A Method to Correct for the Influence of Gas Density on Maximal Expiratory Flow Rate

Maximal expiratory flow rate (V?max) was measured at 20, 35, 50, 65, and 80% vital capacity in 4 young healthy subjects breathing air, SF₆/O₂, and He/O₂ mixtures. The flows of SF₆/O₂ and He/O₂ were corrected to normal alveolar gasflow by means of only the density of the gases. The values for normal alveolar gasflow and corrected SF₆/O₂ flow were identical at 35% VC and larger volumes while the values for normal alveolar gasflow and corrected He/O₂ flow were not. The results indicate that in young healthy subjects it is possible to correct Vmax at lung volumes above 359: VC for the changes induced by an increase in density of the gas breathed, provided viscosity is not much changed. Without correction, V?max after O₂-breathing will be underestimated by about 6%, compared with V?max for normal alveolar gas, whereas a change in alveolar CO₂ concentrations between 3 and 9% only causes a 1 % decrease of V? max.     

The Compliance Curve for the Flow Limiting Segments of the Airway. I. Model Studies

By means of a pitot-static tube airway compliance curves describing the cross-sectional area (A) as a function of transmural pressure (Ptm) were constructed for several locations in the elastic airway of a mechanical model of the lung. From these curves local relations between elastic recoil pressure of the lung (Pel) and maximal expiratory flow (V?max) were calculated and compared with the experimentally determined Pel-V?max curve for the entire airway, i.e. all parts in series. Theory and experiments showed that the latter was the lower borderline of all the local Pel-v?max curves. This means that the maximal flow through the entire airway at a given Pel is determined by the segment of the airway, having the smallest v?max, just as the maximal strength of a chain is determined by its weakest link. The relation between the critical transmural pressure (Ptm‘) and the corresponding cross-sectional area (A’) was derived from theexperimental Pel-V?max curve. This Ptm‘-A’ curve had a composed appearance, which was found to reflect parts of the different local Ptm-A curves and transitions between them because of movement of the flow limiting site within the airway. The Ptm‘-A’ curve depends on the elastic properties of the flow limiting segment, and the slope of this curve (dA‘/dPtm’) is the compliance of the flow limiting segment. Significant frictional pressure losses upstream from the site of flow limitation caused underestimation of both A‘ and dA’/dPtm“, but downstream pressure losses had no influence on the Ptm‘-A’ curve.     

Mechanisms compensating for altered resistance to respiration during muscular exercise in man

Alterations in respiratory parameters following the substitution of a helium-oxygen (He−O₂) or sulfur hexafluoride-oxygen (SF₆−O₂) mixture for air were analyzed during the first 10 respiratory cycles in human volunteers exposed to either of these mixtures for 3 min at rest and during forced respiration. Both at rest and during moderate physical exercise neither the volume of pulrnonary ventilation nor the partial carbon dioxide pressure differed significantly in the subjects breathing air, He−O₂, or SF₆−O₂. When the He−O₂ mixture was substituted for air, the forces developed by the inspiratory muscles, the work of breathing, the activity of the parasternal intercostal muscles, and the central inspiratory activity were all reduced, whereas substitution of the SF₆−O₂ mixture for air led to significant increases in these four parameters. It is concluded that compensatory responses of the respiratory system to altered density of the gaseous medium develop on the basis of the afferent impulse traffic from mechanoreceptors of the lungs and respiratory muscles and also on account of segmental reflexes and intrinsic properties of the muscle fibers themselves. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 9, pp. 247–251, September, 1995 Presented by A. D. Ado, Member of the Russian Academy of Medical Sciences     

Effects of gas density on pulmonary gas exchange of normal man at rest and during exercise

Changes in the physical properties of inspired gas might be expected to influence the distribution of ventilation in the lungs as well as the diffusive and convective (cardiogenic) mixing of inspired gas with lung residual gas, thus possibly affecting pulmonary gas exchange for O₂ and CO₂. The purpose of our work was to assess to what extent this occurs in practise in human subjects, who could compensate for the changes directly brought about by altering the physical characteristics of the inhaled gas by changing their breathing pattern. Six healthy, non-smoking men breathed, at rest and during moderate exercise, gas mixtures containing 21% oxygen completed either by 79% nitrogen (air), helium (O₂-He) or sulphur hexafluoride (O₂-SF₆). We observed that the inhalation of these three different gas mixtures whilst at rest did not affect arterial partial pressures of O₂ or CO₂, the physiological dead space to tidal volume ratio, or the alveoloarterial partial pressures differences for O₂ ( \(AaD_{{\text{O}}_2 } \) ) and CO₂ ( \(aAD_{CO_2 } \) ). During exercise, \(AaD_{{\text{O}}_2 } \) was slightly (2–3 mm Hg) but significantly higher with both O₂?He and O₂?SF₆ than with air. Although minute ventilation did not change, breathing frequency was slightly but significantly affected by the type of gas mixture breathed, being lower with O₂?SF₆ and higher with O₂?He. We conclude that, within the range studied, the physical properties of the inhaled gas do not affect pulmonary gas exchange in healthy man, either because the changes affected are minimal or because they compensate for each other.     

Increased reversal and oscillatory shear stress cause smooth muscle contraction-dependent changes in sheep aortic dynamics: role in aortic balloon pump circulatory support

Aims: The intra‐aortic balloon pumping (IABP) changes pressure and increases the aorta shear stress reversal (SS_R) and oscillatory (SS_O) components. Hence, IABP‐dependent changes in aortic biomechanics would be expected, because of vascular smooth muscle (VSM) tone (i.e. flow‐induced endothelium‐dependent response, related to SS_R and SS_O variations) and/or pressure changes. To characterize: (i) the IABP effects on the aortic and global (systemic circulation) biomechanics, analysing their dependence on pressure and VSM basic tone changes and (ii) the relation between the SS_R and SS_O and the aortic biomechanical changes associated with the VSM tone variations. Methods: Aortic flow, pressure and diameter were measured in eight sheep during basal, augmented and assisted beats (1 : 1 and 1 : 2 IABP modalities). Calculations: (i) aortic effective and isobaric elasticity, viscosity, circumferential stress, pulse wave velocity, shear stress and buffer and conduit functions, (ii) peripheral resistance, global compliance, reflection coefficient and wave propagation times and (iii) the relation between SS_R and SS_O and biomechanical changes associated with variations in the aortic VSM tone. Results: Augmented and assisted beats showed: global VSM relaxation pattern (reduced peripheral resistance and reflection coefficient; increased propagation times) and local VSM contraction pattern (increased viscosity; reduced diameter, elasticity and circumferential stress), associated with SS_R and SS_O, levels and changes. The vascular changes reduced the ventricle afterload determinants, increased the vascular buffer performance and kept the conduit capability. Conclusion: In addition to pressure‐dependent changes, IABP determined biomechanical changes related to variations in the VSM tone. The increased SS_R and SS_O were associated with the aortic VSM contraction pattern and biomechanical changes.     

Oxygen transport and utilization in chronic nonpulsatile blood flow

Oxygen transport and utilization during rest and progressive exercise in chronic nonpulsatile blood flow was reviewed. In a chronic nonpulsatile animal model, (1) basal oxygen consumption of a 4-month old calf was 6.3±0.3 ml/kg/min; (2)PvO₂ decreased when the pump flow rate was reduced (29.6±1.0, 28.3±1.2, and 23.8±0.9 mmHg at 120, 100, and 90 ml/kg/min of pump flow, respectively); (3) serum lactate concentration increased significantly at 90 ml/kg/min of pump flow compared with other rates of pump flow. These results suggest that a critical flow level to maintain oxidative metabolism in the calf with chronic nonpulsatile flow exists between 90 and 100 ml/kg/min, andPvO₂ at the critical flow rate was between 24 and 28 mm Hg. Exercise data showed a significant correlation between O₂ delivery and the maximal O₂ consumption at each nominal flow rate, and suggested that a maximum of 78% of the oxygen delivered can be extracted and utilized during maximal exercise in animals with chronic nonpulsatile blood flow. These data suggest that chronic nonpulsatile blood flow is not a limiting factor for oxygen transport during rest and progressive exercise. However, further studies are needed to directly compare oxygen transport properties in pulsatile and nonpulsatile blood flow models.     

Estimating transit time for capillary blood in selected muscles of exercising animals

The mean minimal capillary transit time was estimated in muscles of various animals using a combination of physiological and morphometric methods. Radioactive microspheres were injected intravascularly in various animals running on a treadmill at maximum oxygen consumption rate (VO_2,max) to label blood flow to individual muscles. The muscles were then removed and preserved by standard methods for electron microscopy. The volume density of mitochondria was measured to assess muscle oxidative capacity. Capillary densities in muscle cross-sections, capillary diameters and tortuosities were incorporated into an estimate of capillary volume per unit muscle mass. Mean capillary transit time (t _c) in the exercising muscles was estimated by dividing mass-specific capillary volume by mass-specific blood flow. Estimates of t _c ranged from values near 1 s in horse heart and thigh muscles to 0.2 s in duck gastrocnemius. The relationship between muscle blood flow and t _c was hyperbolic. The experimental data indicate a limiting value of 0.2 s for transit times at very high blood flows. There was no correlation between t _c and body-mass-specific VO_2,max.     

Work performance breathing normoxic nitrogen or helium gas mixtures

Summary Twelve subjects completed a progressive treadmill test to maximal aerobic capacity while breathing air or a 79% helium — 21% oxygen gas mixture (HeO₂). Metabolic and thermoregulatory responses to work while breathing the two mixtures were compared at rest, 30–40%, 60–70%, and 85–95% of maximal performance, and at maximal effort. Ventilation, ventilatory equivalent, and respiratory rates were increased and oxygen uptakes decreased by breathing HeO₂ when the level of work exceeded 85–95% of maximum. Heat loss through the respiratory tract was greater breathing HeO₂. The reduction in maximal oxygen uptake is probably due to a reduction in the oxygen cost of breathing a less dense gas. It was not related to a lower body temperature and probably not to O₂ transport or circulatory limitation. HeO₂ breathing had no effect on maximal mechanical work capacity.The nature and purpose of the study and the risks involved were explained verbally and given on a written form to each subject prior to his or her voluntary consent to participate. The protocol and procedures for this study have been approved by the Committee on Activities Involving Human Subjects, of the University of California, Santa Barbara, California, USA     

Low frequency of the "plateau phenomenon" during maximal exercise in elite British athletes

A plateau in oxygen consumption (V̇O₂) has long been considered the criterion for maximal effort during an incremental exercise test. But, surprisingly, the termination of a maximum exercise test often occurs in the absence of a V̇O₂ plateau. To explain this inconsistency, some have proposed that an oxygen limitation in skeletal muscle occurs only in elite athletes. To evaluate this hypothesis, we determined the frequency with which the "plateau phenomenon" developed in a group of elite male and female athletes. Fifty subjects performed a continuous incremental treadmill test to measure maximal oxygen consumption (V̇O_2max). Treadmill velocity increased by 0.31 m s⁻¹ until the respiratory exchange ratio (R) reached 1.00. Thereafter the treadmill gradient increased by 1% each minute until exhaustion. The V̇O_2max was the highest V̇O₂ sustained for 60 s. Three criteria were used to determine maximal efforts: (1) a plateau in the V̇O₂, defined as an increase of less than 1.5 ml kg⁻¹ min⁻¹; (2) a final R of 1.1 or above; (3) a final heart rate (HR) above 95% of the age-related maximum. Mean V̇O_2max exceeded 65 ml kg⁻¹ min⁻¹ in both groups. The criteria for R and HR were satisfied by 72% of males and 56% females, and 55% of males and 69% of females, respectively. In contrast a V̇O₂ plateau was identified in only 39% of males and 25% of females. These findings refute the twin arguments: (1) that the absence of a "plateau phenomenon" results from an inadequate motivational effort in poorly trained athletes and (2) that the "plateau phenomenon" and a consequent skeletal muscle anaerobiosis occur only in athletes with the highest V̇O_2max values.     

Pulmonary function hysteresis during compression to,and decompression from 31.3 ATA

Tracheal gas density breathing heliox at 31.3 atmospheres absolute (O² at 0.42 ATA) is 6.287 g 1^-1, or approximately 5.5 times greater than air at 1 ATA. This constitutes a significant respiratory load, previously shown to induce respiratory adaptation. During a saturation dive to 31.3 ATA, five divers were exposed to this load for 16 days. This project aimed at investigating possible hysteresis in pulmonary function during dive compression, adaptation and decompression phases. Pulmonary function tests were performed at the surface in air, and at four pressure stops during compression and decompression, with divers breathing the helium-oxygen gas mixture. Significant hysteresis patterns were observed for pooled maximal voluntary ventilation, forced expired volume at 1 s, peak expiratory flow, and maximum expiratory flows (P < 0.05), with post-adaptation flows consistently exceeding those observed during compression. Two mechanisms may explain these observations. Differences may be attributable to positive effort-dependence in the forced expiratory flow; or it is possible the subjects adapted to the respiratory load by modifying neural input to airway smooth muscle, thereby modifying airway resistance.     

Influence of matching volume on reproducibility of maximal expiratory flow-volume curves

We examined the influence of "matching volume" on intrasubject variability of the descending limb of maximal expiratory flow-volume (MEFV) curves on air and helium-oxygen (He) in 18 healthy subjects and 28 patients with airflow limitation. Duplicate forced expirations were analysed according to four methods of alignment. With the first method, flows corresponding to identical percentiles of separate FVC (SEPVC) were compared. With the remaining three, we aligned curves at TLC, mid-vital capacity (VC50) and RV, respectively, for comparison of: a) flow at identical percentiles of the averaged FVC and b) expired volume at identical percentiles of the averaged peak flow. In healthy subjects, variability of flow at 50% and 75% of expired FVC (FEF50 and FEF75) did not change significantly with method, except that FEF75 on air varied more with method SEPVC than with VC50. In airflow limitation, FEF75 was significantly less reproducible when curves were matched at RV than at TLC, both on air and He. Over the latter part of expiration, an arbitrary index of variability of flow-defined volume also indicated that method RV gave the poorest precision in patients. We conclude that selection of matching volume does not influence the variability of MEFV-curves in health. In airflow limitation, however, TLC appears to be the most reliable volume for alignment.     

Diffusion-limited gas mixing in the lung and its consequences for transpulmonary gas transport

The ratio of alveolar ventilations of He and SF₆ ( ) was determined in 7 healthy male subjects at rest and at three different levels of exercise on a bicycle ergometer (75, 150 and 225 W). This ratio was calculated from the ratio of the specific ventilations for these gases which were obtained from the decay of the end-tidal partial pressures of He and SF₆ during a simultaneous, multiple-breath washout. In all experiments, for He was larger than for SF₆. On the average, was equal to 1.09, and the mean values of this ratio at rest and at the three levels of exercise were not significantly different. Therefore, the difference in for He and SF₆ increased with increasing work load. Further, we used the mean value obtained for , to calculate the ratio of excretion values (E₁/E₂) for pairs of hypothetical tracer gases with equal blood-gas partition coefficients and with different diffusivities in the gas phase. E₁/E₂ ranged from anity for =0 to about 1.08 for =10. At a given , E₁/E₂ decreased with increasing ventilation-perfusion ratio of the lung. Thus, the difference between the excretion values of light and heavy tracer gases will be most pronounced under rest conditions and for gases that are well soluble in blood.     

A Comparison of Blood Viscosity Measured In Vitro and in a Vascular Bed

Blood viscosity in vivo (“apparent viscosity”) and its variations with flow rate was analyzed in the maximally dilated calf muscle vascular bed of the cat by comparing pressure-flow relationships for blood and a Newtonian fluid (dextran-Tyrode) over a flow range between 60 and 0.2 ml/min × 100 g tissue. Viscosity in vitro for the same perfusates was measured in a cone-plate viscometer.—Apparent viscosity was much lower (approximately 50 %) than in vitro values at high shear rates, with less variation between animals. It increased with decreased flow but was as a maximum only doubled, which occurred at flows around 0.5 ml/min × 100 g. Since such small flows normally occur in constricted vessels with higher flow velocities than at maximal dilatation, the range of viscosity changes with flow in the intact circulation is probably decidedly smaller. The steep rise of viscosity in vitro at quite low shear rates had no counterpart in vivo; in fact, viscosity then tended to fall again. The discrepancies between blood viscosity in vivo and in vitro seem to be related to vascular dimensions, favouring “bolus flow” and hence low regional viscosity in the most narrow vessels, which may become more pronounced at further luminal reduction, active or passive. Addition of high molecular weight dextran (HMD) raised apparent viscosity to seemingly high levels at low flows. However, to a considerable extent this appears to be due to cell aggregation and plugging of microvessels rather than to a genuine increase of blood viscosity.     

Influence of intratubular pressure on proximal tubular compliance and capillary diameter in the rat kidney

Tubular compliance is the response of tubular diameter to changes in intratubular pressure [7]. Proximal tubular compliance was determined directly by measurements of tubular diameter and pressure and indirectly using a mathematical model of tubular fluid flow based on measurements of the hydraulic pressure gradients along the tubule under free flow conditions and during an induced pressure reduction at the end of the proximal tubule. The two independent methods yielded similar values for compliance. Proximal tubular complicance was found to depend upon the intratubular pressure: tubular compliance was significantly higher (P<0.001) when the intratubular pressure was reduced below normal (1.0 m cm H₂O^–1) than when the pressure was increased above the control value (0.4 m cm H₂O^–1) Almost identical compliance values were measured in sodium pentobarbital and inactin anaesthetized rats (P>0.8).Intratubular pressure changes resulted in inverse changes in the diameters of the adjacent capillaries, suggesting that the peritubular capillaries are distensible structures.     

Design and validation of an analyser to measure sulphur hexafluoride gas during respiration

The study presents the results of the development of an analyser to measure sulphur hexafluoride (SF₆) gas in breathing circuits, for application is studies of lung function. The analyser consists of an in-line breathing circuit measurement transducer and a compact unit for signal treatment. The detector unit of the analyser consists of a near-infrared light source, a bandpass filter and a pyro-electrical detector. When incremental steps of SF₆ gas between 0 and 2% were presented to the analyser, the maximum deviation from the theoretical calibration curve was calculated to be 0.01% SF₆. The step response of the analyser (10–90%) was 250 ms. The sensitivity of the analyser to ambient temperature was 0.01% SF₆ °C⁻¹ in the range between 0 and 2% SF₆. It is concluded that the analyser presented is accurate, and has a sufficient response speed to be used in clinical measurement settings. Furthermore, the analyser is resistant to changes in temperature, gas flow, orientation and movement, which are likely to occur in clinical measurement settings.     

Three-dimensional Numerical Modeling and Computational Fluid Dynamics Simulations to Analyze and Improve Oxygen Availability in the AMC Bioartificial Liver

A numerical model to investigate fluid flow and oxygen (O₂) transport and consumption in the AMC-Bioartificial Liver (AMC-BAL) was developed and applied to two representative micro models of the AMC-BAL with two different gas capillary patterns, each combined with two proposed hepatocyte distributions. Parameter studies were performed on each configuration to gain insight in fluid flow, shear stress distribution and oxygen availability in the AMC-BAL. We assessed the function of the internal oxygenator, the effect of changes in hepatocyte oxygen consumption parameters in time and the effect of the change from an experimental to a clinical setting. In addition, different methodologies were studied to improve cellular oxygen availability, i.e. external oxygenation of culture medium, culture medium flow rate, culture gas oxygen content (pO₂) and the number of oxygenation capillaries. Standard operating conditions did not adequately provide all hepatocytes in the AMC-BAL with sufficient oxygen to maintain O₂ consumption at minimally 90% of maximal uptake rate. Cellular oxygen availability was optimized by increasing the number of gas capillaries and pO₂ of the oxygenation gas by a factor two. Pressure drop over the AMC-BAL and maximal shear stresses were low and not considered to be harmful. This information can be used to increase cellular efficiency and may ultimately lead to a more productive AMC-BAL.     

Aerobic and anaerobic energy during a 2-km race simulation in female rowers

The maximal aerobic power (V˙O_2max) and maximal anaerobic capacity (AOD_max) of 16 female rowers were compared to their peak aerobic power (V˙O_2peak) and peak anaerobic capacity (AOD_peak, respectively) during a simulated 2-km race on a rowing ergometer. Each subject completed three tests, which included a 2-min maximal effort bout to determine the AOD_max, a series of four, 4-min submaximal stages with subsequent progression to V˙O_2max and a simulated 2-km race. Aerobic power was determined using an open-circuit system, and the accumulated oxygen deficit method was used to calculate anaerobic capacities from recorded mechanical power on a rowing ergometer. The average V˙O_2peak (3.58?l?·?min^?1), which usually occurred during the last minute of the race simulation, was not significantly different (P?>?0.05) from the V˙O_2max (3.55?l?· min^?1). In addition, the rowers' AOD_max (3.40?l) was not significantly different (P?>?0.05) from their AOD_peak (3.50?l). The average time taken for the rowers to complete the 2-km race simulation was 7.5?min, and the anaerobic system (AOD_peak) accounted for 12% of the rowers' total energy production during the race.     

Hyperoxic Vasoconstriction in the Brain Is Mediated by Inactivation of Nitric Oxide by Superoxide Anions

The hypothesis that decreases in brain blood flow during respiration of hyperbaric oxygen result from inactivation of nitric oxide (NO) by superoxide anions (O_{2 –}) is proposed. Changes in brain blood flow were assessed in conscious rats during respiration of atmospheric air or oxygen at a pressure of 4 atm after dismutation of O_{2 –} with superoxide dismutase or suppression of NO synthesis with the NO synthase inhibitor L-NAME. I.v. administration of superoxide dismutase increased brain blood flow in rats breathing air but was ineffective after previous inhibition of NO synthase. Hyperbaric oxygenation at 4 atm induced decreases in brain blood flow, though prior superoxide dismutase prevented hyperoxic vasoconstriction and increased brain blood flow in rats breathing hyperbaric oxygen. The vasodilatory effect of superoxide dismutase in hyperbaric oxygenation was not seen in animals given prior doses of the NO synthase inhibitor. These results provide evidence that one mechanism for hyperoxic vasoconstriction in the brain consists of inactivation of NO by superoxide anions, decreasing its basal vasorelaxing action.     

The effects of breathing a helium–oxygen gas mixture on maximal pulmonary ventilation and maximal oxygen consumption during exercise in acute moderate hypobaric hypoxia

To test the hypothesis that maximal exercise pulmonary ventilation ( $ \dot{V}{\text{E}}_{ \max } $ ) is a limiting factor affecting maximal oxygen uptake ( $ \dot{V}{\text{O}}_{{ 2 {\text{max}}}} $ ) in moderate hypobaric hypoxia (H), we examined the effect of breathing a helium–oxygen gas mixture (He–O₂; 20.9% O₂), which would reduce air density and would be expected to increase $ \dot{V}{\text{E}}_{ \max } $ . Fourteen healthy young male subjects performed incremental treadmill running tests to exhaustion in normobaric normoxia (N; sea level) and in H (atmospheric pressure equivalent to 2,500 m above sea level). These exercise tests were carried out under three conditions [H with He–O₂, H with normal air and N] in random order. $ \dot{V}{\text{O}}_{{ 2 {\text{max}}}} $ and arterial oxy-hemoglobin saturation (SaO₂) were, respectively, 15.2, 7.5 and 4.0% higher (all p < 0.05) with He–O₂ than with normal air ( $ \dot{V}{\text{E}}_{ \max } $ _, 171.9 ± 16.1 vs. 150.1 ± 16.9 L/min; $ \dot{V}{\text{O}}_{{ 2 {\text{max}}}} $ , 52.50 ± 9.13 vs. 48.72 ± 5.35 mL/kg/min; arterial oxyhemoglobin saturation (SaO₂), 79 ± 3 vs. 76 ± 3%). There was a linear relationship between the increment in $ \dot{V}{\text{E}}_{ \max } $ and the increment in $ \dot{V}{\text{O}}_{{ 2 {\text{max}}}} $ in H (r = 0.77; p < 0.05). When subjects were divided into two groups based on their $ \dot{V}{\text{O}}_{{ 2 {\text{max}}}} $ , both groups showed increased $ \dot{V}{\text{E}}_{ \max } $ and SaO₂ in H with He–O₂, but $ \dot{V}{\text{O}}_{{ 2 {\text{max}}}} $ was increased only in the high $ \dot{V}{\text{O}}_{{ 2 {\text{max}}}} $ group. These findings suggest that in acute moderate hypobaric hypoxia, air-flow resistance can be a limiting factor affecting $ \dot{V}{\text{E}}_{ \max } $ ; consequently, $ \dot{V}{\text{O}}_{{ 2 {\text{max}}}} $ is limited in part by $ \dot{V}{\text{E}}_{ \max } $ , especially in subjects with high $ \dot{V}{\text{O}}_{{ 2 {\text{max}}}} $ .     

Pancreatic O2 consumption and CO2 output during secretin-induced,exocrine secretion from the pancreas in the anesthetized dog

Secretin stimulates pancreatic water and CO₂ excretion as well as pancreatic blood flow. It has been questioned whether the production (i.e. water and CO₂ excretion) is reflected in the input-output difference of nutrients. In pentobarbital anesthetised dogs, pancreatic exocrine secretion was stimulated by secretin, (Karolinska), 1 U/kg injected as an i.v. bolus. Secretion was maximally increased at 2 min after the secretin shot and returned to a basal value at between 16 and 32 min after secretin. Blood flow was also maximally increased at 2 min, but decreased to the basal value at between 8 and 16 min. O₂ extraction first decreased (at 2 min) and then gradually increased until it was higher than the basal value (at 16 min) and then returned to the basal level (at 32 min). O₂ consumption increased quickly, reached a plateau, lasting from 1 to 16 min, and then decreased to the basal level (32 min). CO₂ transfer from blood to tissue reached a maximum at 4 min and then decreased to the basal value (at between 16 and 32 min). The curves for CO₂ transfer from tissue to pancreatic secretion and for CO₂ in the secretion had the same shape. It is concluded that the curve of production (of water and CO₂ excretion) parallels the curve of O₂ consumption fairly well. The O₂ consumption curve did not correlate either with the blood flow curve or with the O₂ extraction curve. About one quarter of the excreted CO₂ originated from pancreatic metabolism and the remaining three quarters were transferred from blood, through the pancreatic tissue into the secretion. The increase in O₂ consumption was achieved by an increase in blood flow, followed by an increase in O₂ extraction. The release of a vasodilator metabolite by the pancreatic cells upon arrival of the secretin molecules, may explain both the increase in blood flow and the successive increase in O₂ extraction. Therefore these data can be interpreted according to the model for metabolic control of tissue oxygenation.