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

Verbanck, Sylvia, Hans Larsson, Dag Linnarsson, G. KimPrisk, John B. West, and Manuel Paiva. Pulmonary tissue volume, cardiac output and diffusing capacity in sustained microgravity. J. Appl. Physiol. 83(3): 810-816, 1997.In microgravity (µG) humans have marked changes in bodyfluids, with a combination of an overall fluid loss and aredistribution of fluids in the cranial direction. We investigatedwhether interstitial pulmonary edema develops as a result of a headwardfluid shift or whether pulmonary tissue fluid volume is reduced as aresult of the overall loss of body fluid. We measured pulmonary tissuevolume (Vti), capillary blood flow, and diffusing capacity in foursubjects before, during, and after 10 days of exposure to µG duringspaceflight. Measurements were made by rebreathing a gas mixturecontaining small amounts of acetylene, carbon monoxide, and argon.Measurements made early in flight in two subjects showed no change inVti despite large increases in stroke volume (40%) and diffusingcapacity (13%) consistent with increased pulmonary capillary bloodvolume. Late in-flight measurements in four subjects showed a 25%reduction in Vti compared with preflight controls(P < 0.001). There was aconcomittant reduction in stroke volume, to the extent that it was nolonger significantly different from preflight control. Diffusingcapacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despiteincreased pulmonary perfusion and pulmonary capillary blood volume,interstitial pulmonary edema does not result from exposure to µG.

     

Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis

Hsia, C. C. W., C. J. C. Chuong, and R. L. Johnson, Jr.Red cell distortion and conceptual basis of diffusing capacity estimates: finite element analysis. J. Appl.Physiol. 83(4): 1397-1404, 1997.To understandthe effects of dynamic shape distortion of red blood cells (RBCs) as itdevelops under high-flow conditions on the standard physiological andmorphometric methods of estimating pulmonary diffusing capacity, wecomputed the uptake of CO across a two-dimensional geometric capillarymodel containing a variable number of equally spaced RBCs. RBCs arecircular or parachute shaped, with the same perimeter length. Total COdiffusing capacity (DL_CO)and membrane diffusing capacity(DM_CO)were calculated by a finite element method.DL_COcalculated at two levels of alveolar PO₂ were used to estimateDM_CO by theRoughton-Forster (RF) technique. The same capillary model was subjectedto morphometric analysis by the random linear intercept method toobtain morphometric estimates ofDM_CO. Results show thatshape distortion of RBCs significantly reduces capillary diffusive gasuptake. Shape distortion exaggerates the conceptual errors inherent inthe RF technique (J. Appl. Physiol.79: 1039-1047, 1995); errors are exaggerated at a high capillaryhematocrit. Shape distortion also introduces additional error inmorphometric estimates ofDM_CO causedby a biased sampling distribution of random linear intercepts; errors are exaggerated at a low capillary hematocrit.

     

Atrial distension in humans during microgravity induced by parabolic flights

Videbaek, Regitze, and Peter Norsk. Atrialdistension in humans during microgravity induced by parabolic flights.J. Appl. Physiol. 83(6):1862-1866, 1997.The hypothesis was tested that human cardiacfilling pressures increase and the left atrium is distended during 20-speriods of microgravity (µG) created by parabolic flights, comparedwith values of the 1-G supine position. Left atrial diameter(n = 8, echocardiography) increasedsignificantly during µG from 26.8 ± 1.2 to 30.4 ± 0.7 mm(P < 0.05). Simultaneously, centralvenous pressure (CVP; n = 6, transducer-tipped catheter) decreased from 5.8 ± 1.5 to 4.5 ± 1.1 mmHg (P < 0.05), and esophageal pressure (EP; n = 6) decreased from1.5 ± 1.6 to 4.1 ± 1.7 mmHg (P < 0.05). Thus transmural CVP(TCVP = CVP  EP; n = 4)increased during µG from 6.1 ± 3.2 to 10.4 ± 2.7 mmHg(P < 0.05). It is concluded thatshort periods of µG during parabolic flights induce an increase inTCVP and left atrial diameter in humans, compared with the resultsobtained in the 1-G horizontal supine position, despite a decrease inCVP.

     

A finite-element model of oxygen diffusion in the pulmonary capillaries

Frank, Andreas O., C. J. Charles Chuong, and Robert L. Johnson. A finite-element model of oxygen diffusion in thepulmonary capillaries. J. Appl.Physiol. 82(6): 2036-2044, 1997.We determined the overall pulmonary diffusing capacity(DL) and the diffusing capacities of the alveolar membrane (Dm) and the red blood cell (RBC)segments (De) of the diffusional pathway forO₂ by using a two-dimensionalfinite-element model developed to represent the sheet-flowcharacteristics of pulmonary capillaries. An axisymmetric model wasalso considered to assess the effect of geometric configuration. Results showed the membrane segment contributing the major resistance, with the RBC segment resistance increasing asO₂ saturation(SO₂) rises during the RBC transit:RBC contributed 7% of the total resistance at the capillary inlet (SO₂ = 75%) and 30% toward thecapillary end (SO₂ = 95%) for a 45%hematocrit (Hct). Both Dm and DLincreased as the Hct increased but began approaching a plateau near anHct of 35%, due to competition between RBCs forO₂ influx. Both Dm andDL were found to be relatively insensitive (2~4%) to changes in plasma protein concentration (28~45%). Axisymmetric results showed similar trends for all Hct andprotein concentrations but consistently overestimated the diffusingcapacities (~2.2 times), primarily because of an exaggerated air-tissue barrier surface area. The two-dimensional model correlated reasonably well with experimental data and can better represent theO₂ uptake of the pulmonarycapillary bed.

     

Effects of anatomic variability on blood flow and pressure gradients in the pulmonary capillaries

Dhadwal, Amit, Barry Wiggs, Claire M. Doerschuk, and RogerD. Kamm. Effects of anatomic variability on blood flow and pressure gradients in the pulmonary capillaries. J. Appl. Physiol. 83(5): 1711-1720, 1997.Atheoretical model is developed to simulate the flow of blood throughthe capillary network in a single alveolar septum. The objective is tostudy the influence of random variability in capillary dimension andcompliance on flow patterns and pressures within the network. Thecapillary bed is represented as an interconnected rectangular grid ofcapillary segments and junctions; blood flow is produced by applying apressure gradient across the network. Preferred flow channels are shownto be a natural consequence of random anatomic variability, the effectof which is accentuated at low transcapillary pressures. Thedistribution of pressure drops across single capillary segments widenswith increasing network variability and decreasing capillary transmuralpressure. Blockage of one capillary segment causes the pressure dropacross that segment to increase by 60%, but the increase falls to<10% at a distance of three segments. The factors that causenonuniform capillary blood flow through the capillary network arediscussed.

     

Isoproterenol attenuates high vascular pressure-induced permeability increases in isolated rat lungs

Parker, James C., and Claire L. Ivey.Isoproterenol attenuates high vascular pressure-inducedpermeability increases in isolated rat lungs. J. Appl.Physiol. 83(6): 1962-1967, 1997.To separate thecontributions of cellular and basement membrane components of thealveolar capillary barrier to the increased microvascular permeabilityinduced by high pulmonary venous pressures (Ppv), we subjected isolatedrat lungs to increases in Ppv, which increased capillary filtrationcoefficient(K_fc) withoutsignificant hemorrhage (31 cmH₂O)and with obvious extravasation of red blood cells (43 cmH₂O). Isoproterenol (20 µM)was infused in one group (Iso) to identify a reversible cellularcomponent of injury, and residual blood volumes were measured to assessextravasation of red blood cells through ruptured basement membranes.In untreated lungs (High Ppv group),K_fc increased 6.2 ± 1.3 and 38.3 ± 15.2 times baseline during the 31 and 43 cmH₂O Ppv states. In Iso lungs, K_fc was 36.2%(P < 0.05) and 64.3% of that in theHigh Ppv group at these Ppv states. Residual blood volumes calculatedfrom tissue hemoglobin contents were significantly increased by53-66% in the high Ppv groups, compared with low vascularpressure controls, but there was no significant difference between HighPpv and Iso groups. Thus isoproterenol significantly attenuatedvascular pressure-induced K_fc increases atmoderate Ppv, possibly because of an endothelial effect, but it did notaffect red cell extravasation at higher vascular pressures.

     

Paradoxical helium and sulfur hexafluoride single-breath washouts in short-term vs. sustained microgravity

Lauzon, Anne-Marie, G. Kim Prisk, Ann R. Elliott, SylviaVerbanck, Manuel Paiva, and John B. West. Paradoxical helium andsulfur hexafluoride single-breath washouts in short-term vs. sustainedmicrogravity. J. Appl. Physiol. 82(3):859-865, 1997.During single-breath washouts in normal gravity (1 G), the phase III slope of sulfur hexafluoride(SF₆) is steeper than that ofhelium (He). Two mechanisms can account for this:1) the higher diffusivity of Heenhances its homogeneous distribution; and2) the lower diffusivity ofSF₆ results in a more peripherallocation of the diffusion front, where airway asymmetry is larger.These mechanisms were thought to be gravity independent. However, weshowed during the Spacelab Life Sciences-2 spaceflight that insustained microgravity (µG) theSF₆-to-He slope difference isabolished. We repeated the protocol during short periods (27 s) of µG(parabolic flights). The subjects performed a vital-capacityinspiration and expiration of a gas containing 5% He-1.25%SF₆-balanceO₂. As in sustained µG, thephase III slopes of He and SF₆decreased. However, during short-term µG, theSF₆-to-He slope differenceincreased from 0.17 ± 0.03%/l in 1 G to 0.29 ± 0.06%/l inµG, respectively. This is contrary to sustained µG, in which theSF₆-to-He slope difference decreased from 0.25 ± 0.03%/l in 1 G to 0.01 ± 0.06%/lin µG. The increase in phase III slope difference in short-term µGwas caused by a larger decrease of He phase III slope compared with that in sustained µG. This suggests that changes in peripheral gasmixing seen in sustained µG are mainly due to alterations in thediffusive-convective inhomogeneity of He that require >27 s of µGto occur. Changes in pulmonary blood volume distribution or cardiogenicmixing may explain the differences between the results found inshort-term and sustained µG.

     

Fractional changes in lung capillary blood volume and oxygen saturation during the cardiac cycle in rabbits

Topulos, George P., Nina R. Lipsky, John L. Lehr, Rick A. Rogers, and James P. Butler. Fractional changes in lung capillary blood volume and oxygen saturation during the cardiac cycle in rabbits.J. Appl. Physiol. 82(5):1668-1676, 1997.Changes in local pulmonary capillary bloodvolume (Vc) and oxygen saturation (S) have been difficult to measure inlive animals. By utilizing the differences in absorptionof light at two wavelengths (650 and 800 nm), we estimated thefractional change in Vc and S during the course of the cardiac cycle ineight anesthetized, ventilated rabbits at low and high lung volumes.Observations were made of the pattern of diffusely backscattered light,from an ~1-cm³ volume of lungilluminated with a point source placed on the pleural surface through athoracotomy. At low lung volume, the fractional change in Vc was~13%, the change in S was ~4.6%, and the mean S was close to77%. The fluctuations in Vc and S lagged behind peaksystemic blood pressure by about one-fifth and three-fifths of a cycle,respectively. At high lung volume, there were no important fluctuationsin Vc or S, and the mean S was ~82%. These results areconsistent with fluctuations in pulmonary capillary pressure and gasexchange over the cardiac cycle, and with decreasing capillary compliance with increasing lung volume.

     

Pulmonary blood flow distribution has a hilar-to-peripheral gradient in awake, prone sheep

Walther, Sten M., Karen B. Domino, Robb W. Glenny, Nayak L. Polissar, and Michael P. Hlastala. Pulmonary blood flow distribution has a hilar-to-peripheral gradient in awake, prone sheep.J. Appl. Physiol. 82(2): 678-685, 1997.We examined the pulmonary blood flow distribution withintravenous fluorescent microspheres (15 µm) in nine prone,unanesthetized, lambs. Lungs flushed free of blood were air-dried attotal lung capacity and sectioned into~2-cm³ pieces. The pieces wereweighed, identified by lobe, and assigned spatial coordinates.Fluorescence was read on a spectrophotometer, and signals werecorrected for piece weight and normalized to mean flow. Pulmonary bloodflow heterogeneity was assessed by using the coefficient of variationof the flow data. The number of pieces (±SD) analyzed were 1,249 ± 150/animal. Heterogeneity of blood flow was 29.5 ± 6.5%(coefficient of variation = SD/mean). Pulmonary blood flow decreasedwith distance from hilus (P < 0.002) but did not change significantly with vertical height. Distance fromthe hilus was the best predictor of pulmonary blood flow (R² = 0.201) and,together with spatial coordinates and lobe, accounted for 33.7 ± 12.0% of blood flow variability. We conclude that pulmonary blood flowin the awake, prone sheep is distributed with a hilar-to-peripheral gradient but no significant vertical gradient.

     

Pulmonary vascular pressures of exercising Thoroughbred horses with and without endoscopic evidence of EIPH

Manohar, Murli, and Thomas E. Goetz. Pulmonary vascularpressures of exercising Thoroughbred horses with and without endoscopicevidence of EIPH. J. Appl. Physiol.81(4): 1589-1593, 1996.Exercise-induced pulmonary hemorrhage(EIPH) is a common occurrence in racehorses. The objective of thisstudy was to compare pulmonary vascular pressures of healthyThoroughbred horses with and without postexertion endoscopicallydetectable fresh blood in the trachea. The nasopharynx, larynx, andtrachea (down to the carina) of horses were examined weekly with anendoscope 55-60 min postexertion, and the diagnosis of EIPH wasconfirmed by the presence of fresh blood in the trachea. Measurementsof heart rate and right atrial, pulmonary arterial, and pulmonaryarterial wedge pressures were made during quiet rest and duringtreadmill exercise performed at 14.5 m/s on a 5% uphillgrade. This workload elicited maximal heart rate of thehorses. Mean pulmonary capillary pressure was estimated to be halfwaybetween the mean pulmonary arterial pressure and the mean pulmonaryarterial wedge pressure. These data from 7 healthy soundexercise-trained horses that were positive on 12 consecutive occasions(at 1-wk intervals) for the postexercise presence of fresh blood in thetrachea were compared with those in 8 healthy horses that wereconsistently negative for the evidence of fresh blood in the trachea onpostexercise endoscopic examination over 12-16 wk. The heart rateand the right heart and/or pulmonary vascular pressures in the twogroups of horses were similar at rest. Exercise wasattended by a large significant (P < 0.05) increase in these pressures and heart rate in both groups.However, statistically significant differences between endoscopicallyEIPH-positive and endoscopically EIPH-negative horses for heart rateand right atrial and pulmonary vascular pressures were not found duringexercise. Thus these data revealed that the magnitude ofexercise-induced right atrial as well as pulmonary arterial, capillary,and venous hypertension in endoscopically EIPH-positive horses that areotherwise healthy is quite similar to that in endoscopicallyEIPH-negative horses during comparable exertion.

     

Red cell distribution and the recruitment of pulmonary diffusing capacity.

The distribution of red blood cells in alveolar capillaries is typically nonuniform, as shown by intravital microscopy and in alveolar tissue fixed in situ. To determine the effects of red cell distribution on pulmonary diffusive gas transport, we computed the uptake of CO across a two-dimensional geometric capillary model containing a variable number of red blood cells. Red blood cells are spaced uniformly, randomly, or clustered without overlap within the capillary. Total CO diffusing capacity (DLCO) and membrane diffusing capacity (DmCO) are calculated by a finite-element method. Results show that distribution of red blood cells at a fixed hematocrit greatly affects capillary CO uptake. At any given average capillary red cell density, the uniform distribution of red blood cells yields the highest DmCO and DLCO, whereas the clustered distribution yields the lowest values. Random nonuniform distribution of red blood cells within a single capillary segment reduces diffusive CO uptake by up to 30%. Nonuniform distribution of red blood cells among separate capillary segments can reduce diffusive CO uptake by >50%. This analysis demonstrates that pulmonary microvascular recruitment for gas exchange does not depend solely on the number of patent capillaries or the hematocrit; simple redistribution of red blood cells within capillaries can potentially account for 50% of the observed physiological recruitment of DLCO from rest to exercise.     

Evidence against an increase in capillary permeability in subjects exposed to high altitude

Kleger, Gian-Reto, Peter Bärtsch, Peter Vock, BernhardHeilig, L. Jackson Roberts II, and Peter E. Ballmer. Evidence against an increase in capillary permeability in subjects exposed tohigh altitude. J. Appl. Physiol.81(5): 1917-1923, 1996.A potential pathogenetic cofactor for thedevelopment of acute mountain sickness and high-altitude pulmonaryedema is an increase in capillary permeability, which could occur as aresult of an inflammatory reaction and/or free radical-mediatedinjury to the lung. We measured the systemic albumin escape byintravenously injecting 5 µCi of ¹²⁵I-labeled albumin and theplasma concentrations of cytokines, F₂-isoprostanes (products of lipidperoxidation), and acute-phase proteins in 24 subjects exposed to 4,559 m. Ten subjects developed acute mountain sickness, and four subjectsdeveloped high-altitude pulmonary edema. The transcapillary escaperate of albumin was 6.9 ± 2.0%/h (SD) at low (550 m) and 6.3 ± 1.9%/h at high (4,559 m) altitude (P = 0.23; n = 24). The subjects withhigh-altitude pulmonary edema had a modest but insignificant increasein the transcapillary escape rate of albumin (4.6 ± 1.9%/h at lowvs. 5.7 ± 1.9%/h at high altitude;P = 0.42;n = 4). Plasma concentrations offibrinogen, ₁-acidglycoprotein, C-reactive protein, and interleukin-6 were unchanged inthe early phases and significantly increased by the end of theobservation period in the subjects with high-altitude pulmonary edema,whereas tumor necrosis factor- andF₂-isoprostanes did not change atall. This suggests that the inflammatory reaction was rather aconsequence than a causative factor of high-altitude pulmonary edema.In summary, these data argue against a dominant role for increasedsystemic capillary permeability in the development of acute mountainsickness and high-altitude pulmonary edema.

     

Chest wall mechanics in sustained microgravity

We assessed theeffects of sustained weightlessness on chest wall mechanics in fiveastronauts who were studied before, during, and after the 10-daySpacelab D-2 mission (n = 3)and the 180-day Euromir-95 mission (n = 2). We measured flow and pressure at the mouth and rib cage andabdominal volumes during resting breathing and during a relaxationmaneuver from midinspiratory capacity to functional residual capacity.Microgravity produced marked and consistent changes () in thecontribution of the abdomen to tidal volume [Vab/(Vab + Vrc), where Vab is abdominal volume and Vrc is rib cagevolume], which increased from 30.7 ± 3.5 (SE)% at1 G head-to-foot acceleration to 58.3 ± 5.7% at 0 G head-to-foot acceleration (P < 0.005). Values ofVab/(Vab + Vrc) did not change significantly during the 180 days of the Euromir mission, but in the two subjects Vab/(Vab + Vrc) was greater on postflight day1 than on subsequent postflight days or preflight. Inthe two subjects who produced satisfactory relaxation maneuvers, the slope of the Konno-Mead plot decreased in microgravity; this decrease was entirely accounted for by an increase in abdominal compliance because rib cage compliance did not change. These alterations aresimilar to those previously reported during short periods ofweightlessness inside aircrafts flying parabolic trajectories. They arealso qualitatively similar to those observed on going from upright tosupine posture; however, in contrast to microgravity, such posturalchange reduces rib cage compliance.

     

Capillary recruitment and transit time in the rat lung

Presson, Robert G., Jr., Thomas M. Todoran, Bracken J. DeWitt, Ivan F. McMurtry, and Wiltz W. Wagner, Jr.Capillary recruitment and transit time in the rat lung.J. Appl. Physiol. 83(2): 543-549, 1997.Increasing pulmonary blood flow and the associated rise incapillary perfusion pressure cause capillary recruitment. The resultingincrease in capillary volume limits the decrease in capillary transittime. We hypothesize that small species with relatively high restingmetabolic rates are more likely to utilize a larger fraction ofgas-exchange reserve at rest. Without reserve, we anticipate thatcapillary transit time will decrease rapidly as pulmonary blood flowrises. To test this hypothesis, we measured capillary recruitment andtransit time in isolated rat lungs. As flow increased, transit timedecreased, and capillaries were recruited. The decrease in transit timewas limited by an increase in the homogeneity of the transit time distribution and an increased capillary volume due, in part, to recruitment. The recruitable capillaries, however, were nearly completely perfused at flow rates and pressures that were less thanbasal for the intact animal. This suggests that a limited reserve ofrecruitable capillaries in the lungs of species with high restingmetabolic rates may contribute to their inability to raiseO₂ consumption manyfold abovebasal values.

     

Effect of microgravity on the expression of mitochondrial enzymes in rat cardiac and skeletal muscles

Connor, Michael K., and David A. Hood. Effect ofmicrogravity on the expression of mitochondrial enzymes in rat cardiac and skeletal muscles. J. Appl.Physiol. 84(2): 593-598, 1998.The purpose ofthis study was to examine the expression of nuclear and mitochondrialgenes in cardiac and skeletal muscle (triceps brachii) in response toshort-duration microgravity exposure. Six adult male rats were exposedto microgravity for 6 days and were compared with six ground-basedcontrol animals. We observed a significant 32% increase in heartmalate dehydrogenase (MDH) enzyme activity, which was accompanied by a62% elevation in heart MDH mRNA levels after microgravity exposure.Despite modest elevations in the mRNAs encoding subunits III, IV, andVIc as well as a 2.2-fold higher subunit IV protein content afterexposure to microgravity, heart cytochromec oxidase (CytOx) enzyme activityremained unchanged. In skeletal muscle, MDH expression was unaffectedby microgravity, but CytOx activity was significantly reduced 41% bymicrogravity, whereas subunit III, IV, and VIc mRNA levels and subunitIV protein levels were unaltered. Thus tissue-specific (i.e., heart vs.skeletal muscle) differences exist in the regulation of nuclear-encoded mitochondrial proteins in response to microgravity. In addition, theexpression of nuclear-encoded proteins such as CytOx subunit IV andexpression of MDH are differentially regulated within a tissue. Ourdata also illustrate that the heart undergoes previously unidentifiedmitochondrial adaptations in response to short-term microgravityconditions more dramatic than those evident in skeletal muscle. Furtherstudies evaluating the functional consequences of these adaptations inthe heart, as well as those designed to measure protein turnover, arewarranted in response to microgravity.

     

Estimation of amount of stationary pulmonary blood from carbon monoxide uptake measurements

A mathematical model of CO uptake from a single alveolus is modified to include stationary pulmonary blood arising from a pulmonary vascular obstruction. From this model an estimator model is developed that produces simultaneous estimations of the diffusing capacity of the lung for CO and the fraction of the pulmonary capillary blood that is stationary. The estimator model was tested using simulated data from uniform and non-uniform simulators and found to be only mildly sensitive to noise and incorrect values for the pulmonary capillary blood volume. Both the estimator model and breath-to-breath changes in the diffusing capacity of the lung for CO (exhaled) were found to be greatly affected by inhomogeneity of diffusing capacity and ventilation. At times both returned false positive results that limit their use as a screening test for stationary pulmonary blood. Although changes in CO uptake may at times indicate the presence of stationary pulmonary blood, the confounding effects of inhomogeneity of ventilation and diffusing capacity make the use of such changes impractical under most circumstances.     

Spatial pattern of pulmonary blood flow distribution is stable over days

Glenny, Robb W., Steven McKinney, and H. Thomas Robertson.Spatial pattern of pulmonary blood flow distribution is stableover days. J. Appl. Physiol. 82(3):902-907, 1997.Despite the heterogeneous distribution of regionalpulmonary perfusion over space, local perfusion remains stable overshort time periods (20-100 min). The purpose ofthis study was to determine whether the spatial distribution ofpulmonary perfusion remains stable over longer time periods (1-5days). Regional blood flow was measured each day for 5 days in five awake standing dogs. Fluorescent microspheres of differentcolors were injected into a limb vein over 30 s on each day. After thelast microsphere injection, the dogs were killed, and lungs wereflushed free of blood, excised, dried at total lung capacity, and dicedinto ~2-cm³ pieces(n = 1,296-1,487 per dog).Relative blood flow to each piece on each day was determined byextracting the fluorescent dyes and determining the concentrations ofeach color. We established that blood flow is spatiallyheterogeneous with a coefficient of variation of 29.5 ± 2%. Blood flow to each piece is highly correlated with flow to thesame piece on all days (r = 0.930 ± 0.006). The temporal heterogeneity of regional perfusion as measured by the coefficient of variation is 6.9 ± 0.7% over the 5 days and is nonrandom. The magnitude of spatial and temporal variationis significantly less than previously reported in a study in whichanesthetized and mechanically ventilated dogs were used. We concludethat spatial distribution of pulmonary blood flowremains stable over days and we speculate that in the normal awake dogregional perfusion is determined primarily by a fixed structure such asthe geometry of the pulmonary vascular tree rather than by localvasoactive regulators. Anesthesia and/or mechanical ventilationmay increase the temporal variability in regionalperfusion.

     

Rate of uptake of CO by hemoglobin in pig erythrocytes as a function of PO2

Te Nijenhuis, Francis C. A. M., Lydia Lin, Gerko H. Moens,Adrian Versprille, and Robert E. Forster. Rate of uptake of CO byhemoglobin in pig erythrocytes as a function ofPO₂. J. Appl.Physiol. 81(4): 1544-1549, 1996.This study wasinitiated to obtain data on the rate of carbon monoxide (CO) uptake(_CO) by hemoglobin in pigerythrocytes to derive, in a later study, the pulmonary capillary bloodvolume (Qc) in pigs from the Roughton-Forster relationship. Blood fromfive different female pigs was used. The_CO, the milliliters of CO takenup by 1 ml of whole blood per minute per Torr CO tension, wasdetermined on each blood sample with a continuous-flow rapid-mixingapparatus and double-beam spectrophotometry at 37°C and pH 7.4 atfour or five different PO₂ values.Because the individual regression lines of _CO vs.PO₂ were not significantly different,a common regression equation was calculated:1/_CO = 0.0084 PO₂ + 0.63. The slope of thisregression line is significantly steeper than the reported slopes ofthe regression lines for human and dog erythrocytes measured under thesame conditions. Our results revealed that calculation ofQc in pigs by using _CO valuesfor human or dog erythrocytes would result in an underestimation of 51 and 50%, respectively.

     

Nitric oxide-endothelin-1 interaction in humans

Ahlborg, Gunvor, and Jan M. Lundberg. Nitricoxide-endothelin-1 interaction in humans. J. Appl.Physiol. 82(5): 1593-1600, 1997.Healthy menreceived N^G-monomethyl-L-arginine(L-NMMA) intravenously to studycardiovascular and metabolic effects of nitric oxide synthase blockadeand whether this alters the response to endothelin-1 (ET-1) infusion.Controls only received ET-1.L-NMMA effects were that heartrate (17%), cardiac output (17%), and splanchnic and renal blood flow(both 33%) fell promptly (all P < 0.01). Mean arterial blood pressure (6%), and systemic (28%) andpulmonary (40%) vascular resistances increased(P < 0.05 to 0.001). Arterial ET-1levels (21%) increased due to a pulmonary net ET-1 release(P < 0.05 to 0.01). Splanchnic glucose output (SGO) fell (26%, P < 0.01). Arterial insulin and glucagon were unchanged. Subsequent ET-1infusion caused no change in mean arterial pressure, heart rate, orcardiac output, as found in the present controls, or in splanchnic andrenal blood flow or splanchnic glucose output as previously found withET-1 infusion (G. Ahlborg, E. Weitzberg, and J. M. Lundberg.J. Appl. Physiol. 79: 141-145,1995). In conclusion, L-NMMAlike ET-1, induces prolonged cardiovascular effects and suppresses SGO.L-NMMA causes pulmonary ET-1release and blocks responses to ET-1 infusion. The results indicatethat nitric oxide inhibits ET-1 production and thereby interacts withET-1 regarding increase in vascular tone and reduction of SGO inhumans.

     

Cardiovascular and Valsalva responses during parabolic flight

We investigated the integrated cardiovascularresponses of 15 human subjects to the acute gravitational changes(micro- and hypergravity portions) of parabolic flight. Measurementswere made with subjects quietly seated and while subjects performed controlled Valsalva maneuvers. During quiet, seated, parabolic flight,mean arterial pressure increased during the transition into microgravity but decreased as microgravity was sustained. Thedecrease in mean arterial pressure was accompanied by immediate reflexive increases in heart rate but by absent (orlater-than-expected) reflexive increases in total vascular resistance.Mean arterial pressure responses in Valsalva phasesII_l, III, and IV wereaccentuated in hypergravity relative to microgravity(P < 0.01, P < 0.01, andP < 0.05, respectively), butaccentuations differed qualitatively and quantitatively from thoseinduced by a supine-to-seated postural change in 1 G. This study is thefirst systematic evaluation of temporal and Valsalva-related changes incardiovascular parameters during parabolic flight. Results suggest thatarterial baroreflex control of vascular resistance may be modified byalterations of cardiopulmonary, vestibular, and/or otherreceptor activity.