EMBARGOED UNTIL
MONDAY, APRIL 19, 2004
Contact: Donna Krupa
703.967.2751 (cell)
703.527.7357 (office)
djkrupa1@aol.com
APS Newsroom: April 17-21, 2004
Washington, DC Convention Center
East Registration Area/Flex Unit
Telephone: 202.249.4009
Successful Therapy For Head
And Neck Cancer May Lead To Long-Term Circulatory Problems
Small sample study finds radiation damages key
receptors impacting on blood pressure
Washington, DC
– Despite a steady stream of health advisories, younger Americans continue
to light up in bars and restaurants. What many do not realize is that
tobacco and alcohol combined contributes to head and neck cancer. While
this is not one of the more common cancers, it is among the deadliest.
Malignancies in this region of the body are among the most difficult to
treat, resulting in a high mortality rate for these patients.
Specialists have found that
a combination of chemotherapy and radiotherapy extends survival in patients
with head and neck tumors. However, there is a downside to the treatment,
especially radiotherapy. Cellular absorption of ionizing radiation
generates toxic free radicals and leads to faulty repair of DNA breaks and
cell death. Responses to radiotherapy occur in time frames of hours (nausea,
vomiting), days (erythema), weeks (bone marrow supression), months
(fibrosis), and years (carcinogenesis). Among survivors of the cancer
itself, late effects on “bystander” organs -- such as the thyroid and
salivary glands -- have become increasingly prevalent, with secondary
malignancies and infections boosting the levels of sickness and death.
Physicians have noted that after neck irradiation,
long-term injury commonly occurs in the carotid arteries. Atherosclerotic
and thrombotic complications have drawn the most attention. For example, in
a study of 910 patients who survived at least five years after irradiation
of head and neck tumors, stroke occurred in about six percent and clinically
significant carotid stenosis was observed in 17 percent.
A New Study
A new study examines three
cases where symptomatic baroreflex failure occurred apparently as a late
consequence of neck irradiation. The baroflex is originating from the
stimulation of the carotid sinus baroreceptors and plays an important role
in maintaining proper blood pressure.
Results Being Presented At Upcoming Conference
The authors of “Baroreflex Failure as a Late Sequela of
Neck Irradiation,” are Yehonatan Sharabi, Raghuveer Dendi, Courtney Holmes,
and David S. Goldstein, all from the Clinical Neurocardiology Section,
National Institute of Neurological Disorders and Stroke, National Institutes
of Health, Bethesda, MD. They will present their findings at the American
Physiological Society’s (APS) (www.the-aps.org)
annual scientific conference, Experimental Biology 2004, being held
April 17-21, 2004, at the Washington, D.C. Convention Center.
Methodology
This study was comprised of
three patients. Patient #1 was a 51 year old female who was evaluated
for episodes of presyncope (a sense of near fainting) during standing. The
patient had been healthy until the age 18, when she contracted Hodgkin’s
disease. Patient #2 was a 57 year old female
evaluated for orthostatic intolerance (could not stand for more than few
minutes) and episodes of lightheadedness after effort. Thirty-two years
before these symptoms began she had been diagnosed with Hodgkin’s disease,
was treated with mantle field radiation therapy and was considered cured.
Patient #3 was a 58 year old white male was referred for orthostatic
intolerance, dizziness, episodes of presyncope, and unstable blood pressure.
At age 54 he was diagnosed with squamous cell carcinoma of the soft palate,
which was treated with radiation therapy directed to the tumor and adjuvant
preventive radiotherapy to the neck and upper chest.
Since circulatory blood
pressure lability is an indicator of baroreflex failure, the researchers
assessed possible baroreflex-cardiovagal failure using heart rate-systolic
blood pressure relationships during the Valsalva maneuver and after bolus IV
injection of phenylephrine and then nitroglycerine. The integrity of the
cardiovagal efferent limb of the baroreflex was measured through power
spectral analysis of heart rate variability during slow, deep respiration.
To test the sympathetic noradrenergic
limb, the researchers observed blood pressure and heart rate during the cold
pressor test. In addition they measured the blood pressure and plasma levels
of catecholamines during orthostasis. Finally, to detect carotid
atherosclerosis, which could splint carotid arterial baroreceptors and
therefore constitute an afferent baroreflex lesion, they evaluated the
carotid arteries by ultrasound.
Results
The key findings of this
study are noted below.
·
All the patients had no change in
heart rate during Phase II of the Valsalva maneuver. Baroreflex-cardiovagal
gain therefore was zero. Values for baroreflex-cardiovagal were confirmed by
both the phenylephrine and nitroglycerine injection techniques which also
were virtually zero.
·
All three patients had labile blood
pressure, quantified by high standard deviations of the blood pressure
readings during 24-hour monitoring (the upper 90th percentile of
the normal population). All had episodes of rapid increases in blood
pressure over 200 mm Hg. Patients #1 and #2 also had increased average heart
rate. All three patients had episodes of rapid increases and decreases in
pulse rate, paralleling simultaneous blood pressure changes.
·
In Patient #1, plasma
norepinephrine levels were normal during supine rest but increased
exaggeratedly during standing. Patients #2 and #3 had high plasma
norepinephrine levels even during supine rest.
·
The cold pressor test showed not
only large pressor responses but also concurrent increases in pulse rate.
The spectral analysis of heart rate variability demonstrated increases in
high frequency power as a function of respiration.
Conclusions
These findings indicated
intact parasympathetic cardiovagal function. Meanwhile, the pattern of blood
pressure responses to the Valsalva maneuver, high plasma catecholamine
levels during supine rest, increases in plasma catecholamine levels during
orthostasis, and large cold pressor responses excluded sympathetic
neurocirculatory failure. Taken together, the results therefore pointed to
baroreflex failure from decreased afferent baroreceptor input to the brain,
rather than loss of effector system functions. The results call for a
prospective study about the incidence of this complication and its
relationship specifically to carotid arterial stiffening.
The researchers believe this phenomenon is
under-diagnosed by cardiologists, neurologists, and radiation oncologists,
at least partly because clinicians do not appreciate enough the possibility
of this adverse long-term outcome, either when therapeutic options for neck
malignancy are first considered or when, years after successful cure, the
patient develops seemingly unrelated signs and symptoms of baroreflex
failure.
- end -
The
American Physiological Society (APS) was founded in 1887 to foster basic and
applied science, much of it relating to human health. The Bethesda, MD-based
Society has more than 11,000 members and publishes 3,800 articles in its 14
peer-reviewed journals every year.
***
Editor’s
Note: For further information or to schedule an interview with a member of
the research team, please contact Donna Krupa at 703.967.2751 (cell),
703.527.7357 (office) or at
djkrupa1@aol.com. Or contact the APS newsroom at 202.249.4009 between
9:00 AM and 6:00 PM EDT April 17-21, 2004.
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