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