratory Determinants of Cardiac Function Dr HN Mayrovitz 20 of 30  + Intra-thoracic Pressure à + ‘Afterload’ Effect s LV PTH PLV F Thorax Exhale PTH Inhale Time Afterload à s = P r / w = (PLV – PTH) (r/w) During a deep inspiration against a closed glottis PTH can decrease substantially causing a substantial increase in the LV transmural pressure. This increases the effective afterload and may reduce SV Dr HN Mayrovitz 21 of 30  Normal Variation is Systolic BP with Respiration During inspiration - small septum shift & + Lung BV PTH - small Left Ventricle SV decrease Causes small decrease in systolic BP ( 12 mmHg then Pulsus Paradoxus DP Inspiration -PTH à -PSVC à +DP à +VR Q +PTM in vessels Veins Lung More Septum PSVC -R +LBV Displacement RV - SV +VR -LV fill -LV fill Free -EDV Wall -SV (-EDV) -SV -SV +HR -SBP -SBP -SBP Dr HN Mayrovitz Baroreceptors 22 of 30  Intra-Myocardial Pressures Contraction increases ventricular pressure Intramyocardial and intra-myocardial pressure Pressure (mmHg) Stress in myocardial wall (radial and tangential) with contraction is greater towards endocardial vs. epicardial surfaces Left Ventricle Consequence is that during contraction the Pressure (mmHg) blood vessels toward the endocardial surface (subendocardial) are compressed more and blood flow is compromised more This contributes to the increased Compressed more Flow reduced vulnerability of the endocardial part of the during systole ventricle wall to ischemia and injury when r perfusion pressure is reduced P Also explains why most of subendocardial blood flow occurs during diastole sr = [a2P/(b2-a2)] x (1 – b2/r2) After: Pfluegers Arch 1963;278:181 cp196 Dr HN Mayrovitz 23 of 30 Interactive questions as time permits Dr HN Mayrovitz 24 of 30  Interactive “ Review” Questions Arterial pulse pressure increases if: a) arterial compliance decreases b) cardiac contractility decreases c) ventricular ejection rate decreases d) stroke volume decreases e) mean arterial pressure decreases If a vessel has a constant perfusion pressure then blood flow in this vessel is increased the most by: A. Halving its length B. Doubling its radius C. Halving the blood’s viscosity D. Reducing its diameter by a factor of three E. Reducing its cross-sectional area by a factor of three Which of the following is a true statement? A. Blood viscosity can be accurately defined as the ratio shear rate / shear stress. B. Average shear rate is directly proportional to average blood velocity C. Average shear rate is directly proportional to the average diameter D. In a blood vessel, blood viscosity increases with increasing shear rate E. The unit of pressure in the cgs system is mmHg If a blood vessel has a laminar and constant blood flow then the shear stress at the vessel wall: A. Is theoretically zero B. Is less than it is at the center of the vessel C. Increases if the diameter of the vessel increases D. Depends on the inverse 4th power of the diameter E. Depends on the inverse 3rd power of the diameter Dr HN Mayrovitz 25 of 30  Interactive “ Review” Questions The percentage of a fixed cardiac output (CO) that goes to an organ depends on: A. The value of MAP B. The value of CO C. The value of the Heart Rate D. Organ absolute vascular resistance E. Organ relative vascular resistance Dr HN Mayrovitz 26 of 30  Interactive “ Review” Questions Increased sympathetic activation of myocyte b1 receptors results in which of the following effects? A. Positive dromotropic B. Both positive dromotropic & negative chronotropic C. Negative chronotropic D. Negative lusitropic E. Both positive inotropic & negative lusitropic Dr HN Mayrovitz 27 of 30  Interactive “ Review” Questions Shear stress caused by blood flow in a vessel is: A. Greatest at the center of the vessel B. Greatest at the wall of the vessel C. Inversely proportional to the average blood velocity D. Directly proportional to the vessel’s diameter E. Increased if blood’s viscosity decreases Dr HN Mayrovitz 28 of 30  Interactive “ Review” Questions Turbulent blood flow: A. Is a normal feature in most large arteries B. Causes an increase in resistance to blood flow C. Occurs if the Reynolds number is below the critical threshold D. Reduces the amount energy lost as compared to laminar flow E. Causes blood flow to be inversely related to perfusion pressure Dr HN Mayrovitz 29 of 30  Interactive “ Review” Questions In a vascular bed, which of the following decreases blood flow and increases capillary pressure? A. Arteriolar vasoconstriction B. Decreased MAP C. Venous vasoconstriction D. Increased CVP E. Both C and D Dr HN Mayrovitz 30 of 30