Biomedical subjects

E A Aaron

Publications and source records attributed to E A Aaron.

12 recordsLinked to original sources

PubMed2001

Ventilatory response to 2-h sustained hypoxia in humans.

We used two protocols to determine if hypoxic ventilatory decline (HVD) involves changes in slope and/or intercept of the isocapnic HVR (hypoxic ventilatory response, expressed as the increase in VI per percentage decrease in SaO2). Isocapnia was defined as 1.5 mmHg above hyperoxic PET(CO2). HVD was recorded in protocol I during two sequential 25 min exposures to isocapnic hypoxia (85 and 75% SaO2, n=7) and in protocol II during 14 min of isocapnic hypoxia (90% SaO2, FIO2=0.13, n=15), extended to 2 h of hypoxia with CO2-uncontrolled in eight subjects. HVR was measured by the step reduction to sequentially lower levels of SaO2 in protocol I and by 3 min steps to 80% SaO2 at 8, 14 and 120 min in protocol II. The intercept of the HVR (VI predicted at SaO2=100%) decreased after 14 and 25 min in both protocols (P<0.05). Changes in slope were observed only in protocol I at SaO2=75%, suggesting that the slope of the HVR is more sensitive to depth than duration of hypoxic exposure. After 2 h of hypoxia the HVR intercept returned toward control value (P<0.05) with still no significant changes in the HVR slope. We conclude that HVD in humans involves a decrease in hyperoxic ventilatory drive that can occur without significant change in slope of the HVR. The partial reversal of the HVD after 2 h of hypoxia may reflect some components of ventilatory acclimatization to hypoxia.

Adult↗

PubMed2000

Measuring ventilatory acclimatization to hypoxia: comparative aspects.

Acclimatization to hypoxia increases the hypoxic ventilatory response (HVR) in mammals. The literature on humans shows that several protocols can quantify this increase in HVR if isocapnia is maintained, regardless of the exact level of Pa(CO(2)). In rats, the isocapnic HVR also increases with chronic hypoxia and this cannot be explained by a non-specific effect of increased ventilatory drive on the HVR. Changes in arterial pH are predicted to increase the HVR during chronic hypoxia in rats but this has not been quantified. Limitations in determining mechanisms of change in the HVR from reflex experiments are discussed. Chronic hypoxia changes some, but not all, indices of ventilatory motor output that are useful for normalization between experiments on anesthetized rats. Finally, ducks also show time-dependent increases in ventilation during chronic hypoxia and birds provide a good experimental model to study reflex interactions. However, reflexes from intrapulmonary CO(2) chemoreceptors can complicate the measurement of changes in the isocapnic HVR during chronic hypoxia in birds.

Animals↗

PubMed1996

Respiratory muscle fatigue during exercise: implications for performance.

Heavy whole-body exercise, requiring a 10- to 15-fold increase in minute ventilation, encroaches on the capacities of the respiratory muscle system to respond. Recently, using the technique of bilateral phrenic nerve stimulation, it has been shown that heavy endurance exercise (> 85% of VO2max) lasting > 8-10 min causes diaphragmatic fatigue (15-30% reduction in transdiaphragmatic pressures when electrically stimulated at low frequencies [1-20 Hz] supramaximally). The fatigue appears to be due to an interaction of diaphragmatic work (i.e., pressure production) combined with effects related to exercise intensity (i.e., increased blood flow competition with the locomotor muscles and increased production of metabolic by-products) and requires > 60 min for recovery. Fitness (i.e., as implied from VO2max) appears to allow greater diaphragmatic work for a similar degree of fatigue. Unloading the respiratory muscles (with helium/oxygen gas or using a pressure-assist device) during heavy exercise < 90-95% of VO2max does not appear to alter exercise time, VO2max, or minute ventilation, implying that respiratory muscle fatigue plays little role in altering human performance at these work intensities. However, unloading the respiratory system with helium at work intensities > 90-95% of VO2max has been shown to improve exercise time. This would imply that respiratory muscle fatigue may play a role in limiting human performance at the extremes of human performance or that other factors related to the respiratory system (i.e., alterations in the sensation of dyspnea or mechanical load) may play an important role.

Diaphragm↗

PubMed1996

Effect of dichloroacetate on PaCO2 responses to hypoxia in awake goats.

To gain insight into the role of cerebral lactic acidosis in the hypoxic ventilatory response, we administered dichloroacetate (DCA) intravenously to inhibit lactic acid production in 7 awake goats (40-70 kg) during 0.5 h of normoxia (inspired O2 fraction = 0.209) and 5 h of poikilocapnic hypoxia (inspired O2 fraction = 0.125). On separate days, these goats were also studied with a continuous saline infusion (18 ml/h iv) during 5 h of normoxia and hypoxia. Arterial PCO2 (PaCO2) did not change during the 5-h normoxic period. During hypoxia, arterial PO2 fell significantly (P < 0.05) with both saline (from 111.3 to 39.0 Torr) and DCA (from 111.8 to 42.0 Torr) infusions. PaCO2 decreased (P < 0.05) during the first 0.5 h of both the saline and DCA hypoxia protocols. The decrease was greater (P < 0.05) during DCA (from 36.5 to 33.5 Torr) than during saline infusion (from 37.7 to 36.3 Torr). With saline infusion, PaCO2 decreased (P < 0.05) by 4.9 Torr between 0.5 and 5.0 h of hypoxia. However, over this period of DCA hypoxia, PaCO2 did not significantly decrease (P > 0.05). We conclude that the enhanced hyperventilation with DCA during acute hypoxia is consistent with brain lactic acidosis depressing breathing. Absence of additional significant hyperventilation after 0.5 h of DCA hypoxia suggests that a time-dependent alleviation of brain lactic acidosis might normally contribute to ventilatory acclimatization to hypoxia.

Acid-Base Equilibrium↗

PubMed1995

Ventilatory responses to cooling the ventrolateral medullary surface of awake and anesthetized goats.

The ventrolateral medulla (VLM) has been reported to be important as a source of tonic facilitation of dorsal respiratory neurons and as a site critical for respiratory rhythmogenesis. We investigated these theories in awake and anesthetized goats (n = 13) by using chronically implanted thermodes to create reversible neuronal dysfunction at superficial VLM sites between the first hypoglossal rootlet and the pontomedullary junction (area M (rostral) and area S). During halothane anesthesia (arterial PCO2 = 57.4 +/- 4.5 Torr), bilateral cooling (thermode temperature = 20 degrees C) of 60-100% of areas M and S for 30 s produced a sustained apnea (46 +/- 4 s) that lasted beyond the period of cooling. While the animals were awake (arterial PCO2 = 36.0 +/- 1.9 Torr), cooling the identical region in the same goats resulted in a decrease (approximately 50%) in pulmonary ventilation, with a brief apnea seen only in one goat. Reductions in both tidal volume and frequency were observed. Qualitatively similar responses were obtained when cooling caudal area M-rostral area S and rostral area M, but the responses were less pronounced. Minimal effects were seen in response to cooling caudal area S. During anesthesia, breathing is critically dependent on superficial VLM neurons, whereas in the awake state these neurons are not essential for the maintenance of respiratory rhythm. Our data are consistent with these superficial VLM neuronal regions providing tonic facilitation to more dorsal respiratory neurons in both the anesthetized and awake states.

Anesthesia↗

PubMed1995

Effects on breathing of ventrolateral medullary cooling in awake goats.

Our objective was to investigate the role of the ventrolateral medulla (VLM) in the control of breathing during the awake state. In 17 awake adult goats, chronically implanted thermodes were used to cool the VLM and thereby cause reversible neuronal dysfunction in all or portions of the area between the first hypoglossal rootlet and the ponto-medullary junction (so-called area M (rostral) and area S). Within 5 s after the initiation of cooling, 60-100% of areas M and S, pulmonary ventilation (VE) decreased uniformly over conditions of eucapnia, hypercapnia, hypoxia, and exercise (P < 0.05). Between 10 and 20 s of cooling, the reduction in VE was approximately 10% greater during eucapnia and hypercapnia than during hypoxia and exercise (P < 0.05). For the remaining 10 s of cooling and for about 1 min after cooling, VE increased to and above control level. Cooling only rostral area M or only caudal area M-rostral area S affected breathing qualitatively in the same manner as when 60-100% of areas M and S were cooled. However, cooling caudal area S had effects that differed significantly (P < 0.05) from more rostral cooling in that the initial decrease in VE was attenuated and the subsequent increase was accentuated. The initial uniform decreased VE during cooling suggests that superficial VLM nonchemoreceptor neurons facilitate breathing. The subsequent relatively greater effect of cooling during eucapnia and hypercapnia probably reflects dysfunction of chemoreceptor-related neurons that normally stimulate breathing. The stimulation of breathing during the later stages and after cooling may suggest that some VLM neurons inhibit breathing.

Animals↗

PubMed1994

Effect of metabolic rate on ventilatory roll-off during hypoxia.

This study was done to determine 1) whether goats demonstrate the roll-off phenomenon, i.e., a secondary decrease in minute ventilation (VE), after an initial hyperventilation during various levels of hypoxia and, if so, 2) whether roll-off could be due to changes in metabolic rate. We hypothesized that roll-off occurs in the goat during hypoxia but is not due to hypometabolism. To answer question 1, eight unanesthetized adult goats were exposed to 15-20 min of hypoxia at 0.15, 0.12, and 0.09 inspired O2 fraction (FIO2), resulting in 60, 40, and 30 Torr arterial PO2, respectively. Goats were fitted with a face mask connected to a spirometer to measure VE, and arterial blood gas samples were obtained via carotid arterial catheters. Roll-off was seen with 0.15 and 0.12 FIO2, whereas VE steadily increased with 0.09 FIO2. During hypoxia, arterial PCO2 fell 2, 3, and 7 Torr at 0.15, 0.12, and 0.09 FIO2, respectively. In the second series of experiments, nine different goats were exposed to 30 min of 0.12 FIO2. O2 consumption and CO2 production were measured five times during baseline and hypoxia. VE increased to 32% above baseline values after 2 min of hypoxia and then gradually decreased by 18%. Changes in breathing frequency and tidal volume contributed to the roll-off. O2 consumption decreased (P = 0.0029, analysis of variance) and CO2 production increased (P = 0.0027) during hypoxia, although both changes were small (< 7%) compared with the eventual 18% decrease in VE. We conclude that the adult goat demonstrates the roll-off phenomenon during moderate levels of hypoxia. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of chronic hypoxia on hypoxic ventilatory response in awake rats.

We compared the hypoxic ventilatory response (HVR) of two groups of unrestrained awake male rats (300-550 g): those acclimatized to hypoxia > 7 wk at simulated altitude (380 Torr, n = 12) and sea level controls (n = 8). Chronic catheters were placed in the iliac artery and vein 3-7 days before study. An "on-line" system was used to measure arterial PO2 and PCO2. Arterial blood was drawn via a roller pump past O2 and CO2 electrodes and returned to the vein. Batch samples were taken before and after HVR measurements for calibrating and determining arterial pH and hematocrit. Inspired ventilation, tidal volume, and respiratory frequency were measured with barometric pressure plethysmography at several levels of inspired O2 fraction (0.08-0.30) maintained for 15 min. For isocapnic HVR, inspired CO2 fraction was increased as necessary to maintain arterial PCO2 at the hyperoxic level. In both groups, poikilocapnic HVRs (inspired CO2 fraction = 0) were significantly less than isocapnic HVRs. Isocapnic HVRs were significantly greater in hypoxia-acclimatized (2,783 +/- 233 ml.min-1.kg-1) than in sea level control rats (1,826 +/- 106 ml.min-1.kg-1), mainly due to a significant increase in tidal volume (P < 0.05). In conclusion, relieving hypocapnia in hypoxia, by maintaining isocapnia, reveals a significant increase in the ventilatory response to arterial PO2 in awake rats with chronic hypoxia.

Acclimatization↗

PubMed1992

Oxygen cost of exercise hyperpnea: measurement.

To quantitate the O2 cost of maximal exercise hyperpnea, we required eight healthy adult subjects to mimic, at rest, the important mechanical components of submaximal and maximal exercise hyperpnea. Expired minute ventilation (VE), transpulmonary and transdiaphragmatic (Pdi) pressures, and end-expiratory lung volume (EELV) were measured during exercise at 70 and 100% of maximal O2 uptake. At rest, subjects were given visual feedback of their exercise transpulmonary pressure-tidal volume loop (WV), breathing frequency, and EELV, which they mimicked repeatedly for 5 min per trial over several trials, while hypocapnia was prevented. The change in total body O2 uptake (VO2) was measured and presumed to represent the O2 cost of the hyperpnea. In 61 mimicking trials with VE of 115-167 l/min and WV of 124-544 J/min, VE, WV, duty cycle of the breath, and expiratory gastric pressure (Pga) integrated with respect to time (integral of Pga.dt/min) were not different from those observed during maximum exercise. integral of Pdi.dt/min was 14% less and EELV was 6% greater during maximum exercise than during mimicking. The O2 cost measurements within a subject were reproducible over 3-12 trials (coefficient of variation +/- 10% range 5-16%). The O2 costs of hyperpnea correlated highly and positively with VE and WV and less, but significantly, with integral of Pdi.dt and integral of Pga.dt. The O2 cost of VE rose out of proportion to the increasing hyperpnea, so that between 70 and 100% of maximal VO2 delta VO2/delta VE increased 40-60% (1.8 +/- 0.2 to 2.9 +/- 0.1 ml O2/l VE) as VE doubled.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Oxygen cost of exercise hyperpnea: implications for performance.

We addressed two questions concerned with the metabolic cost and performance of respiratory muscles in healthy young subjects during exercise: 1) does exercise hyperpnea ever attain a "critical useful level"? and 2) is the work of breathing (WV) at maximum O2 uptake (VO2max) fatiguing to the respiratory muscles? During progressive exercise to maximum, we measured tidal expiratory flow-volume and transpulmonary pressure- (Ptp) volume loops. At rest, subjects mimicked their maximum and moderate exercise Ptp-volume loops, and we measured the O2 cost of the hyperpnea (VO2RM) and the length of time subjects could maintain reproduction of their maximum exercise loop. At maximum exercise, the O2 cost of ventilation (VE) averaged 10 +/- 0.7% of the VO2max. In subjects who used most of their maximum reserve for expiratory flow and for inspiratory muscle pressure development during maximum exercise, the VO2RM required 13-15% of VO2max. The O2 cost of increasing VE from one work rate to the next rose from 8% of the increase in total body VO2 (VO2T) during moderate exercise to 39 +/- 10% in the transition from heavy to maximum exercise; but in only one case of extreme hyperventilation, combined with a plateauing of the VO2T, did the increase in VO2RM equal the increase in VO2T. All subjects were able to voluntarily mimic maximum exercise WV for 3-10 times longer than the duration of the maximum exercise. We conclude that the O2 cost of exercise hyperpnea is a significant fraction of the total VO2max but is not sufficient to cause a critical level of "useful" hyperpnea to be achieved in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise↗

PubMed1987

Exercise-induced changes in functional residual capacity.

We used a helium-rebreathe technique in nine healthy subjects to determine the effects of exercise intensity and duration on end-expiratory lung volume (EELV). The rebreathe functional residual capacity (FRC) technique was shown: (a) to be similar to that measured in the body plethysmograph, at rest; (b) to agree closely with volitionally induced changes in EELV as determined by inductance plethysmography, at rest; (c) to be reproducible within subjects between trials conducted at rest or exercise on different days (r = 0.96, coefficient of variation +/- 3%); (d) to correlate significantly with coincident changes in end-expiratory esophageal pressure from rest to exercise, with increasing exercise intensity and over time at a constant exercise load. Exercise-induced reductions in EELV occurred in all subjects, averaging 0.3 L (-0.1 to -0.7 L) in light exercise and 0.79 L (-0.5 to -1.2 L) in heavy or maximum exercise. This reduction in EELV accounted for slightly more than one-half of the increase in VT during light exercise and slightly less than one-half of the increased VT in heavy exercise. In heavy prolonged exercise lasting 8-15 min, EELV fell in the initial 2 min and was either sustained at this reduced level or fell further with exercise duration to exhaustion. We found that FRC was reduced even in very light exercise when changes in TE and VE from rest were minimal; further reductions in EELV occurred as end-inspiratory lung volume increased and expiratory time shortened with increasing exercise intensity and duration. Based on these types of changes we speculate that active expiration during exercise in humans may be controlled by a combination of locomotor-related feed-forward and lung volume related feed-back mechanisms.

Adult↗

PubMed1987

Cardiovascular responses to military antishock trouser inflation during standing arm exercise.

Military antishock trousers (MAST) inflated to 50 mmHg were used with 12 healthy males (mean age 28 +/- 1 yr) to determine the effects of lower-body positive pressure on cardiac output (Q), stroke volume (SV), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), total peripheral resistance (TPR), and O2 uptake (VO2) during graded arm-cranking exercise. Subjects were studied while standing at rest and at 25, 50, and 75% of maximal arm-cranking VO2. At each level, rest or work was continued for 6 min with MAST inflated and for 6 min with MAST deflated. Order of inflation and deflation was alternated at each experimental rest or exercise level. Measurements were obtained during the last 2 min at each level. Repeated-measures analysis of variance revealed significant increases (P less than 0.001) in Q, SV, and MABP and a consistent decrease in HR with MAST inflation. There was no apparent change in Q/VO2 between inflated and control conditions. There was no effect of MAST inflation on VO2 or TPR. MAST inflation counteracts the gravitational effect of venous return in upright exercise, restoring central blood volume and thereby increasing Q and MABP from control. HR is decreased consequent to increased MABP through arterial baroreflexes. The associated decrease in TPR is not observed, being offset by the mechanical compression of leg vasculature with MAST inflation.

Adult↗