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Biomedical subjects

D S Ward

Publications and source records attributed to D S Ward.

At least 55 records · Page 3Linked to original sources
PubMed1993

Effect of plasma osmolality on steady-state fluid shifts in perfused cat skeletal muscle.

Fluid redistribution in isolated perfused cat calf muscle caused by rapid increases in plasma osmolality was studied using NaCl or sucrose. Extracellular tracers (51Cr-labeled EDTA or [3H]mannitol) were added to the perfusate 90 min before solutes were added, and samples were taken from plasma immediately before osmolality was increased and 17, 40, and 65 min later. Interstitial fluid volume (IFV) was calculated as extracellular volume (ECV) minus plasma volume (Evans blue dye). Total tissue water changes (delta TTW) were measured by continuous recording of tissue weight. Change in intracellular volume (delta ICV) was obtained from delta TTW--delta IFV. TTW, IFV, ICV, and plasma osmolality were in steady state after 17 min. Changes in hydrostatic and colloid osmotic pressure were insignificant in comparison with small-molecule osmotic pressure changes. The apparent volume of TTW participating in the fluid shift averaged 65 +/- 1 ml/100 g (SE) over a wide range of osmolality increases. In contrast to the large changes in TTW, IFV was not altered by osmolality. Thus decreases in TTW were similar to cell dehydration. Hence, increases in plasma volume induced by hypertonic fluids may come entirely at the expense of cell volume, not interstitial volume.

Animals↗
PubMed1993

Weekly variability in total body water using 2H2O dilution in college-age males.

The variability in measuring total body water (TBW) using deuterium oxide (2H2O) dilution has not been extensively tested. The purpose of this study was to determine the variability of weekly measurements of TBW utilizing the 2H2O dilution technique in 10 males and to determine the amount of biological versus technical variability using a generalizability ANOVA (GENOVA). Ten male subjects aged 21-32 yr were tested on four separate occasions for body weight (BW), underwater weight (UwWt), and TBW. BW remained quite stable across the four sessions with a 0.7% coefficient of variation (CV). Both UwWt and TBW had a CV of 4% across the four sessions. No differences were found between TBW estimates from plasma, saliva, or urine. GENOVA analysis determined that 25-50% of the total variability in measuring TBW was attributed to the sample analysis/separation procedures. Four percent of the TBW in these subjects was 1.8 l. This technique would therefore not be expected to detect changes less than 0.9 l (50% of 1.8 l). The estimates of %FAT from TBW were lower but not significantly different from UwWt. Blood, urine, and saliva were able to produce similarly repeatable measures of TBW.

Adult↗
PubMed1993

Self-selected exercise intensity of habitual walkers.

This study assessed self-selected exercise intensity of habitual walkers. Twenty-nine healthy adults (22 females, 7 males; age (mean +/- SD) = 34.9 +/- 8.6 yr) performed a typical exercise walk while walking speed was measured by an unseen observer. On a subsequent occasion, the subjects walked at the same pace on a treadmill while several variables related to exercise intensity were measured. The mean self-selected walking pace was 1.78 +/- 0.19 m.s-1. Mean percents of VO2max and HRmax elicited by the treadmill exercise were 52 +/- 11% and 70 +/- 9%, respectively. Mean MET level was 5.2 +/- 1.2, and ratings of perceived exertion (RPE) averaged 10.9 +/- 1.6. Based on reported frequency and duration of walking, weekly energy expenditure in exercise walking was estimated to be 1127 +/- 783 kcal.wk-1. These data suggest that the self-selected exercise intensity of healthy, habitual exercise walkers meets the American College Sports Medicine's recommendation for improvement of cardiorespiratory fitness. These data further suggest that, in this population, the average weekly energy expended through walking reaches a level associated with improvements in health and longevity.

Adult↗
PubMed1993

The effects of large-dose flumazenil on midazolam-induced ventilatory depression.

Flumazenil, a benzodiazepine antagonist, clearly reverses midazolam-induced sedation; reversal of ventilatory depression has not been as well demonstrated. Thirty-two subjects completed this randomized, double-blind, placebo-controlled study investigating the dose-response relationship and duration of flumazenil's effects on ventilatory depression and hypnosis induced by a continuous midazolam infusion. A computer-controlled infusion of midazolam was used to titrate the predicted midazolam plasma concentration to a level at which subjects were unresponsive to verbal commands and then to maintain that concentration. Measurements of ventilation and hypnosis were repeated at predetermined intervals: before midazolam administration, before test drug (flumazenil [1, 3, or 10 mg] or placebo), and 5, 30, 60, 120, and 180 min after test drug administration. Ventilation and tidal volume were measured during an isocapnic hyperoxia clamp at a PETCO2 of 46 mm Hg (VE46 and VT46, respectively). A pseudo-rebreathing technique was used to measure the hypercapnic ventilatory response (HCVR) slope and ventilation intercept at a PETCO2 of 58 mm Hg (VE58). Midazolam reduced VE46, VT46, and VE58, as well as hypnosis scores, in all test drug groups. The reduction in HCVR slope, however, was significant only when all 32 subjects were considered in aggregate. All three doses of flumazenil reversed hypnosis and also reversed the reduction in VE46 and VT46 within 5 min. The reduction in VE58, however, was reversed less consistently. Flumazenil's effect on VE46 and VT46 lasted at least 30 min after 1 mg and at least 60 min after 3 mg, paralleling the effect of these doses on hypnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Voluntary dehydration and heat intolerance in cystic fibrosis.

Although exercise may be beneficial in cystic fibrosis (CF), patients' low tolerance to climatic heat stress means that physical exertion can increase morbidity and mortality. We postulated that the high salt content of CF patients' sweat and the consequent absence of body-fluid hyperosmolality during a long episode of sweating might deprive such patients of a thirst stimulus. Eight children with CF (four boys, four girls; aged 9.5-14.1 years) and eight controls, matched for age and sex, attended two randomly ordered sessions of exercise (cycling) in a chamber at 31-33 degrees C, relative humidity 43-47%. 20 min bouts of exercise (at 45% of predetermined maximum oxygen uptake) were interspersed with 25 min rest periods. At one session, chilled water was given every 15-20 min to replace fluid lost; at the other, drinking was guided by the child's thirst. At the thirst-guided session, CF patients drank much less than the controls did (0.80% vs 1.73% initial body weight) and lost twice as much fluid (1.57% vs 0.78% initial body weight). The recovery of heart rate after exercise was slower in CF patients, but there were no other signs of heat strain. The groups did not differ in any variable during the forced drinking session. We conclude that children with CF underestimate their fluid needs and undergo excessive dehydration during extended exposure to hot conditions.

Adolescent↗
PubMed1992

Modelling the dynamic ventilatory response to hypoxia in humans.

A two-component dynamic model was used to describe the ventilatory response to sustained hypoxia in humans. One component (Xs) represents the stimulating effects of hypoxia and the other component (Xd), the hypoxic ventilatory decline. The total ventilatory response to hypoxia is represented by the sum of the two components. A nonlinearity is included to account for the nonlinear steady-state ventilatory response to hypoxia. A sensitivity analysis of the model indicates that, with a step change in F(ETO2) as the input, all the parameters can be estimated from the data except for the nonlinearity. The relative sensitivity of the parameters from the model analysis was confirmed in an experimental study. However, comparing steps into hypoxia versus steps out of hypoxia we found a decrease in the gains of both components. The most likely explanation for the decrease in the gains is that the combination of Xs and Xd is not entirely additive. Other models may be required to completely describe the ventilatory response to inputs more complex than steps.

Adult↗
PubMed1992

Effect of dopamine on ventilatory response to incremental exercise in man.

We investigated whether dopamine, an inhibitory neuromodulator in the carotid body, would alter the ventilatory response typically associated with metabolic (lactic) acidosis during exercise. Six subjects performed incremental cycle ergometer exercise to exhaustion during infusions of dopamine (3 micrograms.kg-1.min-1) or saline. Ventilation and pulmonary gas exchange were computed breath-by-breath; arterialized venous blood was collected every 90 sec for measurement of lactate, potassium and blood gases. The resting ventilatory response to an isocapnic step decrease in end-tidal PO2 to 50 Torr was used as an index of carotid body drive. Dopamine diminished the hypoxic ventilatory response but had no effect on the ventilatory response during exercise. Peak lactate, potassium, and ventilation were unaffected by dopamine, and the degree of respiratory compensation for the metabolic acidosis was the same as in control experiments. Therefore, either the carotid bodies respond differently to hypoxia than to acute metabolic acidosis and/or hyperkalemia during heavy exercise, or the carotid bodies are not the sole mediators of hyperventilation above the lactate threshold.

Adult↗
PubMed1992

Does a subanesthetic concentration of isoflurane blunt the ventilatory response to hypoxia?

The normal ventilatory response to the sudden imposition of sustained hypoxia is characterized by an acute increase followed by a modest decline in ventilation. Since subanesthetic concentrations of potent inhalational anesthetics greatly attenuate the acute response, we hypothesized that ventilation might decrease to less than normoxic levels when hypoxia is sustained. We therefore measured the ventilatory response to 20 min of sustained hypoxia (PETO2 45 mmHg) at two levels of strict isocapnia--normocapnia (PETCO2 1-2 mmHg above resting) and hypercapnia (PETCO2 49 mmHg)--in eight healthy male subjects during inhalation of 0.1 MAC isoflurane or carrier gas (control). An abrupt end-tidal step from normoxia to isocapnic hypoxia was induced using a dynamic end-tidal forcing system. Isoflurane and control experiments were performed on separate days; the order of isoflurane and control days and the order of normocapnia and hypercapnia within days were randomized. Subjects were studied while fasted, always at the same time of day, and were required to watch a documentary videotape to minimize differences in level of consciousness. With normocapnia, there was no difference in ventilation at any time between isoflurane and control (prehypoxic 9.6 +/- 1.5 vs. 9.5 +/- 2.6 1/min, peak hypoxic 24.7 +/- 10.4 vs. 26.2 +/- 10.4 1/min, final hypoxic 15.0 +/- 4.4 vs. 15.9 +/- 3.5 1/min; mean +/- SD). With hypercapnia, prehypoxic ventilation increased to the same level for isoflurane and control (24.8 +/- 6.7 vs. 24.8 +/- 9.6 1/min). Although peak hypoxic ventilation was slightly less in isoflurane than in control hypercapnic experiments, this was not significant (49.6 +/- 16.3 vs. 56.5 +/- 24.3 1/min; P = .22).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate.

Dexmedetomidine (DMED) is a highly selective centrally acting alpha 2-adrenergic agonist thought to provide significant sedation without appreciable ventilatory effects. This double-blind, placebo-controlled experiment evaluated four dose levels of DMED (0.25, 0.5, 1.0, and 2.0 micrograms/kg intravenously over 2 min) in 37 healthy male volunteers. Measurements of sedation, arterial blood gases, resting ventilation, hypercapnic ventilatory response (HVR), and metabolic rate (O2 consumption and CO2 production) were performed at baseline, 10 min after DMED infusion, and thereafter at the end of each subsequent 45-min period. DMED caused sedation resulting in loss of responsiveness in most of the subjects administered 1.0 and 2.0 micrograms/kg; sedation was evident for 195 min following 2.0 micrograms/kg (P < .05). Ten minutes following infusion of 1.0 and 2.0 micrograms/kg, PaCO2 had increased by 5.0 and 4.2 mmHg, respectively (P < .05), and 60 min following 2.0 micrograms/kg, VE had decreased by 28% (P < .05). The placebo group showed a progressive increase in the HVR slope (50% increase by 330 min following the infusion; P < .05). Overall, across all the DMED doses, the slope was decreased (P < .05) at all times after DMED. The calculated ventilation at a PaCO2 of 55 mmHg was decreased (39%; P < .05) 10 min following 1.0 and 2.0 micrograms/kg, returning to control values by 285 min following 2.0 micrograms/kg. O2 consumption increased 16% (P < .05) at 10 min following 2.0 micrograms/kg; CO2 production decreased (22% at 60 min). By 5 h postinfusion, both had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Effects of intravenous dexmedetomidine in humans. II. Hemodynamic changes.

Dexmedetomidine (DMED) is a novel clonidine-like compound known to have sedative, analgesic, and cardiovascular stabilizing qualities. DMED is a more highly selective alpha 2-adrenergic agonist than clonidine. This investigation examined the hemodynamic effects of four selected iv doses in consenting healthy male volunteers. In a randomized, double-blind, placebo-controlled trial subjects received 0 (n = 9), 0.25 (n = 6) 0.5 (n = 6), 1.0 (n = 6), or 2.0 (n = 10) micrograms/kg of DMED by infusion (2 min). ECG, heart rate (HR), arterial blood pressure (MABP), bioimpedance cardiac output (CO), and plasma catecholamines concentrations (CA) were monitored from 90 min before to 360 min after infusion. Plasma DMED concentrations were measured. DMED produced a maximum decrease in MABP at 60 min of 14%, 16%, 23%, and 27% for the 0.25, 0.5, 1.0, and 2.0 micrograms/kg groups, respectively (P < .05). At 330 min MABP remained below baseline by 8% and 17% at the two largest doses (P < .05). Both HR and CO decreased maximally by both 17% at 105 min. The two largest doses produced a transient (peak at 3 min lasting < 11 min) increased in MABP (16 +/- 2.5 and 24 +/- 10 mmHg, respectively; P < .05) with a concomitantly reduced CO (41%, 2 micrograms/kg; P < .05) and HR (22%, 2 micrograms/kg; P < .05), whereas systemic vascular resistance doubled. Even the lowest dose decreased CA immediately to values close to 20 pg/ml for 5 h. A 2-min iv infusion of DMED produced a transient increase in MABP and a longer lasting decrease in MABP and CA. These DMED doses were well tolerated in the healthy volunteers.

Adolescent↗
PubMed1991

Effect of i.v. midazolam on the ventilatory response to sustained hypoxia in man.

The ventilatory response to isocapnic, sustained hypoxia is characterized by initial hyperventilation followed by ventilatory decline. The ventilatory response to isocapnic sustained hypoxia during i.v. administration of midazolam was assessed in five healthy subjects. Compared with control experiments, the hyperventilatory effect of hypoxia was not decreased following administration of midazolam. The hypoxic ventilatory change was significantly greater with midazolam because of a decrease in tidal volume.

Adult↗
PubMed1991

Dynamic response of the peripheral chemoreflex loop to changes in end-tidal O2.

We studied the peripheral ventilatory response dynamics to changes in end-tidal O2 tension (PETO2) in 13 cats anesthetized with alpha-chloralose-urethan. The arterial O2 tension in the medulla oblongata was kept constant using the technique of artificial perfusion of the brain stem. At constant end-tidal CO2 tension, 72 ventilatory on-responses due to stepwise changes in PETO2 from hyperoxia (45-55 kPa) to hypoxia (4.7-9.0 kPa) and 62 ventilatory off-responses due to changes from hypoxia to hyperoxia were assessed. We fitted two exponential functions with the same time delay to the breath-by-breath ventilation and found a fast and a slow component in 85% of the ventilatory on-responses and in 76% of the off-responses. The time constant of the fast component of the ventilatory on-response was 1.6 +/- 1.5 (SD) s, and that of the off-response was 2.4 +/- 1.3 s; the gain of the on-response was smaller than that of the off-response (P = 0.020). For the slow component, the time constant of the on-response (72.6 +/- 36.4 s) was larger (P = 0.028) than that of the off-response (43.7 +/- 28.3 s), whereas the gain of the on-response exceeded that of the off-response (P = 0.031). We conclude that the ventilatory response of the peripheral chemoreflex loop to stepwise changes in PETO2 contains a fast and a slow component.

Animals↗
PubMed1991

Ventilatory response to sustained hypoxia during exercise.

The ventilatory stimulating effects of hypoxia occurring at carotid bodies are potentiated by exercise. However, hypoxia also has central ventilatory depressive effects; the potential interactions between this hypoxic depression and exercise have not been studied. We examined the ventilatory response to a 20 min period of isocapnic hypoxia (end-tidal O2, PETO2, of 50 mm Hg), preceded and followed by a 5 min period of isocapnic hyperoxia in seven normal adult males at rest and during moderate exercise (45-75 W). When hypoxia was introduced at rest (PETO2 = 42 mmHg), ventilation initially increased from 13.73 +/- 3.04 (mean +/- SD) to 23.69 +/- 5.48 1.min-1 and then slowly declined to 19.01 +/- 4.68 1 min-1. The increase was caused by increases in tidal volume and respiratory frequency, but the decline was solely in tidal volume. During a background of moderate exercise (PETCO2 = 46 mmHg), introduction of hypoxia caused ventilation to increase from 30.84 +/- 6.31 to 56.44 +/- 10.58 1.min-1. Ventilation subsequently did not decline; at the end of the hypoxic period, ventilation was 57.06 +/- 12.59 1.min-1. The increase was also associated with an increase in tidal volume and respiratory frequency, as seen as rest, but with much larger magnitudes. Despite the absence of ventilatory decline, there was still a decline in tidal volume, but it was compensated by an increase in respiratory frequency. We conclude that exercise potentiated the acute ventilatory response to hypoxia by modifying both tidal volume and respiratory frequency but that exercise abolished or greatly reduced hypoxic decline by increasing respiratory rate.

Adult↗
PubMed1990

Dynamics of the ventilatory response to central hypoxia in cats.

The dynamics of the effect of central hypoxia on ventilation were investigated by the technique of artificial perfusion of the brain stem in alpha-chloralose-urethan-anesthetized cats. A two-channel roller pump and a four-way valve allowed switching the gas exchanger into and out of the extracorporeal circuit which controlled the brain stem perfusion. When isocapnic hypoxia (arterial PO2 range 18-59 Torr) was limited to the brain stem, a decline in ventilation was consistently found. In 12 cats 47 steps into and 48 steps out of central hypoxia were made. The ventilatory response was fitted using least squares with a model that consisted of a latency followed by a single-exponential function. The latencies for the steps into and out of hypoxia were not significantly different (P = 0.14) and were 32.3 +/- 4.0 and 25.1 +/- 3.6 (SE) s, respectively. The time constant for the steps into hypoxia (149.7 +/- 8.5 s) was significantly longer (P = 0.0002) than for the steps out of hypoxia (105.5 +/- 10.1 s). The time constants for the increase and decrease in ventilation after step changes in the central arterial PCO2 found in a previous study (J. Appl. Physiol. 66: 2168-2172, 1989) were not significantly different (P greater than 0.2) from the corresponding time constants in this study (for 7 cats common to both studies). Theories of the mechanisms behind hypoxic ventilatory decline need to account for the long latency, the similarity between the time constants for the ventilatory response to O2 and CO2, and the differences between the time constants for increasing and decreasing ventilation.

Animals↗
PubMed1990

The effect of total parenteral nutrition and morphine on ventilation.

Total parenteral nutrition (TPN), specifically amino acid infusions, has been shown to increase the ventilatory response to inhaled CO2. The hypothesis tested was that morphine sulfate (known to depress ventilatory CO2 responsiveness) would diminish the augmented ventilatory CO2 response in patients receiving TPN. The influence of morphine on hyperoxic hypercapnic ventilatory response (assessed by the Read rebreathing technique) was therefore examined in four otherwise healthy subjects who were receiving TPN at home for long-standing nutritional support secondary to malabsorption syndrome (short-bowel syndrome), and in a control group of four healthy subjects who were not receiving TPN. The slope and intercept of the CO2 response was estimated by linear regression on the relationship between ventilation (VE) and end-tidal PCO2 (PETCO2). Administration of morphine in the non-TPN group elicited the expected decrease in the VE-PETCO2 slope. In contrast, morphine administration was associated with an increase in the VE-PETCO2 slope in the TPN group. While this investigation does not provide a direct indication of the mechanisms underlying the augmenting action of morphine on the ventilatory response to CO2 in subjects receiving TPN, it does suggest that patients on TPN who demonstrate no impairment of ventilatory control may be given normal doses of morphine sulphate (ie, as for pain control or preoperative medication) with no increased concern for an adverse ventilatory outcome.

Adult↗
PubMed1990

Use of the Borg scale in exercise prescription for overweight youth.

Twenty overweight children, ages 9-15 years, participated in a study on the usefulness of the Borg 6-20 perceived exertion (RPE) scale as a means for exercise prescription. As a criterion measure, they cycled at four intensities, based on pre-determined % peak power, giving RPE ratings at each load. During two return visits subjects were asked to set the resistance on the ergometer (cycle tasks) and to walk or run around an oval track (track tasks) at intensities they perceived as RPE = 7, 10, 13 and 16. HR-on-RPE regressions were compared among the criterion, cycle and track tasks. Cycle and track lines differed from the criterion (p less than .001). Subjects were, however, able to discriminate among each of the RPE prescriptions on the cycle. They overestimated intensities on the track tasks. We conclude that overweight children need additional instruction in using the Borg scale for exercise prescription.

Adolescent↗
PubMed1989

A programmable system for acquisition and reduction of respiratory physiological data.

A portable software package (TIDAL--Tools for Intelligent Data Acquisition in the Laboratory) for acquiring and analyzing respiratory physiological data is described. TIDAL supports flow-, volume-, and concentration-measuring devices, and any other instruments that produce linear analog outputs. The system allows users to specify the names and types of channels to be sampled, and the calculations involved in reducing samples to breath-to-breath values. The specification of channels and calculations is given in EDL, an Experiment Description Language designed for respiratory physiology. EDL comprises a set of internal functions (primitives) which can be combined into arbitrarily complex expressions. To simplify EDL programming, TIDAL includes a macro processor and a standard macro library; the library contains definitions for a wide variety of respiratory variables. Examples are inspiratory and expiratory times and total volumes, mean inspired and expired gas volumes and concentrations, and end-tidal concentrations. Variables that are derived from these primary data, such as respiratory quotient, are also easily specified. TIDAL is written entirely in the C programming language, with special attention to portable coding practices. The code is organized in a modular structure that eases porting to multiple hardware/compiler/operating system environments.

Expert Systems↗