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Normal & Abnormal myocardial function

1. Cellular Basis of Cardiac Contraction

1) cardiac ultrastructure

ventricular myocardiumÀÇ 3/4ÀÌ striated muscle cell(myocyte)·Î ±¸¼ºµÇ¾î ÀÖ´Ù.

myocyteÀÇ Á÷°æÀº 17-25um, ±æÀÌ 60-140um(Fig 231-1A)

* sarcomere ; structural & functional unit of contraction, Z-lineÀ¸·Î °æ°èÁö¿öÁü.

* light & dark band

sarcomereÀÇ center¿¡ ÀÏÁ¤ÇÑ ±æÀÌÀÇ dark band(A band)°¡ ÀÖ°í ¾çÂÊ¿¡ light band

(I band)°¡ Àִµ¥ I band´Â ±æÀ̰¡ ´Ù¾çÇÏ´Ù.

- ¼¼ºÎ´ÜÀ§·Î µé¾î°¡¸é thicker filament(myosin)°ú thinner filament(actin)À¸·Î ±¸¼ºµÇ´Âµ¥

myosin°ú actinÀº A band³»¿¡¼­ ¼­·Î overlapµÇ¾î ÀÖ´Ù.

- ¹Ý¸é I band´Â only thin filament·Î¸¸ ±¸¼ºµÇ¾î ÀÖ´Ù.

- A band³»¿¡¼­ thick & thin filament»çÀÌ¿¡ bridge°¡ Çü¼ºµÈ´Ù.

2) contractile process

¨ç Myosin : rodlike portion

globular portion : ATPase site, myosin°ú actin»çÀÌÀÇ bridgeÇü¼º

¨è Actin : thin filament, double helix

regulatory protein : troponin C, I, T(Fig 231-3)

Ca2+ÀÌ troponin C¿¡ °áÇÕ¿©ºÎ¿¡ µû¶ó troponin I¿Í actin»çÀÌ °áÇÕÇÏ´Â ÈûÀÌ ´Þ¶óÁø´Ù.

3) cardiac activation

* sarcolemma : ³»ºÎ´Â -80 ¡­ -100 mV

: action potentialÀÇ plateauµ¿¾È(phase 2) L-type Ca++ channelÀ» ÅëÇÑ

slow inward current°¡ ÀϾ.

À¯ÀÔÀº ¼Ò·®µÇÁö¸¸ À¯ÀÔµÈ Ca++ÀÌ SR¿¡ ÀúÀåµÇ¾î ÀÖ´ø Ca++À» ´Ù·® ¹æÃâÇÔ.

(Ca2+ induced Ca2+ release)

-> ÀÌ·¸°Ô ¹æÃâµÈ Ca++ÀÌ troponin C¿Í °áÇÕ.

* myosin ATPase activity´Â actin-myosin cross-bridge¸¦ Çü¼ºÇÏ°í ²÷´Â ¼Óµµ¸¦ °áÁ¤ÇÑ´Ù.

* Fig 231-2. Actinomycin ATPase reaction mx - 4 steps

i) step 1 : hydrolysis of myosin-bound ATP

ii) step 2 : Ca++ + troponin C°áÇÕ -> thin filamentÀÇ active site exposure

iii) step 3 : muscle contract

iv) step 4 : resting state·Î Àüȯ

2. Myocardial mechanics -The force-velocity curve

striated m.ÀÇ mechanical activity´Â 2°¡Áö ¹æ½ÄÀ¸·Î Ç¥ÇöµÈ´Ù.

i) by shortening

ii) by the development of tension

- shortening velocity´Â tension development¿Í ¿ª»ó°ü°ü°è°¡ ÀÖ´Ù.

= ¼ÒÀ§ "force-velocity relation"(Fig 231-5)

- ½±°Ô ¸»ÇØ load°¡ ¸¹À»¼ö·Ï shortening velocity ´Â ´õ ³·´Ù.

- myocardial contractile activity´Â resting fiber lengthÀÇ º¯È­,inotropic stateÀÇ º¯È­

(¿¹, contractility)¿¡ ÀÇÇÑ physiologic condition¿¡¼­ ½±°Ô º¯ÇÑ´Ù.

- ÀÌ µÎ°¡Áö°¡ myocardial force-velocity curve¸¦ shift½ÃŲ´Ù.

- ¸¹Àº neurohumoral influence°¡ ¼öÃà·Â¿¡ ¿µÇâÀ» ³¢Ä¡Áö¸¸, most important influence´Â

neurotransmitterÀÎ norepinephrineÀ» ÅëÇØ ÀÛµ¿ÇÏ´Â adrenergic nervous systemÀÌ´Ù.

3. Ventricular ejection & filling

- ÆßÇÁ·Î¼­ÀÇ ½ÉÀåÀº end-diastolic volume(muslce fiber±æÀÌ¿Í °ü·Ã)°ú S.V(Frank-Starling

relation)»çÀÌÀÇ °ü°è°¡ Áß½ÉÀÌ´Ù.

- end-diastolic or "filling" pr´Â ¶§¶§·Î end-diastolic volume´ë½Å »ç¿ëµÈ´Ù.

- S.VÀº diastolic fiber length(preload)¿¡ ºñ·ÊÇϰí, arterial resistance(afterload)¿£ ¹Ýºñ·Ê

ÇÑ´Ù.

- ventricular end-diastolic pr¿Í stroke work(ventricular function curve) »çÀÌÀÇ °ü°è°¡

myocardial contractility levelÀ» Á¤ÀÇÇÑ´Ù(=contractile, or inotropic, state of the ventricle)

- ventricular contractility¡è : ventricular function curve¸¦ upward shift & to the left(greater

stroke work) at any level of ventricular end diastolic pr(or volume) or lower end diastolic

pr at any level of stroke work)

¹Ý´ë·Î contractility¡é : shift downward and to the right(Fig 231-6)

4. Assessment of cardiac function

- HF¿¡¼­´Â rest½Ã ventricular end-diastolic pr°¡ Á¤»óÀ̰ųª Áõ°¡µÇ¾î ÀÖÀ¸¸ç C.O°ú S.VÀÌ

°¨¼ÒµÇ¾î ÀÖ´Ù. ±×·¯³ª µå¹°Áö ¾Ê°Ô Á¤»ó¹üÀ§ÀÌ´Ù.

- EFÀÇ more sensitive index : SV/EDV ratio, normal value 67¡¾8%

: radiocontrast or radionuclide angiography or echography·Î ÃøÁ¤

systolic HF¿¡¼± °¨¼Ò(S.VÀÌ normalÀÌ´õ¶óµµ)

end diastolic volume : normal 70¡¾20 mL/m2

* Diastolic function

doppler echocardiography¸¦ ÀÌ¿ëÇÏ¿© mital valve¸¦ ÅëÇÑ flow velocity¸¦ ÃøÁ¤ÇÏ¿© Æò°¡

ÇÒ¼ö ÀÖ´Ù.

i) normal : early diastole¶§ velocity´Â more rapid

ii) impaired relaxation ; early diastole¶§ filling pr°¨¼Ò, presystolic filling rate¡è

iii) severe impairment : "pseudo-normalized", early ventricular fillingÀÌ more rapid

5. Control of cardiac performance & output

heart muscleÀÇ shorteningÁ¤µµ

±×¸®°í, intact ventriculeÀÇ S.VÀº ´ÙÀ½ ¼¼°¡Áö »óȲ¿¡ ÀÇÇØ °áÁ¤µÈ´Ù.

¨ç contraction´ç½Ã muscle length(preload)

¨è muscleÀÇ inotropic state

: force-velocity-length relation & its end-diastolic-shortening-relation

¨é contractionµ¿¾È muscle tension(afterload¡é)

HR°¡ C.OÀ» °áÁ¤ÇÑ´Ù.

Ventricular fillingÀº myocardial relaxationÁ¤µµ¿Í ¼Óµµ¿¡ ¿µÇâÀ» ¹Þ´Âµ¥ SR¿¡ ÀÇÇÑ

Ca2+ uptake¼Óµµ¿¡ ¿µÇâÀ» ¹ÞÀ¸¸ç ischemia¶§ °¨¼ÒÇÑ´Ù.

1) ventricular end-diastolic volume(preload)

¨ç total body volume

hemorrhage³ª dehydrationµî°ú °°ÀÌ blood volumeÀÌ ºÎÁ·ÇÒ ¶§ heart·ÎÀÇ venous return

ÀÌ °¨¼ÒÇÏ¿© ventricular end-diastolic vol(preload)ÀÌ °¨¼ÒÇÑ´Ù.

¨è distribution fo blood volume

ventricular end-diastolic volumeÀº intra- & extrathoracic compartment»çÀÌÀÇ blood vol.

distribution¿¡ ¿µÇâÀ» ¹Þ´Â´Ù.

i) body position ; upright posture -> extrathoracic bld vol¡è, intrathoracic bld vol¡é

=> ventricular work¡é

ii) intrathoracic pr

intrathoracic pr°¡ negative°¡ µÇ¸é(¿¹, inspiration)

thoracic bld volume¡è, ventricular EDV¡è => venous return¡è

intrathoracic pr°¡ Áõ°¡(¿¹, valsalva maneuver or prolonged bouts of cough or PPV)

=> ¹Ý´ëÈ¿°ú

iii) intrapericardial pr

cardiac tamponadeó·³ intrapericardial pr°¡ Áõ°¡µÈ °æ¿ì cardiac filling ¹æÇØ

-> ventricular diastolic vol¡é

-> S.V & ventricular work¡é

iv) venous tone : vasoconstriction -> intrathoracic blood volume¡è

v) pumping action of the skeletal m.

exercise½Ã intrathoracic bld volumeÀÌ Áõ°¡

-> ventricular EDV & ventricular work Áõ°¡

¨é Atrial contraction

* atrial kick : concentric ventricular hypertrophy¶§ ƯÈ÷ Áß¿äÇÏ´Ù.

- AF¿Í °°ÀÌ atrial systoleÀÌ ¼Ò½ÇµÇ¸é ventricular EDP & volumeÀÌ °¨¼ÒµÇ¾î

°á±¹ myocardial performance°¡ °¨¼ÒµÈ´Ù.

ÀÌó·³ ventricular fillingÀÇ atrial contributionÀÌ °¨¼ÒµÇ´Â ¿¹´Â

i) AV dissociation

ii) PR prolongation of abbreviation(´ÜÃà)

iii) atrial contractility depression

2) inotropic state(myocardial contractility)

* °ü¿©ÇÏ´Â factors

¨ç Adrenergic nerve activity :ºÐºñµÇ´Â norepinephrineÀÇ ¾ç°ú °ü·Ã, most important mx

¨è circulating catecholamine -> HR¡è, myocardial contractility¡è

¨é force-frequency relation

¨ê exogenously administrated inotropic agent

isoproterenol, dopamine, dobutamine, other sympathomimetic agent

¨ë physiologic depressant

¨ì pharmacologic depressant : many antiarrythmic drug(procainamide & disopyramide)

Ca antagonist(verapamil), ¥â-blocker, alcohol, large dose barbiturate

¨í loss of myocyte - ischemia, MI

¨î intrinsic myocardial depression

3) ventricular afterload

ejectionµ¿¾È ventricular wall¿¡¼­ »ý±â´Â tension or stress

±×·¯¹Ç·Î afterload´Â ventricular cavityÀÇ volume thickness»Ó¸¸ ¾Æ´Ï¶ó aortic pr¿¡ ÀÇÇØ

°áÁ¤µÈ´Ù.

* Laplace's law

= tension of the myocardial fiber

= intracavitary ventricular pr & ventricular radius¿¡ ºñ·Ê

wall thickness¿¡ ¹Ýºñ·Ê

¡Å dilated LV of normal thickness°¡ normal-sized ventricleº¸´Ù aortic pr°¡ ´õ ³ô´Ù.

¹Ý´ë·Î °°Àº aortic pr. & ventricular dilastolic volumeÀÏ ¶§ thick-walled ventricleÀÌ

thin-walled chamberº¸´Ù afterload°¡ ´õ ³·´Ù.

4) exercise

6. Failing heart

* systolic HF : myocardial contractility¼Õ»ó -> systolic contraction ¾àÈ­

-> S.V, C.O¡é, inadequate ventricular emptying

cardiac dilatation, ventricular diastolic pr¡è

prototype) idiopathic DCM

* diastolic HF : impaired relaxation & ventricular fillingÀÇ Àå¾Ö

-> ventricular diastolic pr¡è(Fig 231-9)

¿¹) ischemia - functional & transient

typical - restrictive CMP secondary to infiltrative conditions(amyloidosis &

hemchromatosis), HCM

1) Adaptive mx

¨ç Frank-Starling mx

EDVÁõ°¡´Â sarcomere stretching°ú °ü·Ã

-> antin & myosin filament»çÀÌÀÇ »óÈ£ÀÛ¿ë Áõ°¡

Ca2+ sensitivity¡è

severe AR or MR°ú °°ÀÌ ventricular dilatationÀÌ °úµµÇÒ¶§´Â maladptive.

=> Laplace's law¿¡ ÀÇÇØ wall stressÁõ°¡, shortening°¨¼Ò

¨è afterload¡è(AS & hypertension)

=> wall tension¡è => concentric hypertrophy

=> elevated ventricular wall stress¸¦ normal·Î µ¹·Á³õÀ½.

±×·¯³ª ventricular hypertrophy´Â ventricular filling¿¡ Àå¾Ö¸¦ ÃÊ·¡Çϰí, wall stress¸¦ Á¤»ó

À¸·Î ȸº¹Çϱ⿡ ºÒÃæºÐÇÏ´Ù¸é, ventricleÀº dilatationµÇ¾î wall stress°¡ ´õ¿í Ä¿Á® vicious

cycle·Î µé¾î°¡°Ô µÈ´Ù.

¨é Redistribution of a subnormal cardiac output

skin, skeletal m. kidney -> brain, heart·Î blood flow redistribution

¨ê neurohumoral adjustment

arterial pr¸¦ À¯ÁöÇϱâ À§ÇÑ ±âÀü.

neurohumoral adjustment°¡ ½ÉÇÏ°í ¸¸¼ºÀûÀ϶§´Â cardiac functionÀ» ¼Õ»ó½ÃŲ´Ù.

2) Biochemical abnormalitis in HF

3) Neurohumomal and cytokine adjustment

neurohumoral adjustment -> hemodynamic burden, oxygen requirement Áõ°¡

¨ç The adrenergic nervous system

HF¿¡¼­´Â circulatory norepinephrineÀÌ Å©°Ô Áõ°¡µÇ¾î ÀÖ´Ù.

ÀÌ´Â ¿¹ÈÄ¿Í ¹Ýºñ·ÊÇÑ´Ù.

* chronic adrenergic stimultion

+- vascular resistance·Î Áõ°¡·Î ÀÎÇØ afterloadÁõ°¡

| cardiac arrhythmia

+- Ca2+ overload¿¡ ÀÇÇØ myocyte¼Õ»ó

chronic severe HF¿¡¼­ adrenergic receptor density & cardiac NE ³óµµ ¸ðµÎ °¨¼ÒµÇ¾î

ÀÖ´Ù.

adenylate cyclase activity¡é

=> intracellular cAMP¡é

=> protein kinase Ȱ¼ºµµ¡é, phosphorylation of Ca2+ channel¡é

transsarcolemmal Ca2+ entry¡é

=> Ca2+ reuptake¡é

G protein : inhibitory subunit¡è

¨è Renin-angiotensin-aldosterone system

C.OÀÌ °¨¼ÒÇÒ ¶§ RAA systemÀÌ activationµÇ¾î ÀÖ´Ù.

circulating angiotensin II & aldosteroneµÑ´Ù Áõ°¡µÇ¾î ÀÖ´Ù.

angiotensin II : vasoconstriction

aldosterone : salt & water retention, cardiac fibrosis

local(tissue) renin-angiotensin systemµµ activationµÇ¾î ÀÖ´Ù.

ACE inhibitor, angiotensin II receptor block, aldosterone antagonist¸¦ HF¸¦ È£Àü½Ãų¼ö

ÀÖ´Ù. (Fig 231-11)

¨é endothelin : very powerful vasoconstrictior

HF¿¡¼­ Áõ°¡

endothelin receptor¸¦ blockÇϸé LV fxÀÌ È£ÀüµÈ´Ù.

¨ê TNF-¥á

TNF-¥á¿Í °°Àº cytokineÀÇ overexpressionÀÌ HF pathogenesis¿¡ Áß¿äÇÑ ¿ªÇÒÀ» ÇÑ´Ù.

overexpressed TNF-¥á : systolic dysfunction, myocarditis, ventricular dilatation

shortened survival°ú °ü·ÃÀÖ´Ù.

¨ë Vasodilator peptide

: ANP, BNP

=> ¡è cGMP in the kidney, adrenal glomerulose, vascular smooth m & platelet

urine volume & sodium excretion¡è, vascular resistance¡é, renin release¡è,aldosterone

secretion¡é°ú °°Àº benefical effect¸¦ º¸ÀÌÁö¸¸ ÃæºÐÈ÷ powerfulÇÏÁø ¾Ê´Ù.

* ANP(ƯÈ÷ BNP)ÀÇ Áõ°¡ = poor Px