September 1, 2006

The Heart of the Matter: Electrical Disorganization spells D-E-A-T-H


By Dr. Howard Glicksman

Observations from the Peanut Gallery
I’m driving down the highway with my precocious ten year-old daughter in the front seat. She notices that when I push down on the accelerator the car speeds up, and when I press my foot on the brake pedal, it starts to slow down. She watches this activity for a short time before she just blurts out the question “Daddy, why does the car go faster when you push down on the right pedal and then slow down when you push down on the left one?”

I smile to myself, wondering how difficult it’s going to be to get out of this Q&A session with my budding genius since I have a lot of things on my mind. But being a parent that tries to foster knowledge and imaginative thought in my children, I decide to at least give her an answer that I hope will satisfy her curiosity and leave me to my own thoughts.

“Oh, Kristina, that’s a good question. Actually, when I push the right pedal I send the car a message that tells it to go faster and when I push the left pedal I send it a message to tell it to slow down. It’s just like when I tell you to run faster when you’re playing soccer, and you do, or I tell you to slow down when you are running in the house, and you do.”

“Oh, I see” she says. But a few seconds later there’s this puzzled look on her face and you can see her mind at work as she begins to formulate another question based on what you have just told her. “But Daddy, when you tell me to speed up or slow down, I know that it’s me who is doing the speeding up and slowing down and I know how I do it. How does the car actually speed up and slow down when you send it the message?”

So now what is supposed to be a leisurely drive that allows me to think about some important issues is turning out to be a chance to engage the young mind of my daughter. Only a detailed description of the physics of motion, the potential energy in fossil fuels, and auto mechanics, will serve to satisfy her curiosity.

Having completed my parental task I settle in to do some critical thinking. Then a tap on my shoulder and Kristina asks “Daddy, since you’re a doctor, can you tell me why when I run or get scared I can feel my heart beat harder and faster but when I’m not I don’t even feel it? Does my heart have its own accelerator and brake pedals like the car? Did Uncle Chuck’s pedals break last month when he almost died because, like you told me then, his heart was at first going too fast and then too slow, so they put that little box in his chest?”

Out of the Mouths of Babes
Kristina’s questions reflect the universal human desire to know and understand the truth; to go beyond the superficial aspect of mere observation and to dig down deeper to find out the mechanism behind what makes something work. The car speeds up and slows down when I press the accelerator and brake respectively. This observation led her to question what these pedals actually do in the car to accomplish these effects. Only an answer that explains the mechanisms involved and how they achieve their effects is sufficient for the human intellect.

Yet Kristina also recognized that my analogy was imperfect because even though in some way I “tell” the car to speed up or slow down by pressing the accelerator or the brake, it is not the same when applied to telling her to speed up or slow down. She now knows that when I step on those pedals that that they access a mechanism that is part of the car. But when I tell her to speed up or slow down she is the intelligent agent telling her body to indirectly listen to my command.

But her inquisitive mind immediately connects the speeding up and slowing down with what has recently happened to her uncle’s heart. She realizes that when she runs or gets scared, she can feel her heart beating harder and faster and she sees the connection between what she experiences and what the accelerator does for the car. I’ve just told her how and why the car responds to the accelerator and the brake and her logical mind now wonders how her own heart does the same thing in response to her activity.

But just as I had to prepare her for understanding how the car works by explaining the basic physics of motion and the chemistry of fossil fuels; before she can understand how the heartbeat comes about and can be moderated by activity, Kristina must first have a basic understanding of cell electrophysiology. That is exactly where we are going from here. But don’t panic. If you have no problem understanding that the body needs certain chemicals; like sodium (Na), potassium (K) and calcium (Ca), then you’ll be able to understand how the heartbeat works and more importantly, how things can easily go wrong very quickly and result in disorders of rhythm and even sudden death.

We are about to enter the credibility zone, where a thorough understanding of how easy it is for heart electrophysiology to fail by disease and dysfunction, often resulting in death, is sure to make you wonder how anyone could believe that this intricate system, so important for human life, but itself, so dependent on all of the other metabolic and organ systems of the body, could have indeed come into being without an intellect at work.

Certainly this scientific information will teach you what really needs to be explained by evolutionary biologists before their claims should be accepted.

The Heart of the Matter
Before trying to tackle how the heartbeat is generated and can be moderated by the nervous system, I’d like to gently remind you of some basic human physiology. Each of our cells requires oxygen, water and nutrients for survival. They obtain this from the blood which is circulated throughout the body by the heart. One of the commonest causes of death is what is known as sudden cardiac death. This usually is erroneously described in the media as someone having had a massive heart attack and dying. Medical science has shown that most of the time there is no evidence for there having been recent heart muscle damage (which is what a heart attack means). So what caused their death? Keep reading to learn more about how sophisticated our hearts are and how easily they can dysfunction and cause death; in this case, sudden death. Let’s start with some basics about the heart and then we’ll look at the heartbeat.

The Circulatory System
After the blood has been pumped from the left side of the heart through the main artery (aorta), coursing its way through ever decreasing caliber vessels to the capillaries in the tissues and it has given off some of its supply of nutrients and oxygen, it returns through ever increasing caliber veins to the right side of the heart. As it flows through the abdominal cavity, it picks up a new supply of nutrients. From the right side of the heart the blood is propelled to the lungs where it picks up a new supply of oxygen. Then the blood returns to the left side of the heart where it is pumped through the aorta and the whole cycle begins again.
www.imcpl.org/kids/guides/health/circulatorysystem.html

Heart Anatomy
The human heart is a muscular pump that is divided into a right and left side by a wall called the septum. Each side in turn is divided into an antechamber called an atrium and a more muscular chamber called the ventricle. It is the right and left ventricles that do the lion’s share of pumping the blood to the lungs and the tissues respectively.
http://texasheart.org/HIC/Anatomy/Anatomy.cfm

Pumping blood to the lungs and throughout the body requires that the heart be able to generate enough force to counteract barriers to blood flow such as gravity and friction. The heart does this not only by its muscular strength but also by having valves between the atria and the ventricles and in the outflow tracts of each ventricle. This allows the necessary pressure to build up in each chamber and facilitates the release of blood out of the heart with enough force to reach its intended target.
http://texasheart.org/HIC/Anatomy/valves.cfm

Coronary Artery Anatomy
Since the heart itself consists of muscular tissue, it also needs its own supply of nutrients and oxygen. This is provided by the blood that courses through the coronary arteries that turn back over the heart just as the blood exits the left ventricle into the aorta.
http://texasheart.org/HIC/Anatomy/coroanat.cfm

Brief Summary
We now have a muscular pump with internal valves and a septum to make it mechanically efficient. It has its own blood supply so the muscular tissue can receive nutrients and oxygen in order to function. But that’s not enough for the heart to work properly. We need one more piece added to the puzzle. A piece so vital and sensitive that when it dysfunctions the result is often sudden cardiac death; something that happens to about ½ million people per year in America. What we’re talking about is the electrical conducting system that gets the heart pumping in the first place.

Electricity is the Key
Unlike skeletal muscle, which generally starts coordinated contraction under the command of the nervous system, the heart marches to a different drummer of its own making. The nervous system is able to modulate the frequency and strength of the heart beat in relation to the body’s ongoing needs but the impulse that tells the heart to contract is home-grown in the heart automatically.

In order for coordinated heart muscle contraction to take place in proper sequence to allow for adequate heart function the heartbeat is set into motion by the pacemaker cells in the sinoatrial node (SAN) which is located laterally high up in the right atrium very close to superior vena cava. Go to: http://texasheart.org/HIC/Anatomy/conduct.cfm

From the sinoatrial node the impulse spreads to both atria, causing them to contract, and is then sent to the atrioventricular node (AVN). This part of the conduction system is generally the only pathway for the impulse to bridge the gap between the atria and the ventricles. The AVN slows the conduction of the impulse message, delaying it by about one-tenth of a second. This slowing of the impulse through the AVN is very important because it allows the atria to fully contract before the message can be sent on to the ventricles. Atrial emptying of blood into the ventricles just before they are to beat (called the pre-systolic kick), allows the heart to function more efficiently and it is known that people who lose this function have reduced exercise tolerance.

It is evident that the ability for the heart to keep sending impulses from the sinoatrial node along the conduction pathway that intersects with the atrioventricular node that allows for the pre-systolic kick and then the coordinated contraction of the ventricles is vital for life. In order to make a judgment about how likely it was that this system came into being simply by the forces of nature without a possibility of intelligent agency, one first must have a basic understanding of how it works at the molecular and cellular levels and more importantly, how easy it is for it to breakdown and cause death pretty quickly.

What is it within cardiac electrophysiology that allows the SAN to, second by second, continuously stimulate the heart into coordinated contraction and then allow it to supply the body with enough blood without misfiring? We’re going to start to answer this question right now by looking at the relationships between the different concentrations of certain chemicals inside and outside certain cells and how their movements result in what we know to be neuromuscular and cardiac function.

I hope you don’t get too nervous because if you just take it very slowly I think you’ll be rewarded with a deeper appreciation of how it is you can sit there and read this column.

But of course, once you realize on what your very life depends, it may scare you too.

Either way, the scientific information laid out for you here will teach you what really needs to be explained by evolutionary biologists.

Cell Basics
All physical life forms, including our own, consists of cells. Each cell is surrounded by a structure called the cell membrane that separates it from the rest of the world and other cells. The cell substance consists largely of water which contains within it dissolved chemicals in specific concentrations in addition to other structures that are needed for cell preservation and function. In essence the cell and life itself is basically organized dust in water.

It is important for the cell to maintain these chemical concentrations within certain limits for its survival. Some of the more common elements that are found in solution inside and outside the cell are chemicals like sodium (Na), potassium (K) and calcium (Ca). You may recall for example that it is very important that we take in enough table salt, (also known as sodium chloride (NaCl)), in order to stay alive. But when NaCl enters the body it does not stay in crystalline form like we see with table salt. It becomes dissolved in the water contained inside and outside the cells and separates out as sodium ions (Na+) and chloride ions (Cl-). The same also goes for potassium ions (K+) and calcium ions (Ca++). The relative concentrations of Na+, K+ and Ca++ inside the cell in comparison to outside the cell (the fluid between the cells and in the bloodstream) are quite different. The concentration of Na+ outside the cell is over 7X the concentration of it in the cell and the concentration of K+ inside the cell is over 20X the concentration of it outside the cell.

Calcium is present in very small amounts in the cell, over 3,000X less than in the bloodstream and the fluid that surrounds the cells (also known as interstitial fluid).

Most of you have probably had your blood tested at some time and have been told that your sodium, potassium and calcium levels were ok. We don’t test for these chemicals in your blood for no reason at all. If they fall far outside the normal ranges then serious consequences can arise that affect the heartbeat and neuromuscular function. So let’s look a bit deeper and try to understand why it is important, not only for the cell but also the fluid outside of the cell to maintain its proper concentration of Na+, K+ and Ca++ .

Cell Electrophysiology Made Simple:
Lesson #1
As already mentioned, the concentration of Na+, K+ and Ca++ are vastly different inside the cell as compared to outside it. This can only occur because the cell has a cell membrane that separates it from the outside world and allows it to maintain these different concentrations for its survival. The cell accomplishes this by employing specific ion pumps which use the energy it unpacks from glucose in the presence of oxygen to pump these ions where they need to be.

Therefore, as many of my previous articles have documented, when cells lack enough sugar or oxygen, these ion pumps, and other structures, begin to malfunction and the cell dies. Some cells in the body can die without affecting our survival, but when this takes place in the vital nerve center called the brainstem, which tells us to breathe, controls our circulation, and allows us to be conscious, then we die. It’s as simple as that.

Lesson #2
Even though the cell membrane keeps each of the fluids inside and outside the cells intact with their proper ion concentrations in respect to Na+. K+, and Ca++ ions, there exists within that membrane certain proteins that act as pores or ion channels which under certain circumstances allow ions to travel across this membrane. These ion channels are each specific and therefore there exists ones for Na+, K+ and Ca++. When these ion channels open there is a tendency for each positive ion (Na+, K+ or Ca++) to try to cross the membrane barrier down its concentration gradient, like water trying to flow from high to low ground. In other words, given the chance, when the K+ ion channels open, K+ is likely to try to come out of the intracellular fluid and into the extracellular fluid because its concentration in the cell is much higher than outside the cell. Similarly, if the Na+ or Ca++ ion channels open then Na+ and Ca++ ions are going to enter the cell from the extracellular fluid since their concentrations are much higher outside than inside the cell. See: http://www.chemsoc.org/ExemplarChem/entries/2002/Tim_Smith/

Lesson #3
At rest, depending on the cell type, each ion channel has a different degree of efficiency with regard to allowing its specific ion (Na+, K+, Ca++) to move along its concentration gradient (for K+ out of the cell and for Na+ and Ca++ into the cell). Therefore, the plasma membrane has a variable permeability to each of these ions which is dependent on how many of the ion channels are open at a particular time. In fact, at rest, for most cells the plasma membrane is usually between 10 to 100 times more likely to let K+ out of the cell than let Na+ back in and Ca++ ion channels usually aren’t open at cell rest.

Lesson#4
Since at rest, more K+ tends to leak out of the cell through its ion channels than Na+ is able to go back in, there is an overall negative ion balance across the cell membrane. This is known as the resting membrane potential. The actual amount of this difference can be measured and all cells in the body have this resting membrane potential which usually runs between -40 to -90 mV (millivolts). For neurons, skeletal muscle, and the cells of the sinoatrial node it is -70mV, and for ventricular muscle cells it is -90mV.

Emotional Support Break
Now that you understand that all cells in the body have a resting membrane potential with specific ion channels which let ions, like Na+, K+ and Ca++ flow in or out of the cell, we can go on to briefly discuss some of the finer points about neuron and muscle function and then go on to contrast this with cardiac muscle function. Now don’t give up if you’ve come this far. The reward of understanding how it is we are able to survive under the physical and chemical constraints of this world will simply fascinate you and they should make you have a deeper appreciation for the life you lead. For without a firm understanding of how life works, and more importantly, how it dies, how can anyone be able to make an intelligent guess as to its development? After all, without neurons and muscles we would be dead and without the resting membrane potential and the various ion channels, neuron and muscle function would be impossible.

Neuromuscular Electrophysiology Made Simple:
Lesson #1
Nerve and muscle cells are called excitable tissue because when they are adequately stimulated they are able to respond. Nerve cells can be excited by electrical, physical, or chemical means. If you put your right hand in hot water, the heat from it will stimulate a thermal sensor which will send an impulse along a sensory nerve, up the spinal cord and eventually into the sensory cortex on the left side of your brain, telling you that your hand is getting warmer. If the heat builds up and begins to burn your hand a pain sensor will be stimulated and it will let you know that if you keep your hand where it is much longer, not only will you have more pain, but you may have some tissue damage. When your brain, either reflexively or consciously, decides that you‘ve had enough, it will send a message along motor nerves that eventually supply the muscles in your right arm and hand to quickly move your hand out of the water and into an area of safety. But what electrically goes on in the nerve and muscle to make this happen and how does that compare with how heart muscle works, especially since many people die of sudden cardiac arrest, which is usually caused by an electrical disorder of the heart?

Lesson #2
When the thermal sensory cell is stimulated this causes its membrane to start opening some of its Na+ channels and allows Na+ ions to enter. Since more Na+ (positive ions), are entering the cell, this makes the membrane potential become less negative (goes from - 70mV up toward -60 mV). This is the beginning of depolarization since the electrical negativity in the cell is heading toward being positive. The ability for the surrounding Na+ ion channels to open up is not only dependent on this kind of stimulus but also the rising membrane potential as it becomes less and less negative. When the membrane potential reaches a threshold level, usually between about -60mV to -50 mV, an all or nothing phenomenon takes place and suddenly a maximum amount of Na+ ion channels open and lets a flood of Na+ ions into the cell. This causes the polarity of the membrane potential to reverse, going from the initial -70mV to about +40mV. The neuron’s membrane potential is suddenly positive instead of being negative. What a reversal of fortune. But so what ???

Lesson #3
The depolarization wave begins to spread along the nerve cell and is called an action potential. The change in polarity travels as an impulse down the sensory nerve cell on its way to the next neuron in order to pass the message on where it will eventually reach the brain so you can become aware of the situation. As the depolarization wave reaches the end of the nerve cell the change in polarity of the membrane potential, going from negative to positive, signals the Ca++ ion channels to open. The sudden entry of Ca++ ions into the end of the neuron is directly responsible for the release of neurotransmitters to the adjacent nerve cell waiting for the message. The nerve that has passed on the message then is able to repolarize itself, by having the Na+ ion channels close and K+ ion channels open up. With K+ ions exiting and Na+ staying outside again the membrane potential will return to -70mV and all will calm down until stimulation occurs again. For more go to: http://faculty.washington.edu/chudler/ap.html

Lesson #4
The neurotransmitter goes across the space between the cells and opens the Na+ ion channels of the next neuron. This allows it to depolarize, the impulse continues down the neuron, and at the end Ca++ ions enter and causes the intermediate neuron to release its neurotransmitter to the next neuron in the sequence. The process continues until the message reaches the brain where it is integrated and interpreted, ie you realize your hand is getting hot. But how does the motor nerve tell you to move your hand from danger?

Lesson #5
The motor message starts in the brain and travels along the various motor nerves in a similar fashion. Chemical stimulation by neurotransmitter tells Na+ ions to enter the neuron through Na+ ion channels until threshold is reached and full depolarization takes place. The impulse continues along the neuron, opening the Ca++ ion channels causing the release of neurotransmitters on to the next nerve in succession.

Lesson#6
When the impulse from the final motor neuron reaches the muscle cell, the release of a specific neurotransmitter called acetylcholine results in the opening of positive ion channels on the muscle cell membrane. When the threshold is met, full depolarization causes the release of internally stored Ca++ ions which causes the muscle proteins in the cell to bind together and contract. Eventually the storage unit in the muscle cell pumps back the Ca++ ions, the muscle proteins detach from each other, contraction resolves, and relaxation of the muscle cell takes place and awaits the next call to perform. For more go to: http://www.people.eku.edu/ritchisong/301notes2.htm and also try: http://www.embl-heidelberg.de/CellBiophys/LocalProbes/motorproteins/myosin.html

OK, take a break and review. Now we’re going to look specifically at the heart.

Neuromuscular vs Cardiac Tissue Function
Lesson #1
There are many similarities between how neuromuscular tissue and cardiac tissue depolarize, resulting in an action potential, and then coordinated muscle contraction. However the differences are very important for our survival. Whereas neuromuscular cells depolarize quickly and have a short action potential, usually about 1-2 milliseconds, cardiac tissue has a more prolonged action potential which usually is between 150-300 milliseconds, over 100 times longer. Since the duration of heart muscle contraction is almost as long as the action potential, this means that normally no new impulse will be available to try to make a part of the heart muscle contract until it has finished its beat.

It is vital that the entire heart muscle be able to complete one coordinated contraction and then be able to fully relax to allow proper filling between beats. If a region of ventricular muscle were to have a significant change in its velocity of depolarization it could bring on disorganized muscle activity known as fibrillation which would be deadly. But what is the mechanism behind why cardiac tissue depolarizes so slowly?

Lesson #2
As we mentioned above, neurons and skeletal muscle cells depolarize by opening up Na+ ion channels that allow quick entry of Na+ ions. But although cardiac tissue begins its depolarization through the stimulation of Na+ ion channels as well, this is very short lived and gives way to Ca++ ion channels which allow Ca++ ions to enter the cell but more slowly. This is why it takes so long for cardiac tissue to depolarize and the action potential lasts so long as compared to the neuromuscular system. Depolarization in cardiac tissue is dependent on the slow movement of Ca++ ions into the cell in contrast to the fast movement of Na+ ions into the cells of the neuromuscular system.

Lesson #3
Here’s another important difference between how skeletal muscle and cardiac muscle work. As mentioned above, when skeletal muscle is stimulated to contract, it results from the release of Ca++ ions from storage units within the muscle cell that allow its contractile proteins to interact and contraction to take place. Cardiac muscle contraction is dependent on, not only the release of Ca++ ions from within its storage units, but also the entry of Ca++ ions directly into the cell through the Ca++ ion channels that takes place during depolarization. We will see later that this is how the contractility of heart muscle can be modulated by the nervous system in appropriate circumstances.

Lesson #4
Whereas the action potential of the neuron has its effect in the neuromuscular system by having the neuron release a neurotransmitter that stimulates or suppresses the next neuron or muscle in line, cardiac tissue is connected by way of specialized connections called gap junctions which allow for intimate ionic transfer that facilitates the rapid spread of the depolarizing wave throughout the conducting system and the atria and ventricles

Now we’re going to look at the differences between the pacemaker cells and the other muscle cells of the heart that allow them to control the heartbeat. We’re getting closer to answering Kristina’s question.

Atrial/Ventricular Muscle vs Sinoatrial Node function
Lesson #1
Like neuromuscular tissue, cardiac tissue repolarizes itself by opening K+ ion channels to allow K+ ions to flow out of the cell and make the membrane potential go from positive back to negative. As mentioned above, in general, neuromuscular, atrial, and ventricular muscle must be stimulated to start depolarization. This means that when the opening of the K+ ion channels and exit of K+ ions has brought these cells back to their normal resting membrane potential, it is maintained until it is stimulated to depolarize again.

Lesson #2
Not so for the sinoatrial node. Its unique set-up of ion channels work differently than the ones in the atria and ventricles. After the sinoatrial node depolarizes and passes the message onto the atria, the Ca++ ion channels slowly close more and more, limiting the entry of Ca++ ions. At the same time, K+ ion channels open up more and more, allowing K+ ions to leave the cell. The net effect of these two activities is for the sinoatrial node cells to start to repolarize (go from positive back to negative). But instead of stopping at the resting membrane level of -70mV, the cell is able to overshoot it and become hyperpolarized (more negative than -70mV). This hyperpolarized state stimulates a specialized Na+ ion channel to open and allow Na+ ions to slowly enter the cell again. This is the Na+ ion channel that accounts for the pacemaker function of the sinoatrial node. The cell continues to spontaneously depolarize with the slow entry of these Na+ ions and eventually causes the Ca++ ion channels to open as well. The Na+ ion channels close and the slowly depolarizing Ca++ ion channels take over until full depolarization takes place and an impulse is generated which results in a heartbeat.

After the depolarization wave is sent on to the atria, the Ca++ ion channels slowly close and the K+ ion channels open again resulting once again in hyperpolarization. This in turn stimulates the unique Na+ ion channels to begin depolarization and then the whole process happens again, and again, and again, and again. Voila: automatic pacing; we now have a continuous heartbeat.

Lesson #3
Many other cells in the heart have the natural ability for automaticity, or pacing the heart. Cells in the atria, AVN, and the conduction system near the ventricles (Purkinje fibers) are also able to spontaneously depolarize like the sinoatrial node to produce impulses that result in ventricular contraction. However the sinoatrial node has an intrinsic rate of 60-100 beats/min while the AVN is set at 40-60 beats and the Purkinje system at 15-40 beats/min. Can you see how this could be effected?

Clearly, these other pacemaker cells that are lower in the hierarchy of heartbeat function must either have a lower membrane potential after repolarization and/or a slower entry of Na+ ions at the beginning of the depolarization process in order for them to have slower impulse formation.

In normal circumstances it is the sinoatrial node that drives the heart since when it sends its impulse it depolarizes the atria, the AVN and the Purkinje system before they can spontaneously depolarize on their own. This will become important when we look at arrhythmias. For more see: http://en.wikipedia.org/wiki/Cardiac_action_potential

Fast and Slow and Staying Alive
But now we get to see how all of this plays out in real life. Don’t forget we said before that although the nervous system doesn’t initiate the heartbeat it is capable of modulating it when the need arises: like when trying to catch prey or evade predators. When you step on the accelerator or the brake to speed up or slow down you have a pretty good idea of what’s going on in the car. So when your heart speeds up or slows down, how exactly does this happen? It would seem to be important for survival that the heart would start beating harder and faster when you need it to and relax and slow down to preserve energy when you don’t.

NeoDarwinism and Macroevolution Check-up
The main premise of these articles is to demonstrate the illogical scientific position of evolutionary biologists to affirm that life has come into being solely by the forces of nature: natural selection acting on random variation without any possibility of intelligent agency: solely by trying to explain how a given biomolecule in a metabolic pathway came into being without generally considering, not only how and when the other necessary parts of the pathway came on the scene, but also the pathway’s ability to allow for survival. For the presence of parts should not assume function and the presence of function should not assume survival capacity.

NeoDarwinian explanations of how life came about always seem to involve only one molecular or microscopic component within a more complex system, or one organ system within a life form which is dependent on many others for survival. It seems to me that they miss the forest from the trees. For no one would propose to show how a car came into being by simply discussing the development of the carburetor without at the same time referring to the gas tank and the fuel pump, or the fuel system independent of the body, the chassis, the transmission, and the cooling and lubrication systems. The same applies to life. Once you understand the mechanisms that bring on death, causing the inability to reproduce, then you immediately see how incomplete and facile is the dogma of macroevolution for Neodarwinian evolutionary biologists.

Fast and Slow and Staying Alive: Redux
When we step on the accelerator we know that more gas goes into the engine and with combustion ends up transferring more energy to the drive train resulting in the wheels turning faster and the car moving faster. When we step on the brake we know that this makes the brake pads press against the wheel drums and the resulting friction slows down the car, assuming that you’ve taken your foot off the accelerator as well. Well now we come to the point of explaining how the body is able to speed up and slow down the heart when it needs to for functional reasons.

N.B.A. and the Heart
Remember the controversy that arose many years ago when several young basketball players in college and the N.B.A. were passing out or dying on the court from sudden cardiac death? You may recall that most of them had already been diagnosed with a particular heart rhythm problem and had been put on medication that was designed to try to prevent this from happening. Unfortunately, one of the side-effects of that medication is not only to slow the heart but also to prevent it from going too fast during activity. Consequently, since they needed all the heart pumping power they could get in order to be meet the peak performance needed for athletic competition, for some of them there was a question of whether they were possibly avoiding some of their medication dose in order to be able to play up to par while at the same time leaving themselves more open for a life-threatening arrhythmia.

This medication was a sympathetic blocking agent that biochemically disrupted the “flight or fight” cardiac response to stress and exercise. The sympathetic and parasympathetic nervous systems, make up what is called the autonomic nervous system that automatically controls many homeostatic mechanisms in the body. It controls the smooth muscles around the intestines and the blood vessels and therefore automatically affects digestion and blood flow and pressure. It has many other functions including controlling heart rate as well. http://faculty.washington.edu/chudler/auto.html

The sympathetic system makes the heart pump harder and faster in times of stress and exercise and the parasympathetic system slows it down and relaxes it. The sympathetic nervous system has neurotransmitters called norepinephrine and epinephrine and the parasympathetic system uses the neurotransmitter acetylcholine. The question now becomes exactly how these biomolecules are able to affect the heart to make it pump either harder and faster, or softer and slower.

Thinking Caps Please
Maybe we can try to figure it out on our own now that we know how the heart works. After all if we were asked to figure out how a car could slow down or stop besides taking the foot off the accelerator or putting on the brake, we know that any clog or dysfunction of the fuel pump or carburetor, or total loss of fuel would do the trick; so would smashing it into a tree or a large building; and so would a critical drop in oil pressure or loss of fluid in the cooling system.

Review how the sinoatrial node and atrial and ventricular contraction takes place and the factors involved. Can you see where a change in any of these critical steps could result in a change in the speed or strength of the heartbeat?

Answer
The heart rate would seem to be dependent on these factors for the sinoatrial node:

  1. how quickly Na+ ions enter the Na+ ion channels to bring it down to the threshold,
  2. how fast Ca++ ions enter the Ca++ ion channels to allow for depolarization, and
  3. how fast K+ ions leave the cell via the K+ ion channels causing hyperpolarization

The force of contraction is known to be directly related to the degree of Ca++ ion entry into the atrial and ventricular muscle cells.

Therefore, the combination of either slowing the flow of ions through the Na+ or Ca++ ion channels, and allowing more ions through the K+ ion channels for more hyperpolarization would seem to have the net effect of slowing the heart rate and making the heart pump less vigorously. Studies seem to show that acetylcholine from the parasympathetic system causes a combination of all of these effects when it attaches itself to receptors on these ion channels.

It is thought that the sympathetic system, through its neurotransmitters, norepinephrine and epinephrine, causes the opposite effect through indirect pathways. Thus, when the basketball stars were given a sympathetic blocker that prevented the natural effect of making the heart speed up and pump harder in order to be able to compete athletically, they found that they couldn’t perform up to their usual level. To be sure, with increased activity, the sympathetic system sent the message along to the heart, but the medication prevented the neurotransmitters from giving the heart the message and so, although the athlete was trying to perform at a professional level, his heart wouldn’t let him. For more detailed information read pages 1-6 from the link: http://gosh.gmxhome.de/work/e-collection/HEART_San_tech_rep_Apr04.pdf

Kristina’s Question Answered

“But Daddy, where did all of these parts, like the different ion channels, come from, and how did they come together? How do they know to make my heart work ok? And what about Uncle Chuck; did his heart forget how to work right? Is that why he almost died?”

“Yes Kristina, those are good questions and I suppose there are teachers in your school who will tell you that these parts just came together by the power of nature. But after we look at what happened to Uncle Chuck I hope you’ll be able to see that each of these parts are needed and must be in perfect working order for us to live and therefore saying that nature made it happen without a further detailed explanation shouldn’t be good enough.

What About Uncle Chuck?
Cardiac Output and Heart Rate
Does the heart rate really matter with respect to our survival? All experience tells us that in order for the body to be able to function adequately for survival it needs the heart to be able to pump enough blood throughout the body to meet its metabolic needs at a given moment. That means that at rest when your muscles are relaxed and not doing any strenuous work, there is a minimum amount of energy required by the body to maintain itself and the heart must be able to pump enough blood to match that metabolic need. Similarly, when one of our hominid ancestors was very active in pursuit of prey, or evasion of being preyed upon, his heart would have had to maximize its pumping ability in order to meet the energy needs of his body or else he would be at great risk of starving to death and being eaten himself. The study of heart function is not just an exercise in intellectual abstraction.

The cardiac output of the heart is dependent upon not only how much blood is ejected from the left ventricle per beat of the heart, but also the heart rate. Since there is a minimum amount of energy that the body needs for survival during rest or activity and there is a limit to how much blood can be released from the heart after each contraction during rest or activity, there also must necessarily be a lower limit for the heart rate below which survival would have been impossible for our hominid ancestors. Generally speaking, experience tells us that if the heart rate drops much below 50 beats/min at rest most people will feel very tired and weak. They will also find that on attempting to do any sort of activity they will often feel short and breath and dizzy and they’ll have to immediately stop what they’re doing and sit or lie down.

But don’t forget about what we said above about the N.B.A. players. That lesson tells us that a discussion about heart rate is always relative. Relative to the energy needs of the body for a particular activity. You might need your heart rate to be at least 40 to 50 beats/min while you’re asleep, but what about when you’re hunting or being hunted?

If you can’t get your heart rate up enough to expend the energy needed for the survival of the fittest, then you’re not going to survive are you? But how fast can you allow it to go?

In addition, to be able to pump enough blood throughout the body to meet its energy needs the heart must be able to fill up with an adequate supply of blood prior to each beat. In order to be able to accomplish this it is imperative that the heart be able to fully relax long enough to allow the ventricles to fill up with blood before contraction occurs again. Ever increasing heart rates soon begin to result in less and less time for the heart to fill up adequately and depending on the person and their heart function, when heart rates from 150-200 beats/min start taking place, people will notice a fluttering in their chest usually accompanied by dizziness and shortness of breath and they’ll have to rest or lie down.

So it is evident that for our survival on earth there are definite limits for the heart rate.

The natural pacemaker in the sinoatrial node of your heart, in conjunction with the autonomic nervous system, automatically tells your heart to pump at the right rate for the right set of circumstances. What I have described for you above explains the mechanisms behind how all of this works to keep you alive. But as Kristina’s last set of questions ask; it doesn’t explain how the body knows when to make these necessary adjustments and how these vital controls came into place; and neither does Neodarwinian macroevolution.

A “just so” story of these parts serendipitously coming together with, at the same time, the inherent ability to detect, adjust, and control cardiac output is a fable that only a materialist would be willing to swallow. For Uncle Chuck’s story will show us exactly how easily all of this can go wrong and cause death; the corollary being that the construction of this incredibly complex and sensitive organ system required a lot of fine tuning; a system that experience tells us could only have arisen from intelligent agency.

What About Uncle Chuck?
Poor Protoplasm
Uncle Chuck began to smoke in his late teens. By the time he was in his early 40’s he had developed not only chronic lung disease but also hardening of the coronary arteries which made him have chest pain whenever he tried to do something strenuous. Finally after having two mild heart attacks, which caused heart muscle damage, and then a heart bypass, he convinced himself that it was time to stop. Over the next 20 years he developed high blood pressure, diabetes, and high cholesterol, none of which he to tried to control. Eventually his kidney function worsened and he began to have chest pains again resulting in further heart weakening.

When the heart is unable to circulate the blood well enough to meet the metabolic needs of the body it is said to be in failure. In an attempt to try to keep pumping as well as before, the weakening heart enlarges to try to compensate and in doing so often stretches the base of the mitral valve resulting in it beginning to leak with each heart beat. With Uncle Chuck having a combination of an enlarged and weakened heart due to coronary artery disease, chronic lung disease, poor blood pressure and diabetic control, worsening kidney function, and an inefficient and leaky mitral valve, it was no surprise when Aunt Barb found him lying unconscious and barely breathing on their living room floor and called “9-1-1”.

What About Uncle Chuck?
Cardiac Arrhythmia: Slow Down
The heart works at peak efficiency when it contracts in a coordinated fashion at the direction of the sinoatrial node. Recall that the cells responsible for either impulse generation and conduction or atrial and ventricular contraction are all excitable. By this is meant that they are capable of depolarizing and repolarizing the cell membrane via ion channels in order to function. Recall also that the autonomic nervous system is able to modulate the heart rate and the force of contraction by releasing different neuro-transmitters that ultimately affect ion channel function.

If the heartbeat is generated by an impulse from the sinoatrial node and the rate is between 60-100 beats/min then the heart is said to be in normal sinus rhythm. If the rate is less than 60 beats/min, as is seen during sleep, increased parasympathetic tone, or with declining automaticity of the sinoatrial node due to degeneration, the heart rhythm is said to be a sinus bradycardia. And if the heart rate is greater than 100 beats/min, as in exercise, anxiety, or increased sympathetic tone, then the heart rhythm is said to be a sinus tachycardia.

Cardiac arrhythmias (more properly dysrhythmias), are simply irregularities in the heart rhythm where some or all of the impulses that result in ventricular contraction are not generated by the sinoatrial node. In the situation where degeneration, inflammation, ischemic heart disease due to coronary artery blockages, systemic or local chemical imbalances (Na+, K+, Ca++), lack of oxygen, or hormone fluctuations take place, ion channel function in the sinoatrial node and the conducting system may result in impaired impulse formation and conduction. When this results in a drop in heart rate that goes below the intrinsic rates of the secondary pacing cells in the atria, the AVN, or the ventricular conducting system, one of them is liable to fire and stimulate ventricular contraction. Depending on the circumstances, this may occur just once in a while or very frequently, even to the point where there is a total dissociation between atrial and ventricular contraction, something that is called 3rd degree heart block. When this happens the ventricles contract at their own intrinsic rate of usually 20-40 beats/min. resulting in the patient feeling very weak and dizzy. Modern medicine is able to solve the problem by inserting an implantable permanent pacemaker which, depending on the type used, is often able to replace the function of the sinoatrial node and bring the heart back up to proper speed.

What About Uncle Chuck?
Cardiac Arrhythmia: Speed Up
The most common types of arrhythmias result in the speeding up of the heart rate rather than it slowing down as mentioned above. Most people at one time or another have noted a skipped beat in their pulse or have felt a brief fluttering in the chest when the heart raced for several seconds. Sometimes, extra, or earlier than expected beats, can come about by enhanced automaticity in one of the pacemaker cells (the unique Na+ ion channel lets Na+ ions enter faster than usual),or earlier than expected depolarization of atrial or ventricular muscle cells because of ion channel dysfunction. For someone with a normal heart these usually are just isolated events that do not go on to more serious life-threatening arrhythmias.

However, in the face of heart tissue with different degrees of ion channel dysfunction and conductivity as is seen with degeneration, inflammation and particularly damage from ischemic heart disease (coronary artery disease), and aggravated by systemic and local chemical imbalances (Na+, K+, Ca++), hypoxemia (low oxygen in the blood) and hormone fluctuations (often elevated adrenaline due to stress on the body), these extra beats can recycle themselves and put the heart into high sustained rates.

When this occurs in the atria, depending on where the impulse is generated from and its conduction pattern, it is usually called atrial tachycardia or atrial flutter and is associated with heart rates of 150 to 200 beats/min. But if several areas of the atria are involved, which is commonly seen in chronic heart or lung disease, further degeneration can take place resulting in total disorganization of atrial contraction called atrial fibrillation. In this setting the atria are literally quivering at a rate of upwards of 300-400 beats/min but since the AVN is limited to how fast it can conduct impulses, usually the associated ventricular rate with atrial fibrillation is 100-180 beats/min. For someone like Uncle Chuck who already has a compromised heart and lung, this would not be very good news.

When the same scenario takes place in the ventricle from the same underlying diseases and aggravating conditions mentioned above, particularly ischemic heart disease, and especially around the time of heart damage from a heart attack, ventricular tachycardia and ventricular flutter may take hold. If these further degenerate into ventricular fibrillation which is a total disorganization of ventricular activity in which the ventricle is unable to contract in a coordinated fashion and simply quivers at a rate of upwards of 400-600 beats/min, then sudden cardiac death is liable to take place. This happens because without the ability of the heart to properly contract and send blood to the brainstem to supply it with oxygen, this vital region of our brains, the part that tells us to breathe, controls our circulation, and makes us conscious, will die; and so will we!! For more see: http://en.wikipedia.org/wiki/Cardiac_arrhythmia

Medical science has developed anti-arrhythmic agents which generally affect either ion channel function or the sympathetic receptor in an effort to reduce the likelihood of these rapid and life-threatening arrhythmias. But in the face of ventricular fibrillation one’s only recourse is to electrically defibrillate the heart in an attempt to put it back into a more functional rhythm. This works by depolarizing large areas of the heart in order to stop all of these irritable cells from firing on their own and thereby tries to allow the sinoatrial node to take over and keep command of the heart if possible. For patients who are very prone to these malignant arrhythmias causing sudden death, an automatic implantable cardioverter-defibrillator (AICD) has been developed. Cardioversion is used for high grade atrial and ventricular arrhythmias (except ventricular fibrillation) in which the patient’s hemodynamic status is compromised. An electrical charge is applied in the same fashion as defibrillation except the energy used is usually lower and the device synchronizes the discharge of energy with ventricular contraction.

In addition to all of the above, it is important to try to correct any other ongoing unstable medical conditions which may have given rise to or aggravated the situation Therefore the patient may need to be intubated and put on a ventilator if he or she is not breathing well enough. But as a bare minimum oxygen will be applied to try to improve the oxygenation of the blood. Medications or procedures that enhance blood flow in the coronary arteries may be needed as well as intravenous fluids and solutions to correct any chemical imbalances that may have arisen.

See: http://en.wikipedia.org/wiki/Antiarrhythmic_agents

See: http://www.fciheart.com/Aicd.htm

What About Uncle Chuck?
The Case Continues
Welcome to Uncle Chuck’s quickly unraveling world. Having the unhealthy combination of coronary artery disease, heart failure, worsening kidney function and poorly controlled blood pressure, mitral valve leakage, and chronic lung disease he was at high risk for atrial fibrillation. When his heart rate suddenly shot up to a sustained level of 150 beats/min, his weakened heart, in the presence of his poorly functioning lungs, couldn’t compensate well enough which caused his oxygen level and blood pressure to suddenly bottom out and he passed out on the living room floor. That’s where Aunt Barb found him. But by the time the paramedics arrived, Uncle Chuck had gone into full blown cardiac arrest due to ventricular fibrillation because this added insult of dropping his oxygen and blood pressure levels further irritated his ventricular muscle.

He was successfully shocked back to life, intubated and put on a ventilator, started on intravenous anti-arrhythmic medications, and transported to the hospital where he was admitted to the C.C.U. (Coronary Care Unit). He was able to come off the ventilator the next day and he continued to be monitored for several more days. He was started on anti-arrhythmic agents to try to keep his heart in normal sinus rhythm. Not only did he continue to have runs of rapid atrial and ventricular arrhythmia, but his heart would also slow down to 30 beats/min and make him feel very dizzy even while lying flat in bed. His medical team conferred with Uncle Chuck and his family and decided to insert a combination pacemaker and automatic implantable cardioverter/defibrillator. Then they were able to adjust his anti-arrhythmic medications so that he didn’t have any seriously fast rates and the pacemaker made sure he didn’t develop any seriously slow rates. He was then able to come home on his new anti-arrhythmic agents with his pacer-AICD providing an extra beat of confidence and protection from sudden death.

What About Uncle Chuck?
Epilogue
Review of how the impulse for the heartbeat is generated and transmitted to the atria and ventricles to allow coordinated contraction will show that there are many factors involved Each must work perfectly in order to allow for proper function and continued survival. Specific ion channel dysfunction and/or conduction difficulties can result in slow heart rates causing weakness and death. Electrically oversensitive areas of the heart causing abnormally quick impulses, or circuits of abnormal conduction that result in very rapid heart rates, can be generated in the atria or the ventricles resulting in weakness and death.

The ability of the heart to be able to generate an impulse that is conducted through the rest of its tissue in a way that allows for coordinated ventricular contraction at a rate that is appropriate for survival is a very complex process that is dependent not only on cardiac factors but also the body’s ability to keep its chemicals in balance. Medical science has developed intelligently designed medications, called anti-arrhythmic agents, that generally target specific ion channels, to try to prevent life-threatening arrhythmias brought on by varying degrees of cardiac electrical disorganization. And failing that it also has developed electromechanical devices (pacemaker and AICD) that try to either compensate for the dysfunction brought on by a degenerated and diseased heart or jumpstart it back into a functioning rhythm to allow for continued survival.

However these medications must be used in proper dosages to have a therapeutic effect. And these devices have to be set just right to be able to perform their functions. Not only will too low of a dose be ineffective, but too high of a dose may cause unwanted side-effects and even other arrhythmias. In fact sometimes even at therapeutic levels these medications can induce life-threatening arrhythmias too. And likewise, the pacemaker and the AICD are quite capable of malfunctioning and causing other unforeseen troubles.

So even when medical science gets in on the action and tries to correct what is going wrong within a human organ system it finds that very careful titration of medication and electromechanical devices is necessary; and even with these precautions it might be making things worse and not better. Yet we are to believe that this intricately sensitive system that can fail so easily with changes in ion channel function, systemic and local chemical imbalances, and hormone fluctuations, came about solely by the random forces of nature. Evolutionary biologists seem to forget that just because life is capable of reproduction and therefore one can retrospectively try to connect the dots regarding how a particular biomolecule or tissue structure may have gradually developed from several others, this does not answer the question of how all of the necessary parts for a specific metabolic pathway or organ system came into being , came together and functioned, nor how the body is capable of keeping any particular metabolic parameter or organ function under adequate control for its survival. It would appear that evolutionary biologists who believe in the dogma of Neodarwinian macroevolution do not seem to trouble themselves with these questions that any ten year old could generate, and therefore conveniently do not have to answer them.

Next time we’ll be looking at lung function and some of the intricacies contained therein.

Dr. G.

Howard Glicksman M.D. graduated from the University of Toronto in 1978. He practiced primary care medicine for almost 25 yrs in Oakville, Ontario and Spring Hill, Florida. He now practices palliative medicine for a Hospice organization in his community. He has a special interest in how the ethos of our culture has been influenced by modern science’s understanding and promotion of what it means to be a human being.

Copyright 2006 Dr. Howard Glicksman. All rights reserved. International copyright secured.
File Date: 09.01.06