Pharyngoglottal closure reflex: characterization in healthy young,elderly and dysphagic patients with predeglutitive aspiration

BACKGROUND: Mechanism(s) of aspiration, a common complication of oropharyngeal dysphagia, is not completely elucidated. Since the pharyngoglottal closure reflex induces vocal cord adduction in healthy young humans, it may help prevent aspiration during premature spill of oral content. OBJECTIVE: The objective of this study was to characterize this reflex in normal young and elderly humans and dysphagic patients with predeglutitive aspiration; a potential group for developing abnormalities of this reflex. METHODS: We used a concurrent video endoscopic and manometric technique for recording of the vocal cords' response to pharyngeal water stimulation. We first studied 9 young (26 +/- 2 years) and 9 elderly (77 +/- 14 years) healthy volunteers to characterize and determine the effect of aging on the pharyngoglottal closure reflex. Subsequently, we studied 8 patients (65 +/- 16 years) with predeglutitive aspiration and 7 age-matched controls to characterize this reflex among patients with compromised airway safety during swallowing. RESULTS: The threshold volume of water for triggering both glottal closure and reflexive pharyngeal swallow in the elderly volunteers for rapid pulse injection was significantly larger than that for the young (p < 0.05). Neither glottal closure reflex nor pharyngeal reflexive swallow could be induced in any of the dysphagic patients with volumes of injected water as large as 1 ml. In contrast, in all age-matched controls, both the pharyngoglottal reflex and reflexive pharyngeal swallow were stimulated with threshold volumes of 0.3 +/- 0.07 and 0.6 +/- 0.05 ml, respectively. CONCLUSIONS: Pharyngeal stimulation by water induces vocal cord adduction in humans; the pharyngoglottal closure reflex. Although preserved, a significantly larger volume of water is required to stimulate this reflex by rapid pulse injection in the elderly, suggesting some deterioration in this age group. The pharyngoglottal closure reflex induced by rapid pulse injection is absent in dysphagic patients with predeglutitive aspiration, suggesting its contribution to airway protection against aspiration.     

Aging-related alterations in human upper esophageal sphincter function

Recent improvements in manometric catheters have made measurement of pharyngeal (P) and upper esophageal sphincter (UES) swallowing mechanics more reliable. Few studies have attempted to evaluate the effect of normal aging on P and UES mechanics. Pharyngeal and upper esophageal sphincter dynamics were studied in 10 healthy elderly adults (age greater than 60; range 62-79 yr) and 10 younger adults (age less than 60; range 24-59 yr). A solid-state intraluminal transducer system was used with a proximal unidirectional Konigsberg microtransducer and a circumferential (sphincter) transducer located 5 cm distally. Mean resting UES pressure was significantly (p less than 0.05) lower in the elderly than in the younger subjects (52 +/- 5 vs 72 +/- 6 (SE)) mm Hg. A significant inverse relation (R = -0.54; p less than 0.02) was found between age and resting UES pressure. Time from peak of pharyngeal contraction to UES nadir was significantly (p less than 0.05) shortened in the healthy elderly vs younger controls (10 +/- 30 vs 90 +/- 20 ms) during dry swallows. Our studies indicate that aging is associated with lower resting UES pressure and delayed UES relaxation, relative to the pharyngeal peak.     

Esophagoglottal closure reflex: a mechanism of airway protection.

Abrupt esophageal distention occurs commonly during gastroesophageal reflux, thereby generating a circumstance favorable to esophagopharyngeal regurgitation and laryngeal aspiration of gastric refluxate. The aims of the present study were to examine the glottal response to esophageal distention by air and regional esophageal distention by a balloon. Fifteen healthy volunteers (age, 25 +/- 5 years) were studied while they were in an upright position. Using concurrent videoendoscopy and manometry, glottal and upper esophageal sphincter (UES) responses to abrupt esophageal distention by air injection (10-60 mL) and balloon distention (1.5, 2.0, and 2.5 cm) were recorded simultaneously. In addition, 6 subjects were studied with concurrent synchronized videofluoroscopy. Results showed that esophageal distention by air at a threshold volume of 10-60 mL caused vocal cord closure. The UES response to this threshold volume was variable. Volumes larger than the threshold value caused complete UES relaxation and belching. In addition to vocal cord closure, belching was accompanied by anterior movement of the glottis. On videofluoroscopy, the hyoid bone moved anteriorly in association with belching, but not with vocal cord closure without belching. Proximal esophageal distention by the balloon also provoked vocal cord closure. This response was less consistent for balloon distention in the middle and distal esophagus. It is concluded that (a) esophageal distention by either air or a balloon evokes a glottal closure mechanism, thereby suggesting the existence of an esophagoglottal reflex; (b) this reflex is elicited most easily by distention of the proximal esophagus; (c) glottal and UES responses to esophageal distention are independent from each other; and (d) the esophagoglottal closure reflex may play an important role in preventing laryngeal aspiration of acid due to gastroesophageal reflux accompanied by acid regurgitation into the pharynx.     

Manometric characteristics of the upper esophageal sphincter recorded with a microsleeve

OBJECTIVES: We compared manometric recordings of the upper esophageal sphincter (UES) recorded with a miniature sleeve to those obtained using standard manometry. METHODS: The UES pressure of eight volunteer subjects was measured by station pull-through (SPT), by rapid pull-through (RPT), and with a microsleeve sensor for 30 min, followed by 15 min of esophageal acid infusion. Deglutitive UES relaxation recorded with a microsleeve and solid state sensor were compared. RESULTS: The UES pressure recorded with the microsleeve (25+/-9 mm Hg) was significantly less than that by SPT (114+/-18 mm Hg) or RPT (152+/-19 mm Hg), and was unaffected by acid infusion. Periods of low UES pressure were observed during long interswallow intervals (11+/-4, range 6-18 mm Hg). Deglutitive relaxation duration and intrabolus pressure measured with the microsleeve were less than those recorded by the solid state transducer. CONCLUSIONS: "Normal" UES pressure is heavily dependent on measurement technique; pressures obtained with a miniature sleeve are a fraction of those obtained by SPT or RPT. During periods of relative comfort with minimal swallowing, UES tone is approximately 10 mm Hg, similar to that during sleep. Volume modulation of deglutitive UES relaxation is demonstrable with a microsleeve, albeit with less precision than with a solid-state transducer.     

Abnormal pressure passive dilatation of cerebral arterioles in the elderly with isolated systolic hypertension

The aim of this study was to investigate the cerebrovascular adaptability to 2 sequential pressor stimuli in elderly patients with isolated systolic hypertension. Ten healthy elderly normotensive subjects (68 to 82 years), 10 elderly subjects with isolated systolic hypertension (63 to 82 years), and 10 young normotensive subjects (24 to 40 years) took part in the study. A pressor reaction, using sequential cold pressor and handgrip stimulation, was induced. The cerebrovascular response to the pressor stimulation was measured by transcranial Doppler determination of the mean flow velocity in the middle cerebral arteries. In all of the subjects, blood pressure increased during handgrip (+12 mm Hg, P<0.001 in the young; +18 mm Hg, P<0.01 in the elderly normotensive subjects; +19 mm Hg, P<0.001 in the hypertensive patients versus baseline). In the hypertensive subjects, the pressure increase persisted well into the recovery period. The pressure increase caused a significant increase in mean flow velocity in the middle cerebral arteries only in the elderly subjects. Cold pressor test increased blood pressure in all of the subjects during stimulation and the first 2 minutes of the recovery period (at whole-curve ANOVA: F=22.03, P<0.001 in the young participants; F=18.3, P<0.001 in the normotensive elderly; and F=13.04, P<0.001 in the hypertensive elderly). Mean flow velocity in the middle cerebral arteries significantly increased only in the hypertensive subjects. In the elderly hypertensive patients, the cerebrovascular reaction to adrenergic stimuli was more impaired than in the elderly normotensive subjects. This event can amplify the pressure insult on cerebral hemodynamics and increase the predisposition to cerebral damage, such as vascular cognitive impairment or stroke.     

The Effects of Age, Sex, and Smoking on Normal Pharyngoesophageal Motility

Previous reports of normal pharyngoesophageal motility have described normal ranges in small numbers of young adults. In this study, the results of upper esophageal sphincter (UES) manometry with a microtransducer assembly in 67 healthy volunteers aged 17-77 yr have been analyzed for possible effects of age, sex, and cigarette smoking. Older subjects were found to have only marginally lower UES tonic pressures, but markedly elevated pharyngeal contraction pressures. Increasing age was associated with a reduction in duration of upper esophageal contractions and, for bread swallows, an increase in pharyngoesophageal wave velocity which may represent compensatory mechanisms for airway protection. Male subjects showed greater UES axial asymmetry than females, perhaps due to sex differences in laryngeal anatomy, whereas females had greater UES wet swallow after-contraction pressures which may be relevant to the generation of globus sensation. All results were independent of cigarette smoking. We conclude that normal values obtained in small numbers of young adults form an inadequate basis for the interpretation of UES tonic and pharyngeal contraction pressures, which are reported to be abnormal in older patients with dysphagia, and that manometric investigation of dysphagic patients requires the analysis of multiple parameters of dynamic pharyngoesophageal function.     

Do patients with globus sensation respond to hypnotically assisted relaxation therapy? A case series report

Globus sensation is a bothersome and difficult symptom to treat. The aims of this study were to evaluate the acceptability and utility of hypnotically‐assisted relaxation (HAR) in decreasing the perception of globus sensation and the effect of HAR on interdeglutitive upper esophageal sphincter (UES) pressure. Sixteen subjects with persistent globus sensation unresponsive to therapy for reflux disease and with normal esophageal/laryngeal imaging studies were invited to participate in a 7‐session clinical protocol. Before and after HAR, subjects completed standard questionnaires including the esophageal symptoms questionnaire. High‐resolution manometric assessment of respiratory augmentation and average resting UES pressure were assessed before and after HAR. Ten of the 16 subjects agreed to participate in the protocol. All participants were women with median age 51.5 (range 30–72 years). The participants found HAR acceptable and completed the entire 7‐session trial. Globus symptom severity varied widely pre‐treatment (median = 52.5, range 16–72), and 9 of 10 subjects reported a reduction in globus symptomatology following treatment (median = 14.0, range 3–19; P = .007). Only 1 subject exhibited abnormal respiratory augmentation of UES pressure (>27 mm Hg) prior to treatment and was normal following treatment (9.9 mm Hg). Resting UES pressure was normal in all subjects (<118 mm Hg). Group respiratory augmentation and average resting UES pressure were unaffected by HAR (P = .48, .89). This case series suggests that HAR can provide a substantial improvement in globus sensation irrespective of cause. UES function was unaffected. We suggest that HAR therapy is an acceptable and useful intervention for patients with globus sensation.     

Renorenal reflexes present in young and captopril-treated adult spontaneously hypertensive rats

In normotensive Sprague-Dawley rats and Wistar-Kyoto (WKY) rats stimulation of renal mechanoreceptors or chemoreceptors by increasing ureteral pressure or renal pelvic perfusion with 0.9 M NaCl results in a contralateral inhibitory renorenal reflex response with contralateral diuresis and natriuresis. However, in 14-15-week-old spontaneously hypertensive rats (SHR) renal sensory receptor stimulation failed to elicit a contralateral inhibitory renorenal reflex response. The present study was performed to examine whether the lack of a renorenal reflex response in SHR was related to elevated arterial pressure by studying the responses to renal sensory receptor stimulation in 5-6-week-old SHR and in 12-16-week-old SHR that had been treated with captopril from 3 weeks of age to prevent the development of hypertension. In 5-6-week-old SHR, mean arterial pressure was 113 +/- 3 mm Hg. Graded increases of ureteral pressure of 15 and 29 mm Hg resulted in graded increases in ipsilateral afferent renal nerve activity of 57 +/- 22% and 120 +/- 38%. Contralateral urinary sodium excretion increased from 0.26 +/- 0.06 to 0.35 +/- 0.07 mumol/min/g and from 0.36 +/- 0.08 to 0.46 +/- 0.11 mumol/min/g, respectively. In captopril-treated SHR, mean arterial pressure was 109 +/- 3 mm Hg. Increasing ureteral pressure by 34 mm Hg increased ipsilateral afferent renal nerve activity 65 +/- 21% and contralateral urinary sodium excretion from 1.28 +/- 0.24 to 1.53 +/- 0.30 mumol/min/g. Similar results were produced by renal chemoreceptor stimulation. It is concluded that renal sensory receptor stimulation results in a contralateral inhibitory renorenal reflex response in 5-6-week-old SHR and in SHR treated with captopril to prevent the development of hypertension. These results suggest that the previously demonstrated lack of a renorenal reflex response to renal sensory receptor stimulation in hypertensive SHR is related to the maintenance of hypertension.     

Comparison of differences in the hemodynamic response to passive postural stress in healthy subjects greater than 70 years and less than 30 years of age

To test the hypothesis that age-related increases in arterial pressure alter the cardiovascular response to physiologic stress, 9 healthy elderly volunteers (74 +/- 2 years) and 7 young subjects (27 +/- 3 years) were subjected to a standard 60 degrees upright tilt. Cardiac volumes were measured with patients in the supine position and 5 minutes after they assumed an upright posture using radionuclide ventriculography, while heart rate, blood pressure and forearm cutaneous flow were recorded continuously and simultaneously. Only the expected age-related increase in mean arterial pressure (young subjects, 79 +/- 1 mm Hg; elderly subjects, 99 +/- 3 mm Hg; p less than 0.001) distinguished the 2 groups at baseline. However, during upright tilt, elderly subjects had significant decreases in stroke volume (supine [108 +/- 9 ml] vs upright [78 +/- 9 ml]; p less than 0.01) and cardiac index (supine [3.4 +/- 0.2 liters/min/m2] vs upright [2.8 +/- 0.2 liters/min/m2]; p less than 0.05) because of an inability to reduce end-systolic volume (supine, 44 +/- 6 ml; upright, 51 +/- 7 ml); however, mean arterial pressure was maintained through an increase in peripheral resistance. In contrast, the young relied solely on cardiac adaptations to postural stress by decreasing end-systolic volume (supine, 62 +/- 5 ml; upright, 39 +/- 5 ml; p less than 0.01) and increasing heart rate (57 +/- 2 min-1 to 71 +/- 3 min-1, p less than 0.01), whereby cardiac output and mean arterial pressure were maintained during tilt.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of age and sodium depletion on cardiovascular response to orthostasis

To test the hypothesis that normal age-related limitations in cardiovascular homeostasis may become clinically significant under stress, the cardiovascular response to postural change was assessed in six young and six old healthy subjects before and after modest diuretic-induced sodium depletion. Before diuresis, systolic blood pressure was maintained (from 110 +/- 4 to 113 +/- 6 mm Hg) while heart rate increased 22% (from 67 +/- 2 to 82 +/- 5 beats/min) at 3 minutes after 60-degree upright tilt in young subjects. After a significant diuretic-induced weight reduction and natriuresis, the young again maintained systolic blood pressure (from 110 +/- 4 to 110 +/- 6 mm Hg) and increased heart rate 49% (from 68 +/- 2 to 101 +/- 5 beats/min; p less than 0.05, compared with prediuresis values) in response to the same postural stimulus. During the prediuresis tilt, the older subjects showed no change in systolic blood pressure (from 132 +/- 4 to 134 +/- 6 mm Hg) and a 9% increase in heart rate (from 68 +/- 3 to 74 +/- 2 beats/min). After a similar significant weight reduction and sodium loss, the older subjects showed a significant reduction in systolic blood pressure (from 132 +/- 6 to 108 +/- 6 mm Hg; p less than 0.05) and a 17% increase in heart rate (from 69 +/- 4 to 81 +/- 3 beats/min; p less than 0.05) during tilt compared with values in young subjects. Three of six elderly subjects noted postural symptoms. These results suggest that, although the healthy old may appear well compensated under optimal conditions, decreased cardiovascular reserve renders them susceptible to postural change following mild sodium depletion.     

Baroreflex function in elderly hypertensives

Baroreflex function was assessed in elderly hypertensive patients and compared with that observed in young hypertensives and young normotensives. Mean arterial pressure was reduced by 20% using intravenous nitroprusside infusion in 10 elderly hypertensive patients (older than 65 years and diastolic pressures over 95 mm Hg), in 10 young hypertensives (under 60 years and diastolic pressures over 95 mm Hg), and in seven young normotensive subjects (under 60 years and diastolic pressures under 95 mm Hg). Elderly subjects demonstrated greater sensitivity (p less than 0.005) and greater variability of response (p less than 0.025) to nitroprusside than either young group. There was no significant difference between the slight heart rate increases observed in the supine position in the three groups. However, in the erect position, heart rate increases were significantly less in the elderly hypertensive group than in the young hypertensive group (p less than 0.01) or the young normotensive group (p less than 0.005). Furthermore, the slope of the regression line relating change in blood pressure with change in R-R interval was less for the elderly patients than for the young hypertensives (p less than 0.05) or the young normotensives (p less than 0.025). We conclude that the heart rate component of the baroreflex is impaired in elderly hypertensives, and anticipate that the clinical response to antihypertensive drugs will be altered.     

Upper esophageal sphincter tone and reactivity to stress in patients with a history of globus sensation

Anxiety and abnormal upper esophageal sphincter function have been ascribed ill- defined roles in the etiology of globus sensation. In this study, we examined the psychological profile and effect of acute mental stress (dichotic listening task) on UES tone in seven patients reporting to the clinic with globus sensation and 13 healthy controls. Alterations in heart rate, blood pressure, frontalis EMG, and skin conductance confirmed the effectiveness of the stress test in patients and controls. During resting conditions, UES pressure (mean±SE) in patients (40.4±4.6 mm Hg) did not differ significantly from controls (46.5±4.7 mm Hg). In response to stress, UES pressure rose by 31% in patients (P=0.04) and by 25% in controls (P=0.002). The stress- induced rise in UES pressure in patients (9.5±3.8 mm Hg) was not significantly different to that observed in controls (11.8±3.0 mm Hg). Psychological profiles of globus patients presenting to the clinic revealed them to be more introverted, anxious, neurotic, and depressed than normal controls. We conclude that in patients with a history of globus sensation, resting UES pressure and its response to stress is normal. Although individuals presenting to the clinic with globus sensation showed increased levels of psychoneurosis, acute, predictable stress is not a factor in the genesis of globus sensation. UES hyperresponsiveness to other stimuli or subjective intolerance to changes in UES pressure could account for symptoms of globus sensation.Dr. Cook is supported by a University of Sydney, Postgraduate Medical Foundation Award. Dr. Dent was supported as a Visiting Professor to McMaster University by a Visiting Scientist Award from the Canadian Medical Research Council.     

Evaluating Oral Stimulation as a Treatment for Dysphagia after Stroke

Deglutitive aspiration is common after stroke and can have devastating consequences. While the application of oral sensory stimulation as a treatment for dysphagia remains controversial, data from our laboratory have suggested that it may increase corticobulbar excitability, which in previous work was correlated with swallowing recovery after stroke. Our study assessed the effects of oral stimulation at the faucial pillar on measures of swallowing and aspiration in patients with dysphagic stroke. Swallowing was assessed before and 60 min after 0.2-Hz electrical or sham stimulation in 16 stroke patients (12 male, mean age = 73 ± 12 years). Swallowing measures included laryngeal closure (initiation and duration) and pharyngeal transit time, taken from digitally acquired videofluoroscopy. Aspiration severity was assessed using a validated penetration-aspiration scale. Preintervention, the initiation of laryngeal closure, was delayed in both groups, occurring 0.66 ± 0.17 s after the bolus arrived at the hypopharynx. The larynx was closed for 0.79 ± 0.07 s and pharyngeal transit time was 0.94 ± 0.06 s. Baseline swallowing measures and aspiration severity were similar between groups (stimulation: 24.9 ± 3.01; sham: 24.9 ± 3.3, p = 0.2). Compared with baseline, no change was observed in the speed of laryngeal elevation, pharyngeal transit time, or aspiration severity within subjects or between groups for either active or sham stimulation. Our study found no evidence for functional change in swallow physiology after faucial pillar stimulation in dysphagic stroke. Therefore, with the parameters used in this study, oral stimulation does not offer an effective treatment for poststroke patients.Abbreviations: mA = milliamps; FP = faucial pillar; LCD = laryngeal closure duration; OTT = oral transit time; PTT = pharyngeal transit time; SRT = swallow response time; TMS = transcranial magnetic stimulation; UES = upper esophageal sphincter.     

Evaluation of the Upper Esophageal Sphincter (UES) Using Simultaneous High-Resolution Endoluminal Sonography (HRES) and Manometry

The aim of this study was to characterize the motion, morphology, and pressure of the upper esophageal sphincter (UES). The UES and its surrounding structures were evaluated in seven normal subjects and four human cadavers, using simultaneous high-resolution endoluminal sonography and manometry. The UES musculature on ultrasound is a C-shaped structure with an angle of 107 +/- 19 degrees. The mean peak resting UES pressure was 74 mm Hg, with a total cross-sectional area (CSA) of 0.87 +/- 0.33 cm2. During swallowing, the UES moved in an orad direction. Localizing the UES sonographically, the peak UES pressure in the cadavers was 19.7 +/- 10.0 mm Hg. The UES has a greater muscular CSA and resting pressure than the upper esophageal body. In the cadaver studies, the UES was imaged in conjunction with a significant increase in pressure, indicating that the pressure is due to passive mechanical conformational changes.     

Study on the function of pharynx＆upper esophageal sphincter in globus hystericus

AIM：Glbus pharyngeus is not an uncommon symptom,Presently,its unclear dated pathophysiology remains unclear and the disease can not be evaluated correctly with routine diagnostic methods.The objective of this study is to establish the normal values of pharyngeal and UES pressure,pharyngeal transit time in healthy volunteers and to compare the differences between healthy volunteers and patients with globus pharyngeus.METHODS:Twenty-four healthy volunteers and thirty-two patients clinically diagnosed as globus pharyngeus entered the study.Pressures of pharynx and UES were measured.Pharyngeal transit time was measured by videofluoroscopic procedure.RESULTS:Normal pressure of pharynx,and normal resting pressure of UESwere 157.81&#177;63.86mmHg and 68.33&#177;37.56mmHg,respectively.The corresponding values in the patients were175.50&#177;93.47mmHgand71.38&#177;41.42mmHg,The pharyngeal transit time was1.44&#177;0.30s in mormal control group,among them there were4cases with stasis of barium in the valleculae and one in the piriform sinus.No laryngeal penetration or aspiration was found.In the patient group,the pharyngeal transit time was1.37&#177;0.41s,amon g them there were6cases with stasis of barium in the valleculae and 5in the piriform sinus,9cases had laryngeal penetration and 2had aspiration.There were no statistical differences of pressures of pharynx,UESand the pharyngeal transit time between the two groups.But the ere was an association between laryngeal penetration and globus pharyngeus.CONCLUSION:Radiographic exaqmination of the pharynx show specific findings of pharyngeal dysfunction in patients with globus pharyngeus.UESpressure is normal in most patients ,Hence,we find no role for UEShypertonicity as an etiologic factor in globus pharyngeus.     

Carotid baroreflex function in young men with borderline blood pressure elevation.

Carotid baroreflex function was assessed in 10 normotensive young men and 20 age-matched subjects with borderline hypertension (successive blood pressures above and below 140/90 mm Hg) by measuring sinus node responses to brief neck suction. Subjects with borderline hypertension were divided into two equal groups according to their average systolic arterial pressures. Baroreflex responses were reset to function at higher pressure levels than normal in subjects with mild borderline hypertension, but reflex sensitivity was normal. Responses were also reset in subjects with more severe borderline hypertension, but reflex was subnormal. The results suggest that a gradation of baroreflex responsiveness exists among patients classified as having borderline hypertension: Subnormal responsiveness was found in those subjects whose resting average systolic arterial pressure was greater than or equal to 140 mm Hg.     

Blood pressure response to controlled diesel exhaust exposure in human subjects

Exposure to traffic-related air pollution is associated with risk of cardiovascular disease and mortality. We examined whether exposure to diesel exhaust increased blood pressure (BP) in human subjects. We analyzed data from 45 nonsmoking subjects, 18 to 49 years of age in double-blinded, crossover exposure studies, randomized to order. Each subject was exposed to diesel exhaust, maintained at 200 μg/m(3) of fine particulate matter, and filtered air for 120 minutes on days separated by ≥2 weeks. We measured BP pre-exposure, at 30-minute intervals during exposure, and 3, 5, 7, and 24 hours from exposure initiation and analyzed changes from pre-exposure values. Compared with filtered air, systolic BP increased at all of the points measured during and after diesel exhaust exposure; the mean effect peaked between 30 and 60 minutes after exposure initiation (3.8 mm Hg [95% CI: -0.4 to 8.0 mm Hg] and 5.1 mm Hg [95% CI: 0.7-9.5 mm Hg], respectively). Sex and metabolic syndrome did not modify this effect. Combining readings between 30 and 90 minutes, diesel exhaust exposure resulted in a 4.4-mm Hg increase in systolic BP, adjusted for participant characteristics and exposure perception (95% CI: 1.1-7.7 mm Hg; P=0.0009). There was no significant effect on heart rate or diastolic pressure. Diesel exhaust inhalation was associated with a rapid, measurable increase in systolic but not diastolic BP in young nonsmokers, independent of perception of exposure. This controlled trial in humans confirms findings from observational studies. The effect may be important on a population basis given the worldwide prevalence of exposure to traffic-related air pollution.     

Ventricular sensory endings mediate reflex bradycardia during coronary arteriography in humans

It has been suggested that the response to the intracoronary injection of radiographic contrast is reflex in origin and results from stimulation of ventricular sensory endings. Cardiac transplantation results in denervation of the ventricles, and thus, may interrupt the afferent limb of this reflex. In contrast, the recipient sinus node and atrial remnant remain innervated, leaving the efferent cardiac limb of this reflex intact. We hypothesized that if contrast-induced reflex bradycardia and hypotension occurred from stimulation of ventricular chemosensitive endings, then this response would be abolished after cardiac transplantation. To test this hypothesis, we determined the changes in recipient (innervated) and donor (denervated) sinus-node rates (SNR) and mean arterial pressure during selective right (RCA) and left coronary artery (LCA) injection during arteriography in cardiac transplant patients and in patients with intact cardiac innervation. An increase in the recipient SNR was observed in cardiac transplant patients during left and right coronary injections (LCA, 6.6 +/- 1.7 beats/min; RCA, 2.4 +/- 1.4 beats/min) compared with a decrease in the control subjects (LCA, -15.3 +/- 2.3 beats/min; RCA, -6.9 +/- 1.9 beats/min; p less than 0.05 vs. control). This occurred despite significant and comparable decreases in mean arterial pressure in cardiac transplant patients (LCA, -12.7 +/- 2.3 mm Hg; RCA, -11.4 +/- 2.2 mm Hg) and control subjects (LCA, -18.7 +/- 1.7 mm Hg; RCA, -10.7 +/- 1.6 mm Hg). The donor SNR slowed for LCA injection (-5.4 +/- 2.1 beats/min, p less than 0.05) and RCA injection (-3.0 +/- 1.7 beats/min), which, for the LCA, was less than the slowing of control subjects (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of aging on control of breathing]

In an attempt of elucidate the effect of aging on control of breathing, we measured hypercapnic ventilatory responses (HCVR) under three different conditions in 14 elderly volunteers (mean age: 69 yrs) and in young control subjects (29 yrs). There was no significant difference in the slope value (S) of HCVR between the two groups when the test was conducted under hyperoxic conditions. However, under hypoxic conditions, the "S" was significantly increased only in the young subjects, but not so in the elderly. When an resistive load (17 cmH2O/L-sec) was added to an inspiratory line, the "S" was not changed as a result of augmented P0.1 response in the young subjects, while the "S" was significantly decreased without any increase in P0.1 response in the elderly. The dyspnea score at the end-tidal PCO2 of 50 Torr, which was evaluated by visual analogue scale, was consistently higher in the elderly than in the young under any conditions. These results suggest that hypoxic-hypercapnic interaction on ventilation and load compensation reflex to inspiratory resistive loading are impired in the elderly subjects and that these are not associated with bluntness of respiratory sensation.     

Effects of aging and hypertension on the microcirculation

Alterations of structure and function of the microcirculation in hypertension in the elderly and changes with normotensive aging have not been fully clarified. We studied capillary pressure, density, and skin microvascular function in 46 subjects in 3 groups: elderly subjects (aged >60 years) with untreated hypertension (n=16), elderly normotensive subjects (n=16), and young normotensive subjects (age <45 years, n=14). In a subgroup of 19 subjects, we also studied resistance artery function in the isometric myograph. Capillary pressure was higher in both elderly groups (elderly hypertensives: 18.6+/-4.7 mm Hg, elderly normotensives: 17.6+/-4.0 mm Hg) compared with young normotensives (13.9+/-2.6 mm Hg, P<0.05), but capillary density did not differ between the groups. Skin vasodilating responses to acetylcholine were greater in young normotensives compared with both elderly groups (P<0.05). In isolated resistance arteries, there was a greater inhibitory effect from blockade of the l-arginine-NO pathway in elderly normotensives (P<0.05) and a reduction in the maximal inhibitory effect of combined blockade of NO, prostanoids, and endothelium-derived hyperpolarizing factor in elderly hypertensives (P<0.05). This study has demonstrated a significant effect of aging but no additional effect of hypertension on capillary pressure and no effect of either on capillary density. Our findings with both in vivo and in vitro methods suggest that normotensive aging may depend on relative preservation of NO-dependent vasodilatation in resistance arteries at the expense of a rise in capillary pressure.