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Biomedical subjects

D Linnarsson

Publications and source records attributed to D Linnarsson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Responses of respiratory drive and breathing pattern to inspiratory loading during nitrous oxide and isoflurane sedation.

BACKGROUND: Increased inspiratory resistance in combination with mild gas narcosis is common during recovery after a general anesthesia, but there are only few previous studies on inspiratory loading during subanesthetic gas narcosis. METHODS: Responses of respiratory drive (central inspiratory activity, P0.1) and ventilatory pattern to an inspiratory threshold load of -6 cm H2O were studied in 16 healthy subjects during mild subanesthetic gas narcosis. One group (n = 9) was exposed to 13, 26 and 39% nitrous oxide (N2O) and air control (Group N). Another group (n = 7) was exposed to 0.1, 0.2 and 0.3% isoflurane and air control (Group I). Measurements were done after 1 min adaptation to the load. RESULTS: Nitrous oxide and isoflurane had no effect on respiratory drive and VT either during unloaded breathing or during inspiratory threshold loading. Across all gas concentrations (including 0% control), inspiratory threshold loading resulted in significant P0.1 increases, amounting to 62% in group N and 38% in group I. At the same time VT decreased by 11 and 12%, respectively. A significantly increased end-expired CO2 and decreased minute volume compared to air control was found during isoflurane inhalation but could be ascribed to normalization of the hyperventilation in the control situation. CONCLUSIONS: It is concluded that the steady-state ventilatory responses to loading, consisting of increased P0.1 and decreased VT, are maintained during inhalation of subanesthetic doses of N2O (0.13-0.38 MAC) and isoflurane (0.09-0.26 MAC).

Adult↗
PubMed1998

Human carotid baroreflex during isometric lower arm contraction and ischemia.

Our aim was to determine the roles of somatomotor activation and muscle ischemia for the tachycardia and hypertension of isometric arm contraction. Carotid-cardiac and carotid-mean arterial pressure (MAP) baroreflex response curves were determined in 10 men during rest, during isometric arm contraction at 30% of maximum, and during postcontraction ischemia. Carotid distending pressure (CDP) was changed by applying pressure and suction in a neck chamber. Pressures ranged from +40 to -80 mmHg and were applied repeatedly for 15 s during the three conditions. Maximum slopes and ranges of the response curves did not differ among conditions. The heart rate (HR) curve was shifted to a 14 +/- 1.8 (mean +/- SE) beats/min higher HR and a 9 +/- 5.7 mmHg higher CDP during contraction and to a 14 +/- 5.9 mmHg higher CDP during postcontraction ischemia with no change of HR compared with rest. The MAP curve was shifted to a 20 +/- 2.8 mmHg higher MAP and to a 18 +/- 5.4 mmHg higher CDP during contraction, and the same shifts were recorded during postcontraction ischemia. We conclude that neither somatomotor activation nor muscle ischemia changes the sensitivity of arterial baroreflexes. The upward shift of the MAP response curve, with no shift of the HR response curve during postexercise ischemia, supports the notion of parallel pathways for MAP and HR regulation in which HR responses are entirely caused by somatomotor activation and the pressor response is mainly caused by muscle ischemia.

Adult↗
PubMed1997

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity.

In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

Blood Gas Analysis↗
PubMed1996

Pulmonary function and cardiopulmonary interactions at microgravity.

During short-lasting microgravity the weights of surrounding organs are eliminated, and the lungs attain a slightly reduced volume. Long-term microgravity may lead to deconditioning of respiratory muscles. The distribution of ventilation becomes more homogeneous but not completely so. Indirect estimates of the perfusion distribution point to a reduction of gross interregional differences but a maintained intraregional inhomogeneity. The gas/blood interface becomes more effective, as shown by an improved diffusion capacity. Thus, data on lung function in man at microgravity confirm that gravity is an important determinant of the distributions of ventilation and perfusion in the lung. However, both for ventilation and perfusion, significant inhomogeneities of distribution persist also in the weightless state, showing that non-gravity-related factors also play important roles. It could be speculated that more homogeneous mechanical properties of the lung tissues surrounding the heart contribute to facilitate cardiac diastolic function in microgravity.

Heart↗
PubMed1996

Blood pressure and heart rate responses to sudden changes of gravity during exercise.

Heart rate (HR) and blood pressure responses to sudden changes of gravity during 80- to 100-W leg exercise were studied. One group was exposed to sudden changes between 1.0 and 0 g in the head-to-foot direction (Gz+), starting upright and with repeated 30-s tilts to the supine position. Another group was exposed to sudden Gz+ changes between 1.8 and 0 g in an aircraft performing parabolic flight. Arterial blood pressure at the level of the carotid (carotid distending pressure, CDP) showed a large transient increase by 27-47 mmHg when Gz+ was suddenly decreased and a similar drop when Gz+ was suddenly increased. HR displayed a reverse pattern with larger transients (-22 to -26 min-1) in response to Gz+ decreases and more sluggish changes of lower amplitude in the other direction. Central blood volume, as estimated from the inverse of transthoracic impedance (1/TTI), varied in concert with Gz+. A model is proposed in which HR responses are described as a function of CDP and 1/TTI after a time delay of 2.3-3.0 s and including a low-pass filter function with time constants of 0.34-0.35 s for decreasing HR and time constants of 2.9-4.6 s for increasing HR. The sensitivity of the carotid component was around -0.8 to -1.0 min-1 . mmHg-1 (4-7 ms/mmHg). The cardiopulmonary baroreceptor component was an additive input but was of modest relative importance during the initial HR responses. For steady-state HR responses, however, our model suggests that inputs from carotid and cardiopulmonary receptors are of equal importance.

Adult↗
PubMed1996

Slowing of carotid-cardiac baroreflex with standing and with isometric and dynamic muscle activity.

We hypothesized that the carotid-cardiac baroreflex becomes slowed in conditions with increased sympathetic activity. Changes in heart rate (HR) and blood pressure in response to 10-s trains of 50-mmHg pulses of neck suction (NS) were studied in six male subjects during supine rest, upright rest, isometric arm exercise at 30% of maximum voluntary contraction, and dynamic leg exercise at 100 W in the sitting position. Estimated mean carotid distending pressure increased by approximately 20 mmHg with 50-mmHg, QRS-triggered, pulsatile NS. Repeated NS sequences were performed in each condition. The amplitude of the bradycardic response was highly variable among the subjects and did not differ significantly between conditions, mean values ranging from 0.3 to 0.6 beats.min-1.mmHg-1. In supine rest, the full bradycardic response appeared within < 1 s, i.e., during or immediately after the R-R interval of the first NS pulse. In the other conditions it took significantly longer, 2-3 s or three to seven R-R intervals, for the full HR responses to develop. Our results support the notion that the carotid-cardiac baroreflex in humans becomes slowed under conditions of concurrent sympathetic stimulation.

Adult↗
PubMed1996

Influence of apnea on cardiovascular responses to neck suction during exercise.

Short-lasting neck suction (NS) is a common method to assess the carotid-cardiac baroreflex, and NS is usually applied during apnea to avoid breath-synchronous variations of heart rate (HR) and blood pressure. We hypothesized that the apnea might provoke cardiovascular effects that could confound the HR and blood pressure responses to NS. HR and blood pressure responses to 10-s trains of 50-mmHg pulses of NS were studied in six male subjects during supine rest, upright rest, isometric arm exercise at 30% of maximal voluntary contraction, and dynamic leg exercise at 100 W in the sitting position. Repeated NS sequences were performed during apnea preceded by a relaxed expiration to functional residual capacity and during eupnea. Initial HR responses to NS were similar during eupnea and apnea in all conditions. However, during isometric and dynamic exercise, recordings made under eupneic and apneic conditions differed during the second half of the NS period. During apneic isometric arm contraction, the elevation of mean carotid distending pressure (MCDP) (arterial pressure at carotid level minus NS pressure) was maintained at a 25-35% higher level than during eupneic isometric exercise over the last half of the NS period. In dynamic exercise, mean arterial pressure and MCDP started to increase after 3-5 s of apneic NS, whereas they were maintained during eupnea. One to three seconds later, HR started to drop markedly in apneic subjects, reaching values 20 beats/min lower than those in eupneic subjects at the end of the NS. We conclude that cardiovascular effects of apnea may appear after only 8 s of apnea in dynamic exercise and therefore could confound responses to NS.

Apnea↗
PubMed1996

Specific ventilation distribution in microgravity.

We studied the contribution of inter- and intraregional inhomogeneities of specific ventilation (delta V/Vo) from the rebreathing inert gas trace in microgravity and on Earth. The rebreathing tests were carried out by four astronauts before, during, and after the 10-day Spacelab D-2 mission. Starting from functional residual capacity, the rebreathing maneuver consisted of eight reinspirations from a bag filled with 1.8-2.2 liters of test gas mixtures containing approximately 5% argon. The rate of argon equilibration in the rebreathing bag, termed RBeq, was quantified by determining the logarithm of the actual minus the equilibrated argon concentrations normalized to the inspired minus the equilibrated argon concentrations. A compartmental model of the lung (S. Verbanck and M. Paiva. J. Appl. Physiol. 76: 445-454, 1994) was used to validate the method for determining RBeq and to simulate the influence of intra- and interregional delta V/Vo inhomogeneities on the RBeq curve. The comparison between the experimental Earth-based and microgravity RBeq curves and model simulations shows that gravity-independent delta V/Vo inhomogeneity is at least as large as gravity-dependent delta V/Vo inhomogeneity.

Adult↗
PubMed1995

Intrapulmonary distribution of alveolar gas exchange during breath-hold diving in humans.

Expirograms for CO2 and O2 obtained immediately after 75-s breath holds (BHs) in thermoneutral conditions were studied in 10 subjects. BHs were performed at normal atmospheric pressure in dry condition (dry surface BH), at normal atmospheric pressure submerged (wet surface BH), and during a transient increase of ambient pressure to 3 atmospheres absolute submerged (wet BH dive). Cardiac index was estimated by means of impedance cardiography. Phase III (alveolar plateau) slopes for CO2 expirograms were lowest after wet surface BH. The greater slope observed after dry surface BH was attributed mainly to intrapulmonary perfusion heterogeneity and the greater slope seen after wet BH dive to continuing alveolar CO2 exchange during expiration. Cardiogenic oscillations in phase III (evaluated by spectral analysis) were largest after dry surface BH, much reduced by wet surface BH, and further reduced by wet BH dive. This was attributed to more even distribution of pulmonary perfusion during submersion and compression. Terminal changes of the expirograms (phase IV) revealed a less even interregional pulmonary distribution of CO2 and a more even distribution of O2 after wet BH dive compared with wet surface BH. This difference was attributed to improved apical pulmonary perfusion at depth during the wet BH dives.

Adolescent↗
PubMed1994

Relative narcotic potency and mode of action of sulfur hexafluoride and nitrogen in humans.

Impairments of psychomotor, perceptual, and cognitive abilities were determined in nine male subjects exposed to inhaled SF6 partial pressures of 0, 52, 104, and 156 kPa and to inhaled N2 partial pressures of 103, 575, 825, and 1,075 kPa. Also data from a previous study with inhaled N2O partial pressures of 0, 13, 26, and 39 kPa were included. With the highest gas concentrations, performances were reduced by 41-57%. Effective doses for a 20% performance impairment were 830, 97, and 21.5 kPa for N2, SF6, and N2O, respectively, yielding relative narcotic potencies of 1.0:8.5:39. The order of narcotic potencies is the same as for the lipid solubility of the three gases. In contrast, the order of increasing tendency for hydrate formation (decreasing hydrate dissociation pressure) for the three gases is N2, N2O, and SF6. Thus, mild to moderate inert gas narcosis in humans shows the same positive relationship to lipid solubility as was shown in previous animal models that utilized much deeper levels of anesthesia.

Adult↗
PubMed1994

Tissue oxygen and carbon dioxide stores and breath-hold diving in humans.

Alveolar gas exchange was studied in 11 submerged subjects during and after 75-s breath holds with or without a transient increase of ambient pressure to 3 ATA (20 msw). During surface breath holds (SBH), cardiac index fell to 73% of eupneic control but was partially restored at depth to 88% of control during breath-hold dives (BHD). O2 uptake fell to 84% of control during SBH and was restored to control level during BHD. The turnover of O2 stores was much slower during SBH than during the ensuing recovery. Carbon dioxide store dynamics were markedly slowed after BHD. We conclude that SBH and BHD are associated with large shifts in tissue O2 and CO2 stores and that much of these shifts can be explained by primary circulatory events. The changes in turnover rate for tissue O2 and CO2 stores could not be explained by the cardiac index changes alone but were compatible with peripheralization of venous blood volume and preferential peripheral vasoconstriction induced by apnea with elevated intrathoracic pressure during SBH. The transient compression during BHD reversed these central and peripheral circulatory changes by counteracting the increase in intrathoracic pressure.

Adolescent↗
PubMed1993

Breath-by-breath determination of inspiratory occlusion pressure.

In order to determine the influence of breath-by-breath measurement of inspiratory occlusion pressure (P0.1) on the pulmonary ventilation, the respiratory timing and the central inspiratory activity as reflected by P0.1 per se, nine healthy males were studied as they breathed in a valve assembly including an externally controlled occlusion valve. A new technique was used, terminating occlusions at a preset inspiratory threshold pressure and determining P0.1 from linear regression of the mouth pressure curve. Subjects were studied at rest and during light exercise, with the occluding function (threshold pressure) on or off during alternating periods. Breath-by-breath variability of P0.1 was of the order of 30%. We found no detectable influence of breath-by-breath short-lasting inspiratory occlusions on tidal volume and ventilation. However, mean inspiratory flow was slightly increased due to a shortened inspiratory duration at rest and during light exercise. Also, raising the threshold pressure for occlusions from 69 to 147 Pa (0.7 to 1.5 cm H2O) resulted in a 20% increase of P0.1. We conclude that breath-by-breath measurement of P0.1 is a feasible technique, and that the slightly shortened inspiratory duration and the increased P0.1 with increased threshold pressure may not necessarily be expressions of a true stimulation of the central inspiratory activity.

Adult↗
PubMed1993

Breathing volumes and gas exchange during simulated rapid free ascent from 100 msw.

The crew of a disabled submarine can be rescued by means of free ascent through the water to the surface. Pulmonary gas exchange was studied during simulated rapid free ascent in subjects standing immersed to the neck in a pressure chamber. The pressure was rapidly increased to 1.1 MPa [100 meters seawater (msw)] followed by decompression at 0.03 MPa/s (3 msw/s). Effective inspired tidal volume, as estimated by an Ar dilution method, fell gradually to zero during decompression from 20 to 0 msw. Directly determined expired tidal volumes were increased up to two to three times at the time of return to surface pressure compared with pre- and postdecompression volumes. End-tidal PCO2 was increased on compression and fell to a nadir of 3.4 kPa (25 Torr) at the time of return to surface pressure. Thus, intrapulmonary gas expansion caused simultaneous inspiratory hypoventilation and expiratory hyperventilation. If O2-enriched gas is to be used to reduce the risk of decompression sickness, it should be administered early during decompression to alter the intrapulmonary gas composition. The time course of arterial PCO2 changes as reflected by end-tidal values during short-lasting compression/decompression would act to promote inert gas supersaturation in the brain.

Adult↗
PubMed1992

Artificial gravity in Space: vestibular tolerance assessed by human centrifuge spinning on Earth.

Artificial gravity created by the astronauts themselves, without any external power supply, by pedalling on coupled counterrotating bicycles along the inner wall of the space module (Twin Bikes System, TBS), was previously suggested (Antonutto et al., 1991) to prevent musculo-skeletal decay and cardiovascular deconditioning during long term space flights. To investigate whether this unusual rotating environment would determine abnormal stimulations of the vestibular system due to Coriolis cross coupled accelerations, thus leading to acute motion sickness (AMS), the conditions of a rotating environment were reproduced in a human centrifuge. A cycloergometer was fixed to the arm of the centrifuge, the rotation speed of which was equal to that yielding 1 g at the feet level in the TBS (i.e. ranging from 19 to 21 RPM). The ergometer position was such that the combination of the horizontal and gravitational acceleration vectors was 1.414 at the inner ear level and was aligned along the head to feet axis. Three subjects, pedalling at 50 W on a cycloergometer during centrifuge's spinning, were asked to move the head following an AMS' provocation protocol. None of them developed any AMS symptoms. This supports the look of the TBS as tool for avoiding musculo-skeletal and cardiovascular deconditioning during long term space flights.

Adult↗
PubMed1992

Effects of sulphur hexafluoride on psychomotor performance.

The narcotic influence of sulphur hexafluoride on mental and psychomotor performance has been studied in 9 subjects at normal atmospheric pressure. Control experiments were performed with air and with nitrous oxide. Psychomotor, perceptual and cognitive abilities were assessed using a computerized test battery. Subjects were exposed to air and six different normoxic gas mixtures: 13, 26, and 39% N2O, and 39, 59, and 79% SF6. Significant performance impairments were found with 13% N2O and gradual further impairment with 26, and 39% N2O. During exposure to 39, 59, and 79% SF6 over-all performance was impaired by 5, 10, and 18%, respectively. Impairment was significant with 59 and 79% SF6. The results indicate that the relative narcotic potency of SF6: N2O is about 1:4 in humans. It is concluded that a normoxic SF6-O2 mixture can be inhaled for lung function studies without any harmful effects and that the short-lasting narcotic effect, although detectable with a test battery, would not impair the ability of the subject to perform simple breathing procedures.

Adult↗