Mechanical constraints on exercise hyperpnea in endurance athletes.

We determined how close highly trained athletes [n = 8; maximal oxygen consumption (VO2max) = 73 +/- 1 ml.kg-1.min-1] came to their mechanical limits for generating expiratory airflow and inspiratory pleural pressure during maximal short-term exercise. Mechanical limits to expiratory flow were assessed at rest by measuring, over a range of lung volumes, the pleural pressures beyond which no further increases in flow rate are observed (Pmaxe). The capacity to generate inspiratory pressure (Pcapi) was also measured at rest over a range of lung volumes and flow rates. During progressive exercise, tidal pleural pressure-volume loops were measured and plotted relative to Pmaxe and Pcapi at the measured end-expiratory lung volume. During maximal exercise, expiratory flow limitation was reached over 27-76% of tidal volume, peak tidal inspiratory pressure reached an average of 89% of Pcapi, and end-inspiratory lung volume averaged 86% of total lung capacity. Mechanical limits to ventilation (VE) were generally reached coincident with the achievement of VO2max; the greater the ventilatory response, the greater was the degree of mechanical limitation. Mean arterial blood gases measured during maximal exercise showed a moderate hyperventilation (arterial PCO2 = 35.8 Torr, alveolar PO2 = 110 Torr), a widened alveolar-to-arterial gas pressure difference (32 Torr), and variable degrees of hypoxemia (arterial PO2 = 78 Torr, range 65-83 Torr). Increasing the stimulus to breathe during maximal exercise by inducing either hypercapnia (end-tidal PCO2 = 65 Torr) or hypoxemia (saturation = 75%) failed to increase VE, inspiratory pressure, or expiratory pressure. We conclude that during maximal exercise, highly trained individuals often reach the mechanical limits of the lung and respiratory muscle for producing alveolar ventilation. This level of ventilation is achieved at a considerable metabolic cost but with a mechanically optimal pattern of breathing and respiratory muscle recruitment and without sacrifice of a significant alveolar hyperventilation.     

A visual aid for teaching ventilation-perfusion relationships

To help students understand the concept of the ventilation-perfusion ratio (VA/Q) and the effects that VA/Q mismatching has on pulmonary gas exchange, a "sliding rectangles" visual aid was developed to teach VA/Q relationships. Adjacent rectangles representing "ventilation" and "perfusion" are slid past one another so that portions of the ventilation and perfusion rectangles are not touching, illustrating the concepts of dead-space ventilation (VD) and shunt flow (QS). The portion of the ventilation bar representing VD is further subdivided into anatomical and alveolar VD and used to show the effects of alveolar dead space on the PO2 (PAO2) and PCO2 of alveolar air (PACO2); movement away from the "ideal" point). Similarly, the portion of the perfusion bar representing QS is used to define anatomical and physiological shunts and the effect of shunts on the PO2 (PaO2) and PCO2 of arterial blood (PaCO2). The genesis of the PAO2-PaO2 (A-a) PO2 difference as well as the effects of VA/Q mismatching and diffusion abnormalities can all be discussed with this visual aid. This approach has greatly assisted some students in mastering this traditionally difficult area of respiratory physiology.     

Pulmonary function of the green sea turtle, Chelonia mydas

Lung volumes, oxygen uptake (VO2), end-tidal PO2, and PCO2, diffusing capacity of the lungs for CO (DLCO), pulmonary blood flow (QL) and respiratory frequency were measured in the green sea turtle (Chelonia mydas) (49-127 kg body wt). Mean lung volume (VL) determined from helium dilution was 57 ml/kg and physiological dead space volume (VD) was about 3.6 ml/kg. QL, determined from acetylene uptake during rebreathing, increased in proportion to VO2 with temperature. Therefore, constant O2 content difference was maintained between pulmonary arterial and venous blood. DLCO, measured using a rebreathing technique, was 0.04 ml X kg-1 X min-1 X Torr-1 at 25 degrees C. Several cardiopulmonary characteristics in C. mydas are advantageous to diving: large tidal volume relative to functional residual capacity promotes fast exchange of the alveolar gas when the turtle surfaces for breathing: and the concomitant rise of pulmonary blood flow and O2 uptake with temperature assures efficient O2 transport regardless of wide temperature variations encountered during migrations.     

High-frequency ventilation in dogs with three gases of different densities

Dogs were ventilated with a high-frequency oscillation device varying the frequency (5-15 Hz), the tidal volume (25-100 ml), and the resident gas (He, N2, SF6). Tidal volume was measured with a body plethysmograph. Blood gases were measured after a quasi-steady state was established. The kinematic viscosity of the breathing gas mixture, which changed by 1,700%, was found to have little effect on arterial PO2 and PCO2. The results are consistent with findings in a branched model that consisted of tubes with a diameter of 1 cm and with the theory of Taylor-type diffusion in turbulent flow. In addition, experiments were performed reducing and increasing the equipment dead space. This resulted in changes of PO2 and PCO2 that were appreciably less than those resulting from variations of tidal volume of the same magnitude.     

Contribution of continuing gas exchange to phase III exhaled PCO2 and PO2 profiles

Changes in PCO2 and PO2 during expiration have been ascribed to simultaneous gas exchange, but other factors such as ventilation-perfusion inhomogeneity in combination with sequential emptying may also contribute. An experimental and model approach was used to study the relationship between gas exchange and changes in expired PCO2 and PO2 in anesthetized dogs during prolonged high tidal volume expirations. Changes in PCO2 and PO2 were quantified by taking the area bounded by the sloping exhalation curve and a line drawn horizontally from a point where the Fowler dead space plus 250 ml had been expired. This procedure is similar to using the slope of the exhalation curve but it circumvents problems caused by nonlinearity of the PCO2 and PO2 curves. The gas exchange components of the CO2 and O2 areas were calculated using a single-alveolus lung model whose input parameters were measured in connection with each prolonged expiration. The relationship between changes in experimental CO2 areas caused by sudden reductions in mixed venous PCO2 (produced by right atrial infusions of NaOH) and those calculated by the model was also studied. In seven dogs, calculated CO2 and O2 areas were 13% higher and 25% lower than the respective experimental areas, but interindividual variations were large. Changes in experimental CO2 areas caused by step changes in mixed venous PCO2 were almost identical to changes in the calculated areas. We conclude that the changes in PCO2 and PO2 during expiration cannot be explained solely by gas exchange. However, the single-alveolus lung model accurately predicts changes in the CO2 exhalation curve caused by alterations in the alveolar CO2 flow.     

Early onset of pulmonary gas exchange disturbance during progressive exercise in healthy active men.

Some recent studies of competitive athletes have shown exercise-induced hypoxemia to begin in submaximal exercise. We examined the role of ventilatory factors in the submaximal exercise gas exchange disturbance (GED) of healthy men involved in regular work-related exercise but not in competitive activities. From the 38 national mountain rescue workers evaluated (36 +/- 1 yr), 14 were classified as GED and were compared with 14 subjects matched for age, height, weight, and maximal oxygen uptake (VO2 max; 3.61 +/- 0.12 l/min) and showing a normal response (N). Mean arterial PO2 was already lower than N (P = 0.05) at 40% VO2 max and continued to fall until VO2 max (GED: 80.2 +/- 1.6 vs. N: 91.7 +/- 1.3 Torr). A parallel upward shift in the alveolar-arterial oxygen difference vs. %VO2 max relationship was observed in GED compared with N from the onset throughout the incremental protocol. At submaximal intensities, ideal alveolar PO2, tidal volume, respiratory frequency, and dead space-to-tidal volume ratio were identical between groups. As per the higher arterial PCO2 of GED at VO2 max, subjects with an exaggerated submaximal alveolar-arterial oxygen difference also showed a relative maximal hypoventilation. Results thus suggest the existence of a common denominator that contributes to the GED of submaximal exercise and affects the maximal ventilatory response.     

Pulmonary gas exchange in panting dogs

Pulmonary gas exchange during panting was studied in seven conscious dogs (32 kg mean body wt) provided with a chronic tracheostomy and an exteriorized carotid artery loop. The animals were acutely exposed to moderately elevated ambient temperature (27.5 degrees C, 65% relative humidity) for 2 h. O2 and CO2 in the tracheostomy tube were continuously monitored by mass spectrometry using a special sample-hold phase-locked sampling technique. PO2 and PCO2 were determined in blood samples obtained from the carotid artery. During the exposure to heat, central body temperature remained unchanged (38.6 +/- 0.6 degrees C) while all animals rapidly switched to steady shallow panting at frequencies close to the resonant frequency of the respiratory system. During panting, the following values were measured (means +/- SD): breathing frequency, 313 +/- 19 breaths/min; tidal volume, 167 +/- 21 ml; total ventilation, 52 +/- 9 l/min; effective alveolar ventilation, 5.5 +/- 1.3 l/min; PaO2, 106.2 +/- 5.9 Torr; PaCO2, 27.2 +/- 3.9 Torr; end-tidal-arterial PO2 difference [(PE' - Pa)O2], 26.0 +/- 5.3 Torr; and arterial-end-tidal PCO2 difference, [(Pa - PE')CO2], 14.9 +/- 2.5 Torr. On the basis of the classical ideal alveolar air approach, parallel dead-space ventilation accounted for 54% of alveolar ventilation and 66% of the (PE' - Pa)O2 difference. But the steepness of the CO2 and O2 expirogram plotted against expired volume suggested a contribution of series in homogeneity due to incomplete gas mixing.     

Periodic breathing in the crocodile, Crocodylus niloticus: consequences for the gas exchange ratio and control of breathing.

The ventilatory pattern in the Nile crocodile consists of episodes of breathing, interrupted by periods of breath-holding, the latter occupying 80% of total time during normal breathing at 25 degrees C. End-tidal gas composition varied with the periodic breathing but PO2 was always high (PO2 less than 110 torr) and PCO2 low (PCO2 less than 25 torr). The alveolar gas exchange ratio, RE, was very low during the non-ventilatory periods (RE congruent to 0.5), but increased markedly during ventilation. Breathing of hypoxic and hpercapnic gases caused a pronounced decrease in the duration of breath-holds. Hypercapnia decreased breathing frequency during ventilatory periods, but increased tidal volume. The results are discussed in relation to the practice of prolonged breath-holding associated with diving in crocodiles.     

Latency to CNS oxygen toxicity in rats as a function of PCO2 and PO2

Central nervous system (CNS) oxygen toxicity can occur as convulsions and loss of consciousness, without any premonitory symptoms. We have made a quantitative study of the effect of inspired carbon dioxide on sensitivity to oxygen toxicity in the rat. Rats were exposed to four oxygen pressures (PO(2); 456, 507, 608 and 709 kPa) and an inspired partial pressure of carbon dioxide (PCO(2)) in the range 0-12 kPa until the appearance of the electroencephalograph first electrical discharge (FED) that precedes the clinical convulsions. Exposures were conducted at a thermoneutral temperature of 27 degrees C. Latency to the FED decreased linearly with the increase in PCO(2) at all four PO(2) values studied. This decrease, which is probably related to the cerebral vasodilatory effect of carbon dioxide, reached a minimal value that remained constant on further elevation of PCO(2). The slopes (absolute value) and intercepts of latency to the FED as a function of carbon dioxide decreased with the increase in PO(2). This log-linear relationship made possible the derivation of equations that describe latency to the FED as a function of both PO(2) and PCO(2) in the PCO(2) - dependent range: Latency (min) = e((5.19-0.0040)(P)(O(2)))-e((2.77-0.0034)(P)(O(2))) x PCO(2) (kPa), and in the PCO(2)-independent range: Latency(min) = e((2.44-0. 0009)(P)(O(2))). A PCO(2) as low as 1 kPa significantly reduced the latency to the FED. It is suggested that in closed-circuit oxygen diving, any accumulation of carbon dioxide should be avoided in order to minimize the risk of CNS oxygen toxicity.     

An assessment of dead space in pulmonary ventilation of the toad Bufo schneideri

The respiratory cycles of Rana and Bufo has been disputed in relation to flow patterns and to the respiratory dead-space of the buccal volume. A small tidal volume combined with a much larger buccal space motivated the "jet steam" model that predicts a coherent expired flow within the dorsal part of the buccal space. Some other studies indicate an extensive mixing of lung gas within the buccal volume. In Bufo schneideri, we measured arterial, end-tidal and intrapulmonary PCO(2) to evaluate dead-space by the Bohr equation. Dead-space was also estimated as: V(D)=(total ventilation-effective ventilation)/f(R), where total ventilation and f(R) were measured by pneumotachography, while effective ventilation was derived from the alveolar ventilation equation. These approaches were consistent with a dead space of 30-40% of tidal volume, which indicates a specific pathway for the expired lung gas.     

The inotropic effect of digoxin on an isolated rat heart in hypercapnia and (or) hypoxia

The explanation for the increased frequency of troubles with digoxin therapy in patients with chronic pulmonary diseases is debated. The reported effects of hypoxia in vivo on myocardial levels of digoxin are contradictory, and there have been few studies on the effects of hypercapnia. In the past, it has been shown in rat myocardial tissue at rest in vitro that hypoxia decreased and hypercapnic acidosis increased the digoxin uptake. We performed a new study in vitro in an isolated beating rat heart perfused at constant flow (37 degrees C) and stimulated at a constant frequency (6 Hz). The performances were recorded with an intraventricular balloon equipped with a tip-manometer catheter. The action of digoxin was studied by recording systolic pressure (PS) and diastolic pressure (PD), the left ventricular developed pressure (LVDP = PS - PD), the (dP/dt)max, and the ratio (dP/dt)max/PS. First, the heart was perfused for 30 min with a modified Tyrode's solution perfusate aerated with carbogen (pH = 7.40; PCO2 = 37 mmHg; PO2 = 530 mmHg) (1 mmHg = 133.32 Pa). Various parameters of contractions were recorded (initial control values). Then the heart was perfused for 15 min with Tyrode's solution aerated either with a hypoxic gas mixture (pH = 7.41; PCO2 = 36 mmHg; PO2 = 122 mmHg), a hypercapnic gas mixture (pH = 7.08; PCO2 75 mmHg; PO2 = 485 mmHg), or a hypoxic-hypercapnic gas mixture (pH = 7.09; PCO2 = 73 mmHg; PO2 = 124 mmHg). Control hearts were continuously perfused with Tyrode's solution aerated with carbogen.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimates of mean alveolar PCO2 during steady-state exercise in man: a theoretical study.

The partial pressure of carbon dioxide in arterial blood is an important operator in the control of breathing, by actions on peripheral and central chemoreceptors. In experiments on man we must often assume that lung alveolar PCO2 equals arterial PCO2 and obtain estimates of the former derived from measurements in expired gas sampled at the mouth. This paper explores the potential errors of such estimates, which are magnified during exercise. We used a published model of the cardiopulmonary system to simulate various levels of exercise up to 300 W. We tested three methods of estimating mean alveolar PCO2 (PACO2) against the true value derived from a time average of the within-breath oscillation in steady-state exercise. We used both sinusoidal and square-wave ventilatory flow wave forms. Over the range 33-133 W end-tidal PCO2 (P(et)CO2) overestimated PACO2 progressively with increasing workload, by about 4 mmHg at 133 W with normal respiratory rate for that load. PCO2 by a graphical approximation technique (PgCO2; "graphical method") underestimated PACO2 by 1-2 mmHg. PCO2 from an experimentally obtained empirical equation (PnjCO2; "empirical method") overestimated PACO2 by 0.5-1.0 mmHg. Graphical and empirical methods were insensitive to alterations in cardiac output or respiratory rate. End-tidal PCO2 was markedly affected by respiratory rate during exercise, the overestimate of PACO2 increasing if respiratory rate was slowed. An increase in anatomical dead space with exercise tends to decrease the error in P(et)CO2 and increase the error in the graphical method. Changes in the proportion of each breath taken up by inspiration make no important difference, and changes in functional residual capacity, while important in principle, are too small to have any major effect on the estimates. Changes in overall alveolar ventilation which alter steady-state PACO2 over a range of 30-50 mmHg have no important effect. At heavy work loads (200-300 W), P(et)CO2 grossly overestimates by 6-9 mmHg. The graphical method progressively underestimates, by about 5 mmHg at 300 W. A simulated CO2 response (the relation between ventilation and increasing PCO2) performed at 100 W suggests that a response slope close to the true one can be obtained by using any of the three methods. The graphical method gave results closest to the true absolute values. Either graphical or empirical methods should be satisfactory for detecting experimentally produced changes in PACO2 during steady-state exercise, to make comparisons between different steady-state exercise loads, and to assess CO2 response in exercise.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cervical preganglionic sympathetic nerve activity and chemoreflexes in the cat

The role of chemoreflexes originating from carotid body and central chemoreceptors in the regulation of cervical preganglionic sympathetic nerve (PSN) activity was studied in anesthetized and spontaneously breathing cats. PSN efferents which responded to hypoxia were selected for the study. The PSN activity, breath-by-breath inspiratory tidal volume, tracheal PO2 and PCO2, and arterial systemic blood pressure were recorded simultaneously. The responses of PSN efferents to transient changes in and steady-state levels of arterial PO2 and PCO2 and to graded bolus injections of intravenous sodium cyanide (50-100 micrograms), nicotine (50-100 micrograms), and dopamine hydrochloride (30-60 micrograms) were compared before and after bilateral section of carotid sinus nerves (CSN). CSN section raised the base-line PSN activity and practically eliminated the responses to brief pharmacological stimuli, but it did not eliminate the responses to transient changes in and steady-state levels of arterial PO2 and PCO2. However, CSN section diminished PSN responses and abolished ventilatory responses to hypoxia. Thus the PSN response to hypoxia was partly independent of peripheral chemoreflex and of respiratory drive. We conclude that carotid body chemoreflex elicits fast PSN responses and that a moderate decline in arterial PO2 causes an additional slow, direct excitation of sympathetic nervous system. The latter indicates O2 chemosensitivity of the system in the physiological range of arterial PO2. This O2-sensing property may allow sympathetic nervous system to initiate chemoreflex responses independent of the peripheral chemoreceptors.     

ESR measurement of dissolved oxygen in 4-day chick embryo blood

The magnetic interactions between dissolved oxygen molecules and nitroxide radical spin probes lead to broadening of electron spin resonance (ESR) lines. Based on this property we described an ESR methodology to measure PO2 values in 4-day chick embryo and adult human blood. The total blood volume required for the measurement was only 9 microliter. Using this method PO2 for adult human mixed venous blood was found to be 36.7 mmHg. This is within the established clinical range of 25-40 mmHg for mixed venous blood PO2. The range of mean PO2 values for 4-day chick embryo blood was 27.3- 35.0 mmHg. This is the first time that PO2 values have been reported for individual chick embryos at such an early stage.     

Simple contrivance "clamps" end-tidal PCO(2) and PO(2) despite rapid changes in ventilation.

The device described in this study uses functionally variable dead space to keep effective alveolar ventilation constant. It is capable of maintaining end-tidal PCO(2) and PO(2) within +/-1 Torr of the set value in the face of increases in breathing above the baseline level. The set level of end-tidal PCO(2) or PO(2) can be independently varied by altering the concentration in fresh gas flow. The device comprises a tee at the mouthpiece, with one inlet providing a limited supply of fresh gas flow and the other providing reinspired alveolar gas when ventilation exceeds fresh gas flow. Because the device does not depend on measurement and correction of end-tidal or arterial gas levels, the response of the device is essentially instantaneous, avoiding the instability of negative feedback systems having significant delay. This contrivance provides a simple means of holding arterial blood gases constant in the face of spontaneous changes in breathing (above a minimum alveolar ventilation), which is useful in respiratory experiments, as well as in functional brain imaging where blood gas changes can confound interpretation by influencing cerebral blood flow.     

Regional venous outflow, blood volume, and sympathetic nerve activity during hypercapnia and hypoxic hypercapnia.

We examined the changes in systemic blood volume and regional venous outflow from the splanchnic, coronary, and other remaining vascular beds in response to acute hypercapnia or hypoxic hypercapnia in dogs, using cardiopulmonary bypass and a reservoir. Hypercapnia (PCO2 = 105 mmHg) (1 mmHg = 133 Pa) and hypoxic hypercapnia (PO2 = 23 mmHg, PCO2 = 99 mmHg) caused marked decreases in systemic blood volume of 14 +/- 3 and 16 +/- 3 mL/kg in spleen-intact dogs, and 3 +/- 2 and 10 +/- 2 mL/kg in splenectomized dogs, respectively. Splanchnic venous outflow increased by 12% at 3.5 min hypercapnia, whereas it decreased by 60% at 3.5 min hypoxic hypercapnia. Coronary venous outflow increased by 85 and 400% at 3.5 min hypercapnia and hypoxic hypercapnia, respectively. Sympathetic efferent nerve activity revealed a significant augmentation during hypoxic hypercapnia and a relatively smaller increase (30% of the response to hypoxic hypercapnia) during hypercapnia. Carotid and aortic chemoreceptor and baroreceptor denervation attenuated significantly the response of systemic blood volume to hypercapnia and hypoxic hypercapnia. The regional venous outflow responses to hypercapnia were not altered after chemodenervation, but those to hypoxic hypercapnia were significantly attenuated after chemodenervation. These results suggest that acute hypercapnia and hypoxic hypercapnia caused a marked decrease in vascular capacitance owing primarily to an increase in sympathetic efferent nerve activity via chemoreceptor stimulation. They also indicate that blood flow to the splanchnic vascular bed during hypercapnia increased (even though the cardiac output was constant), whereas it increased to the extrasplanchnic and coronary vascular beds during hypoxic hypercapnia.     

Gas exchange in healthy rabbits during high-frequency oscillatory ventilation

We examined the effects of oscillatory frequency (f), tidal volume (VT), and mean airway pressure (Paw) on respiratory gas exchange during high-frequency oscillatory ventilation of healthy anesthetized rabbits. Frequencies from 3 to 30 Hz, VT from 0.4 to 2.0 ml/kg body wt (approximately 20-100% of dead space volume), and Paw from 5 to 20 cmH2O were studied. As expected, both arterial partial pressure of O2 and CO2 (PaO2 and PaCO2, respectively) were found to be related to f and VT. Changing Paw had little effect on blood gas tensions. Similar values of PaO2 and PaCO2 were obtained at many different combinations of f and VT. These relationships collapsed onto a single curve when blood gas tensions were plotted as functions of f multiplied by the square of VT (f. VT2). Simultaneous tracheal and alveolar gas samples showed that the gradient for PO2 and PCO2 increased as f. VT2 decreased, indicating alveolar hypoventilation. However, venous admixture also increased as f. VT2 decreased, suggesting that ventilation-perfusion inequality must also have increased.     

Effects of almitrine on hypoglossal and phrenic electroneurograms

Almitrine increases breathing by stimulating peripheral chemoreceptors. Previous studies suggest clinical usefulness in the adult with chronic obstructive pulmonary disease, but little data are available to decide whether almitrine would be helpful in diseases involving pharyngeal airway obstruction, such as apnea of prematurity or obstructive sleep apnea. We investigated the effect of intravenous almitrine on hypoglossal (HG), an upper airway nerve, and phrenic (PHR) neural activity in eight alpha-chloralose-urethan anesthetized, paralyzed, vagotomized, and artificially ventilated cats. Recordings were made of raw and integrated HG and PHR electroneurograms (ENGs), alveolar PCO2, arterial PO2, arterial blood pressure, and rectal temperature. A dose-response study of cumulative almitrine doses ranging from 0.1 to 4.0 mg/kg was performed in three cats. The interactive effects of almitrine and hypoxic stimulation were investigated in four cats. The interactive effects of almitrine and hypercapnic stimulation were investigated in five cats. The interactive effects of almitrine and ventilatory timing were investigated in six cats. We found that 1) almitrine doses as low as 0.1 mg/kg iv increased both HG and PHR ENG activity, with a maximum effect at approximately 1.0 mg/kg; 2) almitrine markedly increased HG and PHR ENG activity at all arterial PO2 values from 35-175 Torr; 3) almitrine increased HG and PHR ENG activity at all arterial PCO2 values from 30-70 Torr; and 4) almitrine increased the ratio of tidal volume to inspiratory time and decreased the inspiratory muscle duty cycle at normoxia and eucapnia.     

Influence of hyperosmotic shrinkage and β-adrenergic stimulation on red blood cell volume regulation and oxygen binding properties in rainbow trout and carp

Whole blood from rainbow trout and carp was subjected to hyperosmotic shock and subsequent beta-adrenergic stimulation (isoprenaline) at different oxygen tension ( PO(2)) and carbon dioxide tension ( PCO(2)) levels with the aim to evaluate changes in red blood cell (RBC) volume, pH and ion concentrations and their ultimate effect on blood O(2) transport characteristics. Hyperosmolality (addition of NaCl) induced RBC shrinkage, which was followed by a regulatory volume increase (RVI) that was larger at low than at high PO(2)and more complete in carp than in trout. Carp RBC showed practically full volume recovery within 140 min at low PO(2)and partial recovery at high PO(2), whereas RVI was partial under all PO(2)and PCO(2)conditions in trout. The RVI increased intracellular [Na(+)], water content, and, in carp, also pH (pHi), suggesting activation of Na(+)/H(+) exchange. In trout RBCs, activation of RVI was rapid but succeeded by deactivation. In carp RBCs, activation of Na(+) influx was slower but it continued, allowing full volume recovery. Shrinkage of the RBCs was associated with only minor decreases in blood oxygen saturation and oxygen affinity in both species. Thus, the oxygen affinity decrease expected on the basis of the increased concentration of intracellular haemoglobin and organic phosphates was small, and it appeared to some extent countered during RVI by an oxygen affinity increase via increased pHi. Addition of isoprenaline increased RBC volume and pHi and increased Hb oxygen saturation. The beta-adrenergic response was stronger at low compared to high PO(2) and at high compared to low PCO(2). The PO(2) dependency was largest in carp, whereas the PCO(2) (pH) dependency was more expressed in trout. The adrenergic response of trout RBCs was similar under isoosmotic and hyperosmotic conditions. In carp RBCs, the response was absent at high PO(2) under isoosmotic conditions, but interestingly it could be induced under hyperosmotic conditions. The data suggest that the RBC shrinkage occurring in fish moving from freshwater to seawater has minimal impact on blood O(2) binding properties.     

Depression of ventilation hypoxia in man.

In five normal male subjects, ventilation, PaO2, and PaCO2 were measured during the rapid progressive isocapnic production of hypoxia (5 min) and during the equally rapid isocapnic reversal of hypoxia. At similar PaO2, PaCO2, and pH, ventilation was less at a time when alveolar PO2 was increasing than when alveolar PO2 was decreasing. We interpret these results as showing that human ventilation is depressed by mild-to-moderate hypoxia (40-60 Torr), that such depression is probably central, and that it is ordinarily masked by peripheral chemoreceptor stimulation. We are not able to distinguish whether the ventilatory depression is caused by decreased central chemoreceptor PCO2 due to an increase in cerebral flow, direct hypoxic depressing of the central respiratory mechanism, or both.