Baroreflex Failure as a Late Sequela of Neck Irradiation

Abstract

Combined chemotherapy and radiotherapy increase long-term survival in patients with head and neck tumors. Late complications of treatment, however, are being recognized increasingly. Surgery or radiotherapy of the carotid sinuses or brain stem can evoke labile hypertension and orthostatic intolerance from acute or subacute baroreflex failure. Here we report cases in which chronic baroreflex failure appeared to develop as a late sequela of neck irradiation. Three patients referred for autonomic nervous system function testing had labile blood pressure and chronic orthostatic intolerance that developed years after neck irradiation for cancer. In each patient, heart rate remained constant during performance of the Valsalva maneuver, suggesting baroreflex-cardiovagal failure. All 3 patients had virtually zero baroreflex-cardiovagal gain, quantified by interbeat interval-systolic blood pressure relationships after intravenous phenylephrine or nitroglycerine. Ambulatory blood pressure monitoring revealed highly variable blood pressure, with sudden pressor and depressor episodes, a characteristic feature of baroreflex failure. Cardiovagal efferent function, assessed by power spectral analysis of heart rate variability during slow, deep respiration, was normal. Sympathetic noradrenergic efferent function, assessed by cold pressor testing and plasma catecholamine levels during supine rest and orthostasis, was also normal or increased. These findings indicated a primarily afferent lesion. Carotid ultrasonography revealed intimal thickening and atheromatous plaques in all 3 patients. We propose that labile hypertension and orthostatic intolerance can develop as a late sequela of neck irradiation, due to chronic carotid baroreflex failure, which in turn is due to radiation-induced accelerated development of carotid arteriosclerosis. Splinting of carotid sinus mechanoreceptors in rigidified arterial walls would impede detection of alterations in blood pressure and thereby disrupt baroreflex regulation of cardiovagal and sympathetic outflows.

Baroreceptors, baroreceptor unloading, and the long-term control of blood pressure

“…Thus complete denervation of carotid baroreceptors does produce a sustained increase in MAP and pressure lability in humans, even though aortic baroreceptors are presumably functioning normally (31,57,59). In contrast, less than complete sinus denervation decreases baroreflex sensitivity and increases MAP variability but does not result in an elevated MAP (59,64).…”

“…Sharabi et al (57) studied three patients with baroreflex failure (defined as chronic orthostatic intolerance and labile blood pressure) that developed years after neck irradiation. Baroreflex-mediated changes in HR in response to phenylephrine and nitroglycerine challenges were absent.…”

Components of arterial systolic pressure and RR-interval oscillation spectra in a case of baroreflex failure, a human open-loop model of vascular control

“…In case of baroreflex failure, the loss of buffering ability is usually secondary to iatrogenic causes such as carotid body tumour resection, neck irradiation, surgical section of glossopharyngeal nerve, carotid bypass surgery and unilateral or bilateral carotid endarterectomy. [16][17][18][19][20][21][22] Moreover, rare reports describe this syndrome as due to degenerative neurological disorders or genetic diseases. [23][24][25][26][27] In our patient, the impairment in baroreceptor reflex was due to a posterior fossa tumour, as already described.…”

Cardiovascular effects of radiotherapy on the patient with cancer

“…Chronic failure of the baroreflex has been attributed to these changes. 40 Diffuse calcification of the thoracic aorta and stenotic lesions of the subclavian arteries have also been reported. These are late-onset sequelae attributed to adjuvant RT, and it has become well-known that all arteries are sensitive to the late-onset effects of radiation.…”