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Biomedical subjects

J A Dempsey

Publications and source records attributed to J A Dempsey.

At least 73 records · Page 4Linked to original sources
PubMed1995

Diastolic time: an important determinant of regional arterial blood flow.

In unanesthetized dogs we measured heart rate, blood pressure, and external iliac, celiac, and renal artery flows on a beat-by-beat basis. All three flows fluctuated in synchrony with breathing. Although the fluctuations in renal flow could to a large degree be explained by fluctuations in blood pressure, this was not the case in the external iliac artery where flow increased when pressure decreased and decreased when pressure increased. These paradoxical fluctuations in flow appear to be caused by respiratory fluctuations in heart rate, since we observed a strong (r = 0.89) correlation between external iliac flow and the length of the preceding diastole. Single long diastolic periods, induced by atropine, were always followed by a beat of increased flow even though arterial pressure was constant. We conclude that diastolic time has a profound impact on blood flow during the next beat. Our data support a model of the arterial system in which backpressure to flow through a bed is dependent on the amount of time for diastolic runoff into the capillaries.

Animals↗
PubMed1995

Hypoxic effects on exercise-induced diaphragmatic fatigue in normal healthy humans.

We examined the effects of hypoxia on exercise-induced diaphragmatic fatigue. Eleven subjects with a mean maximal O2 uptake of 52.4 +/- 0.7 ml.kg-1.min-1 completed one normoxic (arterial O2 saturation 96-94%) and one hypoxic (inspiratory O2 fraction = 0.15; arterial O2 saturation 83-77%) exercise test at 85% maximal O2 uptake to exhaustion on separate days. Supramaximal bilateral phrenic nerve stimulation (BPNS) was used to determine the pressure generation of the diaphragm pre- and postexercise at 1, 10, and 20 Hz. There was increased flow limitation during hypoxic vs. normoxic exercise. There was a decrease in hypoxic exercise time (normoxic 24.9 +/- 0.7 min vs. hypoxic 15.8 +/- 0.8 min; P < 0.05). After exercise the BPNS transdiaphragmatic pressure (Pdi) was significantly reduced at 1 and 10 Hz after both exercise tests. The BPNS Pdi was recovered to control values by 60 min postnormoxic exercise but was still reduced 90 min posthypoxic exercise. The mean percent fall in the stimulated BPNS Pdi was similar (normoxic -24.8 +/- 4.7%; hypoxic -18.8 +/- 3.0%) after both exercise conditions. Experiencing the same amount of diaphragm fatigue in a shorter time period in hypoxic exercise may have been due to 1) the increased expiratory flow limitation and diaphragmatic muscle work, 2) decreased O2 transport to the diaphragm, and/or 3) increased levels of circulating metabolites.

Adult↗
PubMed1995

Respiratory sinus arrhythmia in humans: an obligatory role for vagal feedback from the lungs.

Respiratory sinus arrhythmia (RSA) is used as a noninvasive measure of vagal cardiac input, but its causative mechanisms in humans remain undetermined. We compared the RSA of five lung-denervated double-lung transplant patients with intact hearts to six normal (N) control subjects, five heart-denervated patients, and two liver transplant patients at matched tidal volumes (VT's) and breathing frequencies. In N and liver transplant subjects, RSA was significant during eupnea and increased two- to threefold with increasing VT and inspiratory effort. In heart- and lung-denervated subjects, RSA at eupnea was significant but was only 53% of that in N subjects and was not respondent to changing VT, inspiratory effort, or breathing frequency. We also compared the RSA of N subjects during voluntary (active) and passive positive pressure ventilation at normocapnia. RSA was reduced from 11 +/- 2.2 beats/min during active ventilation to 5.4 +/- 0.8 beats/min during PPV. We conclude that vagal feedback from pulmonary stretch receptors is obligatory for the generation of a neurally mediated RSA in awake humans at normal and raised levels of VT and respiratory motor output. In intact humans, we also hypothesize an important effect for nonpulmonary central and/or peripheral modulation of RSA. It is likely that the key mechanisms for neurally mediated RSA in unanesthetized humans are mutually dependent.

Adult↗
PubMed1995

Role of vagal feedback from the lung in hypoxic-induced tachycardia in humans.

We assessed the cardiovascular responses to systemic normocapnic hypoxia in five normal subjects, five double lung transplant patients with lung denervation and intact hearts, and five patients with denervated hearts. Progressive normocapnic hypoxia was induced over 10-15 min and maintained for 2-3 min each at 90, 87, 84, and 80% arterial O2 saturation (SaO2). Normal subjects showed the most pronounced mean increase in heart rate (dHR/dSaO2 = 0.86 +/- 0.13 beat/min per 1% SaO2). Three lung-denervated subjects had normal tachycardiac responses (1.6, 0.9, and 0.69 beats/min per 1%), whereas the other two had distinctly lower responses (0.34 and 0.39 beat/min per 1%). Most of the lung-denervated subjects also showed a significant tachycardia with even mild hypoxia; none showed a bradycardiac response to any level of hypoxia. In the heart-denervated group, hypoxic tachycardia was significantly lower than normal (0.29 +/- 0.13 beat/min per 1%). We conclude that vagal feedback from the lungs is not required for the normal chronotropic response to hypoxia in humans; however, this mechanism may contribute significantly to the marked variability in hypoxic-induced tachycardia found among human subjects. These data in humans contrast with the progressive bradycardiac response to hypoxia reported in vagally denervated (or nonhyperpneic) dogs and cats.

Adult↗
PubMed1995

Respiratory and cardiovascular responses to increased and decreased carotid sinus pressure in sleeping dogs.

The purpose of this study was to determine the effects of changing blood pressure in the carotid sinus (Pcs) on ventilatory output during wakefulness and non-rapid-eye-movement sleep in unanesthetized dogs. Eight dogs were chronically instrumented so that ventilation, heart rate, and blood pressure could be measured while pressure in the isolated carotid sinus was rapidly changed by means of an extracorporeal perfusion circuit. Raising Pcs 35-75 mmHg consistently reduced ventilation 15-40% in a dose-response fashion, with little or no further diminution in minute ventilation as Pcs was further increased > 75 mmHg above control level. This decrease in minute ventilation was immediate, due primarily to a decrease in tidal volume, and was sustained over the 20-s period of elevated Pcs. Increases in Pcs also caused immediate sustained reductions in systemic blood pressure and heart rate, both of which also fell in a dose-dependent fashion. The ventilatory and systemic cardiovascular responses to increased Pcs were the same during wakefulness and non-rapid-eye-movement sleep. Decreasing Pcs 40-80 mmHg caused a sudden carotid chemoreceptor-mediated hyperpnea that was eliminated by hyperoxia. We conclude that increasing Pcs causes a reflex inhibition of ventilation and that this reflex may play a role in sleep-disordered breathing.

Animals↗
PubMed1995

Effects of raising carotid sinus pressure on upper airway resistance and EEG frequency in sleeping dogs.

The purpose of this study was to determine whether acutely raising carotid sinus pressure (Pcs) causes changes in upper airway resistance and/or electroencephalographic (EEG) frequency during wakefulness and non-rapid-eye-movement (NREM) sleep. Five dogs were chronically instrumented so that breathing, tracheal pressure, mouth pressure, EEG, and electrooculogram could be measured while pressure in the vascularly isolated carotid sinus was rapidly increased between 40 and 150 mmHg via an extracorporeal perfusion circuit. Dogs were studied during both wakefulness and NREM sleep. Multiple trials of increased Pcs were conducted in each dog. We observed that increasing Pcs 40-150 mmHg caused not only a reflex cardiovascular response but also a 15-40% decrease in minute ventilation. Raising Pcs caused no physiologically significant changes in upper airway resistance over the range of airway pressures and flow rates encountered during inspiration and expiration. Even dogs that demonstrated moderate to substantial sleep-induced increases in airway resistance did not consistently increase resistance during superimposed baroreceptor stimulation. Small increases in airway resistance were sometimes observed during baroreceptor stimulation, but this was not a consistent finding. Acute increases in Pcs did not cause measurable changes in EEG frequency during wakefulness or NREM sleep. We conclude that acute stimulation of the carotid sinus baroreceptors does not cause physiologically meaningful changes in upper airway resistance or EEG activity in awake or sleeping dogs.

Airway Resistance↗
PubMed1995

Contribution of diaphragmatic power output to exercise-induced diaphragm fatigue.

In nine normal humans we compared the effects on diaphragm fatigue of whole body exercise to exhaustion (86-93% of maximal O2 uptake for 13.2 +/- 2.0 min) to voluntary increases in the tidal integral of transdiaphragmatic pressure (integral of Pdi) while at rest at the same magnitude and frequency and for the same duration as those during exercise. After the endurance exercise, we found a consistent and significant fall (-26 +/- 2.9%, range -19.2 to -41.0%) in the Pdi response to supramaximal bilateral phrenic nerve stimulation at all stimulation frequencies (1, 10, and 20 Hz). Integral of Pdi.fB (where fB is breathing frequency) achieved during exercise averaged 509 +/- 81.0 cmH2O/min (range 304.0-957.0 cmH2O/min). At rest, voluntary production of integral of Pdi.fB, which was < 550-600 cmH2O/min (approximately 4 times the resting eupenic integral of Pdi.fB or 60-70% of Pdi capacity), did not result in significant diaphragmatic fatigue, whereas sustained voluntary production of integral of Pdi.fB in excess of these threshold values usually did result in significant fatigue. Thus, with few exceptions (5 of 23 tests) the ventilatory requirements of whole body endurance exercise demanded a level of integral of Pdi.fB that, by itself, was not fatiguing. The rested first dorsal interosseous muscle showed no fatigue in response to supramaximal ulnar nerve stimulation after whole body exercise. We postulate that the effects of locomotor muscle activity, such as competition for blood flow distribution and/or extracellular fluid acidosis, in conjunction with a contracting diaphragm account for most of the exercise-induced diaphragm fatigue.

Adult↗
PubMed1995

Longitudinal effects of aging on lung function at rest and exercise in healthy active fit elderly adults.

We retested 18 healthy, active, and highly fit [maximal O2 consumption (VO2max) 201 +/- 12% of predicted] older adults over a 6-yr period (mean age 67-->73 yr) to determine the longitudinal effects of aging on lung function at rest and during exercise. In the 6-yr period, total lung capacity (TLC), functional residual capacity, and diffusion capacity did not change; vital capacity, forced expiratory volume in 1 s, and maximal volitional flow rates decreased; and residual volume and closing capacity/TLC increased 11-13%, all of which were greater than predicted from cross-sectional data. At maximum exercise over the 6-yr period, VO2max fell 11.2 +/- 3.4% (45.0-->40.3 ml.kg-1.min-1), six (of 18) subjects showed significant arterial hypoxemia (arterial O2 saturation < or = 92%), and maximum heart rate and minute ventilation-to-O2 consumption ratio (VF/VO2) were unchanged. At any given submaximal work rate, VE and breathing frequency were higher, the degree of expiratory flow limitation increased, and end-expiratory and end-inspiratory lung volumes were unchanged but remained significantly higher relative to young adults. We conclude that in contrast to implications from cross-sectional data, our longitudinal findings demonstrate that habitual physical activity and high aerobic capacity modify neither the normal deterioration in resting lung function nor the increased levels of ventilatory work during exercise that occur with healthy aging over the sixth and seventh decades of life.

Aerobiosis↗
PubMed1995

Neuromechanical regulation of respiratory motor output in ventilator-dependent C1-C3 quadriplegics.

To evaluate the role of phrenic and sternocleidomastoid afferents as alternate sources of inhibitory feedback during mechanical ventilation, we studied five C2-C3 quadriplegics with sensory denervation of the rib cage and diaphragm, six C1-C2 quadriplegics with additional loss of sensory feedback from the neck muscles, and seven normal subjects. We compared the return of inspiratory muscle activity [the recruitment threshold (PCO2RT)] during mechanical ventilation between subject groups after stepwise increases in end-tidal PCO2 (PETCO2) either by increasing the inspired fraction of CO2 (FICO2), decreasing tidal volume (VT; 50 ml/min), or decreasing frequency (f; 1 breath/2 min). Normal subjects were mechanically hyperventilated via a nasal mask until inspiratory activity was undetectable. Efferent input to the sternocleidomastoid was intact at both levels of spinal cord injury, but phasic activity was not evident at the quadriplegics' baseline resting ventilation. The PCO2RT was defined as the level of PETCO2 at which phasic activity of the diaphragm in normal subjects and of the sternocleidomastoid in C1-C2 and C2-C3 quadriplegics recurred. The mean PCO2RT (in response to raising PETCO2 via increased FICO2 while maintaining a high VT and f) was not significantly different (P = 0.6) between normal subjects (43 +/- 3 Torr) and C2-C3 quadriplegics (38 +/- 5 Torr). Both subject groups demonstrated a frequency- and volume-related inhibition, as evidenced by a substantially lower PCO2RT when PETCO2 was raised by reducing either VT or f. In contrast to the C2-C3 quadriplegics, the C1-C2 quadriplegics responded with a similar PCO2RT among the three different mechanical ventilation trials, independent of whether PETCO2 was raised with high VT and f, with reduced VT, or with reduced f. We conclude that feedback from at least some part of the chest wall is required to produce a volume- and frequency-dependent inhibition of inspiratory muscle activity observed during mechanical ventilation.

Adolescent↗
PubMed1995

Ventilatory effects of specific carotid body hypocapnia in dogs during wakefulness and sleep.

We used extracorporeal perfusion of the vascularly isolated carotid sinus region to determine the effects of specific carotid body chemoreceptor hypocapnia-alkalosis on ventilatory control in the unanesthetized dog. Eight female dogs were studied during wakefulness, non-rapid-eye-movement (NREM) sleep, and rapid eye movement (REM) sleep. Carotid body perfusions lasted from 1 to 2 min, and each trial was preceded by a 1-min control period. Two levels of carotid body hypocapnia were employed, approximately 7 and 14 Torr below eupneic levels in a given dog. We found that 1) During wakefulness and NREM sleep, carotid body hypocapnia caused reduced tidal volume (VT) but not apnea or expiratory time prolongation. 2) The inhibition of ventilation in response to carotid body hypocapnia was graded below normocapnia, showing the highest sensitivity at carotid body PCO2 near 7 Torr below eupneic values. Inhibition reached a maximum near 14 Torr below the eupneic level; VT, inspiratory minute ventilation (VI), and VT-to-inspiratory time ratio fell 31, 23, and 27% in wakefulness and 30, 23, and 30% in NREM sleep. 3) Reductions in ventilation in response to carotid body hypocapnia are lessened but still persist throughout perfusion (up to at least 130 s) despite significant systemic hypercapnia. 4) During REM sleep, carotid body hypocapnia had no consistent inhibitory effect on ventilation until carotid body PCO2 was reduced to values near 14 Torr below the eupneic level, at which point ventilation was similar to wakefulness and NREM. 5) Moderate carotid body hypocapnia was as effective as carotid body hyperoxia in reducing VT and VI. We conclude that carotid body hypocapnia-alkalosis can significantly inhibit eupneic VT and ventilation during wakefulness and NREM sleep and, if the hypocapnia is severe enough, during REM sleep.

Animals↗
PubMed1995

The Breuer-Hering reflex in humans. Effects of pulmonary denervation and hypocapnia.

Passive lung inflation in humans causes reflex expiratory prolongation that is abolished by vagal blockade. We have studied two aspects of this classic Breuer-Hering reflex in humans: the effect of pulmonary denervation from bilateral lung transplantation, and the effect of alveolar hypocapnia. Lung inflations were performed in six normal subjects and four lung transplant patients during triazolam-induced sleep using a negative pressure body box. Lung inflation with isocapnic gas in normal subjects resulted in expiratory prolongation lasting up to 60 s and occurring at a volume threshold of 40 to 60% of inspiratory capacity (1.1 to 1.7 L). Expiratory prolongation increased in a graded fashion as volume of lung inflation increased. Inhibition of inspiration at any given inflation volume was prolonged by inflations with air as compared with inflations with isocapnic gas. In lung transplant patients lung inflations of up to 2 L caused no prolongation of expiration. We conclude that bilateral lung transplantation abolished expression of the reflex in humans, and that in normal intact humans the duration of expiratory prolongation with lung inflation is prolonged by alveolar hypocapnia.

Adult↗
PubMed1994

Effects of REM sleep on the ventilatory response to airway occlusion in the dog.

We determined the effects of sleep state on the ventilatory response following transient airway occlusion and on the response to vagal blockade in the unanesthetized sleeping dog. Three tracheotomized dogs underwent repeated occlusions (159 trials) during rapid eye movement (REM) and nonrapid eye movement (NREM) sleep. In all sleep states we found significant but variable transient hyperventilation following release of occlusion. In NREM sleep, a significant central apnea [expiratory time (TE) prolonged 2-10 times control] followed the hyperpneic response, so long as the increase in tidal volume (VT) during the hyperpnea exceeded three times control VT, that is, a volume-dependent apneic threshold. In REM sleep with maintained levels of eye movement density, hyperventilation commonly followed release of obstruction but only very rarely did VT exceed the volume threshold, and central apnea was rare. Cervical vagal blockade was used to show that significant inhibitory pulmonary stretch receptor reflexes were present in both NREM and REM sleep, although the strength of the reflex was diminished in REM. We postulate that the phasic events of REM sleep inhibit the increase in VT in response to the chemical stimuli accumulated during airway occlusion and also interfere with the prolongation of TE in response to lung stretch and/or transient hypocapnia. The result is that central apnea occurs only very rarely in REM sleep.

Airway Obstruction↗
PubMed1994

Locations of genetic markers on the physical map of the chromosome of Neisseria gonorrhoeae FA1090.

To increase the utility of the previously constructed physical map of the chromosome of Neisseria gonorrhoeae FA1090, 28 additional genetic markers were localized on the map. Cloned gonococcal genes were used to probe Southern blots of restriction enzyme-digested DNA separated on pulsed-field gels, thus identifying the fragment in each of several digests to which the probe hybridized and the map location of each gene. The addition of the new markers brings the total number of mapped loci for this strain to 68; the locations of all of those markers on the updated map are shown.

Chromosomes, Bacterial↗
PubMed1994

Do carotid chemoreceptors inhibit the hyperventilatory response to heavy exercise?

In this paper two types of evidence are presented which question the commonly presumed role of carotid chemoreceptor stimulation as the primary mediator of the hyperventilatory response to heavy exercise. First, carotid-body denervation in ponies increases their hyperventilatory response to heavy exercise. Second, the awake dog and the goat at rest show an immediate and substantial depression of tidal volume and of ventilation when their isolated carotid chemoreceptors are made hypocapnic. Accordingly, it is proposed that during heavy exercise the carotid chemoreceptors are inhibitory to respiratory motor output and that the cause of the hyperventilatory response originates from extrachemoreceptor, locomotor-linked, feed-forward stimuli.

Animals↗