Vidyya Medical News Service
Volume 6 Issue 110 Published - 14:00 UTC 08:00 EST 19-Apr-2004 Next Update - 14:00 UTC 08:00 EST 20-Apr-2004
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Successful therapy for head and neck cancer may lead to long-term circulatory problems

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) ( annual scientific conference, Experimental Biology 2004, being held April 17-21, 2004, at the Washington, D.C. Convention Center.


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.


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.


    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.

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