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J Piiper

Publications and source records attributed to J Piiper.

At least 19 recordsLinked to original sources

Modeling of oxygen transport to skeletal muscle: blood flow distribution, shunt, and diffusion.

By injection of embolizing microspheres, by local radioactive xenon clearance and by inert gas washout in resting and stimulated gastrocnemius dog preparation, experimental evidence for unequal blood flow distribution and for shunt flow has been provided. Model calculations show that in some respect unequal blood flow and shunt produce effects predicted for a homogeneous model with diffusion limitation of O2 supply. This finding must be taken into account when the role of diffusion limitation to O2 supply is to be ascertained.

Animals

Diffusion-perfusion inhomogeneity and alveolar-arterial O2 diffusion limitation: theory.

Unequal distribution of pulmonary O2 diffusing capacity (D) to pulmonary blood flow (Q) (D/Q heterogeneity) leads to decreased alveolar O2 exchange efficacy. It is shown on simple models that the effect increases with increasing amount of inequality and with increasing value of the equilibration index, D/(Q beta) (beta, increment in blood O2 content per partial pressure increment). This inhomogeneity effect, if not taken into account, leads to spurious increases of D in hypoxia and with elevated O2 uptake.

Animals

Convective and diffusive gas transport in canine intrapulmonary airways.

The significance of convective and diffusive gas transport in the respiratory system was assessed from the response of combined inert gas and particle boluses inhaled into the conducting airways. Particles, considered as "nondiffusing gas," served as tracers for convection and two inert gases with widely different diffusive characteristics (He and SF6) as tracers for convection and diffusion. Six-milliliter boluses labeled with monodisperse di-2-ethylhexyl sebacate droplets of 0.86-microns aerodynamic diameter, 2% He, and 2% SF6 were inspired by three anesthetized mechanically ventilated beagle dogs to volumetric lung depths up to 170 ml. Mixing between inspired and residual air caused dispersion of the inspired bolus, which was quantified in terms of the bolus half-width. Dispersion of particles increased with increasing lung depth to which the boluses were inhaled. The increase followed a power law with exponents less than 0.5 (mean 0.39), indicating that the effect of convective mixing per unit volume was reduced with depth. Within the pulmonary dead space, the behavior of the inert gases He and SF6 was similar to that of the particles, suggesting that gas transport was almost solely due to convection. Beyond the dead space, dispersion of He and SF6 increased more rapidly than dispersion of particles, indicating that diffusion became significant. The gas and particle bolus technique offers a suitable approach to differential analysis of gas transport in intrapulmonary airways of lungs.

Animals

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