Search PubMed⌕ Search

Biomedical subjects

J Piiper

Publications and source records attributed to J Piiper.

At least 19 recordsLinked to original sources

Perfusion, diffusion and their heterogeneities limiting blood-tissue O2 transfer in muscle.

The relative roles of blood flow (perfusion) and diffusion in O2 supply to exercising muscle can be estimated using a simple model consisting of an O2-consuming tissue block in contact with blood (perfusion Q, slope of O2 equilibirum curve beta) through a resistance to O2 diffusion (O2-diffusing capacity D). The decisive variable is the 'equilibration index' Y=D/(Qbeta). With decreasing Y, diffusion limitation increases and perfusion limitation decreases (Y > 3 indicates predominant perfusion limitation; 3 > Y > 0.1, combined perfusion and diffusion limitation, Y < 0.1, prevailing diffusion limitation). On the basis of literature data on humans at maximum O2 uptake, O2 supply to muscle is shown to be always limited by both perfusion and diffusion. In nomoxia, perfusion limitation is prevalent, but in hypoxia diffusion limitation becomes predominant. The underlying model assumes perfect homogeneity of muscles with respect to O2 requirement, diffusion conditions and blood flow. In numerous studies on isolated and in situ muscles a pronounced heterogeneity of blood flow has been found, also during exercise and at maximal O2 uptake. It is shown that with unequal distribution of blood flow and/or O2-diffusing capacity the efficiency of O2 transfer is reduced with reference to the homogeneous model. Therefore, the diffusing capacity value calculated on the basis of the homogeneous model is an underestimate of the true diffusing capacity and diffusion limitation is overestimated.

Diffusion↗

Modeling oxygen availability to exercising muscle.

To quantify the role of factors determining O2 availability to exercising muscle, a model previously devised for the analysis of O2 uptake in lungs is used. With the variables: (1) blood flow (Q); (2) slope of the blood O2 equilibrium curve (betaO2); and (3) muscle blood-tissue O2 diffusing capacity (D(O2)), the extent of diffusion and perfusion limitations are determined by the 'equilibration index', Y(O2) = D(O2)/(Q x betaO2). Application to recent literature values on maximal O2 uptake in humans reveals diffusion limitation to be less important than perfusion limitation in normoxia, but to be predominant in deep hypoxia. The validity of the model is restricted by several factors whose disregard leads to an underestimation of muscle D(O2), i.e. an overestimation of diffusion limitation.

Animals↗

Effects of gas density on experimentally obstructed ventilation during acute hypoxia.

When patients with obstructive lung disease breathe helium-oxygen mixtures, their arterial PCO2, is lowered towards normal, indicating more effective ventilation. However, there is a lack of detailed respiratory data from clinical cases, so that the mechanisms remain unclear. To study relevant variables during hypoxemia and obstruction in the absence of disease, we undertook experiments with healthy subjects breathing normoxic and hypoxic gas mixtures of differing densities (air, 13.7% O2 in N2 and 13.7% O2 in helium) through an experimental obstruction (resistive airway loading). This increased airway resistance was twice that reported from the ambient-pleural pressure differences in patients with moderately severe emphysema. Without imposed resistance the total ventilation (VE) increased 27% on both hypoxic mixtures. With normoxia, the obstruction increased tidal volume but decreased frequency so that VE and alveolar ventilation (VA) were essentially unchanged. With hypoxia, breathing pattern changed similarly, but now VE decreased while VA was maintained. Helium returned the breathing patterns toward normal. Obstruction lowered the rapid increase in VE from two or three breaths of N2, but the decrease from two or three breaths of O2 was unchanged. We detected an increase in metabolic rate with obstructed breathing that was reduced by the helium mixtures. The remarkable finding was that despite the obstruction being markedly uncomfortable because of the high resistance, we did not find any substantial disturbance in gas exchange, compared to hypoxia with no obstruction. Thus, the main mechanisms responsible for improved blood gases in patients breathing helium mixtures were outside the scope of our experiment and likely related to disease factors.

Adult↗

Alveolar-capillary gas transfer in lungs: development of concepts and current state.

Progress in research on pulmonary gas exchange, with special reference to the contribution of Gerhard Thews and associates, is reviewed. In particular, the following aspects are considered. (1) Oxygen transfer kinetics of red blood cells. Recent measurements, particularly on red blood cells in thin blood films, yield more rapid equilibration kinetics than previously recorded. A reevaluation of the roles of diffusion and chemical reaction in alveolar O2 uptake may become necessary. (2) Gas exchange in functionally inhomogeneous lungs. Besides the classical ventilation/perfusion (VA/Q) inequality, a variation of the diffusing capacity-to-perfusion ratio (DL/Q) appears to be of importance. The combination of VA/Q and DL 1Q inequalities may lead to a better understanding of alveolar gas exchange, particularly in diseased lungs. (3) Pulmonary diffusing capacity (DL) for oxygen. The rebreathing technique, which strongly reduces the effects of inequal VA/Q distribution effects, appears to be particularly suited for measurement of overall alveolar-capillary diffusion. But neither the factors determining DL, obtained by rebreathing or other methods, nor the relationships between DL for various gases are yet fully understood.

Animals↗

Pulmonary gas exchange during hypoxic exercise in the rat.

Pulmonary gas exchange and O2 transport were studied at rest and during maximal treadmill exercise in rats in acute hypoxia (PIO2 approximately 71 Torr), and in littermates acclimatized to PB = 380 Torr (PIO2 approximately 71 Torr) for 3 weeks (chronic hypoxia). To obtain valid estimates of blood gas partial pressures, particularly during exercise, the temperature coefficients of blood pH, PO2 and PCO2 were determined (Appendix). In both acute and chronic hypoxia, the following changes were observed: alveolar and arterial PO2 increased considerably, but the difference, A-aPO2, did not change significantly; arterial O2 concentration (CaO2) decreased, and apparent pulmonary diffusing capacity for O2, Dapp, increased. The increase in Dapp, together with hyperventilation, may prevent further drop in CaO2 due to a large rightward shift in the blood-O2 equilibrium curve caused by lactic acidosis in conjunction with a large Bohr coefficient characteristic of this species. Comparison with corresponding results obtained in man reveals that during hypoxic exercise, the rat shows a larger increase in PAO2, an increase, instead of a decrease, in PaO2, and a larger increase in Dapp.

Acclimatization↗

Effect of chronic hypoxia on hemodynamics, organ blood flow and O2 supply in rats.

Aortic blood flow, heart rate, blood pressure and blood flow distribution were measured in 10 chronically hypoxic rats (3 weeks, PB 370-380 Torr) breathing 10% O2 (chronic hypoxia) and after 30 min of breathing air (acute normoxia). Controls were 10 normoxic littermates breathing air (normoxia) and 10% O2 for 30 min (acute hypoxia). Acute hypoxia resulted in increased aortic blood flow and heart rate, and decreased total peripheral resistance. Blood flow and oxygen supply to vital organs increased, indicating that blood flow redistribution plays an important role in oxygen supply. In chronic hypoxia, aortic blood flow and heart rate remained elevated, and total peripheral resistance remained decreased. Blood flow distribution returned towards normoxia levels. Oxygen supply was maintained via increased arterial oxygen concentration. Acute normoxia resulted in decreased aortic blood flow and heart rate, and increased blood pressure and total peripheral resistance. Blood flow distribution was similar to that of chronic hypoxia except skeletal muscles, in which blood flow decreased markedly. Oxygen supply remained unchanged or increased.

Acid-Base Equilibrium↗

Regional blood flow in conscious resting rats determined by microsphere distribution.

To determine organ blood flow in the resting state, a box was designed to keep conscious untrained rats minimally disturbed. Blood pressure, heart rate, and organ blood flow, determined by the microsphere distribution and reference sampling technique, were measured in 11 Sprague-Dawley rats. After an acclimation period, 15-microns-diameter microspheres labeled with 113Sn were infused into the ascending aorta, a reference blood sample was withdrawn from the caudal artery, and organ blood flows were computed according to standard procedures. The average values of heart rate (365 beats/min) and blood flow to the brain (45 ml.min-1.100 g-1) and hindlimb muscles (15 ml.min-1.100 g-1) were significantly lower than most values reported earlier, whereas splanchnic blood flow was significantly higher (106 ml.min-1.100 g-1). Blood flow to the soleus muscle, which is considered the most active for postural maintenance, was relatively high (99 ml.min-1.100 g-1). The combination of low skeletal muscle and high visceral blood flows observed in these experiments suggests a low sympathetic tone, which is consistent with the low level of circulating catecholamines also observed in this study. It is hypothesized that the difference between our present and previous results is a lower level of stress, attributable to a more complete acclimation to the experimental environment.

Animals↗

Changes in regional blood flow distribution and oxygen supply during hypoxia in conscious rats.

The effects of acute hypoxia on central hemodynamics, regional blood flow, and regional oxygen supply (blood flow x arterial O2 concentration) were studied in conscious resting rats. Regional blood flow was determined by the radiolabeled microsphere technique. Blood pressure, heart rate; and aortic blood flow increased and total peripheral resistance decreased significantly during hypoxia. Blood flow to brain, respiratory muscles, and liver increased both in absolute value and as a fraction of the aortic blood flow. Fractional blood flow to the gastrointestinal tract, spleen, pancreas, skin, fat, and hindlimb bones decreased during hypoxia; blood flow decreased in absolute values only in stomach and fat. Oxygen supply to brain, respiratory muscles, and liver increased during hypoxia, whereas it decreased in the remaining organs investigated.

Animals↗

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↗