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Biomedical subjects

D Linnarsson

Publications and source records attributed to D Linnarsson.

At least 19 recordsLinked to original sources
PubMed2007

Increase in exhaled nitric oxide and protective role of the nitric oxide system in experimental pulmonary embolism.

BACKGROUND AND PURPOSE: Pulmonary embolism (PE) represents a real diagnostic challenge. PE is associated with pulmonary hypertension due to pulmonary vascular obstruction and vasoconstriction. We recently reported that pulmonary gas embolism transiently increases exhaled nitric oxide (FENO), but it is not known whether solid emboli may alter FENO, and whether an intact endogenous NO synthesis has a beneficial effect in experimental solid pulmonary embolism. EXPERIMENTAL APPROACH: We used anaesthetised and ventilated rabbits in these experiments. To mimic PE, a single intravenous infusion of homogenized autologous skeletal muscle tissue (MPE) was given to rabbits with intact NO production (MPE of 60, 15, or 7.5 mg kg(-1); group 1) and to another group (group 2) with inhibited NO synthesis (L-NAME 30 mg kg(-1); MPE of 7.5, 15 or 30 mg kg(-1)). KEY RESULTS: In group 1, after MPE, FENO increased rapidly and dose-dependently and FENO was still significantly elevated after 60 min with the two highest emboli doses. All these animals survived more than 60 min after embolization. In group 2, MPE of 7.5, 15 and 30 mg kg(-1), in combination with NO synthesis inhibition, resulted in 67%, 50% and 25% survival at 60 min respectively, representing a statistically significant decrease in survival. Cardiovascular and blood-gas changes after MPE were intensified by pre-treatment with NO synthesis inhibitor. CONCLUSIONS AND IMPLICATIONS: We conclude that solid PE causes a sustained, dose-dependent increase in FENO, giving FENO a diagnostic potential in PE. Furthermore, intact NO production appears critical for tolerance to acute PE.

Anesthesia↗
PubMed2006

Time components of circulatory transport from the lungs to a peripheral artery in humans.

Blood gas changes occurring in the lung undergo delay and damping on their way to a peripheral artery sampling site. Knowledge of the time components of circulatory transfer is important for the understanding of respiratory control and cardiovascular reflexes in response to blood gas transients. Providing steady state with regard to VA/Q distribution, cardiac output and peripheral blood flow, the relationship between the time courses of small end-tidal and peripheral PO2 changes is determined by the transfer function of the interposed vascular segment. This transfer function, expressed as delay time TD and mean transit time (MTT), was measured in six well-trained subjects, allowing the calculation of arterial time-courses from end-tidal to the reverse. They were studied at rest and during four different dynamic leg exercise intensities in the supine posture. TD and MTT amounted to 15.8 +/- 1.7 (mean +/- SEM) and 18.3 +/- 2.1 s at rest and were shortened to 7.7 +/- 0.6 and 11.5 +/- 1.8 s during exercise at 170 W. The shortening of TD and MTT did not appear to be simply an inverse function of cardiac output, suggesting that the shortening occurs in the central circulatory segment but not in the arm segment.

Adult↗
PubMed2005

Baroreflex impairment during rapid posture changes at rest and exercise after 120 days of bed rest.

Orthostatic intolerance is common after space flight and head-down tilt (HDT) bed rest. We hypothesized that HDT-induced impairments of arterial blood pressure (AP) control would be more marked during exercise and that recovery of baroreflex function after very long-term HDT would be delayed. Six subjects were studied before (BDC) during (day 60, D60; D113) and after (recovery day 0, R0; R3; R15) 120 days of HDT. Supine resting subjects were exposed to repeated 1 min passive tilts to upright at 3-min interval. During 50 W steady-state exercise corresponding tilt had a 2-min duration at 4-min interval. The amplitudes of the tilt-induced transient beat-by-beat deviations in AP and rate (HR) were determined during the gravity transients. At rest these deviations did not change over time, but during exercise the total peak-to-nadir range of deviations in systolic AP (SAP) at up-tilt and down-tilt increased to 168+/-16% (mean+/-SEM) of BDC at D113 with no clear recovery upto and including R15. Counter-regulatory HR responses were not increased proportionally and especially not tachycardic responses to up-tilt, resulting in a reduction of baroreflex sensitivity (deltaRR-interval/deltaSAP) by 55+/-9% of BDC at D113 with no recovery upto and including R15. We conclude that prolonged bed rest cause long-lasting impairments in AP control and baroreflex function in exercising humans.

Adaptation, Physiological↗
PubMed2004

Distributions of lung ventilation and perfusion in prone and supine humans exposed to hypergravity.

When normal subjects are exposed to hypergravity [5 times normal gravity (5 G)] there is an impaired arterial oxygenation that is less severe in the prone compared with supine posture. We hypothesized that under these conditions the heterogeneities of ventilation and/or perfusion distributions would be less prominent when subjects were prone compared with supine. Expirograms from a combined rebreathing-single breath washout maneuver (Rohdin M, Sundblad P, and Linnarsson D. J Appl Physiol 96: 1470-1477, 2004) were analyzed for vital capacity (VC), phase III slope, and phase IV amplitude, to analyze heterogeneities in ventilation (Ar) and perfusion [CO(2)-to-Ar ratio (CO(2)/Ar)] distribution, respectively. During hypergravity, VC decreased more in the supine than in the prone position (ANOVA, P = 0.02). Phase III slope was more positive for Ar (P = 0.003) and more negative for CO(2)/Ar (P = 0.007) in the supine compared with prone posture at 5 G, in agreement with the notion of a more severe hypergravity-induced ventilation-perfusion mismatch in supine posture. Phase IV amplitude became lower in the supine than in the prone posture for both Ar (P = 0.02) and CO(2)/Ar (P = 0.004) during hypergravity as a result of the more reduced VC in the supine posture. We speculate that results of VC and phase IV amplitude are due to the differences in heart-lung interaction and diaphragm position between postures: a stable position of the heart and diaphragm in prone hypergravity, in contrast to supine in which the weight of the heart and a cephalad shift of the diaphragm compress lung tissue.

Adult↗
PubMed2003

Protective effect of prone posture against hypergravity-induced arterial hypoxaemia in humans.

Patients with acute respiratory distress syndrome have increased lung tissue weight and therefore an increased hydrostatic pressure gradient down the lung. Also, they have a better arterial oxygenation in prone (face down) than in supine (face up) posture. We hypothesized that this effect of the direction of gravity also existed in healthy humans, when increased hydrostatic gradients were induced by hypergravity. Ten healthy subjects were studied in a human centrifuge while exposed to 1 or 5 G in anterio-posterior (supine) or posterio-anterior (prone) direction. We measured blood gases using remote-controlled sampling and gas exchange by mass spectrometry. Hypergravity led to marked impairments of arterial oxygenation in both postures and more so in supine posture. At 5 G, the arterial oxygen saturation was 84.6 +/- 1.2 % (mean +/- S.E.M.) in supine and 89.7 +/- 1.4 % in prone posture (P < 0.001 for supine vs. prone). Ventilation and alveolar PO2 were increased at 5 G and did not differ between postures. The alveolar-to-arterial PO2 difference increased at 5 G to 8.0 +/- 0.2 kPa and 6.6 +/- 0.3 kPa in supine and prone postures (P = 0.003). Arterial oxygenation was less impaired in prone during hypergravity due to a better-preserved alveolo-arterial oxygen transport. We speculate that mammals have developed a cardiopulmonary structure that favours function with the gravitational vector in the posterio-anterior direction.

Adult↗
PubMed2003

Effects of gravity on lung diffusing capacity and cardiac output in prone and supine humans.

Both in normal subjects exposed to hypergravity and in patients with acute respiratory distress syndrome, there are increased hydrostatic pressure gradients down the lung. Also, both conditions show an impaired arterial oxygenation, which is less severe in the prone than in the supine posture. The aim of this study was to use hypergravity to further investigate the mechanisms behind the differences in arterial oxygenation between the prone and the supine posture. Ten healthy subjects were studied in a human centrifuge while exposed to 1 and 5 times normal gravity (1 G, 5 G) in the anterioposterior (supine) and posterioanterior (prone) direction. They performed one rebreathing maneuver after approximately 5 min at each G level and posture. Lung diffusing capacity decreased in hypergravity compared with 1 G (ANOVA, P = 0.002); it decreased by 46% in the supine posture compared with 25% in the prone (P = 0.01 for supine vs. prone). At the same time, functional residual capacity decreased by 33 and 23%, respectively (P < 0.001 for supine vs. prone), and cardiac output by 40 and 31% (P = 0.007 for supine vs. prone), despite an increase in heart rate of 16 and 28% (P < 0.001 for supine vs. prone), respectively. The finding of a more impaired diffusing capacity in the supine posture compared with the prone at 5 G supports our previous observations of more severe arterial hypoxemia in the supine posture during hypergravity. A reduced pulmonary-capillary blood flow and a reduced estimated alveolar volume can explain most of the reduction in diffusing capacity when supine.

Acceleration↗
PubMed2001

Impaired pressor response after spaceflight and bed rest: evidence for cardiovascular dysfunction.

We hypothesized that impaired cardiovascular responses to isometric muscle action contribute to the cardiovascular deconditioning that occurs after space flight (SF) and head-down-tilt bed rest (HDT). Six subjects were studied before, during and after 120 days of -6 degrees HDT, and four subjects were studied before, during (two subjects) and after 179-389 days of SF. Subjects performed a sustained handgrip (SHG) at a force equivalent to 30% of maximum contraction force for 2 min, and heart-rate (HR) and pressor (mean arterial pressure, deltaMAP) responses were recorded. At the same relative force, both deltaHR and deltaMAP were significantly reduced during the first days after HDT (-54%, P<0.05 and -43%, P<0.05). In two subjects studied within 24 h after their return from SF, deltaMAP was practically absent (-79%, P<0.05) whereas in four subjects studied 1-4 days after return from SF, deltaMAP was reduced by 35% (P<0.05). deltaHR was not significantly changed. Our finding of attenuated pressor responses to SHG after HDT and SF supports the notion of impairments at both the neurocirculatory control and effector organ levels.

Adult↗
PubMed2000

Haemodynamic and baroreflex responses to whole-body tilting in exercising men before and after 6 weeks of bedrest.

We sought to determine whether the cardiovascular deconditioning that occurs in exercising men after prolonged (42 days) bedrest in the head-down tilt (HDT) position is primarily related to mechanical changes in the heart or to an impaired arterial-cardiacchronotropic baroreflex. Seven subjects were studied before (C, control) and repeatedly after HDT with rapid tilting between the upright and supine positions during steady-state 50-W dynamic leg exercise. Ventricular interdependence was assumed to be an index of cardiac size; it was assessed on the basis of the initial dip of arterial pulse pressure (PP) induced by a sudden tilt from the upright to the supine position (down-tilt). Arterialcardiac-chronotropic baroreflex sensitivity (ABS) was assessed as the ratio between tilt-induced heart rate transients and the preceding (and reciprocal) transient in arterial pressure. On the first day of recovery, the initial PP dip was -4 (2) mmHg (where 1 mmHg is 0.13 kPa), less than half of the control value; on subsequent recovery days, the initial PP dip was not significantly different from the control value. When tilting from the upright to the supine position, mean ABS ranged from 1.02 to 1.06 bpm/mmHg during three separate control sessions. Tilts in the opposite direction gave lower ABS values because of the more sluggish HR response and ranged from 0.43 to 0.45 bpm/mmHg in the control situations. ABS did not change after HDT. Our results indicate that impairments of the cardiovascular system after long-term bedrest are of haemodynamic rather than baroreflex origin.

Adult↗
PubMed2000

Cardiovascular responses to upright and supine exercise in humans after 6 weeks of head-down tilt (-6 degrees).

Seven healthy men performed steady-state dynamic leg exercise at 50 W in supine and upright postures, before (control) and repeatedly after 42 days of strict head-down tilt (HDT) (-6 degrees) bedrest. Steady-state heart rate (fc), mean arterial blood pressure, cardiac output (Qc), and stroke volume (SV) were recorded. The following data changed significantly from control values. The fc was elevated in both postures at least until 12 days, but not at 32 days after bedrest. Immediately after HDT, SV and Qc were decreased by 25 (SEM 3)% and 19 (SEM 3)% in supine, and by 33 (SEM 5)% and 20 (SEM 3)% in upright postures, respectively. Within 2 days there was a partial recovery of SV in the upright but not in the supine posture. The SV and Qc during supine exercise remained significantly decreased for at least a month. Submaximal oxygen uptake did not change after HDT. We concluded that the cardiovascular response to exercise after prolonged bedrest was impaired for so long that it suggested that structural cardiac changes had developed during the HDT period.

Bed Rest↗
PubMed2000

Short-term cardiovascular responses to rapid whole-body tilting during exercise.

Our objective was to characterize the responses of heart rate (HR) and arterial blood pressure (BP) to changes in posture during concomitant dynamic leg exercise. Ten men performed dynamic leg exercise at 50, 100, and 150 W and were rapidly and repeatedly tilted between supine (0 degrees ) and upright (80 degrees ) positions at 2-min intervals. Continuous recordings of BP and HR were made, and changes in central blood volume were estimated from transthoracic impedance. Short-lasting increases in BP were observed immediately upon tilting from the upright to the supine position (down-tilt), averaging +18 mmHg (50 W) to +31 mmHg (150 W), and there were equally short-lasting decreases in BP, ranging from -26 to -38 mmHg upon tilting from supine to upright (up-tilt). These components occurred for all pressure parameters (systolic, mean, diastolic, and pulse pressures). We propose that these transients reflect mainly tilt-induced changes in total peripheral resistance resulting from decreases and increases of the efficiency of the venous muscle pump. After 3-4 s (down-tilt) and 7-11 s (up-tilt) there were large HR transients in a direction opposite to the pressure transients. These HR transients were larger during the down-tilt (-15 to -26 beats. min(-1)) than during the up-tilt (+13 to +17 beats. min(-1)), and increased in amplitude with work intensity during the down-tilt. The tilt-induced HR fluctuations could be modelled as a basically linear function of an arterial baroreflex input from a site half-way between the heart and the carotid sinus, and with varying contributions of fast vagal and slow sympathetic HR responses resulting in attenuated tachycardic responses to hypotensive stimuli during exercise.

Adult↗
PubMed1999

Implementation of a respiratory drive monitor on a Servo Ventilator.

OBJECTIVE: To design and evaluate a clinical monitor of respiratory drive (P0.1) and other respiratory variables in a simple way, using a commercial ventilator. METHODS: Nine healthy males were studied as they were breathing spontaneously in a Servo 900C Ventilator, at rest and during light exercise (50 W). The ventilator was slightly modified to improve its mechanical performance during spontaneous breathing, and was used as a measuring instrument. All the relevant information was retrieved, calculated and monitored by a PC. Respiratory drive was assessed as occlusion pressures from the inspiratory airway pressure signal. The equipment was compared with a two-way non-rebreathing laboratory system. Furthermore, negative and positive inspiratory pressures were applied from the ventilator, to study respiratory responses to mechanical loads. RESULTS: At rest, the ventilator introduced a minor influence on inspiratory time and P0.1, but not in ventilation, tidal volume, expiratory duration and respiratory frequency. During exercise, the influence was more evident. This effect could also be noticed in the coefficients of variation. The responses to mechanical loads were easily recorded and can be used as a simple test of central load-compensating mechanisms. CONCLUSIONS. The ventilator, with limitations, may be an alternative to conventional techniques, especially in clinical studies of the central inspiratory activity with and without respiratory loading.

Adult↗
PubMed1999

Oxygen cost of dynamic leg exercise on a cycle ergometer: effects of gravity acceleration.

A model of the metabolic internal power (Eint) during cycling, which includes the gravity acceleration (ag) as a variable, is presented. This model predicts that Eint is minimal in microgravity (0 g; g=9. 81 m s-2), and increases linearly with ag, whence the hypothesis that the oxygen uptake (VO2) during cycling depends on ag. Repeated VO2 measurements during steady-state exercise at 50, 75 and 100 W on the cycle ergometer, performed in space (0 g) and on Earth (1 g) on two subjects, validated the model. VO2 was determined from the time course of decreasing O2 fraction during rebreathing. The gas volume during rebreathing was determined by the dilution principle, using an insoluble inert gas (SF6). Average VO2 for subject 1 at each power was 0.99, 1.21 and 1.52 L min-1 at 1 g (n=3) and 0.91, 1.13 and 1.32 L min-1 at 0 g (n=5). For subject 2 it was 0.90, 1.12 and 1. 42 L min-1 at 1 g, and 0.76, 0.98 and 1.21 L min-1 at 0 g. These values corresponded to those predicted from the model. Although resting VO2 was lower at 0 g than at 1 g, the net (total minus resting) exercise VO2 was still smaller at 0 g than at 1 g. This difference reflects the lower Eint at 0 g.

Adult↗
PubMed1999

Slowing and attenuation of baroreflex heart rate control with nitrous oxide in exercising men.

The objective of the present study was to determine whether mild inert-gas narcosis impairs cardiovascular control mechanisms and contributes to the relative bradycardia that occurs in humans exercising in a hyperbaric environment. Eight healthy subjects were exposed to a normoxic 30% nitrous oxide (N(2)O) mixture and an air control during dynamic exercise of 100-W intensity. Beat-by-beat heart rate (HR) and invasive arterial blood pressure measurements were made. The sensitivity and the response latency of the arterial-cardiac-chronotropic baroreflex were determined from repeated blood pressure and HR transients induced by rapid tilts between the upright and supine posture. A significant increase (37%, P </= 0.02) of latency in baroreflex responses was found with 30% N(2)O, as well as a significant depression (16%, P </= 0.05) in baroreflex sensitivity. There were no differences between air and N(2)O in steady-state HR or arterial pressure. We conclude that mild inert-gas narcosis increases the latency and decreases the gain of HR responses to arterial baroreflex stimuli, but this cannot in itself account for the modest, relative bradycardia observed during moderately heavy exercise in a normoxic, hyperbaric environment.

Adult↗
PubMed1999

Hyperbaric bradycardia and hypoventilation in exercising men: effects of ambient pressure and breathing gas.

We sought to determine whether hydrostatic pressure contributed to bradycardia and hypoventilation in hyperbaria. Eight men were studied during exercise at 50, 150, and 250 W while breathing 1) air at 1 bar, 2) helium-oxygen (He-O(2)) at 5.5 bar, 3) sulfur hexafluoride-oxygen (SF(6)-O(2)) at 1.3 bar, and 4) nitrogen-oxygen (N(2)-O(2)) at 5.5 bar. Gas densities were pairwise identical in 1) and 2), and 3) and 4), respectively. Increased hydrostatic pressure to 5.5 bar resulted in a modest but significant relative bradycardia on the order of 6 beats/min, in both the absence [1) vs. 2), P = 0. 0015] and presence [3) vs. 4), P = 0.029] of gases that are both denser than normal and mildly narcotic. In contrast, ventilatory responses appeared not to be influenced by hydrostatic pressure. Also, the combined exposure to increased gas density and mild-to-moderate inert gas narcosis at a given hydrostatic pressure [1) vs. 3), 2) vs. 4)] caused bradycardia (P = 0.032 and 0.061, respectively) of similar magnitude as 5.5-bar hydrostatic pressure. At the same time there was relative hypoventilation at the two higher workloads. We conclude that heart rate control, but not ventilatory control, is sensitive to relatively small increases in hydrostatic pressure.

Adult↗
PubMed1999

Oxygen-conserving effects of apnea in exercising men.

We sought to determine whether apnea-induced cardiovascular responses resulted in a biologically significant temporary O(2) conservation during exercise. Nine healthy men performing steady-state leg exercise carried out repeated apnea (A) and rebreathing (R) maneuvers starting with residual volume +3.5 liters of air. Heart rate (HR), mean arterial pressure (MAP), and arterial O(2) saturation (Sa(O(2)); pulse oximetry) were recorded continuously. Responses (DeltaHR, DeltaMAP) were determined as differences between HR and MAP at baseline before the maneuver and the average of values recorded between 25 and 30 s into each maneuver. The rate of O(2) desaturation (DeltaSa(O(2))/Deltat) was determined during the same time interval. During apnea, DeltaSaO(2)/Deltat had a significant negative correlation to the amplitudes of DeltaHR and DeltaMAP (r(2) = 0.88, P < 0.001); i.e., individuals with the most prominent cardiovascular responses had the slowest DeltaSa(O(2))/Deltat. DeltaHR and DeltaMAP were much larger during A (-44 +/- 8 beats/min, +49 +/- 4 mmHg, respectively) than during R maneuver (+3 +/- 3 beats/min, +30 +/- 5 mmHg, respectively). DeltaSa(O(2))/Deltat during A and R maneuvers was -1.1 +/- 0.1 and -2.2 +/- 0.2% units/s, respectively, and nadir Sa(O(2)) values were 58 +/- 4 and 42 +/- 3% units, respectively. We conclude that bradycardia and hypertension during apnea are associated with a significant temporary O(2) conservation and that respiratory arrest, rather than the associated hypoxia, is essential for these responses.

Adult↗
PubMed1999

Arterial baroreflex control during mild-to-moderate nitrous oxide narcosis.

We hypothesized that light-to-moderate inert gas narcosis might play a role in bradycardia in divers by altering sensitivity or response dynamics of arterial baroreflexes. Carotid-cardiac and carotid-mean arterial pressure (MAP) baroreflex response curves were generated by applying multiple levels of neck pressure and suction. Seven healthy volunteers were studied during air breathing (control) and during inhalation of 39% nitrous oxide (N2O). Baseline (pre-stimulus) heart rate (HR) and MAP were not altered by N2O. Range, threshold level, saturation level, and delay of responses did not differ between conditions. For hypertensive stimuli, sensitivity of responses did not differ between air control and N2O inhalation, but for hypotensive stimuli, maximal response gain for HR tended to be reduced with N2O inhalation (P = 0.054). Our results speak against inert gas narcosis as a primary mechanism for hyperbaric bradycardia, but it remains possible that an attenuation of tachycardic responses to hypotensive stimuli plays a role.

Adult↗
PubMed1998

Lower leg fluid displacement during a simulated space shuttle launch.

Reductions in leg fluid volume of about 1/per leg or 10% of total leg volume have been reported during space flight. We wanted to test the hypothesis that a significant portion of these changes occur during the prelaunch and launch periods. Fluid volume changes in the lower leg were estimated in six men during a simulated Space Shuttle launch. After 2 h in the launch position, i.e. supine with elevated legs, the subjects were exposed to 500 s of two to three times increased g force in the anterio-posterior direction in a human centrifuge. During the prelaunch period one lower leg lost a mean of (113 SD 53) ml of fluid and there was little or no additional fluid reduction during the period of increased g force. This compares with the 178-ml reduction of lower leg volume that has been reported during the 1st day of Shuttle missions. We concluded that a significant portion of the fluid reduction observed in the lower leg during the early stages of space flight had already occurred before the launch.

Adult↗