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Biomedical subjects

J A Dempsey

Publications and source records attributed to J A Dempsey.

At least 163 records · Page 9Linked to original sources
PubMed1984

Changes in the VI-VCO2 relationship during exercise in goats: role of carotid bodies.

To assess the role of carotid bodies in modulating the ventilation-CO2 production relationship, steady-state responses to mild exercise were determined in goats following several experimental manipulations that led to chronic changes in resting ventilation and arterial blood gases. The experimental conditions were 1) control, 2) whole body serotonin depletion (induced by p-chlorophenylalanine, 100 mg/kg), 3) carotid body denervation (CBX), and 4) serotonin depletion with CBX. Resting values of arterial CO2 pressure (Pco2) ranged from 32 to 48 Torr. In each condition, arterial Pco2 was regulated to a similar degree in exercise due to changes in the slope of the ventilation-CO2 production relationship (delta Vi/delta Vco2) in accordance with the requirements of gas exchange. delta Vi/delta Vco2 increased with serotonin depletion both before and after CBX. The principal component of ventilation contributing to changes in delta Vi/delta Vco2 was tidal volume. These results suggest a basic property of the ventilatory control system whereby enhanced ventilatory activity at rest is associated with an increased ventilatory response to exercise via a mechanism that does not require peripheral chemoreceptors.

Animals↗
PubMed1983

Ventilatory response of goats to treadmill exercise: grade effects.

The steady-state ventilatory responses of 7 goats to treadmill exercise were studied at several different combinations of speed (0-7.7 km per hr) and grade (0-15%). Carbon dioxide production (VCO2) increased as much as 6 times the resting value. The goats responded to exercise with hyperventilation and respiratory alkalosis, which was proportional to VCO2. The increased ventilation was due chiefly to increases in breathing frequency (f). When responses to increasing speed at 0% grade were compared to those at 15% grade, there were no differences in expired minute ventilation or PaCO2. There were differences in ventilatory pattern. At a given VCO2, f was higher and tidal volume (VT) lower at 0% grade than at 15% grade. We conclude that ventilatory pattern (at a given VCO2) is influenced by the grade used during treadmill exercise and therefore stimuli other than VCO2 alone must be involved in the generation of ventilatory pattern during treadmill exercise.

Acid-Base Equilibrium↗
PubMed1983

Monoamine neurotransmitter metabolism during acclimatization to hypoxia in rats.

The levels and turnovers of NE, DA and 5HT were determined in whole brain, brain stem, cervical and thoracic spinal cord and carotid bodies (CB) of rats exposed to from 1 h to 7 days of hypobaric hypoxia (PB = 450 torr). Monoamine levels decreased only transiently upon acute exposure to hypoxia. Monoamine turnover in the CNS was estimated from the average of (a) monoamine buildup following inhibition of catabolism, and (b) monoamine breakdown following inhibition of synthesis. Hypoxic effects on CNS monoamine turnover showed that: (a) NE was not affected; (b) DA was not affected in acute hypoxia, but was reduced to about 40% of normoxia control after 1-7 days hypoxia; (c) 5HT fell 50-60% during acute hypoxia but returned to and was maintained at control over 1-7 days of hypoxia; (d) acute restoration of normoxia following acute hypoxia restored 5HT and DA to control or above and in the acclimatized animal acute normoxia increased DA and 5HT turnover to about 1.4 and 1.8 X control. In the CB, DA levels gradually increased to 4 X control after 7 days of hypoxia and further increased to 6 X control upon acute restoration of normoxia. Changes in the metabolism of both central 5HT and CB DA may be related to the mechanisms mediating ventilatory acclimatization to chronic hypoxia.

Adaptation, Physiological↗
PubMed1983

Effects of p-chlorophenylalanine on ventilatory control in goats.

The effects of tryptophan hydroxylase inhibition with p-chlorophenylalanine (PCPA; 100 mg/kg iv) on ventilatory control were studied in awake goats. Ventilation, CO2 production, and blood gases were measured 16-24 h after PCPA at rest and during mild exercise in normoxia and at rest in hypoxia and hypercapnia. PCPA increased ventilation 36% at rest, predominantly through an effect on respiratory frequency, and decreased arterial PCO2 (PaCO2) 6.5 Torr. Ventilatory gain in exercise (delta VI/deltaVCO2) was increased 20% by PCPA thereby maintaining PaCO2 at its new resting value. Hypoxia (fractional inspired O2 concentration = 0.12) had little effect on ventilation or PaCO2 at rest, either on control or on PCPA test days. Ventilatory sensitivity to CO2 at rest (delta VI/delta PaCO2) was unaffected by PCPA. Bilateral carotid body denervation (CBX) was performed in the animals, and experiments were repeated 3 mo after the first administration of PCPA. CBX alone decreased ventilation 29% and increased PaCO2 9.4 Torr. Administration of PCPA increased ventilation 35%, decreased PaCO2 by 10.2 Torr at rest, and increased ventilatory gain in exercise 26%. Thus carotid bodies are not necessary for the ventilatory response to PCPA. Furthermore, the primary neural pathways associated with exercise or hypercapnia are not specifically affected by inhibition of serotonin metabolism via PCPA.

Animals↗
PubMed1983

Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation.

The effect of sleep state on ventilatory rhythmicity following graded hypocapnia was determined in two normal subjects and one patient with a chronic tracheostomy. Passive positive-pressure hyperventilation (PHV) was performed for 3 min awake and during nonrapid-eye-movement (NREM) sleep with hyperoxia [fractional inspired O2 concentration (FIO2) = 0.50], normoxia and hypoxia (FIO2 = 0.12). During wakefulness, no immediate posthyperventilation apnea was noted following abrupt cessation of PHV in 27 of 28 trials [mean hyperventilation end-tidal CO2 partial pressure (PETCO2) 29 +/- 2 Torr, range 22-35]. During spontaneous breathing in hyperoxia, PETCO2 rose from 40.4 +/- 0.7 Torr awake to 43.2 +/- 1.4 Torr during NREM sleep. PHV during NREM sleep caused apnea when PETCO2 was reduced to 3-6 Torr below NREM sleep levels and 1-2 Torr below the waking level. In hypoxia, PETCO2 increased from 37.1 +/- 0.1 awake to 39.8 +/- 0.1 Torr during NREM sleep. PHV caused apnea when PETCO2 was reduced to levels 1-2 Torr below NREM sleep levels and 1-2 Torr above awake levels. Apnea duration (5-45 s) was significantly correlated to the magnitude of hypocapnia (range 27-41 Torr). PHV caused no apnea when isocapnia was maintained via increased inspired CO2. Prolonged hypoxia caused periodic breathing, and the abrupt transition from short-term hypoxic-induced hyperventilation to acute hyperoxia caused apnea during NREM sleep when PETCO2 was lowered to or below the subject's apneic threshold as predetermined (passively) by PHV. We concluded that effective ventilatory rhythmogenesis in the absence of stimuli associated with wakefulness is critically dependent on chemoreceptor stimulation secondary to PCO2-[H+].

Adult↗
PubMed1983

Metabolic acids and [H+] regulation in brain tissue during acclimatization to chronic hypoxia.

Ventilatory acclimatization, arterial acid-base status, brain stem and cortex metabolic acids, and high-energy phosphates were determined in rats during 2-h to 7-days exposure to two levels of hypoxia (O2 inspiratory pressure 75 and 58 Torr), and upon acute restoration of normoxia. Brain lactate concentrations increased during acute exposure to both moderate hypoxia (+52% in cortex and +61% in stem) and severe hypoxia (+211% in cortex and +163% in stem), and during chronic hypoxia remained unchanged or decreased, respectively, as hyperventilation progressed and arterial O2 content rose. Restoration of normoxia after chronic hypoxic exposure resulted in continued hyperventilation and elevated lactate concentrations. Brain intracellular pH was unchanged throughout moderate hypoxia and during severe hypoxia, became acid during acute exposure, but was completely compensated after 72 h of continued hypoxia. Preventing the hypocapnia (via increased inspiratory fraction of CO2) during acute hypoxia or restoring normocapnia during posthypoxic normoxia revealed the effects of hypocapnia independently of hypoxemia. Hypocapnia accounted for all of the changes in brain lactate concentration during moderate hypoxia but only 40-60% of the lactate changes during severe hypoxia. We speculate that the observed changes in plasma and brain tissue metabolic acids and in plasma [HCO-3] would acidify cerebral interstitial fluid (ISF) in chronic hypoxia; however, the time course of this change in ISF acid-base status would be quite different between the two levels of hypoxia and uncorrelated with the patterns of ventilatory acclimatization.

Acid-Base Equilibrium↗
PubMed1983

Method for cisterna magna perfusion of synthetic cerebrospinal fluid in the awake goat.

We developed a method to produce stable alterations in the ionic composition of the medullary chemoreceptor environment. A double-lumen catheter system (Hustead epidural needle and epidural catheter) was placed through a plastic cisternal guide tube into the cisterna magna of awake goats. A push-pull perfusion system using a modified infusion pump delivered matched cerebrospinal fluid (CSF) perfusate inflow and outflow of 3.1 ml/min. Ventilation changed within 15 min of the initiation of perfusion and reached steady state within 45-65 min. Steady-state ventilatory responses could be maintained for up to 240 min and were readily reversed in response to a change in [HCO-3]. Perfusions with normal mock CSF ( [HCO-3] = 23 meq/l) caused no change from nonperfused values. Over the range of CSF perfusate [HCO-3] used (13.5-34.4 meq/l), the gain of the steady-state ventilatory response averaged 0.6 Torr X meq-1 X l. [3H]inulin and [HCO-3] were equal in inflow and outflow by 20-30 min of perfusion indicating complete mixing of bulk CSF in the cistern. Anatomic study after methylene blue dye perfusion showed dye distribution to subarachnoid spaces of midbrain, cervical cord, cerebellum, medulla, and most of the cortex but not to any ventricles. This perfusion technique produces prolonged, stable, reproducible, and repeatable changes in the medullary chemoreceptor ionic environment of awake goats, is relatively atraumatic, and permits high flow through the cisternal subarachnoid space.

Animals↗
PubMed1983

Ventilation and oxygenation changes during sleep in cystic fibrosis.

Oxygen desaturation during sleep in patients with cystic fibrosis has been attributed to changes in the end-expiratory volume during rapid eye movement (REM) sleep, leading to worsening of the ventilation-perfusion distribution. The purpose of this study was to describe the changes in ventilation during sleep that may contribute to the oxygen desaturation. Six adolescent males with moderate to severe cystic fibrosis were studied. It was concluded that hypoventilation during REM may contribute to oxygen desaturation in patients with cystic fibrosis.

Acid-Base Equilibrium↗
PubMed1982

Ventilatory adaptations to resistive loading during wakefulness and non-REM sleep.

Ventilatory and timing responses to repetitive and sustained inspiratory resistive loading were assessed in six naive male subjects during wakefulness (AW) and non-REM sleep (NREM). In five of six subjects, tidal volume (VT) was maintained or increased with repetitive five-breath loading periods during wakefulness. In these five subjects, mouth occlusion pressure (P100) increased with loading during AW (1.8 +/- 0.5 control vs. 2.2 +/- 0.4 cmH2O loaded, P less than 0.05), but not during NREM (2.1 +/- 1.5 control vs. 2.1 + 1.5 cmH2O loaded). For each state, VT and frequency (f) responses to sustained loads were similar to responses to five-breath loads. During sustained loading; a) VT increased 35% during AW, decreased 28% during NREM, b) f decreased 35% during AW, increased 6% during NREM, c) minute ventilation (VE) decreased 12% during AW, decreased 23% during NREM. Ventilatory responses persisted until arousal (0.4--1.7 min) in NREM. With repetitive loading: a) inspiratory duration (TI) increased during AW but did not change during NREM, b) "duty cycle" (TI/TT) increased with loading in both states. These findings suggest that a) NREM abolishes between-breath augmentations in P100, b) within-breath load compensation is operant during both AW (preserved VT) and NREM (failure of predicted TI prolongation) by differing mechanisms, c) arousal may be a ventilatory compensation to inspiratory resistive loading in NREM.

Adult↗
PubMed1982

Ventilation-perfusion ratio distributions by mass spectrometry with membrane catheters.

We previously developed a quadrupole mass spectrometer system for measuring gas phase concentrations of multiple inert gases at trace levels. A new inlet with two silicone rubber membrane catheters now allows quantitative analysis of the inert gas concentrations in both blood and gas phase samples. We have determined the sensitivity, linearity, and reproducibility of this system by measuring blood-to-gas phase calibration curves for the following inert gases: sulfur hexafluoride, krypton, Freon 12, enflurane, diethyl ether, and acetone. We have used our mass spectrometer system to obtain multiple inert gas elimination data from three anesthetized, spontaneously breathing dogs. We conclude that our dual-membrane mass spectrometer system provides useful measurements of trace multiple inert gas concentrations in both blood and gas phase samples. Furthermore, the inert gases in blood can be measured directly without having to extract them into a gas phase, and the multiple inert gas elimination data acquired with our system can be used to provide estimates of ventilation-perfusion ratio distributions. Our mass spectrometer technique provides an alternative to the gas chromatographic approach for these measurements.

Anesthesia, General↗
PubMed1981

Interregional differences in brain intracellular pH and water compartmentation during acute normoxic and hypoxic hypocapnia in the anesthetized dog.

Interregional differences in intracellular pH (pHi) in brain tissue, and its regulation following 1 and 5 h of respiratory alkalosis (with and without hypoxemia) were determined in N2O anesthetized dogs. Two techniques for pHi estimation were used (TCO2 and 14C-DMO) and included corrections for measured extracellular fluid (35SO4(2-)) space (ECS). Cortical pHi by the two techniques agreed closely in control and in 3 of the 4 experimental conditions, suggesting: (a) our estimation of extracellular fluid (ECF) [HCO3-] from measured CSF [HCO3-] was a valid assumption; and (b) our method had sufficient resolution to determine the magnitude of brain pHi regulation during respiratory acid-base disturbances. When moderate normoxic respiratory alkalosis (PaCO2 approximately 25 mm Hg) was imposed for 5 h, pHi (in most brain regions) was well regulated and always exceeded the incomplete regulation noted in bulk CSF. When moderate hypoxemia (PaO2 approximately 45 mm Hg) accompanied hypocapnia, pHi was more closely regulated during the early phase (1 h) of respiratory alkalosis. Increased levels of metabolic acids (especially lactic acid) were critical to brain pHi regulation during the initial hour of respiratory alkalosis and accounted for much of the independent effect of hypoxemia on pHi regulation. However, these metabolic acids remained unchanged as pHi was more completely regulated between 1 and 5 h of continued hypocapnia or hypoxic hypocapnia. This time-dependent regulation of pHi may involve some regulatory role for changed transmembrane fluxes of H+ and/or HCO3-. Significant interregional differences were observed in both pHi and in ECS; with tendencies toward more alkaline pHi and lower ECS in brain stem and white matter. With respiratory alkalosis ECS fell and intracellular fluid increased in both cortex and caudate nucleus, possibly reflecting an osmotic effect of increased metabolic acid levels or reduction in cell membrane ion pumping.

Acid-Base Equilibrium↗
PubMed1981

Correction of CO2 retention during sleep in patients with chronic obstructive pulmonary diseases.

Three normal subjects and 5 patients with chronic obstructive pulmonary disease and chronic CO2 retention were studied to determine the effect of chronic ventilatory stimulation with medroxyprogesterone acetate (MPA) on ventilatory control and pulmonary gas exchange during sleep. All patients had lowered PaCO2 after treatment with MPA while awake. Using a randomized application of treatment and placebo conditions, 4 wk of MPA therapy in the normal subjects caused a reduction in PaCO2 while awake (delta PaCO2 -4 to -7 mmHg) and during non-REM sleep (delta PaCO2 -5 to -7 mmHg). The response consisted of an increased minute ventilation (VE), tidal volume (VT), and mean inspiratory flow (VT/TI) awake and during non-REM sleep. In the patient group, 4 wk of MPA therapy caused significant reductions in PaCO2 while awake (from 54 +/- 2 to 47 +/- 2 mmHg) and during non-REM sleep (from 57 +/- 2 to 49 +/- 2 mmHg). Minute ventilation tidal volume, and mean inspiratory flow increased to a similar extent while awake and during all sleep stages. Improvement in SaO2 during sleep induced by treatment was attributable to an increase in alveolar ventilation rather than a decrease in alveolar-arterial oxygen partial pressure difference. Medroxyprogesterone acetate elicited chronic increases in inspiratory effect, tidal volume, and alveolar ventilation while awake and during all sleep stages in selected patients with chronic CO2 retention despite severe mechanical impairment and maldistribution ventilation:perfusion. The drug drives ventilation by a mechanism of action that is independent of many other peripheral and "central" ventilatory stimuli and/or inhibitors, including higher central nervous system influenced on ventilatory control that are dependent on the state of wakefulness.

Clinical Trials as Topic↗