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J Piiper

Publications and source records attributed to J Piiper.

At least 37 records · Page 2Linked to original sources

Diffusion limitation of O2 supply to tissue in homogeneous and heterogeneous models.

The role of diffusion limitation in O2 supply was studied in cross-sectional elements of the Krogh cylinder model (with O2 supply from a central capillary) and of the solid cylinder model (with O2 supply from the outer surface). The effect of diffusion limitation was quantified in terms of the ratio O2 uptake/O2 requirement (= fraction of cross-sectional area supplied with O2), assuming local O2 requirement per unit volume to be constant and independent of PO2 at PO2 greater than 0. Calculations were performed for single cylinders of varied radius and O2 requirement (homogeneous models). Unequal distribution of diffusion conditions was represented by a model composed of three sorts of Krogh or solid cylinders, with radii in relation 3: square root of 3:1, but of equal cross-sectional area, i.e. number of cylinders of each sort in relation 1:3:9 (heterogeneous models). The results revealed the following main features. (1) At the same outer radius, diffusion limitation sets in at a smaller O2 requirement, and increases more steeply with increasing O2 requirement, in the homogeneous Krogh cylinder model compared with the homogeneous solid cylinder model. A similar behavior is observed when the radius of the cylinder section is increased at constant O2 requirement. (2) Diffusion limitation in the heterogeneous model sets in at a lower O2 requirement value, and increases more gradually with increasing O2 requirement, than in the corresponding homogeneous models with the same average cylinder diameter. This behavior is due to sequential onset, in the heterogeneous model, of anoxia in the cylinder sections of different radii. We conclude that diffusion heterogeneity has to be taken into account when the role of diffusion limitation in tissue O2 supply is investigated.

Animals↗

Effect of the curvature of the O2 equilibrium curve on alveolar O2 uptake: theory.

The effect of the curvature of the O2 equilibrium curve (OEC), in the range between mixed venous and alveolar PO2, on alveolar O2 uptake was quantitatively investigated in a simple homogeneous lung model. The O2 uptake achieved with a linear OEC (Mlin) was subtracted from the O2 uptake (M) attained with the physiologically curved, sigmoid OEC, and the relative difference was considered as the 'curvature effect', CE [= (M - Mlin)/M], indicating, if positive, the enhancement of O2 uptake by the non-linearity of the OEC. Calculations show CE to be close to nil (less than 1%) in normal lungs during rest both in normoxia and in hypoxia. CE is more important in heavy exercise both in normoxia (CE less than 19%) or slight hypoxia (CE less than 15%). In deep hypoxia, CE is negligible again even during exercise. Thus, the simplified approach to the analysis of alveolar O2 uptake using a linear OEC, in the mixed venous-to-alveolar PO2 range, constitutes in most cases a valid approximation.

Models, Biological↗

Diffusion and perfusion limitation in alveolar O2 exchange: shape of the blood O2 equilibrium curve.

The limitations imposed by diffusion (Ldiff) and perfusion (Lperf) on alveolar gas exchange can be estimated using a simple model of alveolar-capillary gas transfer (Piiper and Scheid (1981) Respir, Physiol. 46: 193-208). These limitations indicate the fractional increase of gas exchange that would occur by raising pulmonary conductances for diffusion or perfusion to functionally infinite values. The (simple) model assumes linear relations between concentration and partial pressure for the gases studied. We have investigated in this study the effects of this assumption for estimating Ldiff and Lperf for O2 whose blood equilibrium curve is particularly non-linear in normoxia. The calculations suggest that Lperf is only slightly overestimated by the assumption of linear blood O2 binding. For Ldiff, there is a significant overestimation in normoxia, but in hypoxia the linear equilibrium curve yields sufficiently accurate estimates. Calculations for data estimated for man on the summit of Mt. Everest suggest that alveolar O2 uptake in deep hypoxia at rest is mainly limited by perfusion and to a lesser degree by diffusion (Lperf greater than Ldiff). For the sustained exercise of climbing, on the other hand, diffusion limitation is more prominent than perfusion limitation (Ldiff greater than Lperf). Large values of Ldiff are estimated for normoxic O2 uptake across the skin of the gill-less and lung-less salamander, and here, the effects of the alinearity of the O2 equilibrium curve are pronounced. It is concluded that the simplified model of alveolar-capillary gas transfer, with linear O2 equilibrium curve, can be very useful to estimate diffusion and perfusion limitations from experimental data.

Altitude↗

Oxygen supply and uptake in tissue models with unequal distribution of blood flow and shunt.

The effects of unequal distribution of blood flow on O2 uptake are studied on a model composed of 3 tissues compartments with blood flow/O2 requirement ratios in the relation 9:3:1 (unequal blood flow model), a model with 33% shunt blood flow (shunt model), and a single compartment model without shunt (reference model). Diffusion limitation is assumed to be absent. Total blood flow (Q), arterial O2 content (CaO2) and O2 requirement of tissue are varied singly, and the resulting (mixed) venous O2 content (CvO2) and O2 uptake are calculated. In the reference model, CvO2 become zero, and O2 uptake starts falling below the O2 requirement, as soon as the O2 delivery (Q.CaO2) becomes smaller than the O2 requirement. In contrast, in the unequal blood flow model, decrease in the ratio O2 uptake/O2 requirement and in CvO2 sets in earlier, and proceeds more gradually, with decreasing Q or CaO2 or increasing O2 requirement; this is, because O2 delivery limitation sets in sequentially in the compartments, starting with the least perfused compartment. The shunt model behaves similarly to the reference model if Q or O2 requirement is varied, and to the unequal blood flow model if CaO2 is varied. Some features such as the parallel fall of O2 uptake and of CVO2 with decreasing CaO2, common to the unequal blood flow and shunt models, are similar to expected effects of diffusion limitation. Therefore, when the influence of diffusion limitation on tissue O2 supply is to be investigated quantitatively, the effects of a possible unequal distribution of blood flow must be taken into account.

Animals↗

Carbon dioxide-oxygen relationships in gas exchange of animals. In memory of Hermann Rahn.

In external gas exchange of vertebrates, behavior of the respiratory gases CO2 and O2 can in many cases adequately be explained by the different physico-chemical properties of the gases, including solubility, chemical combination in blood and tissue, and diffusivity. In particular, the differences in behavior between CO2 and O2 are often of particular relevance. This is demonstrated on a number of examples of gas exchange mechanisms in vertebrates, including (1) exchange ratio after changes in ventilation, (2) local variations of pulmonary ventilation/perfusion ratio, (3) absorption of gas from gas pockets, (4) water vs. air breathing, (5) multimodal breathing, (6) skin breathing, (7) gas exchange of avian eggs, (8) anomalous gas/blood CO2 equilibration, (9) blood/gas CO2 equilibration in avian lungs, (10) pulmonary diffusing capacity, (11) blood/water CO2 equilibration in fish gills, (12) deposition of gas into fish swim bladder.

Air↗

Counter-current blood flow in tissues: protection against adverse effects.

In hypoxia, the tissue counter-current can thus, by virtue of the Bohr effect, increase tissue Po2 and thus tissue oxygenation. In hyperoxia, on the other hand, the counter-current system, acting as a diffusion shunt, can protect the tissue against adverse O2-toxic effects. It thus appears, that the counter-current system is advantageous for O2 supply to tissues.

Animals↗

Cardiogenic oscillations of He and SF6 in expired gas in dogs.

Quantitative analysis of cardiogenic oscillations of He and SF6 during airway and venous loading demonstrated that both VA/Q and VA/VA inequalities were involved in the lung gas inhomogeneity producing cardiac oscillations in the expirogram. Both inequalities were coupled in such a manner that low VA/Q units had high VA/VA. The oscillations were modified in conducting airways where SF6 oscillations were attenuated more than He oscillations, probably by laminar Taylor dispersion.

Animals↗

Significance of cardiogenic mixing in dog lungs.

Single-breath washout of two inert gases (He and SF6) in anesthetized mechanically ventilated dogs in normal conditions with the heart beating and during reversible heart arrest revealed no effects attributable to the action of the beating heart. It is concluded that in the conditions of the experiments convective mixing by the cardiac action played an insignificant role in promoting intrapulmonary mixing and transport.

Animals↗

Multiple breath washout of He and SF6 in panting dogs.

Pulmonary gas transport mechanisms in panting were studied by multiple breath washout of two poorly soluble inert gases of similar solubility but different diffusivity (He and SF6). The experiments were performed in 6 chronically tracheotomized conscious dogs (mean body weight 31.0 kg) which, upon exposure to elevated room temperature, were enforced to thermal panting (mean breathing frequency 288/min). After equilibration of lung gas with 1% He and 1% SF6 followed by changeover to test gas-free air, end-tidal gas concentrations during multiple breath washout were recorded by mass spectrometry. The washout time course was analyzed into 3 exponential components. The initial fast component was considered to be in part determined by the transient response of the measuring system, whereas the intermediate and the slow component could be attributed to lung washout. The mean He/SF6 ratio of medium and slow rate constants was 1.06 and 1.13, respectively (both values differing from 1.0 at P less than 0.001). It is concluded that gas transport in dog lungs during panting was mainly determined by convection, diffusion-dependent processes being discernible but playing a minor role.

Animals↗

Sloping alveolar plateaus of CO2, O2, and intravenously infused C2H2 and CHClF2 in the dog.

To investigate the role of the various mechanisms assumed to contribute to the slope of the alveolar plateau, two test gases exhibiting identical solubility but two-fold differing diffusivity, acetylene (C2H2) and chlorodifluoromethane (Freon 22, CHClF2), dissolved in saline were intravenously infused in 10 anesthetized, paralyzed, artificially ventilated dogs (mean body mass, 18 kg). The partial pressures of C2H2, CHClF2, CO2 and O2 during a constant-flow single-breath washout maneuver were recorded by mass spectrometry and analyzed in terms of slope of the alveolar plateau (phase III) and series (Fowler) dead space. The slope of the alveolar plateau (S) was determined as the relative alveolar slope normalized to mixed-expired partial pressure and referred to expired volume (VE), S(V) = delta PE/(PE - PI)/delta VE or expiration time (tE), S(t) = delta PE/(PE - PI)/delta tE (subscripts I, E, and E refer to inspired, instantaneous expired and mixed-expired gas, respectively). The effects of expiratory flow rate (VE), and time of breath-hold (BH) were studied with reference to control conditions (VI = 0.5 L.sec-1, VE = 0.1 L.sec-1, VI = 50% and VE = 75% of volume at FRC, BH = 0 sec). In control conditions, the following significantly different S(V) values (units: L-1), grouped in ascending order, were obtained (means +/- SD): CO2, 0.83 +/- 0.26; C2H2, 0.93 +/- 0.18; CHClF2, 1.00 +/- 0.20; O2, 1.07 +/- 0.29. The mean C2H2/CHClF2 ratio for S(V), 0.94 (SD +/- 0.03), was statistically different from unity. In line with model calculations, the experimental findings suggest that three mechanisms contribute to the sloping alveolar plateaus: 1, continuing gas exchange during expiration; 2, ventilation-perfusion inequality combined with sequential emptying; 3, intrapulmonary diffusion limitation.

Acetylene↗

Pulmonary diffusing capacities for nitric oxide and carbon monoxide determined by rebreathing in dogs.

Pulmonary diffusing capacities (DL) of NO and CO were determined simultaneously from rebreathing equilibration kinetics in anesthetized paralyzed supine dogs (mean body wt 20 kg) after denitrogenation (replacement of N2 by Ar). During rebreathing the dogs were ventilated in closed circuit with a gas mixture containing 0.06% NO, 0.06% 13C18O, and 1% He in Ar for 15 s, with tidal volume of 0.5 liter and frequency of 60/min. The partial pressures of NO, 13C18O, 16O18O, N2, Ar, CO2, and He in the trachea were continuously analyzed by mass spectrometry. Measurements were performed at various O2 levels characterized by the mean end-expired PO2 during rebreathing (PE'O2). In control conditions ("normoxia," PE'O2 = 67 +/- 8 Torr) the following mean +/- SD values were obtained (in ml.min-1.Torr-1): DLNO = 52.4 +/- 11.0 and DLCO = 15.4 +/- 2.9. In hypoxia (PE'O2 = 24 +/- 7 Torr) DLNO increased by 11 +/- 8% and DLCO by 19 +/- 10%, and in hyperoxia (PE'O2 = 390 +/- 26 Torr) DLNO decreased to 87 +/- 3% and DLCO to 56 +/- 8% with respect to values in normoxia. DLNO/DLCO of 3.24 +/- 0.06 (hypoxia), 3.38 +/- 0.31 (normoxia), and 5.54 +/- 1.04 (hyperoxia) were significantly higher than the NO/CO Krogh diffusion constant ratio (1.92) predicted for simple diffusion through aqueous layers. With increasing O2 uptake elicited by 2,4-dinitrophenol, DLNO and DLCO increased and DLNO/DLCO remained close to unchanged. The results suggest that the combined effects of diffusion and chemical reaction with hemoglobin limit alveolar-capillary transport of CO. If it is assumed that reaction kinetics of NO with hemoglobin (known to be extremely fast) are not rate limiting for NO uptake, the contribution of the slow chemical reaction with hemoglobin to the total CO uptake resistance (= 1/DLCO) was estimated to be 38% in hypoxia, 41% in normoxia, and 64% in hyperoxia. The various factors expected to restrict the validity of this analysis are discussed, in particular the effects of functional inhomogeneity.

2,4-Dinitrophenol↗

Alveolar slope and dead space of He and SF6 in dogs: comparison of airway and venous loading.

Series (Fowler) dead space (VD) and slope of the alveolar plateau of two inert gases (He and SF6) with similar blood-gas partition coefficients (approximately 0.01) but different diffusivities were analyzed in 10 anesthetized paralyzed mechanically ventilated dogs (mean body wt 20 kg). Single-breath constant-flow expirograms were simultaneously recorded in two conditions: 1) after equilibration of lung gas with the inert gases at tracer concentrations [airway loading (AL)] and 2) during steady-state elimination of the inert gases continuously introduced into venous blood by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)]. VD was consistently larger for SF6 than for He, but there was no difference between AL and VL. The relative alveolar slope, defined as increment of partial pressure per increment of expired volume and normalized to mixed expired-inspired partial pressure difference, was larger by a factor of two in VL than in AL for both He and SF6. The He-to-SF6 ratio of relative alveolar slope was generally smaller than unity in both VL and AL. Whereas unequal ventilation-volume distribution combined with sequential emptying of parallel lung regions appears to be responsible for the sloping alveolar plateau during AL, the steeper slope during VL is attributed to the combined effects of continuing gas exchange and ventilation-perfusion inequality coupled with sequential emptying. The differences between He and SF6 point at the contributing role of diffusion-dependent mechanisms in intrapulmonary gas mixing.

Administration, Inhalation↗

Cardiogenic oscillations in He and SF6 expirograms during airway and venous loading.

Cardiogenic oscillations in the expired partial pressure profiles of two inert gases (He and SF6) were monitored in seven anesthetized paralyzed mechanically ventilated dogs. He and SF6 were administered either intravenously by a membrane oxygenator and partial arteriovenous bypass [venous loading (VL)] or by washin into lung gas [airway loading (AL)]. The single-breath expirograms obtained during constant-flow expiration after inspiration of test gas-free air displayed distinct and regular cardiogenic oscillations. The relative oscillation amplitude (ROA), calculated as oscillation amplitude divided by mixed expired-inspired partial pressure difference, was in the range of 1-8%. The ROA for both He and SF6 was approximately 4.2 times higher in VL than in AL, which indicated that among lung units that emptied sequentially in the cardiac cycle, the effects of alveolar ventilation-perfusion (VA/Q) inequality were more pronounced than those of alveolar ventilation-alveolar volume (VA/VA) inequality. In AL, He and SF6 oscillations were 180 degrees out of phase compared with CO2 and O2 oscillations and with He and SF6 oscillations in VL, which suggests that regions with low VA/VA had high VA/Q and very low Q/VA. The ROA was practically unaffected by breath holding in both AL and VL, which indicates that there was little diffusive or convective (cardiogenic) mixing between the lung units that were responsible for cardiogenic oscillations. The ROA was consistently higher for He than for SF6, and the He-to-SF6 ratio was independent of route of test gas loading, averaging 1.6 in both AL and VL. This result may be explained by laminar Taylor dispersion, whereby oscillations generated in peripheral lung regions are dissipated in inverse proportion to diffusion coefficient during transit through the proximal (larger) airways.

Administration, Inhalation↗

Spatial and temporal variability of blood flow in stimulated dog gastrocnemius muscle.

The distribution of blood flow in skeletal muscle stimulated to rhythmic isotonic contractions was studied by injections of radioactive microspheres into the arterial supply of gastrocnemius muscles (mean weight 88 g) subsequently cut into 0.5 g pieces for determination of radioactivity. The coefficient of variation (CV = SD/mean) of the ratio of simultaneously injected 10 microns and 15 microns microspheres, 0.12, was taken as the inherent scatter of the method. The average spatial distribution inequality of 10-15 microns microspheres corresponded to a CV of 0.45 and the specific local blood flow inhomogeneity to a CV = 0.43 (= square root of 0.45(2) - 0.12(2)), but there were marked differences between muscles. The temporal variability of blood flow in individual muscle pieces was obtained from the comparison of fractional trapping of 4 to 5 differently labeled microspheres injected at intervals of 2 minutes into steadily stimulated muscles. The mean CV for the variations in time was 0.23 and that corrected for methodological scatter, 0.19. There were large differences between muscle pieces within a muscle and between muscles. The presence of considerable spatial and temporal variations of blood flow in exercising muscle during apparent steady state may be important in limiting and/or modulating tissue O2 supply.

Animals↗

Helium and SF6 washout from dog lungs during high-frequency ventilation.

Simultaneous washout of He and SF6 was studied in anesthetized paralyzed dogs (mean body weight 19 kg) subjected to high-frequency ventilation at varying frequencies (10-40 Hz), stroke volumes (20-40 ml), lung volumes (0.8-1.2 L) and fresh gas flow rates (7-13 L/min). The washout curves could be analyzed into three exponential components for both test gases. The rate constants of the intermediate and slow components were slightly but significantly higher for He than for SF6 while the fast component was the same for the two test gases. The data were analyzed on the basis of a series lung model with a dead space compartment and two serially arranged alveolar compartments. The He/SF6 ratio of the effective conductances for gas transfer between the alveolar compartments averaged 1.15 +/- 0.08 (SD). Since this ratio is much closer to unity, predicted for convective transport, than 6 to 7, predicted for diffusive transport, it is concluded that during high-frequency ventilation gas transport in peripheral airways occurs by both convection and diffusion, convection being quantitatively more important.

Animals↗

Oxygen transfer kinetics of red blood cells of the turtle Pseudemys scripta elegans.

The kinetics of O2 uptake into, and release from, the red blood cells (RBC) of the turtle Pseudemys scripta elegans were determined with a stopped-flow technique at varied temperature (10-30 degrees C) and pH (7.5-7.9). The results were compared to those obtained for RBC of other vertebrates and related to morphometric and physiological data on gas/blood diffusion in turtle lungs. The O2 transfer conductance of RBC, G, for O2 release into high concentrations of dithionite, considered to represent the best estimate of true RBC transfer conductance for O2 uptake and release, averaged 0.17 +/- 0.01 at 30 degrees C, 0.13 +/- 0.01 at 20 degrees C, 0.09 +/- 0.01 at 10 degrees C (mean +/- SD, in mmol.min-1.Torr-1.(mlRBC)-1). These values are about one half the corresponding value for human RBC, and this difference may be due to the larger size of turtle RBC (volume, 327 microns 3) compared to human RBC (90 microns 3). The temperature dependence of G, Q10 = 1.3 indicates that, as in human RBC, diffusion through aqueous media is the main limiting factor for O2 exchange. Morphometric data on the lungs of Pseudemys scripta suggest that the resistance to O2 transfer by RBC is lower than that offered by the gas-blood barrier. The total apparent transfer resistance to CO, obtained from previous measurements of pulmonary diffusing capacity for CO in the same species, is much higher than that predicted from the combination of RBC O2 kinetics and morphometric data on gas-blood barrier.

Animals↗

Significance of the Bohr effect for tissue oxygenation in a model with counter-current blood flow.

Counter-current arrangement of afferent and efferent blood flow in tissues is commonly considered to be detrimental to tissue oxygenation, since O2 diffusion would shunt O2 away from the tissue. We have investigated the combined effects of counter-current CO2 and O2 exchange in a simple model, paying particular attention to the Bohr effect. We have obtained the following main results. (1) Back-diffusion of CO2 leads to increasing CO2 partial pressure (PCO2) and CO2 content along the afferent vessel. This is enhanced when fixed acid is released by the tissue into the venous blood, e.g. during hypoxia, which leads to a further PCO2 increase therein. (2) The increasing PCO2, with concomitant decrease in pH, in the afferent blood leads to a decrease in blood O2 affinity (Bohr effect) and thus results in increased PO2. (3) The resulting O2 diffusion shunt diminishes the O2 content in afferent blood, but for most conditions its PO2 remains higher than without the Bohr effect. (4) During hypoxia, both the PO2 in blood reaching the tissue (Pta) as well as in that leaving it (Ptv) are significantly elevated above the level without the Bohr effect. Moreover, with fixed acid release both Pta and Ptv for O2 can be higher than the arterial PO2 value. (5) During hyperoxia, O2 diffusion shunt prevents the tissue PO2 levels from increasing to levels that might be regarded as toxic. It is concluded that a diffusion shunt in tissues stabilizes the O2 partial pressure at the tissue when it varies in arterial blood (hypoxia or hyperoxia).

Arteries↗

Cyclooxygenase inhibition and effects of hypoxia on pulmonary circulation and gas exchange in anesthetized dogs.

To investigate whether endogenously produced prostanoids are involved in hypoxic pulmonary vasoconstriction, pulmonary hemodynamic and gas exchange parameters and eicosanoid metabolites were measured in 5 anesthetized, artificially ventilated dogs (mean body weight 27 kg). Hypoxia elicited pulmonary vasoconstriction, but blood plasma levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F 1 alpha (6kPGF1 alpha) (stable metabolites of TXA2 and prostaglandin I2, respectively) remained unchanged. Administration of the cyclooxygenase inhibitor indomethacin blocked the synthesis of prostanoids, so that 6kPGF1 alpha and TXB2 levels decreased to values below the detection level (10 pg.ml-1) both during normoxia or hypoxia, but did not affect pulmonary vascular resistance or the alveolar-arterial PO2 difference (PAi-Pa)O2. The pulmonary vascular bed remained, however, responsive to TXA2 as evidenced by infusion of the TXA2 mimetic, U 46619, which significantly increased the pulmonary vascular resistance and (PAi-Pa)O2. Our data suggest that prostanoids are not involved in eliciting the effects of hypoxia on pulmonary hemodynamics and gas exchange efficiency.

6-Ketoprostaglandin F1 alpha↗