Muscle Tissue Structure and Function

Final Review (Modules 4-6)

• Skeletal muscle is striated and under voluntary control
• Skeletal muscle is innervated at the neuromuscular junction by acetylcholine (ACh)
• Muscle fibers run the length of the entire muscle

Muscle Fibre

• Muscle fibers run parallel to each other and are surrounded by connective tissue
• Muscle fibers are single, multinucleated cells with plenty of mitochondria

Myofibrils

• Muscle fibers are divided into discrete contractile elements called myofibrils
• Myofibrils have bands (light and dark) which give them a striated appearance in side view
• The cross-section of myofibrils shows thick and thin filaments (myosin and actin)

Myofibril Structure

• Myofibrils are contractile elements of muscle fibers
• They exhibit light and dark bands (I and A bands)
• A bands: dark bands of stacked thin and thick filaments running parallel to each other, with borders defined by thick filaments
• I bands: light bands that contain portions of thin filaments that do not extend into the A band
• H zone: the lighter portion of the A band where myosin does not overlap actin
• M line: proteins that hold thick filaments together in a stack and runs down the H zone
• Z line: vertical line within the I band, with the region between two Z lines defining a sarcomere

Sarcomere

• The relaxed sarcomere is 2.5 μm wide
• Growing muscles extend the length of muscle fibers by adding new sarcomeres to the ends
• The A band contains myosin and actin overlap, which forms cross-bridges when thin filaments bind

Muscle Proteins

• Muscle proteins are the building blocks of muscle fibers

Thick Filament

• Myosin uses ATP to move along actin filaments
• Myosin is a dimer consisting of 2 subunits, each with a long shaft and a globular head (golf club shape)
• The shafts of myosin wrap around each other
• Myosin heads stick out, forming actin binding sites and myosin ATPase sites

Thin Filament

• Actin filaments are composed of individual, spherical actin molecules arranged in a double helix formation
• Tropomyosin is a thin, double helix protein that lies along the actin filament
• Tropomyosin regulates muscle contraction by covering active binding sites on actin
• Troponin is a regulatory protein made of 3 polypeptides and binds to tropomyosin, actin, and Ca2+

Muscular Contraction

• Muscular contraction is initiated by the sliding filament mechanism

Sliding Filament Mechanism

• Cross-bridges formed between myosin heads and actin filaments form the basis for muscle contraction
• Contraction is the activation of tension-generating sites within muscle fibers, resulting in shortening of the muscle fiber

Sliding Filament Mechanism: Process

• During contraction, thin filaments move inward over thick filaments, causing the Z lines to move closer together, shortening the sarcomeres
• The degree of overlap between myosin and actin increases
• The muscle shortens, resulting in concentric contraction

Power Stroke

• The power stroke is an interaction between myosin and actin that initiates sarcomere shortening
• The power stroke occurs when a cross-bridge bends, pulling the thin myofilament inward
  • Myosin cross-bridge binds to an actin molecule
  • The myosin head bends, pulling the thin myofilament inward
  • The cross-bridge detaches at the end of the power stroke and returns to its original conformation
  • The cross-bridge binds to a more distal actin molecule, repeating the cycle
• Actin is pulled closer to myosin during the power stroke
• Not all cross-bridges are actively pulling
• Some hold actin in position until the next power stroke

Excitation-Contraction Coupling

• Excitation-contraction coupling is the process of converting an electrical signal to contraction
• Muscles rely on two structures to transmit the signal:

Key Events in Excitation-Contraction Coupling

• Acetylcholine (ACh) release at the neuromuscular junction causes permeability changes and initiates an action potential across the muscle membrane

Sarcoplasmic Reticulum (SR)

• The SR is a membranous structure running parallel to muscle fibers
• Lateral sacs at the end of the SR are in close proximity to T-tubules
• The SR stores Ca2+ ions

T-Tubules

• T-tubules are invaginations of the plasma membrane (PM) at the junction of A and I bands
• T-tubules dip into the fiber and run perpendicular to it

Relationship Between T-Tubules and SR

• Plasma membrane depolarization causes a wave to spread across the cell (T-tubules)

• The signal is also transmitted from the T-tubule to the SR

• The SR runs longitudinally with sacs lying adjacent to the T-tubules and dips in junctions between A and I bands

• The surface of the T-tubules has dihydropyridine receptors (voltage-sensor) that sense the wave

• Opposite the T-tubules, the SR has ryanodine receptors

• Excitation enters the T-tubules and is sensed by dihydropyridine receptors, which influence ryanodine receptors of the SR, causing a conformational change Ryanodine receptors form a Ca2+ channel Activation of the Ca2+ channel allows Ca2+ to enter the cytoplasm

Calcium Release

• Ca2+ is the primary trigger for skeletal muscle contraction
  • When a muscle is excited, Ca2+ enters the muscle fiber and binds to troponin
  • This causes a conformational change, moving tropomyosin out of the way and exposing myosin binding sites on actin

Relaxation

• Relaxation occurs with decreased nerve activity at the neuromuscular junction
  • Acetylcholinesterase removes remaining ACh, stopping the generation of action potentials
  • The SR stops releasing Ca2+
  • Ca2+-ATPase pumps Ca2+ back into the SR from the cytosol
  • The troponin-tropomyosin complex covers actin molecules again
  • Cross-bridge cycling ceases, and exposure of actin binding sites allows ATP-powered cross-bridge cycling

ATP in the Cross-Bridge Cycle

1. ATP binds to the ATPase binding site on myosin, breaking it down into ADP. Energy is transferred to the myosin cross-bridge.
2. The presence of Ca2+ allows the troponin-tropomyosin complex to expose actin for binding, causing cross-bridge swings and the power-stroke
3. Phosphate (Pi) and ADP are released, but the cross-bridge remains bound to actin
4. The binding of a new ATP molecule causes the cross-bridge to detach and return to its un-cocked shape

• If no ATP is available, Ca2+ continues to increase, and the cells remain contracted until they run out of ATP
• Protons decay and relax the cell

Temporal Relationship Between Electrical and Mechanical Activity

• Increased electrical activity in the muscle leads to increased mechanical activity

Latent Period

• Muscle activation is required to exert force, leading to muscle shortening
• The latent period is the delay between the action potential and the start of contraction

Contraction Time

• The contraction time is the time it takes for actin filaments to slide along myosin filaments
• Peak tension occurs between 40-120 msec
• Variability is due to the type of muscle fibers and their location

Motor Units

• The force generated by a muscle depends on motor units

Twitch

• A twitch is a single muscle fiber contraction
• To develop more tension in a muscle, more fibers need to twitch

Motor Unit Recruitment

• Greater numbers of recruited fibers result in greater muscle tension
• Motor neurons enter the muscle and innervate multiple fibers
  • Activation of a motor neuron causes all fibers to contract as a single motor unit
  • The body selectively rotates activation of motor units to prevent fatigue

Frequency of Stimulation

• The membrane recovers quickly from short action potentials to undergo another

  • If a muscle fiber is restimulated after complete relaxation, the second twitch has the same magnitude as the first
  • If a muscle fiber is restimulated before complete relaxation, the second twitch is added, resulting in twitch summation
  • When muscle fiber twitches overlap, it results in tetanic contraction

• Unfused tetanus: fibers partially relax between stimuli

• Fused tetanus: no relaxation between stimuli. Fused tetanus is the strongest and most common type of twitch

Optimal Muscle Length

• Every muscle has an optimal resting length (l0), which leads to maximum cross-bridge availability for binding

• At the optimal length, the maximum force can be generated

• Less than l0: thin filament overlaps thick filaments without many cross-bridges, decreasing contraction efficiency and tension. If muscle shortening occurs too much, actin from opposite sides of sarcomere may overlap, with thick filaments in contact with z-lines

• At l0: maximal cross-bridges are available for binding, typically optimal at rest to allow maximum contraction

• Greater than l0: overlap of filaments decreases, and less cross-bridges are available

Muscle Tension and Bone

• Muscles are attached to bones around a joint Connective tissue forms tendons, making physical connections to bones and allowing contraction or relaxation

Muscle Tension with a Load

• Muscles must exceed forces that oppose the movement of bone
  • If there is an external load to the biceps, the muscle must contract to overcome the force exerted by the triceps to move the weight

Muscle Soreness: Myalgia

• Contusion: muscle subjected to sudden, heavy extrinsic compressive force
• Strain: muscle exposed to excessive force caused by intrinsic tension
• Laceration: deep cut/tear of muscle

Types of Muscle Contraction

• Types of muscle contraction depends on the level of muscle interaction

At the Motor Unit Level

• Isotonic contraction: tension remains constant as muscle length changes
• Isometric contraction: tension increases while muscle length remains static

At the Whole Muscle Level (Requires Work)

• Concentric dynamic contraction: muscle produces tension as it shortens
• Eccentric dynamic contraction: muscle produces tension as it lengthens

Muscle Cells: Fatigue

• Fatigue is a state where contractile activity cannot be maintained, and tension declines

Central Fatigue

• Central fatigue is when the central nervous system (CNS) decreases activation of motor neurons, slowing down or stopping activity even if muscle fibers are not fatigued

Muscle Fatigue

• Muscle fatigue is a mechanism to protect muscle cells, where contractile activity is reduced when ATP supplies run out or tetanus occurs
  • Local accumulation of ADP+Pi from ATP hydrolysis interferes with cross-bridge cycling (CBC)
  • Accumulation of lactic acid inhibits glycolytic enzymes
  • Accumulation of extracellular K+ (Eck+) causes depolarization, making muscle fibers less excitable
  • Depletion of glycogen

Muscle Fibre Types

• Muscle fibre types describe traits of slow and fast twitches

Slow Twitch (Type I)

• Slow twitch muscle fibers are found in slower muscles

• Slow twitch muscle fibers are innervated by alpha 2 motor neurons

• Slow twitch have smaller and lower activation thresholds and slower condition speeds

• Because of the properties of slow twitch muscles, they contract and relax at slower rates

• ATPase in slow twitch myosin heards has slower rate of CBC

• Slow twitch muscles produce ATP through aerobic processes and are slow oxidative

Fast Twitch (Type II)

• Fast twitch muscle fibers are found In fast twitch muscles

• Fast twitch muscles are innervated by alpha 1 motor neurons with large, high activation thresholds and faster conduction speeds.

• ATPase in fast twitch myosin heads has higher rate of CBC

• Fast twitch can be fast oxidative glycolytic, produceing ATP through aeorbic an anaerobic pathways

• Fast twitch can be fast glycolytic, producing ATP through exclusively anaerobic means

Colour of Muscle Fibres

• Colour of muscle fibres is affected by how they produce energy
• Red fibres are slow oxidative and fast oxidative glycolytic (FOG), vascularized, and have numerous mitochondria
• Myoglobin in red fibres supports oxygen us and binds both iron and oxygen → creating the red colour
• White fibres are exclusively fast glycolytic relying on anaerobic metabolism

Afferent Input for Motor Control

• Skeletal muscle can be contracted, relaxed, or both, requiring CNS input
  • Input from proprioception occurs due to of skeletal muscles
  • Muscle receptors also contribute input

Muscle Receptors; Muscle Spindles

• Muscle spindles monitor changes in muscle length and play a role in stretch reflexes
• Muscle spindles are distributed through specialized muscle cells (intrafusal fibers) and lie within spindle shaped connective tissue among extrafusal fibers
  • Only the ends of intrafusal fibres are contractile
  • Gamma motor neurons innervate muscle spindles
  • The central region of muscle spindles has sensory afferent fibers activated by stretch

Golgi Tendon Organs

• Golgi tendon organs regulate tension

  • Receptors are found at the junction of tendons and muscle fibers
  • Extrafusal fibers contract, increasing tension and activating afferent fibers

• A stronger pull leads to a higher rate of firing from Golgi afferent fibers.

• Golgi tendon organs are mostly subconscious

Neural Inputs

• Afferent neurons are involved in spinal reflexes, maintaining posture and protective movements

Primary Motor Cortex

• Fibers descend and terminate directly on motor neurons in the spinal cord
  • The corticospinal motor system mediates fine voluntary movement

Brain Stem

• The brain stem is a multineuronal motor system influenced by motor regions of the cortex, cerebellum, and basal nuclei
  • The Brain regulates body posture and involuntary movements

Smooth Muscle Structure

• Smooth Muscle is found in walls of hollow organs and tubes and in the heart (cardiac Muscle).

• There are 3 Filaments in contraction in Smooth Muscle -Thick Myosin Filaments -Longer -Thin Actin Filaments with Tropomyosin (No Troponin) -Intermediate Filaments that Support Cytoskeletal Framework

• Smooth Muscle has no Z-Lines (Instead dense bodies) -Anchors intermediate contractile filaments -Form diamond-like pattern in cell

Smooth Muscle Mechanism of Contraction

• There is no Troponin in Smooth Muscle -Therefore, Actin + Myosin cannot form Cross Bridges at rest

• Myosin Light chain plays a role in Cross Bridge Formation -Therefore, it must have Myosin light Chain for CB formation

• Cross Bridge Activation*

  1. Ca2+ enters Smooth Muscle Cell and binds to Calmodulin
  2. Ca2+ Calmodulin Complex binds to; or activates, Myosin light Chain Kinase
  3. Now there is Kinase Phosphorylates Mysoin Light Chain -It allows Myosin to Bind to Actin Calcium Sources in Smooth Muscle

• Entry From ECF* -V-gated Dihydropyridine Receptors allows for Ca2+ Channels to become active. -Depolarization of Ca2+ Enters channel from ECF

• Release From SR* -Once Cells Enter from ECF; Activate calmodulin, or stimulate SR to Release Ca2+ -SR Release Via Ca2+ -Induced Ca2+ Realease (CICR)

• Smooth Muscle Excitation* -Depends on if there are single, or multi units

• Single Unit* -All Muscle, fibers are electronically connected via Gap Junctions -Excited as Functional Syncytium

• Found in: GI, Reproducible, Urinal Tracts; and small BV

• Multiunit* -Distinct Group innervated by Nerves (ANS)

• Neurogenic Stimulations* -Found in: Large BV; Airways to Lungs; and Base of Hair Follicles

• Myogenic Single Unit Smooth Muscle*

• Self-Excite -Only Requires Nerve Stimulations

• Clusters of Specialized Smooth Muscle Cells are Automatic -Spontaneously Depolarized to Generate for AP

• Two Types of Spontaneous Depolarization* -Pacemaker Potential -Slow-Wave Potential

• Pacemaker Potentials* -Mem Gradually Depolarized to Threshold -Have iF channels permeable to Na+ and K+ lons -Mem Repolarizes

• Channels Close & Ca2+ channels Open

• Slow - Wave Potentials*

• Active Transports of C+ across Membrane

• Causes Oscillating for for Wave of Alternating Hyper: & Depolarization

• Single Unit Smooth Muscle Innervation

• By Branches For RNS -Modifies Rales + STrength; For Contractions -Postganglionic for Autonomic Neurons Travel across Mem

• Release Neurotransmission Varies

• SIngle NEuron;Affects; Large # of cells

• Length - Tension Relationship -Length is Far Below Optimal Tension: At Rest -Allows Small Membrane: When Distended, Stretched to Generate Stronger Contractions

• Cardiac Muscle*

More longer AP

• Fibers Joined in Branching NW

• Striated W: Thick & Thin Filaments-& Sarcomeres

• Troponin: Tropomyosin

• 7Tubules; SR + Lots of MItocandria,

• Defined by L-T Relationship

• Ca2+ ECF+SR

• Interconnected By Gap Junctions Innervated by ANS

Intro to the Cardiovascular System

• Transports Matericals Throughout Body -3 Basic Components -Heart: Pressure for Move Blood -BV: Deliver nutrients & Carry Metabolic Wastes Away -Blood Transport media

Functions Of The Circulatory System

1. Gas Exchanges: 02/ C02
2. Nutrients Water Delivery:Absorption
3. Removal Of Heats: Metabolic Waste
4. Immunity 4 Defense
5. Cell Communications

• Organization of The Circulatory System*

• Pulmonary Circulatory For System: Moves blood to & from Lungs

• Systemic Circulatory System*

• Moves Blood Throughout body Blood Leaves Blood Leaves the Left Side of the Heart is=Systemic=Into The Right Side.Of The Heart -Then flows into The Lungs

• Blood Flow Serial & Parallel*

• Whole System Serial

• Systemic ; Parallel Direct Blood To

• Tissues/ Organs

• Structure of The Heart R'L Sides*

• Two Pumps Each SIde divided to Artrium + Ventrical Chamber

• Atria: RI receive Blood Returning to Heart

• Ventricles Pump Blood out of Heart

• Major Vessels* =Veins Carry Blood Towards The Heart =Arteries: Carry Blood away from Heart

• Blood Flow Through Body (Process)*

  1. 02 Rich

• Blood* Pumped from (LV to aorta)

• Delivered to/ Issues/ organs 2. 02 Rich Blood Removed Coz (Waste Added to Blood)

  3. .02 Circulatory Veins

• Blood Returns to Right in Atria Via Venae Cavae*

• Into Rv, Pumped out by Arterial* (to Lungs

1. .02 With Lungs

• .C0 removed*. .02 Added
• Rich Back to LA pulmonary vein*.LV start again.
• Blood Flow Unidirectional*
• Maintain constant delivery*. for 02 blood

Valve for Pressure / Operated on One Way

• Valves Pressure*
• Pressure is greater enough Valves Allow
• Pressure Decreased Flow Valves shut to Stop (Blood Flow Backwards) Heart Valves
• Two Types*:
• to Atrioventricular
• For Arterial to ventricles Atria

P: Atria Valves =Open + Blood Flow

• Prevent * eversion
• +Connected Papillary for Muscular ventricles,walls Chordae Tendinae Right VA=Tricuspid valves*
• Cups Leaflets Left 53575 Valve Bicuspid & V Valve (Mitral Valve)
• Semilunar Valves*
• BV Ventricles Arteies*
• Pulmonary Valve = RV Pulmonary /Aterial Aritatic BV = Arterial LV Shape; Half moons; Prevent*
• Clinical Applications of; Heart. Valves*
• Value for Hearts for diseases*VHD-dysfunction w Valves
• Regurgitation*: Close value
• Blood flows: Properly Back Stenosis:
• narrowing of value Inflammation
• inhibition /Flourish Requiring

Cardiac Muscle Ribers "Activiled Sarcormeres

• Smalleed Cells that Run a Length of Muscle Connected End to End Forming of Bra
• Intercalated Discs*
• Composed for (Gap Junctions)Desmosomes
• Desmiosmems*
• Mech Hold Cell Tog

Gap Junctions

• Allows Communications: Spreads Ap-BT Cells
• Thes allows chamber; to contact wave like to push blood
• Cardiac Muscule Fibre Arrangement*
• Spiral Arount; circumference Heart

when muscle tracts Squezing

• Inging Generate* - Pressure Im Chamber
• Pericardial Sac*
• Protection from Chest Lavity Double walled Membrane : Two Layers

Anchors: To Surround for 1T

• In place

The 2: Layers Parietal Pericatdium Visceralt Petcaddium

• Lurincates - Hearls: wi Pencaiddial Fluid

• Electrical Activity for For Heart Heart=Electiic & Mechanical

• for Cardiac Autorhythrnic cells (Heart* -Specialized cells that General AP;

• Ions Channels that Mens Potential; SlowlyDepolaiized; To Threshold

1. I =Channels. Activated: Both Nat

• Activated to the

• Hyperpolarization*. Cyclic Nuve Tide

• GapChannel - T-Type Cart Channel

• Ustroke For Al from L Type for Cart Channel*

• Cardiac Canductnfor Systen "Artithm cells localized w 4 Specific Region . Sinatral Aade

• Located to WA: All near Cpenining for: Superior Yana

• Atrioventicular Located: HA All Whore ha; RV Comerg "Bundle for His .Cell specialized

• Arise from AV Rode-

• Divides 2 Brandles :Down each side Septum : Cune Rack to Atria

Purkinje Fibres

• Branch off Bundle of His and spread along the endocardial surface of the ventricles

Normal Pacemaker Activity of Heart

• Autorhythmic cells within the SA node have the fastest rate of depolarization (controls the heart)

Cardiac Excitation Requirements

• Action potential spreads through the heart for efficient conduction
  • Atrial excitation and contraction prior to the ventricular contractions
  • Cardiac muscle fibre excitation must be coordinated
  • Pairs of ventricular and atrial chambers must be functionally coordinated

Atrial Excitation

• The SAN node fires AP and travels through two atria by two main mechanisms

  • Gap junctions
  • Move AP faster during intraatrial and internodal pathways

• AV (Atrioventricular Node)

• Atria muscle cells are separated at the musc cells from the ventricle density CT av to Bundle HIS only means ap moved between Atria and Ventricle

• AV Nodal Delay

• Rate condition slow AV node assure A nave rate that affect

• To contract for v (Maximized atrial emptying in to V)

Ventricular Excitation

• Wave spreads down the RSL (right and left) bundles of his Purkinje Fibres (Gap Junctions and communicate spreads from purkie to cells (Innervaved
• Cardiac Action Potential* v-gated. ion channels wli ventricular musc.cells
• RMP -80 mv*.
• remains. steady untill excitad #reaches threshold. ungates.
• Nat pen* #mem depolarizes*to 450mv.

2. #rapid. depalarization activates other ion chennels* . -Transient butward kt chennels.

• Counter rat intinx*

• L-type* cat. chennels delayed rectifying kt channel* - current's areate balance of mempat = plantan potential-type cart in active transiant outwardkt outward Kt mouement through delayed rectifier allons call to hyperpolarife > RMP

""Carolaic Ecxitation~ contracion"Coupling"" Process of how AP Causes cardiac myocyte + Contract #AP. Cardiac contractile cell during plataan lutyse coat, channels will tubbies open*. Release ol cat-. Calcium has a options: OR- directly. interact w contraclile. aparatus

• Interact n ryanodine receptors of SH- triggers internal. stare release. of cort.

""Contraction"" influe cart initiates cardiac musc contraction

AP Duration' I Length af. Coutractine- length of cardiac prevent -twitch summatian = long Ap ducts plantan plate

#de Polarized mempol keeps Natchennel. inactivatad Cell be restimulated refractory. period length enough so most. Contraction Over

The Electrocardiogram ECG

• This distinctive patttern of electro~mechanical actintyThe First Elect

• Electra~ Mech (ECG) showed A distinctive pattern

• The EGG recorded 3 leads placed on right arm left.

• Ground. eleetrade n right leg

• Lead 1: right arm tal arm, & right am tal right, a Lead left

• and a Lead + 12 ~form Einthatan Triangke""Modern Day EE"""~46 "lead**-*Atra

• • 3 previausl""17 y mannealed +60~chast around heart

• -Ametheatily.derived"-meqsures slechical actintly indiecly."the charges al"ale C.Patentials**

Q ECG Recording

• #depalarization upward positive .-Aepolarizotion down wards (negative) * *t initiate heat seat "SA

nodes**-Plware SA made Triggers Doth atra to undergoes depalarization. "QRs.complex""T-A"lowing"AV medal,dolay wave travel down bundle" + purkines fibres to depalarize ventriales"#1-wave""~wantricles -depalarize P segmeatAV medal delay*"###ST Segheat ventricle* - Contract Emplying-###TP interval ventricle."

• reloxiny -Filling* "Qt.Segment+Electrical depanrizalin and repolarization of Ventricles. *A Atilal repalarization lost

Heart Rate (Cardiac Rythm Disturbances)

High HR; Tachycartia =1 OObpm-Cardiac Output Decreases reduced ventrical filling or based on ars complex Heart Beat: initioted by purkines or not san ode signs for reducing oxygenation and heart mucles - y contract before A is now optimal""/ filled for blood for reducations for" ventricles Quivers""Instead.of Pumping*- irregular""+unformed: ars +complat hear block for AV+BlockIm pulse to the"SA". mode or AV+ mode independent the attirate "p wave regula 7 of 85 is also folum and has been removed. and you have a great time at a rate 444 the

Mechanical Activity for HeartCardia Cycle

• Alternatirly for Contraction Systate Roloxatoo** -Vartucles Flows L/ /to "la"".av". val. ofblood 82 pusses la. iv. for* atua Contact Pwove-- Blood:for, for Forvely for forSquized" of lav: 1 Continus"Thugh AV nodal: dalay
• EGG""atria: Depolarzed flat until""aynodal daley"" wave Trevals Domn""for "7""87s***+ porknjes* for depolarize. ventricle for same volume""contractions. began Clove Av"". Volv, by a open aotic. valués isoualumetnc.Contrachm Euentual lu/ 1 pressure" aort aopens for 54 / val"" blood mores" #Ventrieles. Poloves by /B atuas .vav. alues again forfor

"Heart. Sounds " #Heart Valuse""Mech Barriers that Cause Virbrators Whm they closes Av" Valves close Signals Venrical Sysele #pub for Semiunlar "Close Signal Verticluor Diosyestole

Cardiac Output

Vo1"" Blood pumped out by each Y over I minute MR by Stokes volume = CO /bom(42

"51.pm""Out""Evey to Con Exceed" #LOA During Exercise"" regulation "" 3 CD To Charge for HR # Must Charoge for #Sa" node #