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Biomedical subjects

J R Gillespie

Publications and source records attributed to J R Gillespie.

At least 37 records · Page 2Linked to original sources
PubMed1996

Exercise intolerance in endurance horses.

Endurance competition requires synchronism and development of metabolic and musculoskeletal systems. An understanding of the existence of performance-limiting factors may permit the detection of exercise intolerance that could lead to performance failure, fatigue, and exhaustion. New concepts for assessment of fitness have increased the understanding of individual capacities and deficiencies and the interaction of the different systems involved in exercise.

Animals↗
PubMed1994

Dual divalent cation requirement of the MutT dGTPase. Kinetic and magnetic resonance studies of the metal and substrate complexes.

Kinetic analyses of both the Mn(2+)- and Mg(2+)-activated hydrolysis of dGTP by MutT show the requirement for two divalent cations. Whereas Mn2+ supports a 20-fold lower kcat (0.19 s-1) than Mg2+ (4.0 s-1), the Km of Mn2+.dGTP (6.3 microM) is 45-fold lower than that of Mg2+.dGTP (284 microM). Adenosine 5'-(alpha,beta-methylenetriphosphate) (AMPCPP) is a linear competitive inhibitor with respect to dGTP with a Ki for Mg2+.AMPCPP (42 microM) which is 57-fold lower than the Ki of Mg2+.AMPCPP (2.4 mM). Such tightening suggests that a metal-bridge E.M2+.NTP.M2+ complex is the catalytically active species. The 12 dissociation constants describing the quaternary MutT.M2+.AMPCPP.M2+ complex were evaluated for both Mn2+ and Mg2+, using EPR and NMR methods. MutT binds a single Mn2+ with a Kd of 130 +/- 40 microM in reasonable agreement with the kinetically determined activator constant of Mn2+ of 230 +/- 72 microM. The MutT.AMPCPP complex binds two Mn2+ ions, the weaker of which has a Kd of 16 +/- 2 microM in agreement with the kinetically determined KmMn2+ of 26 +/- 10 microM. MutT.Mn2+ binds Mn2+.AMPCPP with Kd of 16 +/- 4 microM, whereas MutT alone binds Mn2+.AMPCPP with a Kd of 135 +/- 30 microM. The 17-fold enhanced paramagnetic effect of Mn2+ on the longitudinal relaxation rate of water protons found with the binary MutT.Mn2+ complex decreases to 4.7-fold upon binding of AMPCPP and to 8.7-fold upon binding of Mn2+.AMPCPP, further supporting a metal-bridge MutT.M2+.NTP.M2+ complex. By competition with Mn2+ MutT binds Mg2+ at one site with a Kd of 7.5 mM, and MutT.AMPCPP binds Mg2+ at two sites, the weaker of which has a Kd of 0.9 mM. These values are comparable to the kinetically determined KaMg of 15 +/- 7 mM and KmMg of 1.7 +/- 0.7 mM, respectively. Studies with the racemic, substitution-inert beta, gamma-bidentate tetraamminecobalt (III)-beta,gamma-phosphate-ATP (Co3+(NH3)4ATP) complex show that MutT slowly hydrolyzes only the lambda stereoisomer but requires Mg2+ or Mn2+ to do so, confirming a dual metal ion requirement.

Adenosine Triphosphate↗
PubMed1993

Characterization of particles, ammonia and endotoxin in swine confinement operations.

To define the atmospheres swine confinement operations, we measured concentrations of total and respirable dust particles, ammonia and endotoxin in the nursery and grower areas of 4 swine confinement houses. Increased ventilation in spring-summer relative to that in winter reduced concentrations of large dust particles more rapidly than it did smaller particles or ammonia. The greater decrease in large particles correlating to increased room air velocity may reflect larger particles' momentum causing impaction on surfaces. There was significant spatial variation in the concentration of airborne endotoxin within individual swine rooms and pens reflecting different mixing of large feed and smaller manure particles. Smaller particles had 4-fold higher concentrations of endotoxin than did larger particles, suggesting they had higher fecal material concentrations. Total airborne endotoxin and total suspended particulates correlated to the fraction of functional endotoxin contained in large particles, suggesting that small particles (0.5-2.0 micrometers) collide with large particles (50 micrometers). These data suggest that large non-respirable particles remove smaller respirable particles from indoor atmospheres due to kinematic coagulation.

Air Pollution, Indoor↗
PubMed1989

High frequency jet ventilation in horses: an experimental study.

High frequency jet ventilation (HFJV) is a recently developed mode of ventilation that delivers small tidal volumes at frequencies greater than 60 cycles per min via an injection catheter to the animal's airway. The construction of a high frequency jet ventilator suitable for use in adult horses is described. The effectiveness of this ventilator in maintaining normal arterial blood-gas tension was evaluated in five healthy adult horses. The horses were anaesthetised with intravenous acetylpromazine, guaifenesin, and thiamylal, positioned in lateral recumbency and baseline measurements were made during spontaneous ventilation. The horses were then paralysed with succinylcholine and ventilated for at least 20 mins with HFJV. Air was delivered from the ventilator to the animal by a polyethylene tube. The tip of this tube remained within and approximately 30 cm from the cuffed end of a standard 30 mm internal diameter large animal orotracheal tube. Frequency of flow interruption was 3 Hz with a constant source pressure of 275 kPa and an inspiratory to expiratory ratio of approximately 1:2.6. Gas delivery to the horse, as estimated with a resonator system was approximately 2 litres/breath. During HFJV, arterial carbon dioxide tension was significantly reduced and arterial oxygen tension significantly increased above measurements made when the horses were spontaneously breathing air.

Animals↗
PubMed1989

Mechanism of exercise-induced hypoxemia in horses.

Arterial hypoxemia has been reported in horses during heavy exercise, but its mechanism has not been determined. With the use of the multiple inert gas elimination technique, we studied five horses, each on two separate occasions, to determine the physiological basis of the hypoxemia that developed during horizontal treadmill exercise at speeds of 4, 10, 12, and 13-14 m/s. Mean, blood temperature-corrected, arterial PO2 fell from 89.4 Torr at rest to 80.7 and 72.1 Torr at 12 and 13-14 m/s, respectively, whereas corresponding PaCO2 values were 40.3, 40.3, and 39.2 Torr. Alveolar-arterial PO2 differences (AaDO2) thus increased from 11.4 Torr at rest to 24.9 and 30.7 Torr at 12 and 13-14 m/s. In 8 of the 10 studies there was no change in ventilation-perfusion (VA/Q) relationships with exercise (despite bronchoscopic evidence of airway bleeding in 3) and total shunt was always less than 1% of the cardiac output. Below 10 m/s, the AaDO2 was due only to VA/Q mismatch, but at higher speeds, diffusion limitation of O2 uptake was increasingly evident, accounting for 76% of the AaDO2 at 13-14 m/s. Most of the exercise-induced hypoxemia is thus the result of diffusion limitation with a smaller contribution from VA/Q inequality and essentially none from shunting.

Animals↗
PubMed1988

O2 transport in the horse during rest and exercise.

We studied mechanisms of O2 transport in 6 adult (2-5 year old) horses at rest and during steady-state exercise on a treadmill (0% slope) at 12 m/s (a submaximal gallop). Oxygen consumption was measured using an open-flow system. Arterial and mixed venous blood samples were simultaneously obtained for measurement of O2 content and hemoglobin concentration. VO2 increased from 1.5 +/- 0.2 L/min at rest to 46.2 +/- 4.8 L/min during exercise. HR increased from a resting value of 36.9 +/- 2.5 bpm to 196.5 +/- 10.9 bpm and the arterio-venous O2 content difference (a-v O2) increased from 4.2 +/- 0.8 ml O2/100 ml blood to 20.3 +/- 1.6 ml O2/100 ml blood. The 30.4-fold increase in oxygen consumption in the horse at submaximal VO2 versus only a 10-fold increase in man at VO2 max demonstrates the marked ability of the horse to transfer O2 at each step in the O2 transport pathway.

Animals↗
PubMed1986

Linear-lumped-parameter modeling of pulmonary impedance in monkeys.

Pulmonary impedance, ZL, measured from 2 to 32 Hz in anesthetized, intubated and paralyzed bonnet monkeys (Macaca radiata) was fitted to a variety of linear-lumped parameter mechanical networks. Parameter values for each network were obtained by minimizing the average of the percent distance, Dr, between the computed network impedance and measured ZL at all frequencies. Measured resistance, RL, decreased from 2 to 8 Hz and increased from 8 to 32 Hz indicating that a single series resistance-inertance-compliance (RIC) network was not optimal (Dr approximately 19%). Networks consisting of two series RIC pathways in parallel resulted in a lower Dr (approximately 14%), but parameter values were difficult to interpret. Despite not modeling the decrease in RL with frequency below 8 Hz, an airway wall compliance, Caw, network in which the airways were separated into central and peripheral components resulted in an even lower Dr (approximately 11%). In addition, parameter values were easy to interpret, consistent among our "normal" monkeys and changed consistently and explainably with change in lung mechanics induced by decrease in lung volume. We conclude that networks containing both parallel pathways and Caw are necessary to model ZL over the entire frequency range (2-32 Hz), the effect of Caw is an important determinant of ZL above 8 Hz, and a six-parameter Caw network with the ratio of Caw to parenchymal compliance, Cp, fixed may prove useful in interpreting changes in ZL induced by alterations in lung mechanics in monkeys.

Airway Resistance↗
PubMed1984

Dynamic respiratory mechanics in monkeys measured by forced oscillations.

We measured impedances of the lungs (ZL) and respiratory system (Zrs) by discrete frequency (f) forced oscillations in adult bonnet monkeys at two lung volumes, FRC and at transrespiratory system pressure (Prs) of -5 cm H2O. Measurements were made from 2 to 32 Hz to study f dependence of effective resistances (Reff) and reactances, and from 1 to 8 Hz to study f dependence of effective pulmonary compliance (Ceff,L). Estimates of resistances (R), inertances (I) and compliances (C) of the lungs (L), chest wall (W) and respiratory system (rs) were obtained by fitting the 2-32 Hz data to a series RIC network model. Reff,L, Reff,W and Reff,rs were found to be f dependent. The magnitude of ZL was small relative to that of Zrs at all f with RL only 30% of Rrs and CL six times Crs. Decreasing lung volume from FRC to Prs = -5 cm H2O increased RL, RW and Rrs, slightly decreased CL, CW and Crs, slightly increased resonance frequencies, and increased the f dependent behavior of Ceff,L. Our results indicate both similarities and differences between the respiratory system of these primates and man.

Airway Resistance↗
PubMed1984

CO2 elimination and airway opening pressure during high frequency oscillation in dogs.

CO2 elimination (VCO2) and pressure at the airway opening (Pao) were measured over a wide range of frequencies (f) (5-40 Hz) and tidal volumes (VT) (1-45 ml) during high frequency oscillatory ventilation (HFO) in 11 anesthetized, paralyzed dogs. CO2 elimination was found to depend primarily on the product off and VT which is consistent with theoretical predictions of gas exchange by augmented dispersion. Airway opening pressures during HFO were frequency dependent. At frequencies near 5 Hz Pao was lower, while at frequencies above 5 Hz Pao was higher than Pao during conventional mechanical ventilation (12 cm H2O). The minimum Pao (5 cm H2O) achieved while maintaining VCO2 equivalent to normal metabolic CO2 production occurred when VT was near that of the dead space volume and frequency was near 5 Hz. At lower VT, higher frequencies were required to maintain VCO2 and this increased frequency resulted in an increase in Pao amplitude (10-15 cm H2O).

Animals↗
PubMed1982

Impedance of the lower respiratory system in ducks measured by forced oscillations during normal breathing.

The lower respiratory system of 10 conscious Pekin ducks breathing normally was subjected to superimposed oscillations of 1.3 to 16 Hz by a small volume piston pump. Induced sinusoidal flow (VO) and pressure (PO) signals were measured in late expiration, when the gas flow ventilated by the animal was minimum. The modulus of the respiratory impedance was calculated as the ratio PO/VO. The values obtained at the various oscillatory frequencies were compared to those predicted on the basis of a series mechanical network model consisting of resistive, inertial and compliant elements (RIC) using a least squares non linear regression method. The experimental data fitted well the frequency response of a simple RIC mathematical model. After correcting for the effects of the endotracheal tube, the mean values +/- SE of the optimized parameters were: resistance 4.8 +/- 0.4 cm H2O . L-1 . sec; inertance: 0.05 +/- 0.01 cm H2O . L-1 . sec2; compliance: 7.7 +/- 0.5 ml . cm H2O-1; natural frequency: 8.0 +/- 0.4 Hz. It is concluded that: (1) the lower respiratory system in ducks can be closely modeled by a RIC mechanical series network model; (2) the forced oscillation method can be used to investigate avian mechanics of breathing, with the birds awake and breathing spontaneously.

Airway Resistance↗
PubMed1982

Respiratory mechanics of Pekin ducks under four conditions: pressure breathing, anesthesia, paralysis or breathing CO2-enriched gas.

Impedance magnitude (Z) of the lower respiratory system was studied in Pekin ducks, using forced oscillations of a small volume at the airways opening in the range 1.6-16 Hz. The experiments were performed on 5 awake ducks enclosed in a body plethysmograph and spontaneously breathing ambient air at a transrespiratory pressure (Prs, the pressure difference between the lung and the body surface) which was varied in steps from -10 cm H2O (compression) to +10 cm H2O (distension). In 3 anesthetized birds, the effects of CO2 breathing and muscular paralysis were also studied. Analysis of end-expiratory Z data yielded estimates of respiratory resistance (R), inertance (I) and compliance (C). During positive or negative pressure breathing in conscious ducks, minute volume (V) and end-tidal CO2 (PETCO2) remained unchanged from normal (Prs = zero) while tidal volume (VT) and ventilatory period (Ttot) decreased. The respiratory system in late expiration can be modelled well with a simple series R-I-C mechanical model at Prs values of zero, +10 and -10 cm H2O. The value of Z increased at all frequencies studied during compression of the respiratory system (Prs = -10 cm H2O) and did not change much from normal (Prs = zero) during distension (Prs = +10 cm H2O). Both resistance and inertance increased during compression. During distension contradictory changes in resistance and inertance suggest that complex changes in flow profile and/or in flow pathways occurred with positive pressure breathing. Anesthesia or paralysis did not noticeably change the oscillatory resistance or inertance, but increased oscillatory compliance. CO2-breathing did not affect the respiratory impedance in late expiration, but reduced its flow dependence along the ventilatory cycle.

Airway Resistance↗
PubMed1981

Compartmental analysis of the steady-state distribution of 15O2 and H215O in total body.

It has been suggested that regional oxygen metabolism may be measured quantitatively by analysis of the steady-state distribution of O-15 (T1/2 = 122 sec). For this analysis we have developed a compartmental model that incorporates corrections due to clearance and recirculation of water of metabolism. The oxygen utilization rate is simply proportional to the local O-15 activity if water of metabolism is not recirculated from other tissues and is not lost to the circulation for a time long compared with the half-life of O-15. We evaluated the magnitude of biological metabolic water loss and uptake in the steady state. Our analysis indicates that the magnitude of these effects for rapidly exchanging tissues (such as cerebral gray and white matter), may preclude a simple, noninvasive, and quantitative determination of regional oxygen metabolism. Slowly exchanging compartments, however (such as skeletal muscle and perhaps some tumors), appear amenable to correction for clearance and recirculation effects with sufficient accuracy to make determinations of regional oxygen metabolism feasible.

Adult↗
PubMed1979

Respiratory mechanics in normal bonnet and rhesus monkeys.

We measured lung volumes and quasi-static volume-pressure relationships in 22 normal upright bonnet (Macaca radiata) and 12 rhesus (M. mulatta) monkeys. In comparison with interspecies pulmonary function/body weight regressions our monkeys' lung volumes are larger and their lungs are considerably more compliant, but their chest wall compliance is similar to a wide range of mammalian species. However, chest wall compliance of our monkeys was found to be considerably less than that of other more commonly used experimental mammals such as dogs, cats, and rodents. The monkey chest walls were found to be about four times as stiff (3.3 +/- 0.1 (ml/cmH2O)/kg), whereas their lungs were nearly twice as compliant (9.2 +/- 0.7 (ml/cmH2O)/kg) compared to those of supine beagle dogs. Thus, their stiff chest wall sets their functional residual capacity (64.1 +/- 1.2% TLC30) at a much larger percentage of total lung capacity (TLC30) than that of the supine beagle dog (33.8% TLC30). Residual volume (13.2 +/- 1.9% TLC30) equaled the trapped gas volume after bilateral thoracotomy and was set by airway closure. We found more hysteresis area in the chest wall than in the lungs. Our measurements indicate that the static mechanical behavior of the respiratory system of the monkey compares well to man and that the monkey has considerable merit as an animal model for human respiratory function and disease research.

Animals↗
PubMed1979

Flow-volume curves and total pulmonary resistance in normal bonnet and rhesus monkeys.

We measured expiratory flow-volume curves and total pulmonary resistance in 15 normal, anesthetized, upright bonnet (Macaca radiata) and 8 rhesus (M. mulatta) monkeys. Absolute maximum flows are about half that found in humans, but, if expressed in vital capacities per second, monkey flows are about four times that of humans. However, irrespective of flow rate, the typical shape of maximum expiratory flow-volume (MEFV) curves of rhesus monkeys is similar to that of normal young adults and that of bonnet monkeys is similar to that of normal older adults. Flow-limiting mechanisms that may determine MEFV curve shape and explain the differences and similarities of monkey and human MEFV curves are discussed. We propose that differences in function between bonnet and rhesus monkeys relates to the concept of dysanaptic lung growth that evolved to subserve behavioral differences between the two species of monkey.

Airway Resistance↗
PubMed1979

Breathing responses of unanesthetized man and guinea pigs to increased transrespiratory pressure.

We compared the breathing responses of unanesthetized men and guinea pigs to externally imposed shifts in lung volume produced by steady pressures applied to the body surface while the mouth remained near atmospheric pressure. Lung inflation caused no consistent or significant changes either in frequency or end-tidal CO2 in the three men. In contrast, during lung inflation the guinea pigs breathed at low frequencies and smaller tidal volumes and showed consistent increases in arterial PCO2 lasting up to 10 min. The changes seen immediately on application of pressure, namely apneic periods followed by breathing in which inspiratory duration was shortened while expiratory duration was substantially increased, indicates that conscious guinea pigs have active inflation reflexes. We concluded that the reflex responses rather than mechanical factors probably account for the underventilation in the guinea pigs and that guinea pigs are not nearly as well equipped as is man to defend gas exchange in the face of nonmetabolic shifts in lung volume.

Animals↗
PubMed1979

Influence of ruminal insufflation on pulmonary function and diaphragmatic electromyography in cattle.

In 8 healthy, awake cows with permanent cannulated ruminal fistulas and carotid artery loops, respiratory mechanics, ventilation, and diaphragmatic electrical activity were studied before and during stepwise insufflation of the rumen with air pressure to 40 mm of Hg. We found that ruminal insufflation increased intraperitoneal, intrapleural, and transdiaphragmatic pressures and decreased lung volume and lung compliance. In individual cows with rumen insufflation there was an increase in pulmonary resistance, but this trend was not significant in the group. Peak expiratory flow rate was increased and peak inspiratory flow rate was unchanged. Inspiratory duration (Ti) decidal volume decreased slightly, breathing frequency decreased markedly, and minute volume decreased. When intraruminal pressure reached 40 mm of Hg, arterial partial pressure of carbon dioxide (PaCO2) increased (P less than 0.01) and that of oxygen (PaO2) decreased (P less than 0,01) and arterial blood pH decreased (P less than 0.02). Diaphragmatic electromyographic activity was increased, but mechanical effectiveness of the diaphragm was reduced at increased intraruminal pressures.

Animals↗
PubMed1977

Morphometry of the distal air spaces in lungs of aging dogs.

Changes in pulmonary morphometric measurements with age were examined by manual and automated methods in 14 normal beagle dogs aged 289-3,694 days. The study was instituted as a statistical adjunct to previous morphological studies on these dogs that showed anthracosis and associated dilatations in the distal airways in aged dogs. With increasing age, the volumetric density of alveolar ducts increased concomitantly with decreases in the volumetric densities of alveoli and alveolar parenchymal tissue. The numerical and surface densities of alveoli also decreased with age. A comparison of an automated method with accepted manual methods showed no significant differences in stereological measurements of the distal air spaces with the exception of an overestimation of surface density by the automated method. The automated method was found to be a satisfactory method for evaluating the relative differences in alveolar surface densities and the volumetric densities of respiratory air space and parenchymal tissue.

Aging↗