The effects of acute normobaric hypoxia on vestibular-evoked balance responses in humans.

BACKGROUND: Hypoxia influences standing balance and vestibular function. OBJECTIVE: The purpose here was to investigate the effect of hypoxia on the vestibular control of balance. METHODS: Twenty participants (10 males; 10 females) were tested over two days (normobaric hypoxia and normoxia). Participants stood on a force plate (head rotated leftward) and experienced random, continuous electrical vestibular stimulation (EVS) during trials of eyes open (EO) and closed (EC) at baseline (BL), after 5 (H1), 30 (H2) and 55-min (H3) of hypoxia, and 10-min into normoxic recovery (NR). Vestibular-evoked balance responses were quantified using cumulant density, coherence, and gain functions between EVS and anteroposterior forces. RESULTS: Oxyhemoglobin saturation, end-tidal oxygen and carbon dioxide decreased for H1-3 compared to BL; however, end-tidal carbon dioxide remained reduced at NR with EC (p≤0.003). EVS-AP force peak-to-peak amplitude was lower at H3 and NR than at BL (p≤0.01). At multiple frequencies, EVS-AP force coherence and gain estimates were lower at H3 and NR than BL for females; however, this was only observed for coherence for males. CONCLUSIONS: Overall, vestibular-evoked balance responses are blunted following normobaric hypoxia >30 min, which persists into NR and may contribute to the reported increases in postural sway.

Role of CO2 in the cerebral hyperemic response to incremental normoxic and hyperoxic exercise.

Cerebral blood flow (CBF) is temporally related to exercise-induced changes in partial pressure of end-tidal carbon dioxide (PetCO2 ); hyperoxia is known to enhance this relationship. We examined the hypothesis that preventing PetCO2 from rising (isocapnia) during submaximal exercise with and without hyperoxia [end-tidal Po2(PetO2 ) = 300 mmHg] would attenuate the increases in CBF. Additionally, we aimed to identify the magnitude that breathing, per se, influences the CBF response to normoxic and hyperoxic exercise. In 14 participants, CBF (intra- and extracranial) measurements were measured during exercise [20, 40, 60, and 80% of maximum workload (Wmax)] and during rest while ventilation (V̇e) was volitionally increased to mimic volumes achieved during exercise (isocapnic hyperpnea). While V̇ewas uncontrolled during poikilocapnic exercise, during isocapnic exercise and isocapnic hyperpnea, V̇ewas increased to prevent PetCO2 from rising above resting values (∼40 mmHg). Although PetCO2 differed by 2 ± 3 mmHg during normoxic poikilocapnic and isocapnic exercise, except for a greater poikilocapnic compared with isocapnic increase in blood velocity in the posterior cerebral artery at 60% Wmax, the between condition increases in intracranial (∼12-15%) and extracranial (15-20%) blood flow were similar at each workload. The poikilocapnic hyperoxic increases in both intra- and extracranial blood-flow (∼17-29%) were greater compared with poikilocapnic normoxia (∼8-20%) at intensities >40% Wmax(P< 0.01). During both normoxic and hyperoxic conditions, isocapnia normalized both the intracranial and extracranial blood-flow differences. Isocapnic hyperpnea did not alter CBF. Our findings demonstrate a differential effect of PetCO2 on CBF during exercise influenced by the prevailing PetO2.

Precise mimicking of exercise hyperpnea to investigate the oxygen cost of breathing.

The oxygen cost of exercise hyperpnea (V˙(O2 RM)) has been quantified using a variety of techniques with inconsistent findings. Between-study variation relates to poor control of breathing patterns and lung mechanics. We developed a methodology allowing precise matching of exercising WOB in order to estimate V˙(O2 RM). Thirteen healthy young subjects (7 male) completed an incremental cycle exercise test, familiarization and experimental days where exercise hyperpnea was mimicked. On experimental days, feedback of exercise flow, volume and the respiratory pressures were provided while end-tidal CO2 was kept at exercise levels during each 5-min trial. Minute ventilation levels between 50 and 100% maximum were mimicked 3-5 times. The r(2) between exercise and mimic trails was 0.99 for frequency, tidal volume and minute ventilation; 0.86 for esophageal pressure swings and 0.93 for WOB. The coefficient of variation for (V˙(O2) averaged 4.3, 4.4 and 5.7% for 50, 75 and 100% ventilation trials. When WOB and other respiratory parameters are tightly controlled, the V˙(O2 RM) can be consistently estimated.

Effects of intermittent hypoxia on erythropoietin, soluble erythropoietin receptor and ventilation in humans.

Erythropoietin (EPO) and soluble EPO receptors (sEPOR) have been proposed to play a central role in the ventilatory acclimatisation to continuous hypoxia in mice. In this study, we demonstrated for the first time in humans (n = 9) that sEPOR is downregulated upon daytime exposure to 4 days of intermittent hypoxia (IH; 6 h·day⁻¹, cycles of 2 min of hypoxia followed by 2 min of reoxygenation; peak end-tidal oxygen tension (P(ET,O2)) 88 Torr, nadir P(ET,O2)) 45 Torr), thereby allowing EPO concentration to rise. We also determined the strength of the association between these haematological adaptations and alterations in the acute hypoxic ventilatory response (AHVR). We observed a nadir in sEPOR on day 2 (-70%), concomitant with the peak in EPO concentration (+50%). Following exposure to IH, tidal volume (V(T)) increased, respiratory frequency remained unchanged, and minute ventilation (V'(E)) was increased. There was a negative correlation between EPO and sEPOR (r = -0.261; p = 0.05), and between sEPOR and V(T) (r = -0.331; p = 0.02). EPO was positively correlated with V'(E) (r = 0.458; p = 0.001). In conclusion, the downregulation of sEPOR by IH modulates the subsequent EPO response. Furthermore, the alterations in AHVR and breathing pattern following IH appear to be mediated, at least in part, by the increase in EPO.

The human diving response, its function, and its control.

The purpose of this review is to outline the physiological responses associated with the diving response, its functional significance, and its cardiorespiratory control. This review is separated into four major sections. Section one outlines the diving response and its physiology. Section two provides support for the hypothesis that the primary role of the diving response is the conservation of oxygen. The third section describes how the diving response is controlled and provides a model that illustrates the cardiorespiratory interaction. Finally, the fourth section illustrates potential adaptations that result after regular exposure to an asphyxic environment. The cardiovascular and endocrine responses associated with the diving response and apnea are bradycardia, vasoconstriction, and an increase in secretion of suprarenal catecholamines. These responses require the integration of both the cardiovascular system and the respiratory system. The primary role of the diving response is likely to conserve oxygen for sensitive brain and heart tissue and to lengthen the time before the onset of serious hypoxic damage. We suggest that future research should be focused towards understanding the role of altered ventilatory responses in human breath-hold athletes as well as in patients suffering from sleep-disordered breathing.

Long-term results of the Angelchik prosthesis for gastro-oesophageal reflux.

INTRODUCTION: Between 1982 and 1989, 46 patients had insertion of an Angelchik prosthesis for gastro-oesophageal reflux. Eleven patients (24 per cent) subsequently had the prosthesis removed, all but one for intractable dysphagia. METHODS: Thirty-six of the original patients were followed by questionnaire, and 32 of these had a barium marshmallow swallow investigation. RESULTS: A high proportion of patients (20 of 26) with a prosthesis in situ had symptoms of dysphagia. On objective evaluation by marshmallow swallow, the transit time was significantly slower than that of an age-matched control group (P < 0.01), but showed no significant deterioration with time compared with previous postinsertion studies. CONCLUSION: The Angelchik prosthesis causes long-term dysphagia in a high proportion of patients, severe enough in one-quarter to necessitate its removal. Its continued use cannot, therefore, be recommended.

A trial of glucagon in the treatment of painful biliary tract disease.

Seventy-one patients with a clinical diagnosis of painful biliary tract disease have been entered into a double-blind trial of glucagon. Twenty-eight were excluded as gallstones were not proved: of the remainder, 21 patients received glucagon and 22 placebo. Glucagon-treated patients were pain free 14.26 h (+/- 2.77 s.e.m.) after commencing treatment compared to 29.14 h (+/- 6.01 s.e.m.) for the placebo group (P less than 0.05). Tenderness in the right hypochondrium showed a significant improvement when assessed at 12 h (P less than 0.02) and 24 h (P less than 0.1) for those given glucagon. A significant difference in blood glucose levels was seen between the two groups (P less than 0.05). No serious side effects were observed. Glucagon relieves the pain and tenderness associated with painful biliary tract disease more effectively than conventional therapy.

The action of porcine glucagon on the motility of the canine duodenum and jejunum.

1 Intravenous bolus doses of porcine glucagon of 0.001-0.05 mg kg-1 caused intense stimulation of the duodenum and jejunum of the dog. 2 Intravenous infusion of porcine glucagon at 0.025-0.05 mg kg-1 h-1 caused similar stimulation. In both cases the stimulation was phasic in nature. 3 Stimulation of the duodenum and jejunum following glucagon was accompanied by a decrease in frequency of the intestinal basic electrical rhythm (BER). No change was seen in the intervals between successive periods of phase III motor activity.

Outpatient flexible fibreoptic sigmoidoscopy, diagnostic yield and the value of glucagon.

One hundred patients had flexible fibreoptic sigmoidoscopy in an outpatient clinic after preparation with a phosphate enema but without sedation. Patients were randomized to receive 1 mg of glucagon intravenously or a matching placebo. The discomfort of the patients and the ease of the procedure were similar in both groups. Nine patients were excluded from the final analysis as they had low rectal or anal lesions. In the remaining 91 patients, abnormalities were found in 27 (29.6 per cent) including 16 adenomatous polyps and 1 carcinoma. Only 3 lesions were below 20 cm and might have been easily visualized using a rigid sigmoidoscope.

Clinical and economic consequences of wound sepsis after appendicectomy and their modification by metronidazole or povidone iodine.

The effects of intrarectal metronidazole and intraincisional povidone iodine on sepsis after emergency appendicectomy were compared in a double-blind randomised controlled trial in 496 patients. Wound sepsis occurred in 12.3% of metronidazole-treated patients compared with 24% in the povidone-iodine group and 23.5% in an untreated control group. The metronidazole-treated patients left hospital approximately 2 days earlier than patients in the other two groups. They returned to work sooner and receiver fewer visits from the district nursing service. A short six-dose course of metronidazole significantly reduces the wound-infection rate in patients over the age of 12 undergoing emergency appendicectomy. If the clinical and economic benefits of metronidazole shown by this study are confirmed, the drug should be considered for routine use in emergency appendicectomy.

Effect of some i.v. anaesthetic agents on canine gastrointestinal motility.

Thiopentone 20 mg kg-1, ketamine 8 mg kg-1 and minaxolone 2 mg kg-1 were administered to fasting greyhound dogs. Mechanical and electrical activities from stomach, duodenum, jejunum and ileum were recorded using strain gauge force transducers and implanted bipolar electrodes. Thiopentone and minaxolone caused intense activity in the duodenum and jejunum (phase I and phase II of the interdigestive cycle), but not the stomach or ileum. The activity following injection of thiopentone or minaxolone was prevented by premedication with either atropine 0.05 mg kg-1 or pentolinium 0.2 mg kg-1. Ketamine had no influence on gastrointestinal activity or the response to thiopentone or minaxolone. None of these drugs altered the basal electrical rhythm of the intestine.

Dose beta-blockade affect surgical performance? a double blind trial of oxprenolol.

Heart rates of surgeons rise when they carry out operations and this rise is abolished by beta-blockade. In an assessment of the effect of oxprenolol on surgical performance a group of surgeons took double blind either oxprenolol 40 mg or a matching placebo. Oxprenolol abolished increases in heart rate (P < 0.001) but had no effect on a profile of performance test assessing tremor, suturing accuracy and co-ordination. Reaction time of the surgeons was significantly slowed by oxprenolol (P < 0.01). Using a self-administered visual analogue scoring system the surgeons recorded no subjective changes in mood after beta-blockade and were surprisingly unaware of whether they had taken oxprenolol or placebo.

Heart-rates of surgeons during operations and other clinical activities and their modification by oxprenolol.

The heart-rates of surgeons were recorded by ambulatory monitoring methods while they operated and while they conducted surgical outpatient clinics. Heart-rates during operations were also monitored 1 hour after the surgeons had taken an oral dose of 40 mg oxprenolol. During operations the mean heart-rate of 8 surgeons was 121/min with maximum rates in some cases of over 150/min. The tachycardia was abolished by 40 mg of oxprenolol which reduced heart-rates during operations to below those recorded during surgical outpatient clinics. Physical work necessary to reproduce the mean heart-rate whilst operating could not be sustained for more than 10--15 min.