Contractility Flashcards
systole - defined
*left ventricle (and right ventricle) contract
*sending blood out the pulmonic and aortic valves
diastole - defined
*left ventricle (and right ventricle) relax
*ventricles allow themselves to fill with blood to prepare for the next heartbeat
LV ejection fraction (EF) - defined
*EF is an index of ventricular contractility (how much blood the left ventricle ejects in 1 heartbeat)
*normal EF is > 50% (generally 50-70%)
*in essence: EF = (amount of blood pumped out of the ventricle) / (total amount of blood in ventricle)
LV ejection fraction - formula
EF = SV / EDV
note: SV = EDV - ESV
EDV = end diastolic volume (represents when the LV has the most blood in it)
ESV = end systolic volume
SV = stroke volume
stroke volume (SV) - formula
SV = EDV - ESV
EDV = end diastolic volume
ESV = end systolic volume
gold standard test used to measure LV ejection fraction
cardiac MRI
cardiac output - defined
*the amount of fluid pumped through the heart in 1 minute (measured in L/min)
-note: organs receive different amounts of cardiac output (ex. brain receives 15%, kidneys receive 20-25%, heart receives 5%)
-normal range: 4-8 L/min (but there is significant variation related to body size)
cardiac output - formula
CO = SV x HR
CO: cardiac output (measured in L/min)
SV: stroke volume (SV = EDV - ESV)
HR: heart rate
cardiac index
*a measure used in many intensive care settings to account for body size by normalizing the cardiac output relative to body surface area
*cardiac index = CO / body surface area
*normal cardiac index ranges from 2.5 L/min/m2 to 4.5 L/min/m2
note: a cardiac index < 1 L/min/m2 is not compatible with life
a cardiac index < ? is incompatible with life?
cardiac index < 1 L/min/m2 is not compatible with life
Swan-Ganz catheter
*small tube, typically placed in someone’s jugular vein or subclavian vein
*allows for the direct measurement of pressure and obtain blood samples throughout the right-sided circulation system
*used to calculate cardiac output (based on Fick Principle)
Fick Principle as a measure of cardiac output
CO = (rate of O2 consumption) / (arterial O2 content - venous O2 content)
examples of how different factors can affect CO using Fick Principle
*if the rate of O2 consumption increases (exercise, increased metabolism, etc), the cardiac output increases
*if cardiac output decreases (and metabolism remains the same), then the cells/tissues of the body get their oxygen by attempting to extract more oxygen from the bloodstream
Fick Principle: obtaining the measures
*arterial O2 content: measured from a peripheral artery
*venous O2 content: measured from the pulmonary artery (via the Swan-Ganz catheter)
*a commonly used value for rate of O2 consumption at rest is 125 mL O2/min/m2
*however, OXYGEN CONTENT can be DIRECTLY CALCULATED using:
([Hb] x 1.34 x O2 sat) + 0.003(PaO2)
thermodilution method for measuring CO
*measures CO (using Swan-Ganz catheter) by extrapolating flow based on the change in temperature at distal post after injection of a cooled solution at a more proximal port
factors that affect stroke volume
*contractility: increase in contractility increases SV
*preload: increase in preload increases SV
*afterload: DECREASE in afterload increases SV
sarcomeres in the heart - general principles
*sarcomeres are the heart’s building blocks
*many sarcomeres are contained within a single muscle cell
*muscle cells are organized into myofibrils, which are themselves organized into muscle fibers
*muscle fibers are organized into different regions of the heart, such as the endocardium, myocardium, and epicardium
sarcomeres - bands & filaments
*recall: myosin is the thick filaments, and actin is the thin filaments
*I band: actin + titin
*H band: myosin only
*A band: actin-myosin overlap + myosin only
*with contraction, both the H and I bands narrow, but the A band stays the same
sarcomere electron micrograph
troponin complex
*composed of troponin C, troponin I, and troponin T
*when calcium becomes bound to specific sites in the troponin complex, a series of protein structural changes such that tropomyosin is rolled away from myosin-binding sites on actin, allowing myosin to attach to the thin filament and SHORTEN THE SARCOMERE, which produces force
troponin C
*binds to calcium ions to produce a conformational change in troponin I
*part of the troponin complex
troponin T
*binds to tropomyosin, interlocking them to form a troponin-tropomyosin complex
*part of the troponin complex
troponin I
*binds to actin in thin myofilaments to hold the troponin-tropomyosin complex in place
*part of the troponin complex
actin and myosin cross-links during contraction
*for most circumstances, the more actin-myosin cross-links, the more force is generated
*actin-myosin will continue to form cross-links until enough force has been generated for the sarcomere to shorten
*if only 1 actin-myosin cross-link is needed to generate sufficient force to shorten, then it will obviously shorten faster than if 4 actin-myosin cross-links were needed
titin: contraction & relaxation
*during contraction, titin gets compressed like a spring as myosin travels down the actin filament
*during relaxation, the potential energy stored in the spring of titin gets released as the myosin dissociates from actin, and results in the RECOIL of the left ventricle (causes the pressure in the left ventricle to decrease such that it is lower than the left atrial pressure, so that the LV is sucking blood in)
sarcolemma
*myocardial cell membrane
*has deep invaginations with the purpose to get extra-cellular fluid (containing CALCIUM) as close to the sarcomere & sarcoplasmic reticulum as possible
*the sarcoplasmic reticulum contains calcium used to contract the heart muscle, but MOST of the contraction is generated from the extra-cellular fluid
microphysiology of CONTRACTION in the heart
- as depolarization travels down the cell membrane, the voltage-gated calcium channel opens (allowing extra-cellular calcium to flow into the cell)
- calcium from the voltage-gated calcium channel activates the ryanodine calcium channel (of the sarcoplasmic reticulum)
- calcium from both the voltage-gated calcium channel and ryanodine calcium channel bind to troponin, allowing for myosin-actin cross-bridging and subsequent sarcomere contraction
microphysiology of RELAXATION in the heart
- both the voltage-gated calcium and the ryanodine calcium channel are closed
- using ATP, the SERCA-2 ATPase on the sarcoplasmic reticulum (SR) transports calcium BACK INTO THE SR
- using the energy stored in the sodium gradient between the intra- and extra-cellular environments (extra- concentration > intra), sodium goes down its gradient in order to move calcium against its gradient and get CALCIUM OUT OF THE CELL (allow one sodium into cell to get one calcium out)
- with calcium removed, troponin prevents myosin-actin cross-bridge formation, preventing contraction (ie. allowing relaxation)
microphysiologic ways to increase contractility
- allow more calcium channels to open for more calcium to enter the myocyte
- increase SERCA-2 activity to allow sarcoplasmic reticulum to hold more calcium (such that it can release more calcium)
- make it easier for troponin-C to move out of the way to allow for more actin-myosin cross-links to form
beta-1 receptor and increases in contractility
*the binding of an agonist (epinephrine) to the beta-1 adrenergic receptor increases contractility/relaxation in several ways:
1. increased influx of calcium ions (by phosphorylation of calcium channel)
2. increased removal of calcium ions for relaxation by phosphorylation of phospholamban (which prevents it from inhibits SERCA-2)
3. phosphorylation of troponin-I results in a faster relaxation (more difficult for it to bind to calcium; as such, breaks up actin-myosin cross-links)
beta-1 receptor agonists
*epinephrine
*norepinephrine
*isoproteronol
*dopamine
*dobutamine
beta-1 receptor antagonists
beta blockers (metoprolol, carvedilol)
effects of a phosphodiesterase inhibitor on the beta-1 receptor
*cAMP is broken down by phosphodiesterase
*inhibition of phosphodiesterase allows cAMP to stick around longer (allowing for increased beta-1 activity)
*ex. milrinone
heart rate and contractility - Bowditch Effect (Force Frequency)
*at higher heart rates, there is less time for the Na/K ATPase pump to restore electrolyte gradients
*as a result, the intra-cellular calcium increases because there is less time for the Ca/Na exchanger to remove calcium from the cell
*more calcium will be removed by SERCA, which means more calcium will be released by the sarcoplasmic reticulum
*NET RESULT: INCREASED HEART RATE → INCREASED CONTRACTILITY
calcium and contractility - general principles
*higher intra-cellular calcium means more actin-myosin cross-bridges
*in general, more actin-myosin cross-bridges results in more force being generated
*high heart rate increases intra-cellular calcium (Bowditch Effect)
*inhibition of Na/K ATPase inhibits the Na/Ca exchanger, thus increasing intra-cellular calcium
mavacemten
*a novel myosin inhibitor
*reduces cardiac contraction by stabilizing the state of relaxation of beta-cardiac myosin
omecamtiv
*a novel myosin activator
*enhances cardiac contraction
