Cheney heart study longish but simple by Sieverling

[Guest guest]

See also: *Cardiac Insufficiency Hypothesis* from the The M.E.

Society of America at: http://www.cfids-cab.org/MESA/Lerner.html

CFS, Heart Problems, and a Risky Procedure: A Warning from Dr. Chene

Posted by: " DFW CFIDS " dfwcfids58@... silverlining3

Sat Jul 22, 2006 5:11 pm (PST)

CFS, Heart Problems, and a Risky Procedure: A Warning from Dr. Cheney

by Carol Sieverling, reviewed and edited by R. Cheney, M.D.,

Ph.D.

I had a relatively brief appointment with Dr. Cheney at the end of

June. He is very concerned that the CFS community will hear that he

has detected a heart problem called Patent Foramen Ovale (PFO) in a

significant number of his patients, and that as a result, many CFS

patients will pursue a corrective procedure that is potentially very

dangerous. He asked me to write an article informing CFS patients

about the risks of undergoing a catheterization procedure to close a

PFO or Atrial Septal Defect (ASD).

Background - Virtually All CFS Patients Have Diastolic Dysfunction

As most are already aware, Dr. Cheney has found that the cellular

energy deficit at the core of CFS results in diastolic heart

dysfunction. This heart condition does not trigger CFS. However, the

heart is affected as CFS progresses and cellular energy disturbances

mount. About 100 of his patients have been tested in his clinic via

echocardiography (a sonogram of the heart) and all but one were

positive by one or more parameters indicative of diastolic

dysfunction. The exception is a 21-year-old patient and her age may

have been a factor.

For those who want more technical details on testing for diastolic

dysfunction, all patients (except the 21-year-old) evidenced

diastolic dysfunction by their pulmonary vein D/S ratio. In addition,

Dr. Cheney is finding that his older patients, typically over 50,

manifest diastolic dysfunction by the classical reversal of the

mitral in-flow E/A ratio. This E/A reversal accounts for 40% of all

the patients he's tested so far. This ratio jumps to 60% if the TDI

e'/a' reversal is also used as either/or criteria for diastolic

dysfunction. Younger patients manifest diastolic dysfunction

primarily as left atrial cavitation during 70-degree head-up tilt.

(The tilt is part of his echo protocol). Seventy percent of his

patients are in this category. Except for a small group of middle-

aged patients, the E/A or e'/a' reversal as compared to atrial

cavitation is usually mutually exclusive. However, both aberrations

can exist together in the middle-aged patient.

There have been other online postings that discuss Dr. Cheney's

understanding of diastolic dysfunction in CFS (Co-Cure.org), as well

as the three-hour video of Dr. Cheney's presentation to our support

group just over a year ago. A few of those videos are still available

from dfwcfids.org. (A new Cheney video and/or DVD should be available

this fall).

What is a PFO?

In most people, the right and left sides of the heart have no opening

between them. Circulated blood flows into the right side of the

heart. It then goes to the lungs to pick up oxygen, dump carbon

dioxide, and has mini-clots filtered out as well as potential portal

vein toxins and toxic gases produced by fermentation in the gut. From

the lungs it goes to the left side of the heart, which sends it on to

the brain and body.

When the fetus is in the womb, however, it relies on its mother for

clean, oxygenated blood from the umbilical cord blood and does not

use its lungs. As a result, the fetal heart has an opening known as

the Patent Foramen Ovale (PFO). This opening allows blood to take a

short cut from the right atrium (upper chamber of the right heart) to

the left atrium, which sends it on its usual path through the left

ventricle and out the aorta to the rest of the body. The PFO is

formed by two overlapping tissues or septi, the septum primum and the

septum secundum.

Typically, when the lungs kick into action at birth, pressure in the

right heart substantially decreases relative to the left side and the

PFO slams shut and the two tissues grow together, forming a permanent

seal. But in up to 20 to 30 percent of the general population, the

flaps of both tissues press together but never fuse. This can

potentially allow unfiltered blood to escape into the left side of

the heart from the right, depending on the difference in pressure

between the right and left sides. However, the normal pressures in a

healthy heart (left side greater than right) keep the flap valve from

opening, so the vast majority of people with a PFO experience no

problems.

A PFO opens when more pressure is created in the right side of the

heart. This can be produced acutely by a Valsalva maneuver, and can

occur when people cough, sneeze, lift something heavy, or strain at

stool. If the pressure is enough to open the PFO, blood can flow from

the right atrium to the left.

Dr. Cheney demonstrates the basics of a PFO visually with his hands.

Hold your hands as if in prayer against your chest. Tilt your hands

down and point them away from you, but keep them against your chest.

(They represent the wall separating your atria, the two upper

chambers of your heart.) Slide the left one down so that your left

index finger is aligned with your right ring finger. Your right hand

stays stationary. Your left hand is the " valve " that moves. Keep your

little finger still - it's the hinge - while tilting your left hand

away from your right. This is a rudimentary representation of a PFO.

With your hands in this position, you should be able to feel why

higher pressure on the left keeps the PFO shut. (Your left hand

pushes against your right.) Conversely, higher pressures on the right

cause the valve of the PFO to open. (Your left hand tilts away from

your right.)

For excellent diagrams and a good description of the development of a

PFO in utero and after birth see www.oucom.ohiou.edu/dbms-

witmer/Downloads/Witmer%2008-21-02%20Heart%20defects.pdf. (See pages

7-9, Atrial Partitioning II-IV).

Most (Perhaps All?) CFS Patients Have a PFO

In late April Dr. Cheney began looking for PFOs in his patients based

on evidence of high right-sided pressures and low left-sided

pressures in CFS patients. To date he has administered contrast echos

to 24 patients. Seventy-eight percent of those not on the treatment

protocol for his current research study were positive - a PFO opened

and visibly shunted blood from one atrium to the other. A Valsalva

maneuver is used to induce the PFO to open while the contrast IV

saline with micro-bubbles of air flow through the heart. This is

called a saline bubble test. (Actual echo photos of a positive test

result will be posted on dfwcfids.org in our " Cheney section " .)

One published study found that when contrast IV saline was

administered in the arm as opposed to the groin area during this

test, a false negative rate of 30% occurred. Since the groin area

cannot be used for the IV in the setting of Dr. Cheney's clinic, and

the arm is typically used by most physicians, it's possible that

virtually all of his patients have (or had) PFOs that shunt blood

from one atrium to the other. This obviously assumes that those who

tested negative actually have PFOs that went undetected (i.e. false

negatives).

Dr. Cheney suspects that the PFOs of most CFS patients open only

transiently, not chronically. In other words, the flap valve only

opens occasionally. However, the size of the PFO and how often it

opens varies from patient to patient. During the contrast echo, some

patients clearly had a large opening, allowing more bubbles to cross

into the left atrium. Others only had a very few bubbles moving

across, indicating a much smaller opening or less pressure difference

between the right and left atria.

Consequences of a PFO

In adults, this two-flap valve (PFO) between the right and left

atrium allows blood to flow either way, though it tends to flow

predominantly in one direction in any one person. A right to left

shunt (flow) increases the risk of a stroke, since the lungs have not

filtered out mini-clots. (Taking low-dose aspirin three times a week

along with a daily supplement of Nattokinase or Lumbrokinase, is not

a bad idea. For a comparison of the latter two, see

www.allergyresearchgroup.com/faq/index.php?article=182.)

Dr. Cheney suspects that these mini-clots explain why so many CFS

patients (up to 50%) have punctate lesions or Unidentified Bright

Objects (UBOs) on their MRI brain scans. Each UBO may actually be a

very tiny area damaged by a mini clot.

Migraines have also been linked to PFOs that shunt right to left.

Clinical trials are underway to close PFOs in patients with severe

migraines that are non-responsive to medication. Dr. Cheney pointed

out that carbon dioxide levels in the blood rise with a right to left

shunt since unoxygenated blood from the right side gets dumped into

the left arterial circulation. Since carbon dioxide is a vasodilator

it would cause arteries in the brain to dilate, which could trigger a

migraine.

The increased carbon dioxide could also cause slight brain swelling,

which could be mistaken for Chiari I Malformation. Many will remember

all the publicity that this defect received a few years ago as it

mimics CFS, and the brain surgery that some underwent with mixed

results.

Higher levels of carbon dioxide would also explain some patients Dr.

Cheney has seen through the years whose symptoms seemed to mimic

carbon monoxide poisoning.

There are different risks if the PFO primarily shunts from left to

right, sending blood from the left atrium to the right atrium. From

there it's pumped through the right ventricle into the pulmonary

artery and into the lungs. Increasing the amount of blood in the

right atrium can increase the pressure of the blood moving into the

lungs. If the pressure on the right side of the heart is high enough,

pulmonary hypertension can develop and eventually become life

threatening if it rises too high. (Pulmonary hypertension is a

disorder in which the blood pressure in the pulmonary artery rises

far above normal levels.)

A left to right shunt also reduces the efficiency of the heart as

oxygenated blood is returned to the right heart, going in the wrong

direction. The heart has to work harder to overcome this inefficiency.

Cause of PFOs and ASDs in CFS Patients

Researchers state that between 20% and 30% of the general population

has a PFO, yet Dr. Cheney's findings as of July 19th indicate that

78% of his " non-study " CFS patients have one. Are people with PFOs at

risk for CFS, or does CFS create PFOs? Though there is no definite

answer as yet, Dr. Cheney strongly suspects the latter.

There is evidence in CFS patients that right-sided pressures are

higher than normal and left-sided pressures are lower than normal.

There's a complex explanation for this that I'm not sure I fully

understand - see the note at the end for my attempt at an explanation

(thankfully heavily edited by Dr. Cheney). The bottom line is that

when the pressure on the right side of the heart rises high enough in

relation to the pressure on the left side, it's possible that a PFO

sealed after birth could pop open. Thus CFS could conceivably create

PFOs.

Once a PFO exists, whether it never sealed after birth or was later

blown open by the pressure differential of the two sides of the

heart, CFS can enlarge it through the following process: (1) The

cellular energy deficit of CFS leads to diastolic dysfunction of the

heart. (2) Textbooks state that diastolic dysfunction leads to

dilation (enlargement) of the left atrium and increased right

ventricular systolic force. (3) Referring to the diagrams on the

website given above or to the arrangement of your hands described

above, imagine the two opposing flaps that make up the PFO being

pulled farther and farther apart by the left atrial enlargement. (The

lower hand being pulled down). The flap that moves and is considered

to be the valve is the lower one and is structurally part of the left

atrium.

The combination of left atrial enlargement and a high right to left

pressure difference could explain why nearly 80% of CFS patients have

tested positive for PFOs, and why their primary shunting is typically

from right to left.

As the left atrium expands over time, the PFO may gradually

transition from a flap valve to an actual hole. Cardiologists then

call it an ASD and usually insist that it has existed since birth,

which may or may not be the case in CFS patients. In the context of

CFS, with left atrial enlargement and a high right to left pressure

differential, the difference between a PFO and an ASD is simply a

matter of degree - a distinction without a difference. When the flaps

can no longer oppose each other, the PFO becomes an ASD.

There is precedent for a disorder in which left atrial enlargement

can lead to the formation of an ASD. It's called Lutembacher

Syndrome. This disorder is defined as a combination of mitral

stenosis and an ASD shunting left-to-right and even bi-directionally.

(Mitral stenosis is a narrowing of the valve that lies between the

left atrium and left ventricle.) Classic Lutembacher Syndrome is

usually described as a congenital mitral stenosis and an acquired

ASD. Recently, several variants have been described.

Dr. Cheney's research into this subject revealed that left atrial

enlargement is part of Lutembacher Syndrome and that left atrial

enlargement could produce an ASD by enlarging a PFO or enlarging a

pre-existing small ASD. It's worth noting that less than one percent

of the general population has an ASD, but that people with mitral

stenosis have a much higher incidence rate of ASDs, suggesting that

something (such as left atrial enlargement) is actually creating the

ASD.

Why Not Close the PFO or ASD?

Until a few years ago, all PFO and ASD closures involved open-heart

surgery and the use of a heart-lung bypass machine. In 2000 the FDA

approved a device called CardioSeal. In 2002 the Amplatzer device was

approved. CardioSeal contains a nickel-cobalt-chromium-molybdenum

alloy. Amplatzer contains nickel and titanium. Both devices are

collapsible discs that are threaded though the femoral vein into the

heart. Once in place, they open up like umbrellas and anchor to the

wall of the atrium with hooks. The ASD or PFO is sandwiched between

the two connected metallic mesh discs.

Approximately a year ago a patient of Dr. Cheney's with a 15-year

history of CFS had a device implanted in his atrial wall via a

catheter threaded up the femoral vein. His story is very enlightening.

He had several echos done from 2001 to 2004 that showed pulmonary

hypertension, but there was no mention of a PFO or ASD in the echo

reports. (After recently examining some of those earlier echos, Dr.

Cheney noted the classic E/A reversal that denotes diastolic

dysfunction.) During that same period the patient was also having

brief, unsustained bouts of atrial fibrillation that were gradually

becoming worse.

In the spring of 2005 the patient had another echo done in his

hometown that revealed a 50% ejection fraction (above 55% is normal),

mild regurgitation in the tricuspid and mitral valves, a slightly

enlarged left atrium, pulmonary hypertension of about 50 mm Hg

(normal is 16 mm Hg, primary pulmonary hypertension is anything above

25 mm Hg at rest), and most disconcertingly a very large ASD.

The cardiologist emphasized the size of the hole in the atrial wall

and told him he'd probably had it since birth. The patient isn't sure

he's had the ASD since birth, given his previous health history and

the large size of the ASD. It's highly unlikely such a large hole in

the heart would go undetected for nearly 60 years.

A procedure to close it was done about a year ago. He is the first

and only patient of Dr. Cheney to undergo this procedure - at least

so far. After a short bout of atrial fibrillation immediately after

the procedure, he experienced three weeks during which he felt as if

he had been cured. In the last 20 years he'd never felt that good.

Then his atrial fibrillation recurred, soon becoming chronic and

unresponsive to therapy. Months went by and nothing could control it.

His left atrium further enlarged and he deteriorated clinically.

Atrial fibrillation is very poorly tolerated when one also has

diastolic dysfunction.

In February of this year, he went to a nationally renowned clinic for

a consultation about his chronic atrial fibrillation. This national

clinic is well known for its expertise in a laser procedure called a

Mini-Maze used to cure atrial fibrillation. They did an echo and

discovered that his heart had nearly been destroyed. Both atrio-

ventricular valves were now severely leaking and his ejection

fraction was down to 30%. They told him he would die without urgent

open-heart surgery. His diagnosis was changed from " chronic atrial

fibrillation following ASD closure " alone to now include " valvular

heart disease " , a diagnosis he'd never had before.

He had both valves repaired and the Mini-Maze laser procedure was

ultimately successful at stopping the atrial fibrillation. Dr. Cheney

credits the surgeon and clinic with saving the patient's life. They

told him that with the fibrillation halted, his left atrium would

reduce in size. They also told him that the ASD closure device

appeared to have " traumatized " tissue growing over its metallic mesh

surfaces. (It's normal for endothelial cells to gradually cover the

implanted device, though it's not normal for them to

become " traumatized " .)

In May, the patient made several trips to the ER, most for

tachycardia (rapid beating of the heart). His fourth trip was

prompted by trouble breathing and feeling faint. They found he was

experiencing cardiac tamponade - the heart was being compressed by

fluid accumulating in the space between his heart muscle and the

outer covering of the heart, known as the pericardial sac. That day

and the next they used a syringe to draw out a total of over 3 liters

of fluid from that space. (That's over 3 quarts!).

The patient stabilized enough to finally see Dr. Cheney the last week

of June. (I saw Dr. Cheney two days later, after he'd had time to

start processing all that he had learned from this patient.) Dr.

Cheney noted that the echo done at the patient's June visit

looked " pretty good " , except that his left atrium was larger than

ever, and he still had a significant pericardial effusion (fluid

gathering in the pericardial sac) and continued evidence of diastolic

dysfunction. His ejection fraction was normal and his heart valves

were no longer leaking. In many ways, his situation was pretty stable

considering all that had happened.

Conclusions

Dr. Cheney spent much time describing this case to me, and in turn I

have devoted much space to it here because it illuminates some very

important points. While it's very likely that some elements of his

story are unique to this patient, there is much that suggests that

implanting these devices in a CFS patient carries significant risks

of which cardiologists may be unaware.

His shunting before the closure was likely in both directions. Now,

without the ability to shunt blood over to the left side, too much

pressure might build up in the right side. He no longer has the

safety of the pop-off or release valve effect of the ASD. Some

cardiologists are hesitant to close some ASDs for this very reason.

The problem is a conundrum because failure to close a large ASD could

also result in increased right-sided pressure if the shunt is

predominantly left to right under high pressure.

The traumatized tissue on the implanted device is what concerns Dr.

Cheney the most. The device used for this procedure contains nickel,

a heavy metal, and Dr. Cheney believes that the tissue could be

reacting to it. (A friend of mine with CFS once mentioned that some

of her earrings caused her ear lobes to swell and turn red. She

finally figured out that this only happened when the earrings

contained nickel.) Nickel poisoning could set in motion Fenton

chemistry that could increase his diastolic dysfunction, which would

further enlarge his left atrium. Therefore, the use of nickel could

be contributing to the very disease process that made its use seem

necessary in the first place. (Nickel testing may reveal if he is, in

fact, reacting to it).

The diastolic dysfunction itself most likely started the enlargement

of his left atrium, which may have widened an existing PFO or smaller

ASD, and even contributed to the development of atrial fibrillation.

Dr. Cheney is convinced that CFS created or interacted with the

patient's ASD, especially in light of the new data on CFS and PFOs.

His cognitive complaints were slowly developing after CFS onset and

may have been connected to or even caused by the evolving ASD and

increased right to left shunting.

Dr. Cheney's major concerns:

[1] If the left atrium is enlarging due to CFS associated diastolic

dysfunction, should you even consider implanting a device into it?

The continued enlargement expected in untreated diastolic dysfunction

might simply cause the tissue growing over the device to stretch and

tear. The resulting damage and inflammation might cause the heart to

react by building up fluid around it that may result in tamponade

(compression of the heart with fluid) or evoke chronic atrial

fibrillation. Needless to say, Dr. Cheney has serious reservations

about implanting a device to close a PFO in a CFS patient if the left

atrium has not yet been stabilized by treating the underlying

diastolic dysfunction.

[2] Dr. Cheney is also very concerned about the interaction of nickel

and the pathophysiology of CFS. Implantation of the closure device

containing nickel puts CFS patients at risk for the induction of

Fenton chemistry, which will exacerbate the underlying CFS

pathophysiology and further enlarge the left atrium.

[3] Dr. Cheney suspects that we do not really understand the

implications of the presence of the PFO/ASD in the setting of such a

complex disorder as CFS, and all the interrelationships that exist.

The pop-off valve effect of a PFO/ASD that releases pressure is an

example. He is concerned that if the PFO/ASD is closed, a lot of

physiology could be changed abruptly, and because it is so complex

and interrelated the patient could get worse.

Signs of Hope

I have saved this final point for last because it's hopeful. Dr.

Cheney is very intrigued that the patient described above, who

clearly has CFS associated diastolic dysfunction, felt cured for

three weeks after his ASD was closed. Obviously, there were problems

that would have surfaced eventually, given the state of the tissue

over the device and the development of chronic atrial fibrillation.

But his " three-week cure " raises the possibility that if it were

possible to restore normal pressures to the heart and keep PFOs from

opening, or to stabilize the left atrium and keep PFOs from

developing into larger PFOs or ASDs, a significant positive clinical

transformation might be possible. Dr. Cheney wonders how many of our

symptoms are totally, or at least partly, derived from a PFO. He

doesn't yet know for sure, but the possibilities are intriguing.

Other than open-heart surgery or the implantation of a device

containing nickel through a femoral vein, cardiologists have little

to offer. However, Dr. Cheney's current study protocol is yielding

very interesting early results. And it is early - the study will not

be fully completed until late this year or early next year. There are

two distinct stages of treatment, and the second has two different

dosage groups. There are about 20 participants and they are at

different points on the study timeline. Many are just starting the

second phase of treatment, so the full benefits of the study protocol

have yet to be seen.

Two early hopeful indications from the study relate to PFOs and

suggest that the treatment protocol is leading to an improvement that

is normalizing pressures in the heart and keeping PFOs closed.

First, the numbers change as more patients are tested, but currently

67% of study patients test positive for a shunting PFO versus 78% of

those not on the study treatment protocol. And it's possible many

study patients who are testing positive now will test negative after

they've been treated for a longer time.

The hope is that those study patients who tested negative are not

false negative (i.e. actually have a shunting PFO that was not

detected), but have been on the treatment protocol long enough to

have improved their cardiac function to the point of keeping a PFO

shut. Unfortunately at the time the study began, PFOs were not even

on the radar thus making a true baseline for a shunting PFO

impossible to determine for many study patients.

If this data holds true over time and with larger numbers, this could

represent an alternative to open-heart surgery or having a device

implanted, at least for many CFS patients.

Second, my own experience suggests that the treatment does indeed

normalize heart pressures and may keep a PFO closed. I am in the

study and have been on the second phase, the porcine heart cell

signaling factors, since May 24th. While it was not possible to test

me early enough to get a true baseline for a shunting PFO, there is

evidence that I have a PFO that was shunting, albeit perhaps only to

a mild degree, until just recently.

I was negative on the contrast echo at my June 30th appointment,

indicating that no shunting was taking place, which is great news and

matches my overall improvement.

Indications that I may have a PFO that was shunting right to left and

is now likely staying closed are:

*Increased pressure on the right side of the heart (TRmaxPG on the

echo). A high pressure in September of 2005 dropped 35% into the

normal range on both my 2006 April and June echos.

*Venous blood gas testing showed low PO2 levels in March (possible

shunting), but normal levels in May (no shunting).

*The echo sonographer described the area of my left atrium where a

PFO would be located as " very thin " . Dr. Cheney said that's how a PFO

typically looks, though this is far from definitive.

*I have a history of migraines that do not respond to medication, but

have not had any recently.

*I had " punctate lesions " or UBOs on an MRI done several years ago.

*While wearing a pulse-oximeter clipped to my finger in Dr. Cheney's

office in April of this year, my oxygen saturation suddenly and

inexplicably dropped to 81% and then rose back to normal (98%). I

have been monitoring it since May, and it has not dropped into the

80's (except during intentional breath holding) at any time that I

have been aware of.

With few study participants even at the halfway point yet, Dr. Cheney

is not comfortable giving out treatment protocol information. And

even if adjustments in the protocol are not made at the conclusion of

the study, his primary concern is that no treatment protocol is ever

one-size-fits-all. It's always individualized for each patient. So

the treatment protocol needs to be presented in a setting that allows

him to provide a context and go into more detail.

Dr. Cheney is light years ahead of where he was a year ago when he

spoke to our support group here in the Dallas - Fort Worth area. He

wants to come speak again and we are working to arrange a date in

late August or September. A DVD of the presentation should be

available some time after the seminar. Watch for online announcements

on the Co-Cure.org announcement list or see our website,

dfwcfids.org, for details as they become available.

In the meantime, if you are a CFIDS patient and discover you have a

PFO or ASD, please think twice before allowing the implantation of a

device containing nickel into an atrial wall that is, or will likely

be, expanding. Please wait until more is known about these complex

issues and until we see what benefit Dr. Cheney's current research

study protocol has to offer.

*********************************************************************

Note from the section on the cause of PFOs and ASDs in CFS patients:

The increased pressure on the right side of the heart may in part be

a result of a left shift on the oxygen-hemoglobin dissociation curve

observed in most CFS patients. Interestingly, babies in the womb are

left-shifted due to fetal hemoglobin and therefore have higher

pressure on the right side of the heart, and of course they have a

PFO. All of this is normal, even necessary, for fetuses - but not for

adults. In a sense, the left shift and higher right-sided pressures

the left shift produces are telling our bodies that we are back in

the womb and therefore a PFO is necessary for life - a fact that is

not true for adults.

The left shift on the oxygen-hemoglobin dissociation curve and the

resulting reduction in oxygen transfer into the cells of the body is

actually a defense against the redox (reduction-oxidation) problem

described in my 2004 article on the heart which can be found on our

website, dfwcfids.org. It describes Pall's work, particularly

the production of energy (ATP) which generates superoxide in the

mitochondria, which under normal circumstances is safely reduced to

water by enzymes embedded in the mitochondria and just outside the

mitochondria.

However, in CFS the enzymes do not seem to function effectively due

to a variety of reasons, most of which are the subject of

speculation. This allows superoxide to leak out of the mitochondria

where it can combine with nitric oxide to form peroxynitrite, a very

deadly free radical. Because it takes one superoxide molecule

combining with one nitric oxide molecule to produce one molecule of

peroxynitrite, the levels of peroxynitrite in the body can be

significantly reduced if there isn't much superoxide available to

combine with nitric oxide. And in CFS that's exactly how the body

defends itself against terrible damage from peroxynitrite - it cuts

back on energy production which in turn lowers the production of

superoxide.

Note: Increasing the energy of a CFS patient is extremely dangerous

unless you first restore the enzymes in the mitochondria and the

supporting co-factors they need to work well. If superoxide cannot be

safely broken down into water and/or peroxynitrite neutralized,

inducing energy in a CFS patient will likely result in a major

relapse, perhaps worse than any state previously experienced. Be very

cautious with any product on the market designed to increase cellular

energy in CFS if you haven't first restored the function of the

enzymes needed to handle the by-products of such energy production.

Of course Dr. Cheney's current study protocols are intended to

address this very problem.

The push-crash phenomenon, whether on the small day-to-day scale or

on a much broader scale, is actually part of the CFS case definition

and the principle cause of CFS disability. In effect, the fatigue of

CFS is a defense mechanism, and push-crash is simply a way to enforce

this mechanism and protect the patient.

To summarize, the redox problem in CFS causes the body to actually

put mechanisms in place to lower the amount of oxygen getting into

cells. This is a protective, compensatory measure. This acute

reduction in oxygen to the cells is caused by a left shift on the

oxygen-hemoglobin dissociation curve. This results in increased right-

sided pressures in the heart. When these pressures are high enough,

they can pop open a PFO that was previously sealed at birth.

The diastolic dysfunction of CFS also plays into this picture by

causing left atrial dilatation and by increasing the right

ventricular systolic squeeze. Unfortunately, a PFO with a right to

left shunt forces a shift to the right on the oxygen-hemoglobin

dissociation curve and can therefore cause serious redox problems by

driving oxygen into the cells. PFOs in a CFS patient are therefore a

serious menace as they effectively evoke oxygen toxicity throughout

the body. In a curious way, CFS and newborns are both supersensitive

to oxygen toxicity and for similar reasons.

Edited by R. Cheney MD, PhD