Chewing-induced hypertension in afferent baroreflex failure: a sympathetic response?

Abstract

What is the central question of this study? Our goal was to understand the autonomic responses to eating in patients with congenital afferent baroreflex failure, by documenting changes in blood pressure and heart rate with chewing, swallowing and stomach distension. What is the main finding and its importance? Patients born with lesions in the afferent baroreceptor pathways have an exaggerated pressor response to food intake. This appears to be a sympathetically mediated response, triggered by chewing, that occurs independently of swallowing or distension of the stomach. The chewing-induced pressor response may be useful as a counter-manoeuvre to prevent orthostatic hypotension in these patients. Familial dysautonomia (FD) is a rare genetic disease with extremely labile blood pressure resulting from baroreflex deafferentation. Patients have marked surges in sympathetic activity, frequently surrounding meals. We conducted an observational study to document the autonomic responses to eating in patients with FD and to determine whether sympathetic activation was caused by chewing, swallowing or stomach distension. Blood pressure and R-R intervals were measured continuously while chewing gum (n = 15), eating (n = 20) and distending the stomach by percutaneous endoscopic gastrostomy tube feeding (n = 9). Responses were compared with those of normal control subjects (n = 10) and of patients with efferent autonomic failure (n = 10) who have chronically impaired sympathetic outflow. In patients with FD, eating was associated with a marked but transient pressor response (P < 0.0001) and additional signs of sympathetic activation, including tachycardia, diaphoresis and flushing of the skin. Chewing gum evoked a similar increase in blood pressure that was higher in patients with FD than in control subjects (P = 0.0001), but was absent in patients with autonomic failure. In patients with FD, distending the stomach by percutaneous endoscopic gastrostomy tube feeding failed to elicit a pressor response. The results provide indirect evidence that chewing triggers sympathetic activation. The increase in blood pressure is exaggerated in patients with FD as a result of blunted afferent baroreceptor signalling. The chewing pressor response may be useful as a counter-manoeuvre to raise blood pressure and prevent symptomatic orthostatic hypotension in patients with FD.

Figure 1

Schematic showing lesions in neural autonomic pathways in familial dysautonomia (FD), pure autonomic failure (PAF) and multiple system atrophy (MSA). Afferent baroreceptor neurones are shown in blue, central neurones in red and efferent sympathetic neurones in green. Patients with FD have a selective deficit in afferent pathways relaying information from the arterial baroreceptors to the CNS (Norcliffe-Kaufmann et al., 2010). PAF affects peripheral efferent sympathetic fibres (Hague et al., 1997). MSA affects mostly neurones in the central autonomic network preventing descending spinal pathways from activating efferent sympathetic neurones (Tellez et al., 2009).

Figure 2. Effect of chewing, swallowing and stomach distension in familial dysautonomia

Systolic blood pressure (SBP, top) and heart rate (HR, bottom) at rest and the maximum captured peak value when chewing (left), eating by mouth (middle) and distending the stomach with a gastrostomy feed (right). There was a significant increase in blood pressure and heart rate triggered by chewing and swallowing, but not when distending the stomach. All measurements were taken in the seated position. Individual data are linked by lines. Bars represent average values. Comparisons were made with paired student t-test.

Figure 3. Examples of heart rate and blood pressure responses to eating and stomach distension in patients with familial dysautonomia

A) Shows blood pressure (BP) and heart rate (HR) in a 29-year-old female patient while continuously eating pistachio nuts. Facial flushing and diaphoresis were noted while eating. B) Shows similar increase in blood pressure and heart rate when eating a soft-boiled egg in a 6 year old who followed a strictly low-tyramine diet. The patient also appeared flushed and sweaty. The pressor response did not appear to be affected by the consistency of the food. C) Shows the absence of a pressor response or tachycardia when food (300 ml of formula) was given directly into the stomach, bypassing the need to chew and swallow in a 20 year-old female patient. All measurements were taken while seated.

Figure 4. Comparison of responses to chewing, swallowing and stomach distension in patients with familial dysautonomia

A) Shows significantly greater increase in systolic blood pressure (SBP) when chewing and swallowing compared to when distending the stomach alone during a tube feed. B) Shows area under the curve (AUC) for change in SBP in the first 5 minutes was greater when chewing gum and eating orally compared with feeding directly into the stomach (gastrostomy tube). C) Shows significantly greater increase in heart rate (HR) when eating by mouth compared with chewing gum and gastrostomy feedings. D) Shows area under the curve for change in HR in the first 5 minutes, which was greatest when eating orally. All measurements were taken in the seated position. p-values derived from ANOVA with post-hoc multiple comparisons.

Figure 5. Responses to chewing in afferent baroreflex failure, efferent autonomic failure and controls

A) Peak increase in systolic blood pressure (SBP) was exaggerated in patients with familial dysautonomia (FD) who fail to restrain sympathetic outflow due to baroreflex deafferentation. B) Area under the curve (AUC) for change in systolic blood pressure when chewing showed greater chewing pressor response in patients with afferent baroreflex failure (FD). C) Shows blunted HR increase in response to chewing in efferent autonomic failure. D) Area under the curve for change in heart rate when chewing was greater in afferent baroreflex failure and controls compared to patients with efferent autonomic failure. No increase in blood pressure or heart rate was observed in patients with efferent autonomic failure (AF) and chronically impaired sympathetic outflow – suggesting the chewing pressor response is sympathetically mediated.

Figure 6. Examples of heart rate and blood pressure responses to eating and stomach distension in patients with familial dysautonomia

A) Shows transient increase in blood pressure (BP) and heart rate (HR) in a 34-year-old male patient while chewing gum without swallowing. Facial flushing and diaphoresis were noted while eating. B) Shows absence of pressor effect and tachycardia in a 70-year old man with pure autonomic failure. C) Shows increase in heart rate without change in blood pressure in a 20-year old healthy female control. All measurements were taken while seated.