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.
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.
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.