Heart As A Pump 1 Flashcards
Whaat are the 3 major types cardiac muscle?
- Atrial muscle
- Ventricular muscle
- Specialized excitatory and conductive muscle fibers
Summarize how cardiac muscle contracts
The atrial and ventricular types of muscle contract like skeletal muscle except, the duration of contraction is much longer.
The specialized excitatory and conductive fibers exhibit either automatic rhythmic electrical discharge in the form of action potentials or conduction of the action potentials through the heart. This is the excitatory system that controls the rhythmical beating of the heart. This conducting system is be discussed in the cardiac action potential lecture.
Contrast cardiac and skeletal muscle
- Form branching network of cells (separated by intercalated discs)
- Low resistance gap junctions which allow action potentials to spread from cell to cell
- Tetanic contractions are not possible because of long refractory period of cardiac action potentials
This features identified allows the contracting cardiac muscle to function as a synctium, thus allowing it to operate as a pump
What are determinants of myocardial performance?
- preload
- afterload
- Contractility
Explain preload
The degree of tension or load on the ventricular muscle when it begins to contract/at the end of diastole. It cannot be measured directly. Instead indices such as left ventricular end-diastolic volume and left ventricular end-diastolic pressure are measured directly. The preload can be explained on the basis of change in sarcomere length.
Explain after load
The load that the heart must eject blood against. It is the pressure in the aorta leading from the ventricle. The afterload of the ventricle corresponds to the systolic pressure described by the phase III curve of the volume-pressure diagram. The best ‘marker’ of afterload is systemic vascular resistance also called peripheral resistance
Explain what is contractility
Change in performance at a given preload or afterload. Change in force of contraction at any given sarcomere length. Acute changes in intracellular calcium and drugs can alter the contractility. Contractility affects the rate at which a muscle can develop active tension. Ejection fraction is the best index of contractility.
Describe the mechanics of cardiac muscle contraction
Cross bridge contraction enables a muscle to develop force (isometric contraction) or to shorten (isotonic contraction). Which one it does depends on the phase of the cardiac cycle.
During Isovolumetric phase (inlet and outlet valves are closed) contraction is isometric and ventricle develops a force (tension ) but there is little or no shortening of the muscle fibers
Once aortic valves are open, contraction becomes isotonic and ventricles shorten and eject blood
Summarize isometric contractions mechanisms
- Stretching myocardial muscle fibers will increase the active tension it can develop-up to a point.
- Lmax is the optimum muscle length at which maximum tension can occur. Cardiac muscles operate around 50% Lmax
- small changes in myocardial muscle fiber length—> large changes in active tension
- Cardiac muscle is much stiffer than skeletal muscle (resting tension is much greater)
- Good thing that cardiac muscle is not too distensible otherwise it may distend too much
What is resting tension ?
Force required to stretch a resting muscle to different lengths
What is active tension?
When a muscle is stimulated to contract whilst it’s length it’s held constant, it develops an additional force called active tension
What is peak isometric tension?
The total tension developed(active and passive)
The amount of active tension developed by a cardiac muscle during an isometric contraction depends on the initial myocardial muscle length. Stretching the resting myocardial muscle fiber before it contracts will increase the amount of tension it can develop
How do we calculate total tension?
Peak isometric tension/ total tension= resting tension + active tension
Summarize isometric contraction
- As the resting muscle fiber is stretched, tension developed increases—> increases force of contraction
- Length-dependent change in sensitivity of the myofilaments to calcium. (As muscle length is increased ability of TN-C to bind Ca is increased) Results in optimal overlap between actin and myosin filaments (as in skeletal muscle)
- Resting muscle fiber length is increased by increasing the load on the muscle (before it contracts). This load-termed preload
- Increased preload—>. Increased force of contraction
How would changes in contractility affect isometric tension?
Increased contractility
-At a particular muscle length, NE makes the myocardium contract with a greater force. This is described as an increase in contractility or a positive inotropic effect
What is inotropism?
Inotropism (contractility) is a change in active force development in the absence of a change in preload (I.e. resting muscle length)
Summarize sympathetic effects on inotropic actions
Increasing the resting length of a myocardial fiber will increase the tension developed when the fiber contracts. Length-tension relationship
-Sympathetic activity via NE and B1 activation increases the contractility of the myocardium I.e. in the presence of NE the myocardial fibers develop a greater tension from the same myocardial muscle fiber length
Common confusion- the term contractility refers to how efficiently the myocardium contracts from a given myocardial muscle length. NE increases contractility and is therefore described as having positive inotropic actions
Describe length-tension relationships in isotonic contractions
In this type of contraction, muscle fibers contract against an “afterload” . Initially the fibers need to develop an isometric tension (force) that is equal to the afterload, and once that is achieved the muscle can then shorten. When the muscle actually shortens the tension in the muscle doesn’t change (i.e. isotonic)
What are the effects of increasing contractility with Norepinephrine in isotonic contractions?
Sympathetic activity via NE & B activation shifts the peak isometric tension curve up and to the left. When the heart now contracts isotonically it is able to shorten more in the presence of NE.
Positive inotropes shift the isometric length-tension curve to the left (and up) thereby increasing the extent of shortening of muscle at any given set of preload and afterload
The smaller the afterload…
The faster the shortening velocity
If the muscle is stretched(increased preload)…
The velocity of shortening is greater
Describe velocity relationships effects changing preload on velocity shortening
A positive inotrope allows cardiac muscle, at any given length (preload) to move a heavier load faster than that possible with normal myocardium at the same preload
Vmax represents max rate of Crossbridge cycling
Note: increasing contractility in cardiac muscle will increase Vmax. So Vmax in cardiac muscle is NOT constant (unlike skm)
Positive inotropes increase Vmax, negative inotropes decreased Vmax
Give a brief overview of the Frank-sterling experiment
Investigated pressure and volume changes in the whole isolated heart in the early 1900s
Pressure changes is equivalent to tension changes in the myocardium
Volume changes results in changes in length of myocardial fibers
What are the results of Frank starlings results?
The intrinsic ability of the heart to adapt to increasing volumes of inflowing blood is called the Frank Starling mechanism of the heart
This led to Starling’s heart: As EDV, increasesstroke volume increases
What is the mechanism of Frank-Sterling’s results?
Mechanism:
-increased calcium sensitivity of TN-C, and increased actin-myosin interaction
- The energy of contraction of a cardiac muscle fiber is proportional to the initial muscle fiber length
- End-diastolic volume (preload) determines myocardial fiber length
Increased EDV—> INCREASED PRELOAD
increased preload—> increased stroke volume by increasing EDV
Explain Frank-Starling’s law of the heart
Explains the ability of the heart to change its force of contraction, and therefore it’s SV in response to changes in ventricular EDV
Volume of blood ejected in systole depends on the volume of blood present in the ventricle at the end of the previous diastole
Frank-Starling relationship ensures that the output from the LV and RV are closely matched overtime . Output from right ventricle is matched to its veinous return
Example: exercise
Contrast ventricular function curve and cardiac performance (function) curve
Any graph whose x-axis is a function of myocardial muscle fiber length and whose y-axis is a reflection of contractile energy is called a VENTRICULAR FUNCTION CURVE
A Ventricuar function curve whose y-axis is stroke work (or stroke volume) and x-axis is called a cardiac performance curve
What is the relationship between LVED volume and LVED pressure?
- LV end diastolic causes changes in LV end diastolic pressure
- However LV end diastolic pressure is also related to distensibility (stiffness) of the myocardium which can change in pathological conditions
Nite that when EDV is 120 ml, the stiffer ventricle has a much greater pressure. This has implications for the P-V loop
What is the effect of decreased ventricular compliance on stroke volume?
A stiffened ventricle has a decreased compliance which means that LV end diastolic pressure rises more quickly. This will result in the earlier closure of mitral valves and decreased filling of the heart such that the LV end diastolic volume is decreased.
In the diagram a normal ventricle has about 120 ml of blood before LVEDP reaches 8 mmHg but the pressure in the stiffened ventricle reaches 8 mmHg when EDV is about 100 ml causing premature closing of mitral valve
A major cause of decreased compliance is ventricular hypertrophy caused by uncontrolled hypertension
What are the 3 scenarios in which afterload is increased?
- When aortic pressure is increased (elevated mean arterial pressure )- The higher the aortic pressure the more tension the ventricle must generate and the more the heart has to work. I.e. the greater it’s workload
- When systemic vascular/total peripheral resistance is increased, resulting in increased resistance and compliance. The total peripheral resistance (TPR) which determines the diastolic BP (about 80 mmHg)
- In aortic stenosis- pressure overload on the left ventricle
What is the main application/ concept of afterload in the circulatory system?
Afterload can be thought of as the stress (tension) in the ventricle wall necessary to generate the pressure required to open the the aortic valve and eject blood into the aorta
-to open the aortic valves and eject blood out into the aorta, the LV must develop a tension that generates a pressure slightly greater than the aortic pressure (which is about 80 mmHg)
What is Laplace’s law?
If we consider the heart as a separate sphere, another factor comes into play when considering the amount of tension the ventricles can develop and that is the radius of the sphere and thickness of the walls
The relationship between tension developed, wall thickness and radius is described by Laplace’s Law
What are the mathematical implications of Laplace’s law?
The pressure generated in a sphere is directly proportional to the active tension (T) developed in the walls times the thickness of the walls, and inversely related to the radius of the sphere
h= wall thickness
P=2Th/ r
Tension(wall stress)= pressure x radius / 2 x h
How does Laplace’s heart apply to dilated heart?
To generate the same pressure (ventricular pressure) in heart A (very small) and heart B(very big) - the ventricle has to develop greater tension in heart B. So, a distended heart has to work harder to eject the same volume of blood into the aorta.
So the “afterload” on heart B is larger
Explain the clinical Correlation of Laplace’s law and hypertension
- In a hypertensive patient, the heart must generate higher LV pressure (and therefore wall stress) in order to exceed the higher aortic pressure (that exists), to open the aortic valve and eject the stroke volume
- In chronic hypertension the heart compensates by thickening it’s walls (concentric hypertrophy) . This then increases h (in Laplace’s Eqn)
Tension (stress)=. Pressure x radius/ 2 x h
Increasing h - this reduces the amount of tension the ventricles have to develop
An example of an initial compensatory response to hypertension
What is the clinical correlation of Laplace’s law and athletes?
Athletes also develop hypertrophy of left ventricle
The wall tension developed needs to be less than in non-athletes
-During the cardiac cycle when blood is being ejected from the ventricles into the aorta the radius of the ventricles is smaller , so the ventricles need to generate less tension
Ejection becomes easier as it proceeds
Tension (wall stress)= pressure x radius/ 2 x h
How does capntractolity (inotropism) affect stroke volume?
Force of contraction achieved from a given initial fiber length
OR
A change in the contractile energy of the heart that is NOT due to changes in fiber length
Changes in contractility are caused by intrinsic cellular mechanisms
Physiologically the most important inotrope is sympathetic activity via release of NE (EPI) acting via B1 receptors
What is the effect of changing contractility on the FRANK-starling (ventricular performance) curve?
- positive inotropes shift the Frank-Starling curve upwards and to the left such that SV is increased at a particular level of EDV
- negative inotropes soft curve down and to the right
- The Frank starling mechanism operates at a particular level of contractility and afterload.
Changes in contractility and afterload SHIFT the Frank-starling curve
How is contractility increased?
Factors or drugs which increased contractility (inotropism) by increased calcium via:
- increased iCa
- increased rate of uptake of calcium into SR leading to increased stored calcium in SR
- inhibiting calcium-ATPase pump
- inhibiting the Na-Ca exchanger
Acute changes in contractility are due to changes in the intracellular dynamics of calcium
Drugs that increase contractility usually provide more calcium and at a faster rate to the contractile machinery
More calcium increases the availability of cross-link sites on the actin, increasing cross-linking and the force of contraction during systole
Give the mode of action of NE & EPI in increasing contractility
NE, Epinelhrine—> B1 cardiac receptors—> Adenylate cyclase—> increased cAMP—> protein kinase A—> increased iCa—> increased Ca transient —> increased CICR —> increased cytosolic Ca—> increased force of contraction —> increased stroke volume
Other positive inotropes:
B receptor agonists: isoprenaline, dobutamine
Cardiac glycosides: digoxin
What is the mode of action of Digixin?
Digixin inhibits Na-K ATPase—> increased intracellular Na—> decreased extrusion of Ca by the Na-Ca exchanger—> more cytosolic Ca—> more Ca pumped back into SR—> more Ca available in the SR for cardiac contraction —> increased contractility of the heart
What drugs are negative inotropes?
Non physiological
- Drugs: Ca channel blockers: Verapamil
B receptor blockers: propanolol
How is cardiac pathology a negative inotropic?
Myocardial infarction
Cardiac failure
Calcium dynamics doesn’t explain chronic losses in contractility, which in most cases are due to overall myocyte dysfunction.
Myocardial infarction leads to increased proton concentration . Protons compete with Ca for binding to troponin ( OR decreased affinity for TN-C for Ca)
Cardiac failure: decreased expression of Ca-ATPase pump —> decreased Ca2+ stored in SR leading to decreased Ca2+ available for contraction—> decrased contractility
