Biomedical subjects

Dag Linnarsson

Publications and source records attributed to Dag Linnarsson.

16 recordsLinked to original sources

PubMed2006

Posture primarily affects lung tissue distribution with minor effect on blood flow and ventilation.

We used quantitative single photon emission computed tomography to estimate the proportion of the observed redistribution of blood flow and ventilation that is due to lung tissue shift with a change in posture. Seven healthy volunteers were studied awake, breathing spontaneously. Regional blood flow and ventilation were marked using radiotracers that remain fixed in the lung after administration. The radiotracers were administered in prone or supine at separate occasions, at both occasions followed by imaging in both postures. Images showed greater blood flow and ventilation to regions dependent at the time of imaging, regardless of posture at radiotracer administration. The results suggest that a shift in lung parenchyma has a major influence on the imaged distributions. We conclude that a change from the supine to the prone posture primarily causes a change in the vertical distribution of lung tissue. The effect on the vertical distribution of blood flow and ventilation within the lung parenchyma is much less.

Adult↗

PubMed2006

Non-invasive continuous estimation of blood flow changes in human patellar bone.

A photoplethysmographic (PPG) technique to assess blood flow in bone tissue has been developed and tested. The signal detected by the PPG consists of a constant-level (DC) component-which is related to the relative vascularization of the tissue-and a pulsatile (AC) component-which is synchronous with the pumping action of the heart. The PPG probe was applied on the skin over the patella. The probe uses near-infrared (804 nm) and green (560 nm) light sources and the AC component of the PPG signals of the two wavelengths was used to monitor pulsatile blood flow in the patellar bone and the overlying skin, respectively. Twenty healthy subjects were studied and arterial occlusion resulted in elimination of PPG signals at both wavelengths, whereas occlusion of skin blood flow by local surface pressure eliminated only the PPG signal at 560 nm. In a parallel study on a physical model with a rigid tube we showed that the AC component of the PPG signal originates from pulsations of blood flow in a rigid structure and not necessarily from volume pulsations. We conclude that pulsatile blood flow in the patellar bone can be assessed with the present PPG technique.

Adult↗

PubMed2006

Increased expired NO and roles of CO2 and endogenous NO after venous gas embolism in rabbits.

Venous gas embolism (VGE) is a feared complication in diving, aviation, surgery and trauma. We hypothesized that air emboli in the lung circulation might change expired nitric oxide (FeNO). A single intravenous infusion of air was given (100 mul kg(-1)) to three groups of anaesthetized mechanically ventilated rabbits: (A) one with intact NO production, (B) one with intact NO production and where end-tidal CO(2) was controlled, and (C) one with endogenous NO synthesis blockade (L: -NAME, 30 mg kg(-1)). Air infusions resulted in increased FeNO of the control group from 20 (4) [mean (SD)] ppb to a peak value of 39 (4) ppb within 5 min (P < 0.05), and FeNO was still significantly elevated [27 (2) ppb] after 20 min (P < 0.05). Parallel to the NO increase there were significant decreases in end-tidal CO(2 )(ETCO(2)) and mean arterial pressure and an increase in insufflation pressure. In group B, when CO(2) was supplemented after air infusion, NO was suppressed (P = 0.033), but was still significantly elevated compared with pre-infusion control (P < 0.05). In group C, all animals died within 40 min of air infusion whereas all animals in the other groups were still alive at this time point. We conclude that venous air embolization increases FeNO, and that a part of this effect is due to the concomitant decrease in ETCO(2). Furthermore, an intact NO production may be critical for the tolerance to VGE. Finally, FeNO might have a potential in the diagnosis and monitoring of pulmonary gas embolism.

Animals↗

PubMed2005

Paradoxical redistribution of pulmonary blood flow in prone and supine humans exposed to hypergravity.

We hypothesized that exposure to hypergravity in the supine and prone postures causes a redistribution of pulmonary blood flow to dependent lung regions. Four normal subjects were exposed to hypergravity by use of a human centrifuge. Regional lung perfusion was estimated by single-photon-emission computed tomography (SPECT) after administration of (99m)Tc-labeled albumin macroaggregates during normal and three times normal gravity conditions in the supine and prone postures. All images were obtained during normal gravity. Exposure to hypergravity caused a redistribution of blood flow from dependent to nondependent lung regions in all subjects in both postures. We speculate that this unexpected and paradoxical redistribution is a consequence of airway closure in dependent lung regions causing alveolar hypoxia and hypoxic vasoconstriction. Alternatively, increased vascular resistance in dependent lung regions is caused by distortion of lung parenchyma. The redistribution of blood flow is likely to attenuate rather than contribute to the arterial desaturation caused by hypergravity.

Adaptation, Physiological↗

PubMed2005

Effects of gravity and blood volume shifts on cardiogenic oscillations in respired gas.

During the cardiac cycle, cardiogenic oscillations of expired gas (x) concentrations (COS([x])) are generated. At the same time, there are heart-synchronous cardiogenic oscillations of airway flow (COS(flow)), where inflow occurs during systole. We hypothesized that both phenomena, although primarily generated by the heartbeat, would react differently to the cephalad blood shift caused by inflation of an anti-gravity (anti-G) suit and to changes in gravity. Twelve seated subjects performed a rebreathing-breath-holding-expiration maneuver with a gas mixture containing O2 and He at normal (1 G) and moderately increased gravity (2 G); an anti-G suit was inflated to 85 mmHg in each condition. When the anti-G suit was inflated, COS(flow) amplitude increased (P = 0.0028) at 1 G to 186% of the control value without inflation (1-G control) and at 2 G to 203% of the control value without inflation (2-G control). In contrast, the amplitude of COS of the concentration of the blood-soluble gas O2 (COS([O2/He])), an index of the differences in pulmonary perfusion between lung units, declined to 75% of the 1-G control value and to 74% of the 2-G control value (P = 0.0030). There were no significant changes in COS(flow) or COS([O2/He]) amplitudes with gravity. We conclude that the heart-synchronous mechanical agitation of the lungs, as expressed by COS(flow), is highly dependent on peripheral-to-central blood shifts. In contrast, COS([blood-soluble gas]) appears relatively independent of this mechanical agitation and seems to be determined mainly by differences in intrapulmonary perfusion.

Adaptation, Physiological↗

PubMed2005

Cardiovascular effects of anti-G suit inflation at 1 and 2 G.

We sought to determine to which pressure a full-coverage anti-G suit needs to be inflated in order to obtain the same stroke volume during a brief exposure to twice the normal gravity (2 G) as that at 1 G without anti-G suit inflation. Nine sitting subjects were studied at normal (1 G) and during 20 s of exposure to 2 G. They wore anti-G suits, which were inflated at both G-levels to the following target pressures: 0, 70, 140 and 210 mmHg. Stroke volume was computed from cardiac output, which was measured by rebreathing. Heart rate and mean arterial pressure at heart level were recorded. Inflation to 70 mmHg compensated for the decrease in stroke volume and cardiac output caused by hypergravity. Mean arterial pressure at heart level was comparable at 1 G and at 2 G and increased gradually and similarly with inflation (P<0.001) at both gravity levels. Thus, anti-G suits act by increasing both preload and afterload but the two effects counteract each other in terms of cardiac output, so that cardiac output at 2 G is maintained at its 1 G level. This effect is reached already at 70 mmHg of inflation. Greater inflation pressure further increases mean arterial pressure at heart level and compensates for the increased difference in hydrostatic pressure between heart and head in moderate hypergravity.

Abdominal Pain↗

PubMed2005

Residual heterogeneity of intra- and interregional pulmonary perfusion in short-term microgravity.

We hypothesized that the perfusion heterogeneity in the human, upright lung is determined by nongravitational more than gravitational factors. Twelve and six subjects were studied during two series of parabolic flights. We used cardiogenic oscillations of O(2)/SF(6) as an indirect estimate of intraregional perfusion heterogeneity (series 1) and phase IV amplitude (P(4)) as a indirect estimate of interregional perfusion heterogeneity (series 2). A rebreathing-breath holding-expiration maneuver was performed. In flight, breath holding and expiration were performed either in microgravity (0 G) or in hypergravity. Controls were performed at normal gravity (1 G). In series 1, expiration was performed at 0 G. Cardiogenic oscillations of O(2)/SF(6) were 19% lower when breath holding was performed at 0 G than when breath holding was performed at 1 G [means (SD): 1.7 (0.3) and 2.3 (0.6)% units] (P = 0.044). When breath holding was performed at 1.8 G, values did not differ from 1-G control [2.6 (0.8)% units, P = 0.15], but they were 17% larger at 1.8 G than at 1 G. In series 2, expiration was performed at 1.7 G. P(4) changed with gravity (P < 0.001). When breath holding was performed at 0 G, P(4) values were 45 (46)% of control. When breath holding was performed at 1.7 G, P(4) values were 183 (101)% of control. We conclude that more than one-half of indexes of perfusion heterogeneity at 1 G are caused by nongravitational mechanisms.

Adaptation, Physiological↗

PubMed2004

Long-term bed rest-induced reductions in stroke volume during rest and exercise: cardiac dysfunction vs. volume depletion.

Long-term head-down-tilt bed rest (HDT) causes cardiovascular deconditioning, attributed to reflex dysfunctions, plasma volume reduction, or cardiac impairments. Our objective with the present study was to evaluate the functional importance and relative contribution of these during rest and exercise in supine and upright postures. We studied six subjects before (baseline), during [days 60 (D60) and 113 (D113)], and after [recovery days 0 (R0), 3 (R3), and 15 (R15)] 120 days of -6 degrees HDT. We determined cardiac output, stroke volume (SV), mean arterial pressure, and heart rate during rest and exercise in supine and upright postures. Cardiac output and SV decreased significantly in all four conditions, but the time courses differed for rest and exercise. Upright resting SV was decreased by 24 +/- 9% at D60 compared with baseline but had recovered already at R3. Supine exercise SV decreased more slowly (by 5 +/- 8% at D60 and by 18 +/- 4% at D113) and recovered more slowly after HDT termination. Steady-state mean arterial pressure showed no changes. Heart rate had increased by 18 +/- 4% at D60 and had recovered partially at R3. Our data indicate that long-term HDT causes both a rapid, preload-dependent reduction in SV, most evident during rest in the upright position, and a more slowly developing cardiac dysfunction, most evident during supine exercise. However, the ability to maintain blood pressure and to perform sustained low levels of dynamic exercise is not influenced by HDT.

Adaptation, Physiological↗

PubMed2004

Novel hand-held device for exhaled nitric oxide-analysis in research and clinical applications.

Changes in expired nitric oxide (NO) occur in airway inflammation and have proved to be important in the monitoring of inflammatory disease processes such as asthma. We set out to develop a novel hand-held NO-analyzer with a performance comparable to the present more costly and complex chemiluminescence instruments. The new device is based on a specially designed electrochemical sensor, where we have developed a novel sampling and analysis technology, compensating for the relatively slow response properties of the electrochemical sensor technique. A Lowest Detection Limit in NO-analysis from reference gas tests of less than 3 ppb and a response time of 15 seconds together with an average precision in human breath measurements of 1.4 ppb were obtained. We also show an agreement with the existing 'gold standard' FENO measurement technique, within 0.5 ppb in a group of 19 subjects together with a high linearity and accuracy compared to reference gases. The new analyzer enables affordable monitoring of inflammatory airway diseases in research and routine clinical practice.

Asthma↗

PubMed2003

Effects of hypergravity on the distributions of lung ventilation and perfusion in sitting humans assessed with a simple two-step maneuver.

Increased gravity impairs pulmonary distributions of ventilation and perfusion. We sought to develop a method for rapid, simultaneous, and noninvasive assessments of ventilation and perfusion distributions during a short-duration hypergravity exposure. Nine sitting subjects were exposed to one, two, and three times normal gravity (1, 2, and 3 G) in the head-to-feet direction and performed a rebreathing and a single-breath washout maneuver with a gas mixture containing C(2)H(2), O(2), and Ar. Expirograms were analyzed for cardiogenic oscillations (COS) and for phase IV amplitude to analyze inhomogeneities in ventilation (Ar) and perfusion [CO(2)-to-Ar ratio (CO(2)/Ar)] distribution, respectively. COS were normalized for changes in stroke volume. COS for Ar increased from 1-G control to 128 +/- 6% (mean +/- SE) at 2 G (P = 0.02 for 1 vs. 2 G) and 165 +/- 13% at 3 G (P = 0.002 for 2 vs. 3 G). Corresponding values for CO(2)/Ar were 135 +/- 12% (P = 0.04) and 146 +/- 13%. Phase IV amplitude for Ar increased to 193 +/- 39% (P = 0.008) at 2 G and 229 +/- 51% at 3 G compared with 1 G. Corresponding values for CO(2)/Ar were 188 +/- 29% (P = 0.02) and 219 +/- 18%. We conclude that not only large-scale ventilation and perfusion inhomogeneities, as reflected by phase IV amplitude, but also smaller-scale inhomogeneities, as reflected by the ratio of COS to stroke volume, increase with hypergravity. Except for small-scale ventilation distribution, most of the impairments observed at 3 G had been attained at 2 G. For some of the parameters and gravity levels, previous comparable data support the present simplified method.

Adult↗

PubMed2003

Physiological evaluation of a new quantitative SPECT method measuring regional ventilation and perfusion.

We have developed a new quantitative single-photon-emission computed tomography (SPECT) method that uses (113m)In-labeled albumin macroaggregates and Technegas ((99m)Tc) to estimate the distributions of regional ventilation and perfusion for the whole lung. The multiple inert-gas elimination technique (MIGET) and whole lung respiratory gas exchange were used as physiological evaluations of the SPECT method. Regional ventilation and perfusion were estimated by SPECT in nine healthy volunteers during awake, spontaneous breathing. Radiotracers were administered with subjects sitting upright, and SPECT images were acquired with subjects supine. Whole lung gas exchange of MIGET gases and arterial Po(2) and Pco(2) gases was predicted from estimates of regional ventilation and perfusion. We found a good agreement between measured and SPECT-predicted exchange of MIGET and respiratory gases. Correlations (r(2)) between SPECT-predicted and measured inert-gas excretions and retentions were 0.99. The method offers a new tool for measuring regional ventilation and perfusion in humans.

Adult↗

PubMed2003

Relationship between breath-synchronous arterial pressure and heart rate variations during orthostatic stress.

It has recently been shown that the phase relationship between respiration-induced changes in arterial pressure (AP) and heart rate (HR) are different in supine and upright postures. We wanted to further analyse the coupling between respiration, arterial blood pressure and HR in the time domain, and how this coupling was altered during orthostatic stress. Nine healthy subjects were studied. Respiration-induced changes in AP and HR were recorded during frequency- and volume-controlled breathing. This was done during supine rest with and without lower body negative pressure (-50 mmHg) (LBNP). All experiments were performed after beta1-blockade. Responses were averaged breath-by-breath to enhance the time resolution and to eliminate noise. The respiration-induced changes in arterial pulse pressure (PP) were different between control and LBNP: The peak in PP during the respiratory cycle occurred 0.9 +/- 0.8 (mean +/- SD) s before the onset of inspiration during supine control and 0.8 +/- 2.1 s after the onset of inspiration during LBNP (P = 0.03). These changes in the timing of peak PP significantly distorted the cyclic systolic AP and mean AP fluctuations during LBNP. Despite the altered AP response with LBNP, HR fluctuations closely correlated in time with respiration in all conditions, albeit with a significantly reduced amplitude during LBNP (-49%, P = 0.01). The results points to a lack of coupling between AP and HR during paced breathing and thus suggest that respiratory sinus dysrhythmia at least, to a large extent, is independent of the arterial baroreflex.

Adult↗

PubMed2002

Pulmonary gas exchange during apnoea in exercising men.

There is indirect evidence that cardiovascular responses to apnoea result in a temporary slowing of the O(2) uptake in the lungs in exercising humans. The present study was undertaken in an attempt to determine directly to what extent this occurs, and whether the magnitude of this slowing is such that it must be the result of concomitant cardiovascular readjustments and not merely a result of an isolated apnoea-induced fall in the arterial O(2) saturation ( S(a)O(2)). Eight men performed 120 W leg exercise and performed repeated apnoeas of 10-40 s duration. Heart rate, S(a)O(2), and breath-by-breath gas exchange were determined. Pulmonary O(2) uptake fell gradually as breath-holds proceeded by [mean (SEM)] 74 (3)% of the pre-apnoea O(2) uptake. This decrease was significantly larger than could be accounted for by the fall in S(a)O(2) alone [ S(a)O(2) fall -30 (3)%], which it is estimated would have resulted in a fall of pulmonary O(2) uptake of -54 (5)%. We conclude that cardiovascular responses to apnoea contribute significantly to reducing pulmonary O(2) uptake during apnoea in exercising men.

Adolescent↗

PubMed2002

Role of hypoxemia for the cardiovascular responses to apnea during exercise.

We sought to define the role of hypoxemia in eliciting the cardiovascular responses to apnea during exercise. Eleven men performed repeated apneas during 100-W steady-state exercise, either with normoxic gas (air) or 95% oxygen (oxygen). Beat-by-beat arterial blood pressure, arterial oxygen saturation, and heart rate (HR) were determined, and stroke volume (SV) was estimated from impedance cardiography calibrated with soluble gas rebreathing. There were large interindividual variabilities of HR, mean arterial pressure (MAP), and total peripheral resistance (TPR) at end-apnea (ea). However, for each individual, HR(ea), MAP(ea), and TPR(ea) were highly correlated between air and oxygen (R = 0.94, 0.78, and 0.93). HR decreased and MAP increased faster during apnea with air than with oxygen (ANOVA, P < 0.05), but MAP(ea) was not different between conditions. Cardiac output was reduced by 33% with air and by 11% with oxygen (P < 0.001 for air vs. oxygen). We conclude that the hypoxemia component cannot account for the wide interindividual differences of HR and TPR responses to apnea. However, hypoxemia augments the HR and TPR responses and may limit the MAP response to apnea by preventing a bradycardia-associated increase of SV.

Adolescent↗

PubMed2002

Lung function during and after prolonged head-down bed rest.

We determined the effects of prolonged head-down tilt bed rest (HDT) on lung mechanics and gas exchange. Six subjects were studied in supine and upright postures before (control), during [day 113 (D113)], and after (R + number of days of recovery) 120 days of HDT. Peak expiratory flow (PF) never differed between positions at any time and never differed from controls. Maximal midexpiratory flow (FEF(25-75%)) was lower in the supine than in the upright posture before HDT and was reduced in the supine posture by about 20% between baseline and D113, R + 0, and R + 3. The diffusing capacity for carbon monoxide corrected to a standardized alveolar volume (volume-corrected DL(CO)) was lower in the upright than in the supine posture and decreased in both postures by 20% between baseline and R + 0 and by 15% between baseline and R + 15. Pulmonary blood flow (Q(C)) increased from R + 0 to R + 3 by 20 (supine) and 35% (upright). As PF is mostly effort dependent, our data speak against major respiratory muscle deconditioning after 120 days of HDT. The decrease in FEF(25-75%) suggests a reduction in elastic recoil. Time courses of volume-corrected DL(CO) and Q(C) could be explained by a decrease in central blood volume during and immediately after HDT.

Adult↗

PubMed2002

Differential changes of lung diffusing capacity and tissue volume in hypergravity.

In normal gravity, lung diffusing capacity (DL(CO)) and lung tissue volume (LTV; including pulmonary capillary blood volume) change in concert, for example, during shifts between upright and supine. Accordingly, DL(CO) and LTV might be expected to decrease together in sitting subjects in hypergravity due to peripheral pooling of blood and reduced central blood volume. Nine sitting subjects in a human centrifuge were exposed to one, two, and three times increased gravity in the head-to-feet direction (G(z+)) and rebreathed a gas containing trace amounts of acetylene and carbon monoxide. DL(CO) was 25.2 +/- 2.6, 20.0 +/- 2.1, and 16.7 +/- 1.7 ml. min(-1). mbar(-1) (means +/- SE) at 1, 2, and 3 G(z+), respectively (ANOVA P < 0.001). Corresponding values for LTV increased from 541 +/- 34 to 677 +/- 43, and 756 +/- 71 ml (P < 0.001) at 2 and 3 G(z+). Results are compatible with sequestration of blood in the dependent part of the pulmonary circulation just as in the systemic counterpart. DL(CO,) which under normoxic conditions is mainly determined by its membrane component, decreased despite an increased pulmonary capillary blood volume, most likely as a consequence of a less homogenous distribution of alveolar volume with respect to pulmonary capillary blood volume.

Adult↗