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Biomedical subjects

D J Cunningham

Publications and source records attributed to D J Cunningham.

At least 19 recordsLinked to original sources
PubMed1992

Analyses of human respiratory flow patterns.

Respiratory drives follow various afferent pathways to the respiratory centres; nevertheless, steady-state breathing patterns described in terms of tidal volumes and phase durations are largely independent of the nature of the respiratory stimulus. Flow has now been recorded during steady states from six subjects in rest and hyperpnoea induced by exercise, and hypercapnia in euoxia and in hypoxia (asphyxia). Flow patterns from different stimuli were compared isopnoeically. Quantitative methods allowed the patterns to be described in terms of several variables. The consistent small differences in isopnoeic flow patterns were: In asphyxia, the initial inspiratory acceleration was greater than in hypercapnia, and the peak flow was reached earlier. In exercise the peak flow occurred later in inspiration, and the expiratory flow was maintained high until nearer the end of the phase than with the chemical drives so that the flow pattern was less angular in shape. Stimulus-dependent effects, obvious during transient changes, are greatly attenuated rather than absent in steady states.

Adult↗
PubMed1992

Dynamics of the ventilatory response in man to step changes of end-tidal carbon dioxide and of hypoxia during exercise.

1. Four human subjects exercised in hypoxia (end-tidal partial pressure of O2 (P(ET),O2) ca 55 Torr; heart rate ca 100-130 beats min-1), and the contribution to the respiratory drive of the peripheral and central chemoreflex pathways have been separated on the basis of the latencies and the time courses of the responses to sudden changes of stimulus. 2. The subjects were exposed to repeated end-tidal step changes in PCO2 of ca 3-3.5 Torr (at nearly constant P(ET),O2) and PO2 (between ca 55 and 230 Torr) at three regions along the expiratory ventilation VE-P(ET),CO2 response line (hypocapnia, eucapnia, hypercapnia). The dynamics of the ventilatory responses were calculated using a two-compartment non-linear least-squares optimization method. 3. The component of the response attributable to the peripheral chemoreflex loop may in some subjects contribute up to 75% of the ventilatory drive during mild hypocapnic hypoxic exercise and ca 72% of the total gain following steps of P(ET),CO2 during hypoxic exercise. These data support the notion that the effectiveness of the peripheral chemoreceptor pathway is enhanced in moderate exercise. 4. During hypoxic exercise, the time delays and time constants attributed to the peripheral chemoreflex pathways (ca 3.5 and 9 s respectively) and to the central chemoreflex pathways (ca 9.5 and 47 s respectively) are some of the shortest reported. 5. The dynamics of the peripheral and central chemoreflex pathways appeared to be largely independent of each other. 6. There was a notable absence of systematic change of inspiratory and expiratory durations during the step-induced transients.

Carbon Dioxide↗
PubMed1986

Patterns of breathing in response to alternating patterns of alveolar carbon dioxide pressures in man.

The time profile of alveolar PCO2 within the respiratory cycle has been forced to follow contrasting patterns in alternate breaths, in two different ways. Within-breath changes (w.b.c., with a CO2-rich inspirate supplied early or late in alternate inspirations) involved minimal alternation of end-tidal PCO2. Between-breath changes (b.b.c., with whole inspirates of CO2-free or CO2-rich gas) involved large swings of end-tidal PCO2. As previously reported (Metias, Cunningham, Howson, Petersen & Wolff, 1981), both patterns of forcing were associated with alternation of ventilation, but only when hypoxia was present. The patterns of the alternating reflex responses in 118 runs on four human subjects in steady hypoxia are described in terms of alternation of inspiratory and expiratory tidal volume, time and mean flow. These patterns often disappeared, or changed unpredictably in mid-run. The inspiratory pattern of reflex alternation depended in part on the type of forcing, but alternation of inspiratory tidal volume was usually observed with both types. No single pattern of expiratory alternation emerged as predominant. The pattern of reflex expiratory alternation was surprisingly independent of the pattern of inspiratory alternation: indeed, in w.b.c., but not in b.b.c., alternation of mean expiratory flow and of mean inspiratory flow were mutually exclusive. It is concluded that in man, as in cats and dogs, the arterial chemoreceptor pathway has access to various parts of the respiratory pattern generator, the exact response depending to some extent on the timing within the respiratory cycle. In particular, expiratory variables may be influenced directly through the arterial chemoreceptor pathway, i.e. without any supposedly mediating inspiratory alternation being demonstrable. The results are discussed briefly in relation to some current views on the organization of respiratory control.

Carbon Dioxide↗
PubMed1979

Inspiratory-expiratory responses to alternate-breath oscillation of PACO2 and PAO2.

Breath-by-breath respiratory responses of three healthy adults to imposed alternate-breath oscillation of end-tidal PCO2 (between +5 and +15 torr above the eupnoeic level) and/or PO2 (between 80 and 45 torr) were studied at rest and during mild cycle ergometer exercise. There was often alternation in inspiratory and expiratory tidal volumes and mean flows, and in expiratory duration, but not in inspiratory duration. The latency of responses, estimated by cross-correlation, corresponded closely to the lung-ear transport delay (measured by oximetry). There were two general patterns of response: in-phase, with inspiratory responses leading expiratory, and, more often, out-of-phase, with expiratory responses leading inspiratory. These patterns were associated with arrival of the onset of the alternating signal at the ear in inspiration and expiration, respectively. It is concluded that the timing of alternating humoral signals at the carotid bodies in relation to the phase of respiration determines the pattern of inspiratory-expiratory response, and that expiratory events can be independent of the previous inspiration.

Adult↗
PubMed1978

Comparative thermoregulatory responses of resting men and women.

Three men and three women were exposed to transients of air temperature (range, 16--48 degrees C). Whole-body sweating rate, local tissue heat flows, and O2 consumption in the cold were linearly related to a weighted sum of tympanic and mean skin temperatures, called "central drive," During changes in air temperature, changes in subjects' scaled estimates of thermal sensation and discomfort led changes in the physiological responses and central drive. Women's thermoregulatory responses were similar to the men's, but were shifted toward higher (warmer) values of central drive. This shift was about 0.3 degrees C for responses to heat and about 0.6 degrees C for responses to cold. With respect to the women, the mean thus showed delayed responses to the cold, and approached steady state in the cold more slowly.

Body Temperature↗
PubMed1977

The chronic toxicity of 3-chloro-4-methyl benzamine HCl to birds.

3-Chloro-4-methyl benzamine HCl (DRC-1339), an avian toxicant, was fed to five species of birds for periods up to 120 days. The 30-day LC50 of uniformly treated feed for starlings was 4.7 ppm and the 90-day LC50 was 1.0 ppm. The 28-day LC50 for coturnix was 18 ppm. The 30-day LC50 for pigeons was less than 100 ppm. Pheasants fed diets containing 2% DRC-1339 baits diluted to a rate of 286 ppm of DRC-1339 died within 22 days. Bobwhite quail fed similar diets suffered some mortality at levels as low as 2.9 ppm, but most survived 10 times this dosage level for the 120-day test period. Application of the Kenaga "Index of Chronicity", resulted in the conclusion that DRC-1339 was cumulatively toxic to birds. Reproduction in coturnix was adversely affectd by treatments at 10 ppm of DRC-1339 and above. Reproduction in pigeons was adversely affectd by a treatment of 25 ppm. In coturnix, DRC-1339 caused an increased incidence of egg breakage and decreased both egg and live chick production. In pigeons, DRC-1339 caused an increase in the proportion of infertile eggs. Reproductive ability to first generation offspring was not affected when parent coturnix and pigeons were fed DRC-1339. These data emphasize the need for care in the use of DRC-1339. The bait should be used only as registered and care exercised in storage and disposal of unused baits to avoid poisoning of nontarget species.

Animals↗
PubMed1977

The relation between hypoxia and CO2-induced reflex alternation of breathing in man.

Four healthy young volunteers, selected for the responsiveness and steadiness of their breathing, were studied in rest and mild exercise while receiving alternate inspirates of low and high PCO2 (0 and 8.6 kPa). PACO2, oscillated between ca. 6 and 7.5 kPa (45-55 torr). PAO2 was held steady at 4-7 levels between 6 and 28 kPa (45-210 torr). Thirteen separate inspiratory and expiratory variables (volumes, times, flows) were recorded and tested for reflex alternation. Matched controls were performed. Responses were generally small in relation to the scatter. Reflex alternation of any one variable was not always evident. The incidences of the responses were, in descending order, inspiratory flows and volumes, expiratory flows and volumes, expiratory duration; inspiratory duration alternated seldom, and then with only small amplitude. Reflex alternation was more likely to be observed in hypoxia than in euoxia or hyperoxia. A tendency for the incidences to be greater in exercise than at rest was not significant, but the amplitudes of alternation showed a significant difference in favour of exercise. In a substantial minority of experiments the amplitude of reflex alternation was significantly and positively correlated with hypoxia (1/(PAO2--C)). Alternation also occurred frequently in another substantial minority of experiments in which, however, there was no significant amplitude-hypoxia correlation. It was concluded that these two groups probably differed not so much in the form of the amplitude-hypoxia relation as in respect of the extent of the scatter in the observations. The results are consistent with interaction of non-steady-state with steady-state signals at the arterial chemoreceptors.

Carbon Dioxide↗
PubMed1977

Separation of the inspiratory and expiratory reflex effects of alternate-breath oscillation of PACO2 during hypoxia.

Four healthy young men and women, selected for the responsiveness and steadiness of their breathing, were studied in rest and mild exercise (58 runs) while receiving alternate inspirates of low and high PCO2 (0 and 8.6 kPa). PACO2 oscillated between ca. 6 and 7.5 kPa (45-55 torr); PACO2 was held steady at more than one level between 6 and 9.6 kPa (45-72 torr). Using cross-correlation analysis, the phase relations were determined between the alternating PACO2 and the following reflex outputs: mean inspiratory and expiratory flows (VI and VE) and the reciprocal of the duration of expiration (1/TE), the two expiratory variables being lumped together for purposes of expression, but not of calculation. T1, being relatively unaffected alternating PACO2, was not re-studied (see companion paper). The common patterns of significant reflex alternation were: VI alone, usually in phase (with PACO2), 24%; VE alone, usually in phase, 17%; both inspiratory and expiratory variables, in phase with CO2 and each other, 15%; both inspiratory and expiratory variables, the expiratory being out of phase with both CO2 and with the inspiratory, 23%. Some runs showed a mixture of phase relations. In 71%, end-expiratory lung volume (VL,E' formerly called FRC) alternated significantly. It is concluded that expiratory events can be influenced by peripheral chemoreceptors independently of inspiration.

Carbon Dioxide↗
PubMed1977

Very small, very short-latency changes in human breathing induced by step changes of alveolar gas composition.

1. Three healthy young males were maintained for sessions of about 1 hr in a state of mild asphyxia (PA,O2 approximately 55, PA,CO2 approximately 45 torr), i.e. with moderately strong drives from both arterial and intracranial chemoreceptors. Tidal volume (VT), breath duration (TT) and duration of inspiration (TI) were recorded, and ventilation (VE) and duration of expiration (TE) were derived breath by breath. 2. The arterial chemoreceptor component of the drive was briefly and abruptly reduced, perhaps silenced, by three separate procedures: the inspiratory pathway was connected for two breaths to a second gas supply line containing, B, hypoxia with Pi,CO2 zero (removal of hypercapnia with maintained hypoxia); C, pure oxygen (removal of asphyxia); and D, oxygen with 40 torr added PCO2 (removal of hypoxia with maintained hypercapnia). In controls, A, the second inspiratory line contained the maintenance mixture so that the switch involved no change of inspiratory gas composition. Each type of test was repeated twenty-four times on each subject. 3. Responses attributable to silencing of arterial chemoreceptors (i.e. with 1 1/2--3 breath latencies about equal to the lung-to-ear circulation time) are reported elsewhere. 4. Very small responses, occurring only half a respiratory cycle after first inhalation of the test mixture, were detected by pooling all responses of each kind from all subjects. When hypoxia was withdrawn, with (C) or without (D) simultaneous withdrawal of hypercapnia, VT and VE were reduced by 3 and 2% respectively, probably because gas mixtures containing high oxygen concentrations are appreciably more viscous than hypoxic mixtures and so require more effort to breathe in and out. When hypercapnia was withdrawn with (C) or without (B) simultaneous withdrawal of hypoxia, TE was significantly lengthened (mean, + 65 +/- 18 msec), 5. The change of TE was discussed in relation to known effects of CO2 on airway receptors in the dog.

Carbon Dioxide↗
PubMed1977

A quantitative description of the pattern of breathing during steady-state CO2 inhalation in man, with special emphasis on expiration.

1. Quantitative data on the pattern of breathing in normal men and women (Gardner, 1977) have been used to derive expressions that are based on known physiological mechanisms.2. The relations between the applied chemical drive to breathing (expressed as DeltaP(A, CO2) in high O(2)) and the several components of the volume-time patterns described in the companion paper were examined. Neither mean tidal volume (V(T)), nor mean inspiratory nor mean expiratory times (T(I), T(E)) were uniquely related to the chemical drive across the breakpoint, which could be demonstrated in two and suspected in the third of these plots.3. Mean inspiratory flow (V(T)/T(I)) was linearly related to P(A, CO2) over the whole range and, like minute ventilation (V), showed no breakpoint. The mean relation was V(T)/T(I) = 0.11 (P(A, CO2) - 35.2). V(T)/T(I) was highly correlated with V; in individuals with healthy lungs and under relatively stable conditions of compliance and resistance it may be accepted as a wholly inspiratory alternative to V as an index, on the efferent side, of the total prevailing chemical drive.4. The description of the relation between T(I) and V(T) was essentially the same as that of Clark & Euler (1972): in range 1, T(I) = either 1.29 - 0.07 V(T)or the constant 1.24 sec, and in range 2, T(I) = 0.65/(V(T) - 0.88) + 0.59.5. Expiration was described by an equation based on the inverse linkage between T(E) and chemical drive and the direct link between both mean and breath-by-breath values of T(I) and T(E): T(E) = pT(I) + q/(drive - r) in which p was 0.64 +/- 0.09, q was 11.1 +/- 2.64 sec. (torr CO(2))(-1) and r was -2.73 +/- 1.09 torr CO(2). All three parameters were necessary for an adequate description.6. It is argued that the first term of the T(E) equation represents influences related to lung volume exerted through the vagus, and that the second represents the effects of over-all chemical stimulation exerted through other pathways.

Adult↗
PubMed1975

The chronic toxicity of methiocarb to grackles, doves, and quail and reproductive effect in quail.

Methiocarb (4-methylthio-3, 5-xylyl N-methyl carbamate, Mesurol, Bay (3744), a bird repellent, was fed in concentrations of 100 to 1,000 ppm to common grackles (Quiscalus quiscula), mourning doves (Zenaida macroura), and breeding pairs of coturnix quail (Coturnix coturnix) to investigate the possibility of cumulative intoxication. Although aversion to treated diets was readily apparent in most of the tests, the 28- to 30-day median lethal concentration (LC50) was determined to be greater than 100 ppm for grackles, 630 ppm (95% confidence limits, 480-830 ppm) for doves, and greater than 1,000 ppm for coturnix quail. Methiocarb appeared to be noncumulative when measured by an index of chronicity: birds consumed several LD50 doses during a day's feeding, and when deaths occurred, they appeared to be due to acute intoxication. Egg production and live chick production were not affected in coturnix fed 100 ppm but were reduced at 316 and 1,000 ppm.

Animals↗
PubMed1975

Leaching and degradation of 4-aminopyridine-14C in several soil systems.

Leaching and degradation of 4-aminopyridine (a frightening agent for protecting grain crops from blackbirds) was studied in seven soils. Carbon 14-labeled 4-aminopyridine was strongly adsorbed onto soil colloids, with the degree of adsorption related to pH. Application of seven in. of simulated rainfall over 20 days to surface-treated alkaline soils leached to 0.02 percent to 0.18 percent of the -14C; radioactivity was detected in the runoff from only one of the four acidic soils. Degradation of 4-aminopyridine-14C to -14CO(2) was negligible in soils incubated up to two months under anaerobic conditions. Under aerobic incubation, there was a one-week lag before extensive breakdown began. Degradation rates increased with increasing temperature and soil moisture during incubation, but soil composition had a greater influence. After three months at 30 degrees C and 50 percent moisture, evolution of -14CO(2) ranged from 0.4 percent for a highly acidic loam (pH 4.1) to more than 50 percent for a lighter-textured, alkaline, loamy sand (pH 7.8); the half-life of 4-aminopyridine in soils under these test conditions ranged from 3 to more than 22 months. A theoretical scheme is presented for the degradation of 4-aminopyridine in soils.

Aerobiosis↗