Cardiovascular lecture notes

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Revision as of 21:12, 7 March 2010

• started here on 02/10/10.

Cardiovascular: The heart

Diagram of heart

• Today will be mostly anatomy.
• There are two pumps, the right heart (pulmonary circulation) and left heart (systemic circulation).
• O2 poor = blue, rich is red.
• Arteries carry blood away from the heart, veins carry it back.
  • Be careful associating this to whether or not it is carrying oxygenated blood or not.

Heart

• Both sides have to pump the same amount b/c it is a closed system.
• They pump about 5 liters per minute.
• The two tracts are not equal in resistance because the pulmonary (less resistance) is shorter and simpler.
• The systemic circulation is much higher resistance with lots of branching.
• Coronary arteries are important for feeding the heart.

Gross anatomy of the heart

• The heart is surrounded by the pericardial sac.
  • It surrounds, anchors, and protects.
  • The pericardial sac is much like a balloon, only it is filled with fluid, not air.
  • The sac is also attached to the major vessels.
  • There are three layers to the pericardium:
    • The outer layer is the fibrous layer which is what anchors the sac to the diaphragm and vessels.
    • The next layer is the serous layer (two layers, because of a folding over) with fluid in between the two layers.
    • Visceral layer of the serous layer is inner-most and fused to the heart.

Pericarditis

• Inflammation of the pericardial membrane, often from a bacterial infection.
• Diagnosis comes through cardiac tapenae. This is caused by excess fluid build up.
• Problems:
  • Initially, there is excess fluid buildup. This can usually be removed by direct needle aspiration because it will otherwise inhibit proper beating.
  • Secondary problems include a decrease in the amount of fluid which generates more friction which leads to adhesions and thus inhibits heart activity.

Myocardial tissue

Myocardium

• Myocardium is composed of muscle cells built on a connective tissue network.
• The cardiac muscle cells are arranged such that they would have maximum efficiency at pumping blood.
• Intercalated discs allow for each heart muscle to interdigitize with the next heart muscle cell.
  • This is key for proper contraction.
  • All along the intercalations are desomosomes and tight junctions that link the cells.
• Gap junctions allow for communication between cells.
  • These allow ions to flow between cells for cell-cell communication.

Endocardium

• The endocardial layer lines the whole inside of the heart and is contiguous with the endothelial cells of the vessels.
• Ventricles do the major pumping.
• There are two sets of valves:
  • Those that connect the atria to the ventricles.
  • Those that connect the ventricles to the vessels.
  • Note that the muscle layer of the left wall (the systemic pump) is bigger than the wall of the right wall (pulmonary pump).

Valves

• The valves open and close in response to pressure changes.
• They are made of a fibrous material (same as that which runs through the rest of the heart to give it structure).
• Atrio-ventrical (AV) valves:
  • Have thin walls.
  • Are open at rest such that blood int he atria leaks into the ventricles.
  • The tricuspid valve has three valves but the mitral (bicuspid) valve has only two.

What is a miter?
*The name of the mitral valve comes with reference to the miter (mitre) which was a religious headgear from long ago ref.

• Semi-lunar (SL) valves:
  • Are closed at rest. This makes sense because blood in the vessels have a back force that will close the semi-lunar valves.

The mechanics

• The pressure of the blood being squeezed by the ventricle closes the AV valve and opens the semilunar valve.
• AV valves have long fibrous strings (chordae tendeneae) which are connected to the papillary muscles (which are on the inside of the ventricle walls).
  • These do not pull the flap open, they only keep the valve from turning inside out when the ventricle begins to compress the blood such that there is force on the valve that would otherwise collapse it.

• The heart can tolerate some leaking (that is, retrograde circulation).
  • Severe leaking is a problem because the heart has to keep pumping stronger or faster or both to maintain circulation which can lead to heart failure.

• Molecular mimicry:
  • There are organisms that have epitopes that are very similar to self-epitopes. So when we generate an immune response to these epitopes (as we should because they are presented by bad guys), we might start attacking host cells, too.
    • Strep is one of these. If it becomes systemic it can generate rheumatic fever (damage to the heart valves) which is thought to occur because of molecular mimicry and the immune system attacking cells of the heart.

Blood flow of the heart

• There are two arteries coming off the aorta artery; these start the coronary circulation.
• Then there are veins that run back from the cardiac tissue and feed into the heart.

Really, the heart? or some big vein?
*Yes, it is actually the atrium into which they dump.

• The heart must have extensive blood flow and therefore the coronary circulation is very extensive.
  • The heart is 1/200th of the body's weight but it has 1/20th of the blood supply.
• Why do we need all this blood flow to the heart?
  • If you start depleting blood flow from skeletal muscles, one can compensate by using ATP reserves, switching to anarobic energy generation, using lactic acid or one can just stop using it.
  • You cannot switch to glycogen metabolism in the heart and it never stops beating, thus it must always have adequate oxygen.
• Ischemia means "reduced blood flow".
• Hypoxia means "low oxygen".
• Coronary atherosclerosis means "a buildup of plaque in heart".

Coronary atherosclerosis

• Coronary atherosclerosis is the same thing as coronary artery disease (CAD).
• Coronary artery disease is the leading causes of death in the US, by a large margin.
• Deposition of plaque in coronary vessels leads to a lowering of cardiac blood circulation.
  • Occlusion of the vessel deprives the heart of the oxygen.
  • In a myocardial infarction, if mycardiocytes die, they are replaced with fibrous scar tissue which isn't contractive.
• Ultimately, CAD leads to a failing of the heart due to low blood supply.

Causes of CAD

• Hypertrophy of the endothelial cells.
• Cholesterol deposition.
• Endothelial cells separate and form gaps which causes platelet aggregation.

What can you do about it?

• You can do a balloon angioplasty to remove circulatory blockage.
  • This is an older procedure, it can be an outpatient procedure.
  • This pushes all the plaque out of the vessel.
  • The problem still exists, however, because the plaque is still there.

• You can ablate plaque with lasers.

• You can pull it out with spinning knives and suction.
  • This and the laser can damage the vessel, so be careful.

• Stents can be placed to hold the vessel open.
  • There are many generations of these.
  • There is a great need for these.
  • These are now coated with things that inhibit clotting and platelet aggregation.
  • We often treat with clot busters like [Delude's_"Clot_Busters!!_-_Discovery_of_thrombolytic_therapy_for_heart_attack_and_stroke"_(2004)| tPA and streptokinase].
  • Removal of the clot can generate emboli which can cause problems, too.

• If nothing else works, we have to do coronary bypass surgery.
  • In this surgery, they replace the coronary vessels with vessels from another part of the body (usually from the leg).
  • It is possible to use other vessels because the coronary flow is not a high pressure flow.
  • It is extremely invasive to get to and work on the heart.

What causes plaque formation?

• High cholesterol contributes to it (but only in 20% of the population).
• Inflammatory responses, perhaps cuased by infections.

Cowley's Newsweek article: Cardiac Contagion

• Contagion: "A disease spread by contact; The spread or transmission of such a disease; The spread of anything harmful, as if it were such a disease...." ref
• There are several types of chlamidya, including respiratory.
• The only way to know if you have respiratory chlamidia is assaying for antibodies.
• They studied rabbits because they don't get CAD.
• They infected rabbits with respiratory disease and they got CAD.
• Clamidia survive in macrophages.
• The article suggests that while a macrophage is attacking the plaque formation, it transfers the chlamidia into the cells lining the vessel thus starting an inflammatory response.
• The authors even suggest that CAD may be somewhat contagious because if you get respiratory chlamidia, you can end up with CAD.

Science articles

• They talk about the correlation of chlamidia and gum disease with CAD. It may be that this correlation is not causation.
• It could also be that chlamidia can start a molecular mimicry problem that attacks the endothelial cells.
  • As in, it generates a peptide that looks like a host peptide and thus starts an auotinflammatory response.

Properties of cardiac muscle fibers

• Shorter and fatter than skeletal muscle.
• Anchored to fibrous network in myocardium.
• Do not function as individual units but as a functional syncytium.
• The ventricles form one functional syncytium, the atria form another.
• Remember that the coordination is generated from good cell-cell communication between the gap junctions and the interdigitation.
• Cardiac muscle is very rich in mitochondria so that they have a constant source of ATP.

Electrical characterisitcs of the heart

• The heart can beat with no intervation.
• If the heart is otherwise healthy, you can cut the nerves and heart will keep on beating.
• If you take it out of the body (and maintain the temperature) it will start beating faster. The innervation actually slows down the heart beat.
• Thus, when you take the heart out, you put it on ice.
• The stimulus for beating comes from the pacemaker cell.
• There are multiple cells that can do this, but the one that fires first wins. The others can take over if need be.
• These are found in the SA node.
• The autonomic nervous system feeds into the node to control the rhymicity of the cell.
• The parasympathetic system slows the heart rate whereas the sympathetic nervous system increases the heart rate.
• Normally the parasympathetic system dominates.
• First, the electrical activity spreads from the SA node over the atrium, then it reconvenes at the AV node, then it spreads down to the tip of the heart via the Purkinje fibers.

Pacemaker cells

• Action potentials through nerves travel really fast--much faster than through cardiac muscle.
• All cells of the body have a spontaneous potential difference measured in volts.
  • The outside of the cell is always greater in charge, so the inside is always negative.
• Each tissue type has different resting potentials.
  • In pacemaker cells it is -40 millivolts (that is, -40 inside compared to outside).
• -40 mV is the threshold in pacemaker cells.
• After an action potential, the potential drops below threshold and then starts leaking back toward threshold such that another action potential is fired.
• The depolarization drift comes from the flow of ions through the desmosomes.
• Upon reaching threshold, Ca++ channels (voltage sensitive) open up and Ca++ rushes into the pacemaker cells. This happens very quickly and drives the potential inside the pacemaker cell well into the positive range.
• Then polarization is maintained by slow calcium channels that open late and stay open for a longer time.
• Then a nearly neutral level of polarization is maintained as potassium channels are opened such that Ca++ is coming in and K+ is going out.
• Then repolarization is achieved through the previously mentioned potassium channels remaining open while the slow calcium channels close, thus allowing potassium to continue out of the cell driving the potential back to the negatives.
• How often this whole process occurs determines how often the heart beats.
• Normal heart beat is about 70 bpm (3 billion action potentials in 70 years).

Regulation of pacemaker activity

• The autorythmicity is about 90-100.
• Neurotransmitters slow the heart rate (those from the parasympathetic system).
• These NTs cause an increased permiability to potassium which drives the refractory polarization to a lower (more negative) number such that it will take a longer time for enough Na+ to leak in to reach threshold.
• The sympathic system affects both the Ca++ channels (makes them faster) and the repolarization.... we'll come back to it.

Alternate pacemakers

• If you lose all the cells in the SA node, the AV node can take over.
• You can survive without the atria working but you must have functional ventricles.
• There are ventricle pacemakers that can take over if you lose the AV node, too, but they are pretty slow (30 bpm) so you're in trouble.

If the SA node is lost, do the atria still contract?
Our study group doesn't think so.  Think back to the loss of the p wave.

• We'll finish the heart next week.

• stopped here on 02/10/10.
• started here on 02/15/10.

Electrical activation of the heart

• The action potentials that are generated at the SA node travel along the conduction system and excited the cardiac muscle fibers.
• The cardiac aps last hundreds of times longer than a typical nerve action potential.
• Contractile fibers have resting membrane potentials of about -90mV.
• In skeletal muscle, you can get tetanus by stimulating the muscle even at the height of the contraction.
• But in cardiac muscle, tetanus doesn't occur because you cannot restimulate during contraction because the refractory period lasts the entire time of the contraction period.

The specifics of contraction

• Three types of channels: sodium, then ...?
• There is a spike from -90 to +20, then a plateau, then a repolarization.
• Sodium is moving into the cells, calcium is moving in, and potassium is moving out.
• The sodium channel / movement is extremely rapid.
• The potassium channel closes almost simultaneously with the sodium channel.
• Long-qt syndrome, the first symptom is death. Stimulation of heart is arrested because of a sodium channel gain of function or a potassium channel loss of function.

EKG or ECG

• We're looking at the waves of electrical activity caused by all the firing.
• There are three waves: P, QRS, and T.
• We're not measuring contractions in the heart, we're measuring electrical activity.
• First the SA node fires, the potential is carried across the atria (the P wave), then to the AV node and down the bundle branches (some complex wave called the QRS wave), then the potential spreads up the ventricles (the QRS wave), and then relaxation of the ventricles (the T wave).
• When the P wave is larger (wider) than a standard, then the atrial muscle area is larger than normal.
  • This is likely to be caused by a leaky mitral valve.
• An absent P wave can occur when the SA node has failed and the pace makers in the AV node have taken over.
• When the R wave is larger than normal, the ventricles are larger than normal.
  • The primary cause of an enlarged R wave is hypertrophy because the ventricles are having to pump harder and are thus growing in size.
• A junctional rhythm marks the loss of the SA node. You can tell because the P wave is completely gone and there are fewer heart beats (because the AV node generates fewer beats per minute than the SA node).
• A heart block pattern is indicated by P waves not being conducted through the AV node.
  • This will result in more P waves than QRS complexes.
  • This indicates that the pacemakers aren't working and there is some blockage of the electrical signal from getting beyond the AV node.
• Ventricular fibrillation:
  • Here the electrical activity makes no sense.
  • This occurs because multiple pacemakers are firing.
  • Often seen in MIs.

Mechanical activity of the heart

• Overview:
  • Atria fill with blood via the veins.
  • Blood begins to flow into the ventricles and this is completed by an atrial contraction.
  • Ventricles contract forcing the AV valves to shut and the semilunar valves to open and expulsion of blood into the artery.
  • Ventricles relax, pressure goes down and the semi-lunar valve closes preventing backflow of blood.
• When we talk about systole and diastole (contraction and relaxation) we are talking about ventricles.
• Find circular figure in book, go over it.
• Figure of everything.

Cardiac output

• The cardiac output (CO) is a measure of the amount of blood pumped out of one side of the heart in one minute.
  • Remember, however, that both ventricles have to pump the same volume of blood.
• CO = heart rate x stroke volumen
• Normal: 6000ml / minu = 75 beats / min x 80 ml / beat.
• This can be increased 3 fold upon need.
• Both heart rate and stroke volume are the function of several different parameters.

Stroke volume

• Remember that there is about 50ml left in the left ventricle at the end of the stroke.
• At rest, you pump out of the ventricle 60% of the blood that was in the ventricle at the end of relaxation.
• SV = end diastolic volume - end systolic volume.
• End systolic volume is the volume of blood left in the ventricle after the contraction.
• End diastolic volume is the amount of blood in the ventricle after diastole (relaxation).
• Frank-Starling law of the heart:
  • There is a proportional relationship between the diastolic volume of the heart and the stroke volume."
  • That is, the heart will pump whatever it receives within limits.

• Preload:
  • Myocytes are set up such that they can always pump whatever they get.
  • They are normally sitting relaxed at a length shorter than their optimal contraction length, such that when you add more blood, they are stretched toward their optimal contraction position.
  • So, a healthy heart can pump all that it is given (within normal bounds).
  • Things that can increase preload:
    • The speed of the venus return can increase cardiact output.
    • An increase blood volume.
    • Increase in heart rate.
    • Cellular hypertrophy: each cardiomyocyte generates more contractile proteins when there is extra strain on the cells. Note that myocytes do not divide!
      • Occurs in athletes, when there are blockages, and when you have heart defects like a messed up valve.

• End systolic volume (contractility):
  • Can be increased by more sympathetic stimulation.
    • Epi, norepi: these increase calcium entry into cells which allow for increased cross-bridge formation and thus generate more contractility.
  • Can be increased through chemicals and hormones.
    • Glucagon and thyroxine increase contractility over a very long time period.
    • Acidosis, increased extracellular K+, and calcium channel blockers can all decrease contractility of the heart.
      • Calcium channel blockers are used to decrease blood pressure.
  • Parasympathetic can decrease contractility and heart rate.
    • Acetylcholine decreases contractility by increase parasympathetic signaling.

• Afterload
  • This is the pressure against which the ventricles must push to open the semilunar valves and to push 60% of the blood volume into the aorta.
  • This can be affected by hypertension, blood volume, and blockages in the vessels.

Neural regulation of heart rate

• The cardiac center of the medulla oblongata receives input from several parts and yields output to the heart which can increase or decrease the heart rate.
• The inputs:
  • The higher brain centers: getting upset, etc.
  • The sensory receptors: proprioceptors, chemoreceptors (oxygen detectors, especially), and baroreceptors.
    • Baroreceptors monitor blood pressure. Baroreceptors become resistant to low pressure signals, however, over time
• The outputs:
  • The spontaneous depolarization at the SA and AV node can be increased or decreased.
  • You can have increased contractility which will increase stroke volume.

• Both contractility and heart rate have to be increased at the same time or you'll have a back up in the circuit.
• At rest, the parasympathetic system is the most important because it brings the heart rate down.
• Effect of NTs on pacemaker cells:
  • Parasympathetic: makes cells more permeable to K+ which increases hyperpolarization.
  • Sympathetic: opens Ca++ channels which increases the Ca++ and reduces repolarization. This means that it is easier to reach threshold.

Hormones

• Epinepherine and thyroxine increase heart rate and contractility.
• Epinepherine as a hormone:
  • Causes vasodilation of skeletal muscle, so that you can run away from the bad guy!
  • Causes vasoconstriction in internal organs and skin, which shunts blood to the heart and brain and skeletal muscles.
  • Causes increased glycogenolysis in liver and muscle, which generates more energy sources for the brain and heart.
  • Causes increased lypolysis in adipose tissue.

• Thyroxine
  • Effects are slow; work on a weekly or monthly period.
  • Over a long period of time can increase heart rate.
  • Increases metabolism and body temperature.
  • Increase oxygenation of blood by increasing breathing rate and RBC production.
  • Increases lipid turnover to liberate lipids which can be converted to energy.
  • Increases protein synthesis.
  • Stimulates GH secretion.

Heart rate, physical changes

• Age
  • Fetal is much higher.
• Gender (25 yos with ideal weight):
  • Women faster than men, fetus much faster than women.
• Exercise increases HR b/c of sympathetic stimulation.
• Temperature decreases HR by slowing rate of depolarization of pacemaker cells.

Cardiac output and energy consumption

• We want the heart to use as little energy (oxygen consumption) as possible to pump blood.

• stopped here on 02/15/10.
• started here on 02/17/10.

• Read through the CF papers on our own because she'll be talking about the ethics.
  • They are long, skip the methods and the histology.
  • You really need to read the introduction and the discussion, and have a look at the results.

Heart - diseases and treatments

Terms

• Tachycardia is a fast heart rate, over 100 beats per minute.
  • Above 170, it is hard for the heart to fill between beats.
• Bradycardia: slow heart rate, lower than 60 beats / minute.
• Congestive heart failure is the inability to generate a normal cardiac output.
  • Most common is left side failure.
  • Causes include MI (with damage), hypertension,

Congestive heart failure

• Adema often arises.
• Pulmonary congestion occurs if the left side fails because there is a backup in the lungs.

MI

• 1.5 million in US.
• 1/3 die immediately, of those that do survive, 1/2 die within a year.
• If patient survives initial lack of oxygen, the risk of reperfusion injury is high.
  • This is not confined to heart, can also occur with kidney diseases.
  • When blood is limited for a bit of time and then it flows back in, an inflammatory response is raised.
  • Lymphocytes and other inflammatory cells are attracted to the area.
  • Cytokines and other chemicals are released.
  • The chemicals are cytotoxic (particularly in the heart) and therefore cause further tissue damage.
  • Cardiac contractility is depressed.

Treatments for heart problems

• Ventricular defibrillators
• Pacemakers
• Nitroglycerine - vasodilator of coronary vessels.
• Cholesterol lower agents
• Beta blockers - block sympathetic nervous system - slow HR and force of contraction.
• Ca+ channel blockers - mainly on vessels, reduces resistance by opening vessels
• ACE inhibitors - reduce cardiac afterload
• Diuretics - remove excess water
• Digitalis (a drug) - slows HR, conserves energy.
  • Used as a poison in the old days.

Ventricular defibrillators

• Devices which shock the heart in case of ventricular fibrillation.
• Used if likely that damaged heart will go into uncontrolled electrical activity.
• Shock the hear tot stTop all electrical activity to it can "reset".
• First used in the 80s.
• Early defibrillators couldn't distinguish between arrhythmia from a rapid heartbeat coming from exercise.
• Current versions are much smaller.

Heart failure

• 100k people in heart failure each year.
• 2.2k donor hearts.
• Shortage.

Article: New directions in cardiac transplantation

• Summary of > 30 years of clinical practical and some of the new directions that are contributing to ...
• Read the first half of the article.
• They studied the mortality in the 90 days post-op and showed that transplants mortality rates are decreasing.
• They also addressed who are good candidates for hearts:
  • In the first two decades of heart transplants we didn't consider people with high age, diabetes, kidney or liver disease, HIV, or hepatitis.
• Ethical issues:
  • Who should get the heart and who shouldn't? Age, weight?
  • Should incurable illnesses be transplanted?
  • Should elderly patients get young hearts because it will likely outlast the recipient.
• Interesting scientific notes:
  • Introduced the idea of using a ventricular assist device, which has increased survival both by keeping the patient alive until a donor is found and aiding in survival after transplantation.
  • In infants, you don't have to match the ABO blood groups because they have low levels of anti-A and anti-B antibodies. They also have an incompetent complement system.

Artificial hearts

• An early approach cut away some of the skeletal muscle and put in a pacemaker cell. But skeletal muscle is not meant to be flexed over and over.
• In 1982, Jarvik made the first artificial heart.
  • It was attached to the atria and there was basically just ventricular.
  • Barney Clark was the first patient. He was a dentist. He lived 112 days.
  • Another patient lived 2 years, in a hospital room hooked up to a loud machine.
  • Problems included blood clots and infections.
  • This was actually banned in 1990.

The next generation of artificial hearts

• Now we use left ventricle assist device.
  • 80% of heart failures are in the LV, hence it assists the LV.
• These are connected to the bottom of the ventricle and pump the blood up into the aorta.
• The grapefruit sized machine is anchored just below the diaphragm.
• Now there is lots of external stuff.
• There is still a risk of infection.
• Blood clotting is controlled by using pig tissues instead of artificial tissues.
• Biggest problem with the HeartMate is the size.
• So the next, next generation has a 10K rpm rotor that pushes blood into the aorta constantly.
  • But with this, you have damage to blood cells and vessels and therefore clotting.
  • This will generate no beat and we thought this would be an issue but it isn't.
  • The internal / external interface is still a problem for infections and such. We're working on electrical field transfer of power.
  • One pt. has made a transatlantic trip and lived 2 years.

• • In January of 2010, the HeartMate II was approved for long-term treatment of heart failure.
  • It is a rotor pump.
  • < 1 lb.
  • 1.5 x 2.5 inches, so it can be used on children.

Theoretical combination therapy

• Assist devices along with other therapies.
  • Sometimes the heart can repair itself to the point that the LVAD can be removed.
• Other therapies may include:
  • Beta agonists like clenbuterol which would cause the cardiac cells to hypertrophy (through increases stimulation by the sympathetic system).
  • Agents that stimulate coronary vessel re-growth.
• The goal is to allow the heart to repair itself.

Space aged vision

• The whole thing weighs two pounds and is completely self contained.
• Blood clots are still an issue.
• Powered through a transcutaneous energy transmission system.
• First recipient lived for 5 months and died of a stroke.

Indianapolis Star, 2004

• This is about a totally artificial heart.
• FDA approved artificial hearts as a temporary measure for heart failure patients.
• Some patients have serious bleeding problems and 22% had infections.

• moved on to Circulatory lectures on 02/17/10.