Muscle Contraction and Contractility Flashcards
Heart chamber cartoon
Circulation map
Isovolumic contraction
The interval between the closing of the atrioventricular or AV (mitral and tricuspid) valves and the opening of the semilunar (aortic and pulmonic) valves. Isovolumetric contraction occurs when the AV valves have closed, the ventricle is contracting and the semilunar valves have not yet opened
S1 vs S2
S1: Closing of the cuspid valves
S2: Closing of the semilunar valves
Wigger’s Diagram
What controls the closing of the AV valves and opening of the semilunar valves?
Pressures rise in the left and right ventricles as blood flows into them from the left and right atria; as soon as ventricular pressure exceeds atrial the AV valves close. Once left ventricular pressure reaches aortic pressure, the aortic valve opens.
Ejection phase
Opening of the semilunar valves (pulmonic and aortic) marks the onset of the ejection phase. Blood is ejected into the aorta from the left ventricle (and into the pulmonary artery from the right ventricle). Not all the blood is ejected into the aorta (or pulmonary artery), normally about 55-65% of the blood is ejected (ejection fraction).
The volume of blood ejected is known as the stroke volume and the amount of blood in the ventricle at the end of systole is the endsystolic volume (ESV).
Calculating ejection fraction
Pend diastolic - Pend systolic
_________________________
Pend diastolic
rapid ejection phase
The initial period of ejection phase, when the rate at which the blood is ejected into the aorta exceeds the rate at which it flows into its branches.
reduced ejection phase
The latter part of systole, when blood flow into the periphery via arteries and arterioles exceeds the flow into the aorta from the ventricle causing a fall in pressure
Isovolumic relaxation
As the ventricle relaxes, left ventricular pressure falls below aortic pressure and the aortic valve closes. Closure of the valve causes the incisura on the descending limb of the aortic pressure curve (looks like a little bump on the pressure curve). Closure of the aortic valve produces the second heart sound. The time from when the semilunar valves (aortic and pulmonic) close and the AV valves (mitral and tricuspid) are open is termed isovolumic relaxation
Rapid ventricular refilling
As ventricular pressure falls below atrial pressure, the AV valve opens. There is a rapid flow of blood from the atria into the ventricle
Diastasis
As the ventricle fills, the pressures in the atrium and ventricle equalize and further flow from the atrium (filling of the ventricle) virtually stops
Atrial systole
At the end of ventricular diastole the atrium contracts and ejects blood to complete ventricular filling
The volume of blood at the end of diastole is called the ___ and the pressure is the ___.
The volume of blood at the end of diastole is called the end-diastolic volume (EDV) and the pressure is the end-diastolic pressure (EDP).
Venous pressure tracing: A waves, C waves, V waves
A wave: Represents pressure generated by atrial contraction during the end of ventricular diastole
C wave: Pressure wave transmitted by closed tricuspid or mitral valve during the initial part of ventricular contraction (as the ventricle begins to contract, the leaflets bulge toward the atrium causing the slight increase in pressure called the C wave)
V wave: Increasing pressure in the atrium as the atrium fills from blood returning from the inferior and superior vena cava (right atrium) or pulmonary veins (left atrium) during right or left ventricular contraction, respectively
There is decrease in peak rate of ___ between the ages of 20 and 80
There is decrease in peak rate of early diastolic filling between the ages of 20 and 80
This probably relates to stiffening / reduced compliance of the ventricle with age, which results in higher ventricular pressures as the ventricle fills.
Atrial Kick
Since volumetric filling of the ventricle during diastole is reduced with age (due to reduced ventricular compliance), older people are more denepdent upon atrial contraction for ventricular filling
Ryanodine receptors are contained within. . .
. . . the subsarcolemmal cisternae
The sarcotubular network is lined with. . .
. . . calcium re-uptake channels
Basic myocardial excitation-contraction coupling
- Action Potential
- Influx of Ca++ through L-type channels of sarcolemma (T-tubules)
- Ca++ release from sarcoplasmic reticulum (calcium triggers ryanodine receptors on SR to release calcium: calcium induced calcium release)
- Increased binding of Ca++ to troponin C
- Actin/myosin cross bridging
Relaxation of cardiac muscle requires. . .
. . . energy! The calcium released from the sarcoplasmic reticulum must be re-uptaken by active transport.
Basic myocardial relaxation
- Increased SR uptake of Ca++ and eflux of Ca++into extracellular space (3 mechanisms)
- SR Ca++ -ATPase (SERCA)
- Sarcolemma Ca++ ATPase
- Na-Ca++ Exchanger
- Decreased Ca++ binding of troponin C
- Tropomyosin blocks actin binding site
- Actin-myosin relaxation
Isometric Contraction
If an isolated muscle strip is stretched and anchored between two rigid points and is then stimulated electrically, it produces tension (force) without muscle shortening. Contraction with the muscle staying at a constant length is called an isometric contraction (force increases; muscle length stays the same).
Isotonic Contraction
If an isolated muscle strip anchored on one end and connected to a weight on other end, it will shorten under constant tension; this is called isotonic contraction (force constant; muscle length decreases)
Muscle ‘performance’
The performance of an isolated cardiac muscle strip is characterized in terms of tension development and changes in length (shortening). Whereas the intact heart (a three dimensional structure comprising many myocytes linked together) generates pressure and has changes in volume
The longer the sarcomere or a muscle, . . .
The longer the sarcomere or a muscle, the more tension that is developed.
This is because:
- More favorable actin-myosin cross bridge interactions
- Length dependent release of calcium from the sarcoplasmic reticulum
- Increased affinity of calcium for troponin
Lmax
The length at which maximal tension is generated in a muscle
If stretched beyond this point, tension declines.
Molecular explanation for Lmax
Inspiratory muscles are longer at ___.
Expiratory muscles are longer at ___.
Inspiratory muscles are longer at low lung volume.
Expiratory muscles are longer at high lung volume.
Preload vs Afterload
Preload: Influences the heart at the end of diastole and positions the sarcomere for the next contraction. The force felt by the muscle before it contracts.
Afterload: Reflects the tension generated in the myocytes during systole. The force felt by a muscle while it contracts.
Frank-Starling Law of the Heart
The greater the stretch of the ventricle at the end of diastole, the greater the stroke volume during systole. In other words, the heart contracts more forcefully during systole when it is filled more during diastole.
In the cardiac cycle, ___ is the preload.
In the cardiac cycle, the end-diastolic volume prior to ventricular contraction is the preload
This is determined by the venous return to the heart.
Contractility
The stroke volume for a given preload.
A characteristic of the heart muscle at a given moment in time and is dependent on the ability of calcium to enter the heart and enhance contraction.
When LVEDP (or LVEDV) increased beyond a certain point, . . .
When LVEDP (or LVEDV) increased beyond a certain point, no further increase in stroke volume will be achieved but pulmonary congestion (pulmonary edema) will ensue.
The same LVEDP will give different LVEDVs in hearts with different. . .
. . . compliance. Since compliance determines how the heart’s volume changes in response to a given pressure.
It is believed that the increased stroke volume that occurs with increased preload stems from the fact . . .
It is believed that the increased stroke volume that occurs with increased preload stems from the fact that with increased end diastolic volume there is increased muscle stretch, which translates into more actin/myosin cross-bridges that are overlapping so there are more units able to participate in contraction (you are closer to the cardiac muscle’s Lmax)
Varying volume (preload) results in an increase in stroke volume by moving. . .
Varying volume (preload) results in an increase in stroke volume by moving along a Frank-Starling curve, not between curves.
Moving between Frank-Starling curves represents a change in. . .
. . . the actual contractile function of the heart, termed contractility or inotropy.
___ leads to increased contractility
Stimulation of the sympathetic nervous system via beta-receptors on the heart muscle leads to increased contractility.
Beta-adrenoceptors are coupled to G-proteins, which activate adenylyl cyclase to form cAMP from ATP. Increased cAMP activates a cAMP-dependent protein kinase (PK-A) that phosphorylates L-type calcium channels, which causes increased calcium entry into the cells.
Various surrogates for end-diastolic muscle fibre length in human physiology
end-diastolic pressure
end-diastolic volume
central venous pressure (just for right heart)
Various surrogates for ventricular peformance / contractility in human physiology
cardiac output
stroke volume
stroke work
Perhaps the most imporant role of the Frank-Starling Law of the Heart is to. . .
. . . match the outputs of the right and left ventricles.
They must be matched because they are connected in series and the output from the right or left cannot exceed (for more than a beat or two) the other or the circuit will not be in equilibrium. Thus, an increase (or decrease) in output from one ventricle will lead to an augmentation (or diminution) of output of the other ventricle mediated by Frank-Starling
Frank-Starling mechanism summary figure
Cardiac cycle plotted as LV pressure by LV volume
Interpreting clinical measurements of ejection fraction
A measure of cardiac contractility
Normal EF > 55%
Severe heart failure EF < 20%
Low ejection fractions indicate ___.
Low ejection fractions indicate systolic dysfunction.
If the pressure at which the aortic valve opens is raised, . . .
. . . the heart will spend more time in isovolumetric contraction, and less time in ejection. Thus, stroke volume will be reduced.
End-systolic pressure
The maximal pressure developed by the ventricle for any given LV end-diastolic volume.
End-systolic pressure volume relationship
The slope of the ESPVR provides an index of myocardial contractility and systolic function. This is termed the End-Systolic Elastance.
A note on afterload
The reality is that there are many factors (e.g., blood pressure, vascular resistance, radius of the ventricle) that can affect afterload; to say that any one of these parameters alone “equals or is the same as” afterload is misleading and oversimplifies the concept.
Beware these explanations online!
Wall stress or wall tension
A somewhat comprehensive definition of afterload. Calculated via LaPlace’s law.
T = P x r
2 x d
Where T = wall stress, P = pressure, r = radius, d = wall thickness
The greater the radius of a heart chamber, . . .
. . . the closer the wall is to a flat surface, and the smaller the inward vector. Thus, to produce a particular pressure within the ventricle, a larger radius increases the wall stress (the myocytes must generate more tension within the wall of the ventricle to produce the same pressure inside the ventricle).
For a given radius, if the ventricle must generate a larger pressure, . . .
. . . wall stress increases, and thereby afterload increases.
Chronically high wall stress will lead to . . .
. . . hypertrophy of myocardial muscle to reduce the stress on any individual cell. Also, increased oxygen demand, as increased oxygen demand is associated with increased wall stress.
For patients with increased resistance and decreased flow in the coronary arteries, increases in wall stress may be associated with . . .
For patients with increased resistance and decreased flow in the coronary arteries, increases in wall stress may be associated with myocardial ischemia and infarction
The radius of the ventricle at end diastole. . .
. . . determines preload (the overlap of actin-myosin in the myocytes) and also affects afterload (wall stress) during the ensuing systole.
Aortic valve-aorta junction
Mean arterial pressure
The pressure in the large arteries averaged over time throughout the entire cardiac cycle. It can be approximated by the formula:
Mean arterial pressure (MAP) = Diastolic Pressure + 1/3 (SBP-DBP)
Pulse pressure
Systolic pressure - diastolic pressure
MAP is closer to diastolic than systolic pressure because. . .
MAP is closer to diastolic than systolic pressure because diastole lasts twice as long as systole
Arterial pressure waveform
Measuring blood pressure continuously
Sphyngomanometry
Changes in blood pressure with aging
Systolic blood pressure remains stable until age 45, and then increases by 5-8 mmHg/ decade in middle age;
diastolic blood pressure increases at 1 mmHg/decade at all ages in men; diastolic blood pressure in women is stable until age 40, increases significantly at age 40-60, then stabilizes or declines after 70.
What causes increased systolic pressure with age?
Decreased elasticity of the arteries due to an increase in collagen and a decrease in elastin leads to increased arterial stiffness and increased systolic blood pressure
What often causes decreased diastolic pressure over time?
Diastolic pressure may fall as the elastic recoil of the artery diminishes
How does chronic salt consumption affect blood pressure?
Chronic salt consumption contributes to arterial stiffness, whereas physical conditioning lessens arterial stiffness (thus, exercise is a good recommendation to reduce blood pressure in individuals with hypertension).
Both contraction of the heart (systole) and relaxation of the heart (diastole) are. . .
. . . processes that require energy
the first is dependent on movement of calcium into the cell and the contractile apparatus, while the second is dependent on moving calcium out of the contractile apparatus and out of the cell
Limbs of the Starling curve
There is an ascending limb and horizontal limb of the Starling Curve; when the heart is on the horizontal or plateau phase of the Starling Curve, additional increase in preload does not lead to increase in stroke volume
When the myocyte is stimulated to contract, it can generate tension or it can shorten. It follows that, in relation to the aortic valve, . . .
The more tension that must be generated before the aortic valve opens, the less work is available for shortening (i.e., for ejecting blood out of the ventricle into the aorta).
Blood pressure is dependent upon . . .
. . . the force and volume of blood ejected from the ventricle as well as the elasticity of the arteries and the resistance imposed by the vascular bed to the flow of blood.
Hypertrophy of cardiac muscle results in ____ compliance.
Hypertrophy of cardiac muscle results in decreased compliance.
This is an adaptive mechanism in the case of hypertension.
Frank-Starling curves of varying contractility
A medication is given which results in the Frank-Starling curves shifting upward and to the left and increases the slope of the curve. The best physiologic description of the effect of this medication is:
Increase in contractility
If there is no change in contractility of the heart, rapid saline administration to a dehydrated patient will result in a change in. . .
Movement rightward on the existing Frank-Starling curve
