Introduction to the Cardiovascular System - part 3 pdf

Myosin light chain phosphorylation leads to cross-bridge formation between the myosin heads and the actin filaments, thus leading to smooth muscle contraction.. In vascular smooth muscle

stimulates vascular smooth muscle

contrac-tion An increase in free intracellular calcium

can result from either increased entry of

cal-cium into the cell through L-type calcal-cium

channels or release of calcium from internal

stores (e.g., sarcoplasmic reticulum) The free

calcium binds to a special calcium-binding

protein called calmodulin The

calcium-calmodulin complex activates myosin light

chain kinase, an enzyme that phosphorylates

myosin light chains in the presence of ATP.

Myosin light chains are regulatory subunits

found on the myosin heads Myosin light

chain phosphorylation leads to cross-bridge

formation between the myosin heads and the

actin filaments, thus leading to smooth muscle

contraction

Intracellular calcium concentrations,therefore, are very important in regulating

smooth muscle contraction The

concentra-tion of intracellular calcium depends on the

balance between the calcium that enters thecells, the calcium that is released by intracel-lular storage sites, and the movement of cal-cium either back into intracellular storagesites or out of the cell Calcium is rese-questered by the sarcoplasmic reticulum by

an ATP-dependent calcium pump similar tothe SERCA pump found in cardiac myocytes.Calcium is removed from the cell to the exter-nal environment by either an ATP-dependentcalcium pump or the sodium–calcium ex-changer, as in cardiac muscle (see Chapter 2).Several signal transduction mechanismsmodulate intracellular calcium concentrationand therefore the state of vascular tone Thissection describes three different pathways: (1)

IP3via Gq-protein activation of phospholipaseC; (2) cAMP via Gs-protein activation ofadenylyl cyclase; and (3) cyclic guanosinemonophosphate (cGMP) via nitric oxide (NO)activation of guanylyl cyclase (Fig 3-10).CELLULAR STRUCTURE AND FUNCTION 53

Gq

AC

SR

GDP GTP

PL-CPIP2

ATP

++

+

+

+ +

+

+

_

_ _

MLCK

Epi Ado PGI2R

L-typeCalciumChannel

re-SR, sarcoplasmic reticulum; MLCK, myosin light chain kinase; Ado, adenosine; PGI 2 , prostacyclin; Epi, epinephrine;

NO, nitric oxide; GC, guanylyl cyclase; AII, angiotensin receptor agonist; ET-1, endothelin-1; NE, norepinephrine; ACh, acetylcholine; GDP, guanosine diphosphate; GTP, guanosine triphosphate; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; cGMP, cyclic guanosine monophosphate.

The IP3pathway in vascular smooth muscle

is similar to that found in the heart

Norepinephrine and epinephrine (via 1

-adrenoceptors), angiotensin II (via AT1

recep-tors), endothelin-I (via ETA receptors), and

acetylcholine (via M3receptors) activate

phos-pholipase C through the Gq-protein, causing

the formation of IP3 from PIP2 IP3 then

di-rectly stimulates the sarcoplasmic reticulum

to release calcium The formation of

diacyl-glycerol from PIP2activates protein kinase C,

which can modulate vascular smooth muscle

contraction as well via protein

phosphoryla-tion

Receptors coupled to the Gs-protein

stim-ulate adenylyl cyclase, which catalyzes the

for-mation of cAMP In vascular smooth muscle,

unlike cardiac myocytes, an increase in cAMP

by a 2-adrenoceptor agonist such as

isopro-terenol causes relaxation The mechanism for

this process is cAMP inhibition of myosin light

chain kinase (see Fig 3-9), which decreases

myosin light chain phosphorylation, thereby

inhibiting the interactions between actin and

myosin Adenosine and prostacyclin (PGI2)

also activate Gs-protein through their

recep-tors, leading to an increase in cAMP and

smooth muscle relaxation Epinephrine

bind-ing to 2-adrenoceptors relaxes vascular

smooth muscle through the Gs-protein

A third important mechanism for

regulat-ing vascular smooth muscle contraction is the

nitric oxide (NO)–cGMP system Many dothelial-dependent vasodilator substances(e.g., acetylcholine, bradykinin, substance P),when bound to their respective endothelialreceptors, stimulate the conversion of L-arginine to NO by activating NO synthase.The NO diffuses from the endothelial cell tothe vascular smooth muscle cells, where it ac-tivates guanylyl cyclase, increases cGMP for-mation, and causes smooth muscle relaxation.The precise mechanisms by which cGMP re-laxes vascular smooth muscle are unclear;however, cGMP can activate a cGMP-depen-dent protein kinase, inhibit calcium entry intothe vascular smooth muscle, activate Kchan-nels causing cellular hyperpolarization, anddecrease IP3

en-Vascular Endothelial Cells

The vascular endothelium is a thin layer ofcells that line all blood vessels Endothelialcells are flat, single-nucleated, elongated cellsthat are 0.2–2.0 m thick and 1-20 µm across(varying by vessel type) Depending on thetype of vessel (e.g., arteriole versus capillary)and tissue location (e.g., renal glomerular ver-sus skeletal muscle capillaries), endothelialcells are joined together by different types ofintercellular junctions Some of these junc-tions are very tight (e.g., all arteries and skele-tal muscle capillaries), whereas others have

cAMP is degraded by a phosphodiesterase Milrinone, a drug sometimes used in the treatment of acute heart failure, is a phosphodiesterase inhibitor that increases cardiac inotropy and relaxes blood vessels by inhibiting the degradation of cAMP Explain why

an increase in cAMP in cardiac muscle increases the force of contraction, whereas an crease in cAMP in vascular smooth muscle cells diminishes the force of contraction.

in-Increasing cAMP in the heart activates protein kinase A, which phosphorylates ferent sites within the cells (see the answer to Problem 3-1) Phosphorylation enhancescalcium influx into the cell and calcium release by the sarcoplasmic reticulum, leading

dif-to an increase in inotropy In vascular smooth muscle, myosin light chain kinase, whenactivated by calcium-calmodulin, phosphorylates myosin light chains to stimulate

smooth muscle contraction cAMP inhibits myosin light chain kinase; therefore, an crease in cAMP by a phosphodiesterase inhibitor such as milrinone further inhibits themyosin light chain kinase, thereby reducing smooth muscle contraction

in-P R O B L E M 3 - 2

gaps between the cells (e.g., capillaries in

spleen and bone marrow) that enable blood

cells to move in and out of the capillary easily

See Chapter 8 for information about different

types of capillaries and endothelium

Endothelial cells have several importantfunctions, including:

1 Serving as a barrier for the exchange of

fluid, electrolytes, macromolecules, andcells between the intravascular and ex-travascular space (see Chapter 8);

2 Regulating smooth muscle function

through the synthesis of several differentvasoactive substances, the most important

of which are NO, PGI2, and endothelin-1;

3 Modulating platelet aggregation primarily

through biosynthesis of NO and PGI2;

4 Modulating leukocyte adhesion and

transendothelial migration through thebiosynthesis of NO and the expression ofsurface adhesion molecules

Vascular endothelial cells continuouslyproduce NO by the enzyme NO synthase,

which converts L-arginine to NO This basal

NO production can be enhanced by (1)

spe-cific agonists (e.g., acetylcholine, bradykinin)

binding to endothelial receptors; (2)

in-creased shearing forces acting on the

en-dothelial surface (e.g., as occurs with

in-creased blood flow); and (3) cytokines such

as tumor necrosis factor and interleukins,

which are released by leukocytes during

in-flammation and infection NO, although very

labile, rapidly diffuses out of endothelial cells

to cause smooth muscle relaxation or inhibit

platelet aggregation in the blood Both of

these actions of NO result from increased

cGMP formation, which occurs in response

to NO activation of guanylyl cyclase (see Fig

3-10) Increased NO within the endothelium

stimulates endothelial cGMP production,

which inhibits the expression of adhesion

mol-ecules involved in attaching leukocytes to the

endothelial surface Therefore,

endothelial-derived NO relaxes smooth muscle, inhibits

platelet function, and inhibits inflamma

tory responses (Fig 3-11) (See Formation

and Physiologic Actions of Nitric Oxide

on CD.)

In addition, endothelial cells synthesize endothelin-1 (ET-1), a powerful vasocon-strictor (see Fig 3-11) Synthesis is stimu-lated by angiotensin II, vasopressin, throm-bin, cytokines, and shearing forces, and it isinhibited by NO and PGI2 ET-1 leaves theendothelial cell and can bind to receptors(ETA) on vascular smooth muscle, whichcauses calcium mobilization and smoothmuscle contraction The smooth muscle ac-tions of ET-1 occur through activation of the

IP3 signaling pathway (see Fig 3-10) (SeeFormation and Physiologic Actions ofEndothelin-1 on CD.)

PGI2 is a product of arachidonic acid tabolism within endothelial cells (SeeFormation and Physiologic Actions ofMetabolites of Arachidonic Acid on CD.) Thetwo primary roles of PGI2formed by endothe-lial cells are smooth muscle relaxation and in-hibition of platelet aggregation (see Fig 3-11),both of which are induced by the formation ofcAMP (see Fig 3-10)

me-The importance of normal endothelialfunction is made clear from examining howendothelial dysfunction contributes to dis-ease states For example, endothelial damageand dysfunction occurs in atherosclerosis,hypertension, diabetes, and hypercholes-terolemia Endothelial dysfunction results inless NO and PGI2production, causing vaso-CELLULAR STRUCTURE AND FUNCTION 55

ContractionVSM

stimulates ( ) or inhibits (-) vascular smooth muscle

(VSM) contraction, platelet aggregation and adhesion,

and leukocyte-endothelial cell adhesion.

constriction, loss of vasodilatory capacity,

thrombosis, and vascular inflammation

Evidence exists that enhanced ET-1

produc-tion contributes to hypertension and other

vascular disorders Damage to the

endothe-lium at the capillary level increases capillary

permeability (see Chapter 8), which leads to

increased capillary fluid filtration and tissue

edema

SUMMARY OF IMPORTANT

CONCEPTS

• The basic contractile unit of a cardiac

myo-cyte is the sarcomere, which contains thick

filaments (myosin) and thin filaments

(actin, troponin, and tropomyosin) During

myocyte contraction, the sarcomere

short-ens as the thick and thin filaments slide

past each other (the sliding filament theory

of muscle contraction)

• The process of excitation–contraction

coupling is initiated by depolarization of

the cardiac myocyte, which causes

cal-cium to enter the cell across the

sar-colemmal membrane, particularly in the

T-tubules This entering calcium triggers

the release of calcium through

calcium-release channels associated with the

ter-minal cisternae of the sarcoplasmic

retic-ulum, which increases intracellular

calcium concentration Calcium thenbinds to TN-C, which induces a confor-mation change in the troponin-tropomyosin complex and exposes amyosin binding site on the actin.Hydrolysis of ATP occurs during actinand myosin binding; it provides the en-ergy for the subsequent movement of thethin filament across the thick filament.Relaxation (also requiring ATP) occurswhen calcium is removed from the TN-Cand is resequestered by the sarcoplasmicreticulum by means of the SERCA pump

• Calcium serves as the primary regulator ofthe force of contraction (inotropy).Increased calcium entry into the cell, in-creased release of calcium by the sar-coplasmic reticulum, and enhanced bind-ing of calcium by TN-C are majormechanisms controlling inotropy Phos-phorylation of myosin light chains may alsoplay a role in modulating inotropy

• Relaxation of cardiac myocytes (lusitropy)

is primarily regulated by the reuptake ofcalcium by the sarcoplasmic reticulum bythe SERCA pump Phospholamban, a reg-ulatory protein associated with SERCA,regulates the activity of SERCA

• The contractile function of cardiac cytes requires large amounts of ATP, which

myo-is generated primarily by oxidative

When acetylcholine is infused into normal coronary arteries, the vessels dilate; ever, if the vessel is diseased and the endothelium damaged, acetylcholine can cause vasoconstriction Explain why acetylcholine can have opposite effects on vascular func- tion depending on the integrity of the vascular endothelium.

how-Acetylcholine has two effects on blood vessels When acetylcholine binds to M2ceptors on the vascular endothelium, it stimulates the formation of nitric oxide (NO) byconstitutive NO synthase The NO can then diffuse from the endothelial cell into theadjacent smooth muscle cells, where it activates guanylyl cyclase to form cGMP

re-Increased cGMP within the smooth muscle cell inhibits calcium entry into the cell,

which leads to relaxation Acetylcholine, however, also can bind to M3receptors cated on the smooth muscle This activates the IP3pathway and stimulates calcium re-lease by the sarcoplasmic reticulum, which leads to increased smooth muscle contrac-tion If the endothelium is intact, stimulation of the NO–cGMP pathway dominates

lo-over the actions of the IP3 pathway; therefore, acetylcholine will cause vasodilation

P R O B L E M 3 - 3

lism of fatty acids and carbohydrates, though the heart is flexible in its use of sub-strates and can also metabolize aminoacids, ketones, and lactate.

al-• Arteries and veins are arranged as three

layers: adventitia, media, and intima

Autonomic nerves and small blood vessels(vasa vasorum in large vessels) are found inthe adventitia; vascular smooth muscle isfound in the media; and the intima is lined

by the endothelium The relative tions of elastin and collagen in the adventi-tia and media influence the elastic proper-ties of blood vessels

propor-• Vascular smooth muscle contains actin and

myosin; however, these components arenot arranged in the same repetitive pattern

as that found in cardiac myocytes Vascularsmooth muscle contraction is slow andtonic, in contrast to the contraction of car-diac myocytes, which is fast and phasic

Vascular smooth muscle contraction is ulated by calcium and the phosphorylation

reg-of myosin light chains by myosin light chainkinase

• Cardiac muscle and vascular smooth

mus-cle contraction is regulated by G-proteinscoupled to membrane receptors Ac-tivation of stimulatory Gs-proteins through

-adrenoceptor stimulation (e.g., by inephrine) increases intracellular cAMP,whereas activation of inhibitory Gi-pro-teins through specific muscarinic or adeno-sine receptors decreases intracellularcAMP Increased cAMP in cardiac my-ocytes increases the force of contraction,whereas increased cAMP in vascularsmooth muscle causes relaxation Ac-tivation of the Gq-protein through an-giotensin II receptors, endothelin-1 recep-tors, or 1-adrenoceptors stimulates theactivity of phospholipase C, which causesthe formation of inositol triphosphate (IP3)

norep-Increased IP3enhances calcium release bythe sarcoplasmic reticulum and increasedcontraction in both cardiac muscle and vas-cular smooth muscle

• The vascular endothelium synthesizes

ni-tric oxide and prostacyclin, both of which relax vascular smooth muscle

Endothelin-1, which is also synthesized bythe endothelium, contracts vascular smoothmuscle

Review Questions

Please refer to the appendix for the answers

to the review questions.

For each question, choose the one best answer:

1 Which of the following is common to bothcardiac myocytes and vascular smoothmuscle cells?

b Calcium binds to troponin-I

c Myosin heads bind to actin

d SERCA pumps calcium out of thesarcoplasmic reticulum

4 Cardiac inotropy is enhanced by

a Agonists coupled to Gi-protein

b Decreased calcium binding to ponin-C

tro-c Decreased release of calcium by minal cisternae

ter-d Protein kinase A phosphorylation ofL-type calcium channels

5 2-adrenoceptor activation in vascularsmooth muscle leads to

a Activation of myosin light chain nase

ki-b Contraction

c Decreased intracellular cAMP

d Dephosphorylation of myosin lightchains

CELLULAR STRUCTURE AND FUNCTION 57

6 Angiotensin II causes contraction of

vas-cular smooth muscle by

Goldstein MA, Schroeter JP Ultrastructure of the heart.

In: Page E, Fozzard HA, Solaro RJ, eds Handbook

of Physiology, vol 1 Bethesda: American

Opie LH The Heart: Physiology from Cell to Circulation 3rd Ed Philadelphia: Lippincott Williams & Wilkins, 1998.

Rhodin JAG Architecture of the vessel wall In: Bohr

DF, Somlyo AP, Sparks HV, eds Handbook of Physiology, vol 2 Bethesda: American Physiological Society, 1980; 1-31.

Sanders KM Invited review: mechanisms of calcium handling in smooth muscles J Appl Physiol 2001;91:1438-1449.

Somlyo AV: Ultrastructure of vascular smooth muscle In: Bohr DF, Somlyo AP, Sparks HV, eds Handbook

of Physiology, vol 2 Bethesda: American Physiological Society, 1980; 33-67.

CD-ROM CONTENTSLEARNING OBJECTIVESINTRODUCTIONCARDIAC ANATOMYFunctional Anatomy of the HeartAutonomic Innervation

THE CARDIAC CYCLECardiac Cycle DiagramSummary of Intracardiac PressuresVentricular Pressure-VolumeRelationship

Altered Pressure and VolumeChanges during the Cardiac Cycle

REGULATION OF CARDIAC OUTPUTInfluence of Heart Rate on CardiacOutput

Regulation of Stroke VolumeMYOCARDIAL OXYGEN CONSUMPTIONHow Myocardial Oxygen

Consumption is DeterminedFactors Influencing Myocardial Oxygen ConsumptionSUMMARY OF IMPORTANT CONCEPTSREVIEW QUESTIONS

Understanding the concepts presented in this chapter will enable the student to:

1 Describe the basic anatomy of the heart, including the names of venous and arterial sels entering and leaving the heart, cardiac chambers, and heart valves; trace the flow of blood through the heart.

ves-2 Describe how each of the following changes during the cardiac cycle:

a electrocardiogram

b left ventricular pressure and volume

c aortic pressure

d aortic flow

e left atrial pressure

f jugular pulse waves

3 Describe the origin of the four heart sounds and show when they occur during the diac cycle.

car-4 Know normal values for end-diastolic and end-systolic left ventricular volumes, atrial and ventricular pressures, and systolic and diastolic aortic and pulmonary arterial pressures.

5 Draw and label ventricular pressure-volume loops derived from ventricular pressure and volume changes during the cardiac cycle.

6 Calculate stroke volume, cardiac output, and ejection fraction from ventricular diastolic and end-systolic volumes and heart rate.

7 Describe how an increase in heart rate affects ventricular filling time, ventricular diastolic volume, and stroke volume.

end-59

cycle diagram in Figure 4-2 depicts changes in

the left side of the heart (left ventricular

pres-sure and volume, left atrial prespres-sure, and

aor-tic pressure) as a function of time Pressure

and volume changes in the right side of the

heart (right atrium and ventricle and

pul-monary artery) are qualitatively similar to

those in the left side Furthermore, the timing

of mechanical events in the right side of the

heart is very similar to that of the left side

The main difference is that the pressures inthe right side of the heart are much lowerthan those found in the left side

A catheter can be placed in the ascendingaorta and left ventricle to obtain the pressureand volume information shown in the cardiaccycle diagram and to measure simultaneouschanges in aortic and intraventricular pressure

as the heart beats This catheter can also beused to inject a radiopaque contrast agent into

MitralValveCloses

AorticValveOpens

AorticValveCloses

MitralValveOpens

80

40

Pressure(mmHg)

LVVolume(ml)ECG

Seconds

HeartSounds

four heart sounds.

the left ventricular chamber This permits

flu-oroscopic imaging (contrast ventriculography)

of the ventricular chamber, from which

esti-mates of ventricular volume can be obtained;

however, real time echocardiography and

nu-clear imaging of the heart are more commonly

used to obtain clinical assessment of volume

and function

In the following discussion, a complete diac cycle is defined as the cardiac events ini-

car-tiated by the P wave in the electrocardiogram

(ECG) and continuing until the next P wave

The cardiac cycle is divided into two general

categories: systole and diastole Systole refers

to events associated with ventricular

contrac-tion and ejeccontrac-tion Diastole refers to the rest

of the cardiac cycle, including ventricular

re-laxation and filling The cardiac cycle is

fur-ther divided into seven phases, beginning

when the P wave appears These phases are

atrial systole, isovolumetric contraction, rapid

ejection, reduced ejection, isovolumetric

re-laxation, rapid filling, and reduced filling The

events associated with each of these phases

are described below

PHASE 1 ATRIAL SYSTOLE: AV

VALVES OPEN; AORTIC AND

PULMONIC VALVES CLOSED

The P wave of the ECG represents electrical

depolarization of the atria, which initiates

con-traction of the atrial musculature As the atria

contract, the pressures within the atrial

cham-bers increase; this drives blood from the atria,

across the open AV valves, and into the

ventri-cles Retrograde atrial flow back into the vena

cava and pulmonary veins is impeded by the

inertial effect of venous return and by the

wave of contraction throughout the atria,

which has a “milking effect.” However, atrial

contraction produces a small increase in

prox-imal venous pressure (i.e., within the

pul-monary veins and vena cava) On the right

side of the heart, this produces the “a-wave”

of the jugular pulse, which can be observed

when a person is recumbent and the jugular

vein in the neck expands with blood

Atrial contraction normally accounts foronly about 10% of left ventricular filling

when a person is at rest and the heart rate islow, because most of the ventricular fillingoccurs before the atria contract Therefore,ventricular filling is mostly passive and de-pends on the venous return However, athigh heart rates (e.g., during exercise), theperiod of diastolic filling is shortened consid-erably (because overall cycle length is de-creased), and the amount of blood that en-ters the ventricle by passive filling isreduced Under these conditions, the relativecontribution of atrial contraction to ventricu-lar filling increases greatly and may accountfor up to 40% of ventricular filling In addi-tion, atrial contribution to ventricular filling

is enhanced by an increase in the force ofatrial contraction caused by sympatheticnerve activation Enhanced ventricular fillingowing to increased atrial contraction is some-times referred to as the “atrial kick.” Duringatrial fibrillation (see Chapter 2), the contri-bution of atrial contraction to ventricular fill-ing is lost This leads to inadequate ventricu-lar filling, particularly when ventricular ratesincrease during physical activity

After atrial contraction is complete, theatrial pressure begins to fall, which causes aslight pressure gradient reversal across the AVvalves This fall in atrial pressure following the

peak of the a-wave is termed the “x-descent.”

As the pressures within the atria fall, the AVvalves float upward (pre-position) before clo-sure

At the end of this phase, the ventricular

volumes are maximal (end-diastolic volume,

EDV) The left ventricular end-diastolic

vol-ume (typically about 120 mL) is associatedwith end-diastolic pressures of 8–12 mm Hg.The right ventricular end-diastolic pressuretypically ranges from 3–6 mm Hg

A heart sound is sometimes heard during

atrial contraction (Fourth Heart Sound, S 4).The sound is caused by vibration of the ven-tricular wall during atrial contraction Thissound generally is noted when the ventriclecompliance is reduced (i.e., “stiff” ventricle),

as occurs in ventricular hypertrophy (seeVentricular Hypertrophy on CD The sound iscommonly present as a normal finding inolder individuals

CARDIAC FUNCTION 63

PHASE 2 ISOVOLUMETRIC

CONTRACTION: ALL VALVES CLOSED

This phase of the cardiac cycle is initiated by

the QRS complex of the ECG, which

repre-sents ventricular depolarization As the

ventri-cles depolarize, myocyte contraction leads to a

rapid increase in intraventricular pressure

The abrupt rise in pressure causes the AV

valves to close as the intraventricular pressure

exceeds atrial pressure Contraction of the

papillary muscles with their attached chordae

tendineae prevents the AV valve leaflets from

bulging back or prolapsing into the atria and

becoming incompetent (i.e., “leaky”) Closure

of the AV valves results in the First heart

sound (S 1 ) A heart sound is generated when

sudden closure of a heart valve and the

ac-companying oscillation of the blood cause

vi-brations (i.e., sound waves) that can be heard

with a stethoscope overlying the heart The

first heart sound is normally split (~0.04 sec)

because mitral valve closure precedes

tricus-pid closure; however, because this very short

time interval normally cannot be perceived

through a stethoscope, only a single sound is

heard

During the time between the closure of the

AV valves and the opening of the semilunar

valves, ventricular pressure rises rapidly

with-out a change in ventricular volume (i.e., no

ejection of blood into the aorta or pulmonary

artery occurs) Ventricular contraction,

there-fore, is said to be “isovolumic” or

“isovolumet-ric” during this phase However, individual

myocyte contraction is not necessarily

isomet-ric Some individual fibers contract

isotoni-cally (i.e., concentric, shortening contraction),

whereas others contract isometrically (i.e.,

with no change in length) or eccentrically (i.e.,

lengthening contraction) Ventricular

cham-ber geometry changes considerably as the

heart becomes more spheroid in shape,

al-though the volume does not change Early in

this phase, the rate of pressure development

becomes maximal The maximal rate of

pres-sure development, abbreviated “dP/dt max,” is

the maximal slope of the ventricular pressure

tracing plotted against time during

isovolu-metric contraction

Atrial pressures transiently increase owing

to continued venous return and possibly tobulging of AV valves back into the atrial

chambers The “c-wave” noted in the jugular

pulse is thought to occur owing to increasedright atrial pressure that results from bulging

of tricuspid valve leaflets back into rightatrium

PHASE 3 RAPID EJECTION: AORTIC AND PULMONIC VALVES OPEN; AV VALVES REMAIN CLOSED

When the intraventricular pressures exceedthe pressures within the aorta and pulmonaryartery, the aortic and pulmonic valves openand blood is ejected out of the ventricles.Ejection occurs because the total energy ofthe blood within the ventricle exceeds the to-tal energy of blood within the aorta The totalenergy of the blood is the sum of the pressureenergy and the kinetic energy; the latter is re-lated to the square of the velocity of the bloodflow (see Energetics of Flowing Blood onCD) In other words, ejection occurs because

an energy gradient is present (mostly owing topressure energy) that propels blood into theaorta and pulmonary artery During thisphase, ventricular pressure normally exceedsoutflow tract pressure by only a few millime-ters of mercury (mm Hg) Although bloodflow across the valves is high, the relativelylarge valve opening (i.e., providing low resis-tance) requires only a few mm Hg of a pres-sure gradient to propel flow across the valve.Maximal outflow velocity is reached early inthe ejection phase, and maximal (systolic) aor-tic and pulmonary artery pressures areachieved

While blood is being ejected and lar volumes decrease, the atria continue to fillwith blood from their respective venous in-flow tracts Although atrial volumes are in-

ventricu-creasing, atrial pressures initially decrease

(x-descent) as the base of the atria is pulled

downward, expanding the atrial chambers

No heart sounds are ordinarily heard

dur-ing ejection The opendur-ing of healthy valves is

silent The presence of a sound during

ejec-tion (i.e., ejecejec-tion murmurs) indicates valve