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Cardiac Mechanics Bioengineering/Physiology 6000 Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I The Heart • Structure – Macro and micro • Function • Cells – Pacemaker – Conduction system – Contractile myocytes • Electrophysiology – Action potentials – Cell to cell coupling • Mechanics – EC coupling – Cardiac cycle Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Average Hemodynamic Values Variable Cow Man Dog Rabbit Rat Weight (kg) 414 70 20 4 0.6 Cardiac Output (ml/ sec) 680 110 42 5.2 1.2 Heart rate (min-1) 71 76 99 288 349 Stroke Volume (ml) 570 87 25 1.1 0.21 16 18 32 22 Velocity in ascending aorta 690 560 .2 (5) 2700 .7 (1.4) Cardiac Mechanics Cardiovascular Physiology By William R. Milnor Bioengineering 6000 -- SystemsPhysiology I Hummingbird Physiology (What we need to explain) • Heart is 20% of body volume (largest of any animal), 2-3% of body mass • Heart rate varies from 30 (deep rest), 500 (while perching), to 1200 (during high speed chases) • Highest known mass-specific metabolic rates among vertebrate homeotherms (100 times greater than elephant) • Eats .5-8 times body weight per day • Respiratory rate of 250 at rest • Dives produce 7-10 G at speeds of up to 100 kph. R.K. Suarez, Hummingbird flight: Sustaining the highest massspecific metabolic rates among vertebrates. Cellular and Molecular Life Sciences (CMLS) 48(6), 1992. Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Electrophysiology Review • Pacemaker cells – Neurogenic vs. myogenic – SA Node – AV Node – Purkinje Fibers • Conduction system • Ventricular myocytes • The Electrocardiogram (ECG) Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Excitation-Contraction Coupling (ECC) Cardiac Mechanics Bioengineering 6000 CV Physiology Structure-Function Relationship Cardiac Mechanics Bioengineering 6000 CV Physiology EC Coupling • Action potential causes influx of Ca2+ • In mammals and birds, this causes release of more Ca2+ • Ca2+ interacts with actin/myosin to cause contraction • Pumps gather up Ca2+ or remove it from cell Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Calcium-induce Calcium Release D.M.Bers Nature VOL 415 10 January 2002 Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Calcium Measurement • Calcium-sensitive dye • Optical recording system • Stimulate cell and synchronize with optics Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I EC Coupling and Ca2+ +40 mV -80 mV diastole 50 ms systole 1) Control 2) SR disabled (caffeine) 3) No Ca2+ entry (Ba2+) Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Ca+2 Measurements http://www.youtube.com/watch?v=x3s2L2rvNLM Cardiovascular Review Bioengineering 6900 B-TAC CICR Summary • Calcium causes contraction • Calcium is stored in the sarcoplasmic reticulum (SR) • A small increase of Ca in the vicinity of the SR causes a much larger release of Ca from the SR. • Contraction can be graded Action Potential AP Contraction 100 [Ca++] gram Cai from ICa t e ng Ra Cai transient mV Tension [% max] ov er Twitch (tension) Rest 0 10-7 Cardiac Mechanics Cai [M] 10-5 Bioengineering 6000 -- SystemsPhysiology I Contractile Proteins Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Pretension, Frank-Starling, and Control of Contraction Cardiac Mechanics Bioengineering 6000 CV Physiology Pretension of Muscle (Explain?) active tension tension Isometric Contraction with Pretension resting tension time Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Isotonic Contraction and Preload 2g 2 2g 1 tension [g] 1g 1 1g 3 1g 2 isotonic tension 4 3 3 2 1 2g 3 2 1 2 3 pretension 1 muscle length Cardiovascular Review Bioengineering 6900 B-TAC Intrinsic Regulation of Cellular Contraction Action Potential Twitch (tension) Cai transient mV [Ca++] Cai from ICa t Total tension Twitch tension 120 Tension [% of maximum] gram 100 80 60 40 20 0 1 1.5 2 2.5 3 3.5 Striation Spacing [µm] 4 • Spacing in contractile elements – Determines contractility – Adjusted passively Passive (rest) tension Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Frank Starling Mechanism Cell Level Muscle Level 120 Whole Heart Level Total tension 80 60 Twitch tension 40 20 0 1 1.5 2 2.5 3 3.5 4 Passive (rest) tension Striation Spacing [µm] • • • • • Increased pretension can increase contraction Cell: striation spacing Muscle: pretension Heart: Increased filling produces increased output Does not require neural input Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Extrinsic Regulation of Contractility AP Contraction Muscle Effect of NE/E er 100 ov Total tension Ra ng e Tension [% max] Cell Rest Muscle tension Tension [% of maximum] 100 0 10-7 Cai [M] 10-5 Twitch tension Passive (rest) tension Whole Heart Muscle length • Free [Ca]i is key component • Positive inotropic agents: – epinephrine: stimulate β receptors and increase Ca influx and uptake (load SR) • Negative inotropic agents: – ACh: acts mostly on atria to shorten AP and reduce [Ca]i – Acidosis Cardiac Mechanics Bioengineering 6000 CV Physiology The Cardiac Cycle and Afterload Cardiac Mechanics Bioengineering 6000 CV Physiology Cardiac Cycle Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Cardiac Cycle Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Work of the Heart • Work = Pressure * Volume (force * distance) • Cardiac cycle as PV diagram • Efficiency – Convert work to O2 consumption – Compare to total O2 consumption – 10--15% efficient Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Effect of E/NE on Contraction tension [g] maximum isotonic tension Pressure Left Ventricle 4 3 2 1 muscle length stroke volume • constant pretension • reduced end-systolic volume • increased stroke volume Volume Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Isotonic Contraction and Afterload 3g 2 tension [g] 1g 1 2g 3g 3 1 Afterload reduces shortening 2g 1g 1g 5 4 isotonic tension 4 3 1g 2g 35 4 2 2 pretension 1 1 Cardiovascular Review muscle length Bioengineering 6900 B-TAC Contraction at the Whole Heart Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Whole Heart Simulation Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Animal Hearts Cardiac Mechanics Bioengineering 6000 CV Physiology Animal Hearts • Air-breathing vs. water breathing vs. fetal • Open Systems • Separate left and right hearts – Higher pressure good for rapid transport but require lymphatic system – Lower pressure (e.g., pulmonary) does not require lymphatics and stays drier – Both sides must have equal flow • Shared ventricles – Shunts from pulmonary to systemic (P->S) – Allows adjustment of flow through lungs/gills – Flows to both parts of circulation are not equal but pressures are Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Open Systems • Blood empties into body space • Bathes tissues directly, blood in small chambers B • Low pressure system (4-10 mm Hg) • Typically limited regulation and low oxygen transport (with exceptions) • Insects bypass lungs and transport oxygen directly so open circulation does not carry oxygen Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Rigid Pericardium • Compliant – Minimal constraint – Lubrication • Non-compliant – contraction of one chamber assists filling the other Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Water Breathing Fishes • 4-chambered, sequential heart with valves • Gills perform gas exchange and also ion balance (like kidneys in mammals) • Gill circulation under higher pressure than systemic circulation Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Air Breathing Fishes • Gills and vascularized air sac both provide O2; gills used for CO2 and ion balance • Blood directed to different parts of system by the heart, also between gills and air-breathing organs Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Amphibians (e.g., Frog) • Shared ventricle but blood separated – Spiral fold – Initial flow through pulmonary because of reduced pressure – Resistance to flow varies with breathing (inhale reduces resistance) Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Frog II • Partial mixing of systemic blood flow – Cerebral flow oxygenated, systemic mixed • http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/AnimalHearts.html Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Reptiles (non crocodilian) • Partial separation of single ventricle by 2 septa • In ventricular systole, flow determined by relative resistances of pulmonary and system, e.g., breathing, diving • Pressure differences in arteries also directs flow: lower pressure value opens first • Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I Fetal Heart • Lungs collapsed so minimal pulmonary flow • Oxygenated blood comes from placenta and some passes through foramen ovale to left atrium • Rest of returning blood goes from RV and most through Ductus ateriosus to aorta • At birth, lungs inflate, flow to them increases, placenta flow gone so systemic resistance increases • Left side pressure increases, D.A. and F.O close Numbers are percentage of ventricular output Cardiac Mechanics Bioengineering 6000 -- SystemsPhysiology I