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Biomedical subjects

J Ponte

Publications and source records attributed to J Ponte.

At least 19 recordsLinked to original sources

Morphine-6-glucuronide: effects on ventilation in normal volunteers.

The respiratory responses to intravenous morphine sulphate (0.12 mg/kg), morphine-6-glucuronide (M6G: 0.03 mg/kg) and placebo were assessed in 6 healthy volunteers, using a single blind randomised crossover design. Five of these subjects underwent an additional study of M6G at 0.06 mg/kg. Respiratory rate, minute volume and end-tidal CO2 were continuously measured using a low resistance non-rebreathing circuit, a mass spectrometer and a dry gas meter. The ventilatory responses to CO2 exposures (5.5% for 4 min) were assessed 40 and 20 min before, and 20, 40 and 80 min after drug administration. Following placebo and M6G (at both doses) no change in end-tidal CO2 occurred whilst the subjects were breathing air, whereas following morphine a significant rise was seen (P less than 0.05). Morphine reduced the ventilatory response to 5.5% CO2 at all times tested (P less than 0.05) and M6G (at both doses) reduced the response to CO2 at 20 and 40 min after administration, but to a lesser degree than did morphine (P less than 0.05).

Adult

Extradurals and shivering: effects of cold and warm extradural saline injections in volunteers.

We tested the hypothesis that cooling the extradural space may provoke shivering, by giving three 80-ml extradural injections of warm (39.8 +/- 1.2 degrees C) or cold (17 +/- 2.2 degrees C) saline to four healthy volunteers, whilst recording central temperature and electromyographic activity from four muscles. The first injection (always cold) did not induce shivering in any of the subjects. The second and third injections, randomly cold or warm, were given after induction of shivering with cold blankets, but had no detectable effects on the intensity of shivering. This suggests that shivering in extradural anaesthesia does not result solely from cooling of the extradural space.

Adult

Shivering during epidural anesthesia.

The authors tested the hypothesis that during epidural anesthesia: 1) shivering-like tremor is primarily normal thermoregulatory shivering; 2) hypothermia does not produce a subjective sensation of cold; and 3) injectate temperature does not influence tremor intensity. An epidural catheter was inserted into ten healthy, nonpregnant volunteers randomly assigned to skin-surface warming below the T10 dermatome (warmed group) or no extra warming (unwarmed group). Each volunteer was given two 30-ml epidural injections of 1% lidocaine (16.0 +/- 4.7 degrees C and 40.6 +/- 0.7 degrees C at the catheter tip), in random order separated by at least 3 h. Skin-temperature gradients (forearm-fingertip) and tympanic membrane and average skin temperatures were recorded; significant vasoconstriction was prospectively defined as a gradient greater than or equal to 4 degrees C. Integrated electromyographic (EMG) intensity was recorded from four upper-body muscles. Overall thermal comfort was evaluated using a visual analog scale. Tympanic membrane temperatures decreased significantly in the unwarmed group (n = 6). Tremor occurred following ten of 12 injections in unwarmed volunteers, but only following one of eight injections in the warmed group. Integrated EMG intensity did not differ significantly following epidural injection of warm and cold lidocaine: tremor started when tympanic membrane temperature decreased about 0.5 degrees C and continued until central temperature returned to within 0.5 degrees C of control. Tremor always was preceded by hypothermia and vasoconstriction in the arms. Thermal comfort increased in both groups after epidural injection, with maximal comfort occurring at the lowest tympanic temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Carotid body chemoreceptor response to prolonged hypoxia in the rabbit: effects of domperidone and propranolol.

1. The discharge of single afferent chemoreceptor fibres was recorded from the cut sinus nerve over periods of 60 or 90 min of constant, isocapnic hypoxia (arterial O2 pressure, Pa,O2, 3.13-5.25 kPa), in twenty anaesthetized rabbits, after dividing the sympathetic supply to the carotid body. 2. Under control conditions, discharge after 60 min of hypoxia adapted to a mean (S.E.M.) of 71.95 (2.75)% of that attained at 5 min of hypoxia in twenty-three hypoxic experiments. This adaptation was more pronounced when Pa,O2 was lower than 4 kPa (30 Torr). 3. Domperidone (1 mg kg-1 bolus + 1 mg kg-1 h-1 infusion I.V.), increased normoxic afferent discharge by a mean of 142%. In ten experiments, discharge after 60 min of hypoxia adapted to a mean (S.E.M.) of 56.22 (+/- 3.40)% of that attained at 5 min of hypoxia which was significantly different from control hypoxic runs (P = 0.006). 4. In seven experiments propranolol (1 mg kg-1 bolus + 1 mg kg-1 h-1 infusion I.V.) did not affect the normoxic discharge. The mean adaptation of discharge after 60 min of hypoxia was to 77.43 (3.97)% of discharge attained at 5 min of hypoxia, which was not significantly different from control hypoxic runs (P = 0.34). 5. Under control conditions plasma [K+] increased steadily during 60 min of hypoxia, in fourteen experiments, from a mean of 2.76 (0.14) to 2.85 (0.12) mmol l-1 but this was not significant (P = 0.21). Domperidone (n = 6) did not affect plasma [K+] at any time, but after propranolol (n = 6) it increased by a mean (S.E.M.) of 0.39 (0.09) mmol l-1 (P = 0.01) in normoxia and by a further 0.62 (0.28) mmol l-1 (P = 0.08) at 60 min of hypoxia. 6. The results suggest that the adaptation of chemoreceptor discharge to hypoxia in the rabbit is not mediated by changes in plasma [K+]; in addition, endogenous dopamine, but not noradrenaline, contributes to the maintenance of chemoreceptor discharge in prolonged hypoxia.

Action Potentials

Effect of chronic airflow limitation on resting oxygen consumption.

The work of breathing in patients with severe chronic airflow limitation is increased even at rest but little is known about the magnitude of this increase. Resting oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ) were measured in 13 patients with severe chronic airflow limitation (mean FEV1 0.78 1, vital capacity 2.1 1) and compared with those of 13 age, weight, and height matched control subjects. Whereas mean RQ was the same in the two groups (0.82), mean VO2 and VCO2 were higher in the patients (+ 18 ml min-1 and + 15 ml min-1 respectively). When VO2 was standardised for body surface area it was 10.9% higher in the patients (p less than 0.05). If the increased resting VO2 in these patients were solely due to increased activity of the respiratory muscles, it would represent a fourfold increase in the oxygen cost of breathing.

Body Surface Area

[Carcinoma in situ in localized Caroli's disease].

A new case of Caroli's disease associated with cholangiocarcinoma is reported. It is the first in situ carcinoma description. Intrahepatic biliary cysts are a predisposing condition, even if mechanism remains hypothetical.

Aged

Effect of halothane, enflurane and isoflurane on carotid body chemoreceptor activity in the rabbit and the cat.

The response of the carotid body chemoreceptors to administration of halothane, enflurane and isoflurane was tested in the rabbit and cat. In the steady-state all three volatile anaesthetics, in doses up to 1%, were mildly chemodepressant. The oxygen response curves were shifted downwards, but hypoxic stimuli below 5.3 kPa overcame this chemodepression. Two-point carbon dioxide response curves were also shifted downwards, but with no change in slope. Possible mechanisms involved in the chemoreceptor response to transient and steady-state anaesthetic administration are discussed.

Action Potentials

Effect of thiopentone, etomidate and propofol on carotid body chemoreceptor activity in the rabbit and the cat.

The response of the carotid body chemoreceptors to intracarotid administration of thiopentone, etomidate and propofol was tested in the rabbit and cat. Thiopentone 3-6 mg min-1 and etomidate 300-600 micrograms min-1 were mildly excitatory, shifting the oxygen and carbon dioxide response curves upwards. Propofol 1.5-3.0 mg min-1 was a potent chemodepressant and abolished discharge at PaO2 values greater than 8 kPa. Prolonged infusion of propofol at higher rates (6 mg min-1) abolished the response to hypoxia completely. The significance of these results is discussed in relation to the known ventilatory effects of the three anaesthetics.

Action Potentials

Interactions between hypoxia, acetylcholine and dopamine in the carotid body of rabbit and cat.

1. Acetylcholine (ACh) and dopamine (DA) were either infused into the carotid artery or applied directly to the surface of the carotid body of twenty-six rabbits and fifteen cats. Afferent discharge of single chemoreceptor units was recorded at a range of Pa,O2 (arterial O2 pressure) values during drug administration. 2. There were no observable systemic effects of either drug when applied to the surface of the carotid body. 3. Acetylcholine tended to depress afferent discharge when applied to the surface of the rabbit carotid body or when infused into the carotid sinus. In the cat, intracarotid and surface application of ACh had mild and inconsistent effects. DA consistently depressed discharge in both species independent of the route of administration. Antagonists of ACh and DA failed to abolish the chemoreceptor response to hypoxia. 4. The changes in afferent discharge elicited by all drugs were small compared with the range of discharge rates attained with physiological stimuli. The effects of ACh and DA were more marked in hyperoxia than in hypoxia for both routes of administration, disappearing at Pa,O2 values close to 20 Torr (7.5 Torr = 1 kPa). 5. A role for DA in the maintenance of the hypoxic response was investigated in six rabbits. After 15 min of hypoxia (Pa,O2 = 21.8 +/- 1.1 Torr; mean +/- S.E.M.) the discharge of single chemoreceptor fibres adapted moderately (to 79.3 +/- 5.2% of maximum discharge). Following administration of domperidone or haloperidol (1.0-5.3 mg kg-1, I.V.) the same fibres responded with equal magnitude to the onset of the hypoxic stimulus but showed a significantly larger adaptation (to 48.5 +/- 4.4%). 6. It is concluded that endogenous ACh and DA are unlikely to mediate the transduction process of the carotid body, but DA may play a role in preventing adaptation to a prolonged hypoxic stimulus.

Acetylcholine

Studies on the regenerated carotid sinus nerve of the rabbit.

1. The central end of the distally cut left carotid sinus nerve was sutured to the tunica media of the external carotid artery, 1 cm cranial to the carotid bifurcation, in nineteen rabbits. The carotid body was removed in fourteen of these rabbits but left in situ in the remaining five. After 56-165 days of recovery a neuroma was identified at the site of the suture. Ventilatory reflexes mediated by both sinus nerves were tested and afferent activity recorded from the regenerated nerve. 2. Ventilatory reflex responses to hypoxia and sodium cyanide were abolished on sectioning the right sinus nerve, whilst the hypercapnic response was maintained. 3. Electrical stimulation of the regenerated sinus nerve caused hypotension and hyperventilation. These responses were attenuated compared to stimulation of the right sinus nerve. 4. A level of afferent activity equivalent to that found in non-regeneration experiments was recorded from all regenerated sinus nerves. Whole-nerve afferent activity was modulated by changes in carotid sinus blood pressure but not by changes in Pa,O2, Pa,CO2 (arterial O2 and CO2 pressures) or intracarotid injection of sodium cyanide. 5. A minimum of thirty single afferent fibres was identified in each experiment, the vast majority of which were mechanoreceptors. In only nine experiments were chemoreceptor fibres found and only twelve chemoreceptor fibres (1.7% of total) were identified in these nine experiments. In ten experiments no chemoreceptor fibres could be found. Leaving the carotid body in situ increased the incidence of chemoreceptive preparations. A small number of fibres unresponsive to mechanical stimulation and asphyxia was also identified. 6. The responses of regenerated chemoreceptor fibres to physiological and pharmacological stimuli were generally similar to those found in control carotid body preparations. Fibres unresponsive to mechanical stimulation and asphyxia did not respond to sodium cyanide, dopamine or isoprenaline; some of these fibres were excited by nicotine. 7. The receptive fields of mechanosensitive fibres were localized on or up to 2 cm away from the neuroma. Surface application of 20-40 microliters sodium cyanide (200 micrograms ml-1) was used to localize the receptive fields of seven of the twelve chemoreceptor fibres. All seven were localized to the site of the carotid body. 8. The neuroma and site of the carotid body were examined under light and electron microscopy. Glomus tissue was absent from the neuroma but was found at the site of the carotid body. 9. In conclusion, recovery of chemoreceptor function after carotid sinus nerve section appears to be associated with reinnervation of glomus tissue.

Action Potentials

Biophysical studies of the cellular elements of the rabbit carotid body.

The carotid body is a major sensor of oxygen partial pressure in the arterial blood, and plays a role in the control of respiration. Despite extensive investigation of the structure, the cellular basis of the transduction mechanism remains poorly understood. We have developed a preparation of freshly dissociated cells from the rabbit carotid body, in which two cell types may be identified using morphological criteria. The preparation allows application of the patch clamp technique to characterize the properties of the cells which have otherwise proved difficult to study in situ. Carotid bodies of rabbits were dissociated using a combination of enzymatic and mechanical procedures. The dissociated preparation obtained consisted of clusters of spherical or ovoid cells of 12-15 microns in diameter and a distinct population of spherical cells of 8-10 microns diameter. Electron microscopic techniques were used to identify the cells present in the preparation. Again two populations of cells could be distinguished. A population of cells 10-12 microns in diameter, often found in clusters, possessed the dense-cored vesicles characteristic of Type I cells, while a population of smaller cells (diameter 5-7 microns) had peripherally condensed nuclear chromatin and fine cytoplasmic surface extensions characteristic of Type II cells. Patch clamp study of the cells showed that they represent two electrophysiologically distinct populations. The larger cells, corresponding to Type I cells, were found to be excitable, generating fast, sodium-dependent action potentials that were recorded both in the cell attached and whole cell recording configurations. The smaller Type II cells did not generate action potentials. Voltage clamp study of Type I cells allowed definition of a range of voltage-gated currents. These included an inactivating, tetrodotoxin-sensitive inward sodium current, a high threshold sustained inward calcium current, and outward potassium currents. A component of the outward current showed a dependence on voltage-gated calcium entry, and was blocked by cobalt or cadmium. Of the calcium-dependent current, a component was sensitive to apamin, and the remaining current was blocked by tetraethylammonium. Type II cells showed only a high threshold outward potassium current. These studies have thus revealed an electrophysiological differentiation that parallels the morphological differentiation of the cells of the carotid body. The Type I cell is essentially neuron-like in its properties, while the Type II cell appears to have properties resembling those of glial elements elsewhere in the nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials

Performance of transcutaneous PO2 and PCO2 dual electrodes in adults.

Three commercially-available combined PO2-PCO2 electrodes were assessed in vitro, and in adults breathing air, hypoxic and hypercapnic mixtures, for speed of response, correlation with end-tidal gas tensions and drift. Differences in the 90% response time of the individual electrodes were more marked in vitro than in vivo. Changes in end-tidal gas tensions were reflected by proportionate changes in transcutaneous oxygen and carbon dioxide (PtcO2 and PtcCO2) but, in the individual subject, PtcO2 and PtcCO2 were generally poor indicators of the end-tidal values. During steady-state recordings, the PtcO2 signal drifted upwards by more than 12 mm Hg during 140 min in vivo recording in all three electrodes, without changes in either PtcCO2 or end-tidal values. The dual electrodes tested provide non-invasive estimates of qualitative, but not quantitative, change in blood-gas tensions and are likely to have only a limited role to play in adult anaesthetic practice.

Adult

Comparison of a total intravenous anaesthetic technique using a propofol infusion, with an inhalational technique using enflurane for day case surgery.

A total intravenous anaesthetic technique with a propofol infusion for maintenance of anaesthesia was compared with an inhalational technique that used oxygen, nitrous oxide and enflurane in 98 unpremedicated patients who presented for day case surgery. Overall quality of anaesthesia during induction and maintenance was comparable in both groups. Quality of maintenance of anaesthesia in the propofol group was improved by an increase of the initial infusion rate from 12 to 15 mg/kg/hour. There was a larger decrease in arterial blood pressure after induction in the propofol group but no difference in blood pressure between the groups during maintenance. Recovery times and scores using the Steward scoring system were not significantly different. Nausea and vomiting were slightly less frequent in the propofol group.

Adult

Sedation.

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Anesthesia, Dental