Systemic hemodynamics affecting cardiac output during hypocapnic and hypercapnic hypoxia

Systemic hemodynamic adjustments involved in the control of cardiac output (CO) were examined in chronically instrumented unanesthetized sheep inhaling gas mixtures resulting in hypocapnic hypoxia (H) [arterial pH (pHa) = 7.53, arterial partial pressure of O2 (Pao2) = 30 Torr, arterial partial pressure of CO2 (Paco2) = 29 Torr] or hypercapnic hypoxia (HCH) (pHa = 7.14, Pao2 = 34 Torr, Paco2 = 72 Torr) for 1 h. H (n = 7) and HCH (n = 6) resulted in 26% and 61% increases in CO, respectively, and mean systemic arterial pressure rose to a greater extent during HCH. Both H and HCH resulted in increased blood flow (microsphere method) to the peripheral systemic circulation including the brain, heart, diaphragm, and nonrespiratory skeletal muscle (the latter blood flow increased 120% during H and 380% during HCH). Gastrointestinal and renal blood flow remained unchanged during H and HCH. Transit time of green dye from the pulmonary artery to regional veins in the hindlimb and intestine was 5.0 and 8.2 s, respectively, during base-line conditions and remained unchanged with HCH. During HCH, regional O2 consumption increased 274% for the hindlimb and decreased 39% for the intestine. Total catecholamines rose 250% during H and 3,700% during HCH. During hypocapnic and hypercapnic hypoxia, CO is augmented in part by systemic hemodynamic adjustments that include a redistribution of blood flow and a translocation of blood volume to the fast transit time peripheral systemic circuit. The sympathetic nervous system may play an important role in mediating these systemic hemodynamic adjustments.     

Arterial blood gases in conscious rats exposed to hypoxia, hypercapnia, or both.

Adult male rats were anesthetized and catheters were implanted in the caudal artery. Soon after recovery from short-lasting anesthesia, a total of 20 groups of six each were individually exposed to five different oxygen levels varying from 21.0 to 9.0% combined with four CO2 levels ranging from 0 to 12.9% at a mean barometric pressure of 744 Torr. Arterial blood samples were collected and analyzed for pH, Po2, and Pco2 before and near the end of 20-min exposures. During an air-breathing control period, pH averaged 7.466 plus or minus 0.020 SD, Paco2 41.2 plus or minus 1.9 Torr and Pao2 91.8 plus or minus 3.5 Torr. During hypoxia, Pao2 levels were similar to that of acutely hypoxic humans. Rats apparently differ from man in that blood buffering is greater, resulting in a higher pH during air breathing and a smaller [H-+] increase with increasing Paco2. Differences between arterial and inspired CO2 were about 10 Torr at 60 and 90 Torr Plco2 and were not influenced by Plo2.     

Exercise responses in pregnant sheep: blood gases, temperatures, and fetal cardiovascular system

In an effort to examine the effects of maternal exercise on the fetus we measured maternal and fetal temperatures and blood gases and calculated uterine O2 consumption in response to three different treadmill exercise regimens in 12 chronically catheterized near-term sheep. We also measured fetal catecholamine concentrations, heart rate, blood pressure, cardiac output, blood flow distribution, blood volume, and placental diffusing capacity. Maternal and fetal temperatures increased a mean maximum of 1.5 +/- 0.5 (SE) and 1.3 +/- 0.1 degrees C, respectively. We corrected maternal and fetal blood gas values for the temperatures in vivo. Maternal arterial partial pressure of O2 (PO2), near exhaustion during prolonged (40 min) exercise at 70% maximal O2 consumption, increased 13% to a maximum of 116.7 +/- 4.0 Torr, whereas partial pressure of CO2 (PCO2) decreased by 28% to 27.6 +/- 2.2 Torr. Fetal arterial PO2 decreased 11% to a minimum of 23.2 +/- 1.6 Torr, O2 content by 26% to 4.3 +/- 0.6 ml X dl -1, PCO2 by 8% to 49.6 +/- 3.2 Torr, but pH did not change significantly. Recovery was virtually complete within 20 min. During exercise total uterine O2 consumption was maintained despite the reduction in uterine blood flow because of hemoconcentration and increased O2 extraction. The decrease of 3 Torr in fetal arterial PO2 and 1.5 ml X dl -1 in O2 content did not result in major cardiovascular changes or catecholamine release. These findings suggest that maternal exercise does not represent a major stressful or hypoxic event to the fetus.     

In vivo evaluation of transcutaneous CO2 partial pressure monitoring

Correlation between transcutaneous and arterial CO2 partial pressure (Ptcco2, and Paco2) under normal and hemorrhagic shock conditions was evaluated in rabbits. Under normal conditions the Paco2-to-Ptcco2 least-squares regression line had a slope of 1.03 an intercept of 4.57 Torr, and a root mean variance of +/- 3.79 Torr. Under hemorrhagic shock conditions the slope remained similar, but the intercept increased, producing a significant difference between arterial and transcutaneous values. The correlation line shifts to the left so that, for a given Paco2, the Ptcco2 value increases. The transcutaneous response time (90%) under conditions produced by breathing 10% CO2 lagged 2.8 +/- 1.4 min behind that of the breathing 10% CO2 lagged 2.8 +/- 1.4 min behind that of the Paco2. The difference between transcutaneous and arterial CO2 observed during hemorrhagic shock and the lag in transcutaneous response time can be altered by topical application of dimethyl sulfoxide, by altering both flow and permeability. These results indicate that good Ptcco2-to-Paco2 correlation exists under normal conditions and that hemorrhagic shock will produce tissue CO2 accumulation and therefore higher than arterial Ptcco2 values.     

Carotid bodies are required for ventilatory acclimatization to chronic hypoxia

We have compared the ventilatory responses of intact and carotid body-denervated (CBD) goats to moderate [partial pressure of O2 in arterial blood; (Pao2) approximately 44 Torr] and severe (Pao2 approximately 33 Torr) many time points for up to 7 days of hypobaria. In the intact group there were significant time-dependent decreases in partial pressure of CO2 in arterial blood (PaCO2) in both moderate and severe hypoxemia (approximately-7 and -11 Torr) that were largely complete by 8 h of hypoxemia and maintained throughout. Acute restoration of normoxia in chronically hypoxic intact animals produced time-dependent increases in Paco2 over 2 h, but hypocapnia persisted relative to sea-level control. Arterial plasma [HCO3-] and [H+] decreased, and [Cl-] increased with a time course and magnitude consistent with developing hypocapnia. Chronic CBD, per se, resulted in a sustained, partially compensated respiratory acidosis, as PaCO2 rose 6 Torr and base excess rose 3 mEq/1, [Cl-] fell 1 mEq/1, and pHa fell 0.01 units. During exposure to identical levels of arterial hypoxemia as in the intact group. CBD animals showed no significant changes in PaCO2, [H+]a, or [HCO3-]a at any time during moderate or severe hypoxemia. Plasma [C1-] remained within the normal range throughout exposure to moderate hypoxia and increased in severe hypoxia. In a few instances some hypocapnia was observed, but this was highly inconsistent and was always less than one-third of that observed in intact goats. In contrast to intact goats, acute restorations of normoxia in the chronically hypoxic CBD goats always caused hyperventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory acclimatization to hypoxia is not dependent on arterial hypoxemia

Goats were prepared so that one carotid body (CB) could be perfused with blood in which the gas tensions could be controlled independently from the blood perfusing the systemic arterial system, including the brain. Since one CB is functionally adequate, the nonperfused CB was excised. To determine whether systemic arterial hypoxemia is necessary for ventilatory acclimatization to hypoxia (VAH), the CB was perfused with hypoxic normocapnic blood for 6 h [means +/- SE: partial pressure of carotid body O2 (PcbO2), 40.6 +/- 0.3 Torr; partial pressure of carotid body CO2 (PcbCO2), 38.8 +/- 0.2 Torr] while the awake goat breathed room air to maintain systemic arterial normoxia. In control periods before and after CB hypoxia the CB was perfused with hyperoxic normocapnic blood. Changes in arterial PCO2 (PaCO2) were used as an index of changes in ventilation. Acute hypoxia (0.5 h of hypoxic perfusion) resulted in hyperventilation sufficient to reduce average PaCO2 by 6.7 Torr from control (P less than 0.05). Over the subsequent 5.5 h of hypoxic perfusion, average PaCO2 decreased further, reaching 4.8 Torr below that observed acutely (P less than 0.05). Acute CB hyperoxic perfusion (20 min) following 6 h of hypoxia resulted in only partial restoration of PaCO2 toward control values; PaCO2 remained 7.9 Torr below control (P less than 0.05). The progressive hyperventilation that occurred during and after 6 h of CB hypoxia with concomitant systemic normoxia is similar to that occurring with total body hypoxia. We conclude that systemic (and probably brain) hypoxia is not a necessary requisite for VAH.     

Hyperventilation in ponies at the onset of and during steady-state exercise

We studied blood gases in ponies to assess the relationship of alveolar ventilation (VA) to pulmonary CO2 delivery during moderate treadmill exercise. In normal ponies for 1.8, 3, or 6 mph, respectively, partial pressure of CO2 in arterial blood (PaCO2) decreased maximally by 3.1, 4.4, and 5.7 Torr at 30-90 s of exercise and remained below rest by 1.4, 2.3, and 4.5 Torr during steady-state (4-8 min) exercise (P less than 0.01). Partial pressure of O2 in arterial blood (PaO2) and arterial pH, (pHa) also reflected hyperventilation. Mixed venus CO2 partial pressure (PVCO2) decreased 2.3 and 2.9 Torr by 30 s for 3 and 6 mph, respectively (P less than 0.05). In work transitions either from 1.8 to 6 mph or from 6 mph to 1.8 mph, respectively, PaCO2 either decreased 3.8 Torr or increased 3.3 Torr by 45 s of the second work load (P less than 0.01). During exercise in acute (2-4 wk) carotid body denervated (CBD) ponies at 1.8, 3, or 6 mph, respectively, PaCO2 decreased maximally below rest by 9.0, 7.6, and 13.2 Torr at 30-45 s of exercise and remained below rest by 1.3, 2.3, and 7.8 Torr during steady-state (4-8 min) exercise (P less than 0.1). In the chronic (1-2 yr) CBD ponies, the hypocapnia was generally greater than normal but less than in the acute CBD ponies. We conclude that in the pony 1) VA is not tightly matched to pulmonary CO2 delivery during exercise, particularly during transitional states, 2) the exercise hyperpnea is not mediated by PaCO2 or PVCO2, and 3) during transitional states in the normal pony, the carotid bodies attenuate VA drive thereby reducing arterial hypocapnia.     

The effects of exogenous extracellular carbonic anhydrase on CO2 excretion in rainbow trout (Oncorhynchus mykiss): role of plasma buffering capacity

The buffering capacity (beta) of rainbow trout (Oncorhynchus mykiss) plasma was manipulated prior to intravascular injection of bovine carbonic anhydrase to test the idea that proton (H+) availability limits the catalysed dehydration of HCO3- within the extracellular compartment. An extracorporeal blood shunt was employed to continuously monitor blood gases in vivo in fish exhibiting normal plasma beta (-3.9+/-0.3 mmol 1(-1) pH unit(-1)), and in fish with experimentally (using N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]) elevated plasma beta (-12.1+/-1.1 mmol 1(-1) pH unit(-1)). An injection of 5 mg kg(-1) carbonic anhydrase equally reduced (after 90 min) the arterial partial pressure of CO2 in trout with regular (-0.23+/-0.05 Torr) or high (-0.20+/-0.05 Torr) plasma beta; saline injection was without effect. Because ventilation and venous blood gases were unaffected by carbonic anhydrase, the effect of extracellular carbonic anhydrase in lowering arterial partial pressure of CO2 was likely caused solely by a specific enhancement of CO2 excretion owing to acceleration of HCO3- dehydration within the plasma. The lowering of arterial partial pressure of CO2 in trout after injection of exogenous carbonic anhydrase provides the first in vivo evidence that the accessibility of plasma HCO3- to red blood cell carbonic anhydrase constrains CO2 excretion under resting conditions. Because the velocity of red blood cell Cl-/HCO3- exchange governs HCO3- accessibility to red blood cell carbonic anhydrase, the present study also provides evidence that CO2 excretion at rest is limited by the relatively slow rate of Cl-/HCO3- exchange. The effect of carbonic anhydrase in lowering arterial partial pressure of CO2 was unrelated to plasma buffering capacity. While these data could suggest that H+ availability does not limit extracellular HCO3- dehydration in vivo at resting rates of CO2 excretion, it is more likely that the degree to which plasma beta was elevated in the present study was insufficient to drive a substantially increased component of HCO3- dehydration through the plasma.     

Cardiopulmonary control during exercise in the duck

To determine the importance of nonhumoral drives to exercise hyperpnea in birds, we exercised adult White Pekin ducks on a treadmill (3 degrees incline) at 1.44 km X h-1 for 15 min during unidirectional artificial ventilation. Intrapulmonary gas concentrations and arterial blood gases could be regulated with this ventilation procedure while allowing ventilatory effort to be measured during both rest and exercise. Ducks were ventilated with gases containing either 4.0 or 5.0% CO2 in 19% O2 (balance N2) at a flow rate of 12 l X min-1. At that flow rate, arterial CO2 partial pressure (PaCO2) could be maintained within +/- 2 Torr of resting values throughout exercise. Arterial O2 partial pressure did not change significantly with exercise. Heart rate, mean arterial blood pressure, and mean right ventricular pressure increased significantly during exercise. On the average, minute ventilation (used as an indicator of the output from the central nervous system) increased approximately 400% over resting levels because of an increase in both tidal volume and respiratory frequency. CO2-sensitivity curves were obtained for each bird during rest. If the CO2 sensitivity remained unchanged during exercise, then the observed 1.5 Torr increase in PaCO2 during exercise would account for only about 6% of the total increase in ventilation over resting levels. During exercise, arterial [H+] increased approximately 4 nmol X l-1; this increase could account for about 18% of the total rise in ventilation. We conclude that only a minor component of the exercise hyperpnea in birds can be accounted for by a humoral mechanism; other factors, possibly from muscle afferents, appear responsible for most of the hyperpnea observed in the running duck.     

Pulmonary venous pressure increases during alveolar hypoxia in isolated lungs of newborn pigs.

The purpose of this study was to determine whether pulmonary venous pressure increases during alveolar hypoxia in lungs of newborn pigs. We isolated and perfused with blood the lungs from seven newborn pigs, 6-7 days old. We maintained blood flow constant at 50 ml.min-1.kg-1 and continuously monitored pulmonary arterial and left atrial pressures. Using the micropuncture technique, we measured pressures in 10 to 60-microns-diam venules during inflation with normoxic (21% O2-69-74% N2-5-10% CO2) and hypoxic (90-95% N2-5-10% CO2) gas mixtures. PO2 was 142 +/- 21 Torr during normoxia and 20 +/- 4 Torr during hypoxia. During micropuncture we inflated the lungs to a constant airway pressure of 5 cmH2O and kept left atrial pressure greater than airway pressure (zone 3). During hypoxia, pulmonary arterial pressure increased by 69 +/- 24% and pressure in small venules increased by 40 +/- 23%. These results are similar to those obtained with newborn lambs and ferrets but differ from results with newborn rabbits. The site of hypoxic vasoconstriction in newborn lungs is species dependent.     

Ventrolateral medullary surface blood flow determined by hydrogen clearance

The H2 clearance technique was used to determine the blood flow of the postulated respiratory chemosensitive areas near the ventrolateral surface of the medulla. In 12 pentobarbital sodium-anesthetized cats, flow (mean +/- SD) was measured from 25-micron Teflon-coated platinum wire electrodes implanted to a depth of 0.3-0.7 mm. Flow (in ml X min-1 X 100 g-1, n = 35) was 52.8 +/- 28.5 in hypocapnia [arterial CO2 partial pressure (PaCO2) = 21.8 +/- 1.6 Torr], 57.8 +/- 27.5 in normocapnia (PaCO2 = 31.9 +/- 2.2 Torr), and 75.0 +/- 31.7 in hypercapnia (PaCO2 = 44.5 +/- 3.0 Torr). Flow determined from 15 electrodes in adjacent pyramidal tracts (white matter) was less at all levels of CO2; 22.9 +/- 12.3 in hypocapnia, 29.1 +/- 15.9 in normocapnia, and 33.9 +/- 13.9 in hypercapnia. In hypoxia [arterial O2 partial pressure (PaO2) = 39.9 +/- 6.3 Torr] ventrolateral surface flow rose to 87.9 +/- 47.6, and adjacent white matter flow was 35.8 +/- 15.6. These results indicate that flow in the postulated central chemoreceptor areas exceeds that of white matter and is sensitive to variations in PaCO2 and PaO2.     

Respiratory changes induced by prolonged laryngeal stimulation in awake piglets

To examine the role of the laryngeal reflex in modulating cardiorespiratory function, we stimulated the superior laryngeal nerves (SLN) bilaterally in unanesthetized, chronically instrumented piglets (n = 10, age 5-14 days). The SLN were placed in cuff electrodes and wires were exteriorized in the neck for stimulation. A cannula placed in the aorta was used for blood pressure recording and arterial blood sampling. During each experiment, 1-2 days after surgery, ventilation was recorded using whole-body plethysmography, and electroencephalogram and electrocardiogram were recorded after acute subcutaneous electrode placement. After base-line recordings, the SLN were electrically stimulated for 1 h. During this period, mean respiratory frequency decreased by 40-75% and apneas of 10-15 s were regularly interspersed between single breaths or clusters of breaths. Periods of breathing were always associated with opening of the eyes and generally with head and body movements, an awakening that occurred every 10-15 s. At 1 h into the stimulus period, minute ventilation had decreased by 57 +/- 7% (mean +/- SE), arterial partial pressure of O2 (PaO2) by 68 +/- 3 Torr, and arterial partial pressure of CO2 (PaCO2) had increased by 19 +/- 2 Torr. Throughout the entire stimulus period, mean blood pressure and average heart rate were maintained within 12% of base line. We suggest that: low-threshold SLN afferents exert primarily respiratory effects and only minor cardiovascular effects; breathing during laryngeal reflex activation is sustained by an arousal system; and the laryngeal reflex does not pose an imminent threat to the unanesthetized, awake, young animal.     

Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA.

Breathing 100% O2 at 1 atmosphere absolute (ATA) is known to be associated with a decrease in cerebral blood flow (CBF). It is also accompanied by a fall in arterial Pco2 leading to uncertainty as to whether the cerebral vasoconstriction is totally or only in part caused by arterial hypocapnia. We tested the hypothesis that the increase in arterial Po2 while O2 was breathed at 1.0 ATA decreases CBF independently of a concurrent fall in arterial Pco2. CBF was measured in seven healthy men aged 21-62 yr by using noninvasive continuous arterial spin-labeled-perfusion MRI. The tracer in this technique, magnetically labeled protons in blood, has a half-life of seconds, allowing repetitive measurements over short time frames without contamination. CBF and arterial blood gases were measured while breathing air, 100% O2, and 4 and 6% CO2 in air and O2 backgrounds. Arterial Po2 increased from 91.7 +/- 6.8 Torr in air to 576.7 +/- 18.9 Torr in O2. Arterial Pco2 fell from 43.3 +/- 1.8 Torr in air to 40.2 +/- 3.3 Torr in O2. CBF-arterial Pco2 response curves for the air and hyperoxic runs were nearly parallel and separated by a distance representing a 28.7-32.6% decrement in CBF. Regression analysis confirmed the independent cerebral vasoconstrictive effect of increased arterial Po2. The present results also demonstrate that the magnitude of this effect at 1.0 ATA is greater than previously measured.     

Operation Everest II: oxygen transport during exercise at extreme simulated altitude

A decrease in maximal O2 uptake has been demonstrated with increasing altitude. However, direct measurements of individual links in the O2 transport chain at extreme altitude have not been obtained previously. In this study we examined eight healthy males, aged 21-31 yr, at rest and during steady-state exercise at sea level and the following inspired O2 pressures (PIO2): 80, 63, 49, and 43 Torr, during a 40-day simulated ascent of Mt. Everest. The subjects exercised on a cycle ergometer, and heart rate was recorded by an electrocardiograph; ventilation, O2 uptake, and CO2 output were measured by open circuit. Arterial and mixed venous blood samples were collected from indwelling radial or brachial and pulmonary arterial catheters for analysis of blood gases, O2 saturation and content, and lactate. As PIO2 decreased, maximal O2 uptake decreased from 3.98 +/- 0.20 l/min at sea level to 1.17 +/- 0.08 l/min at PIO2 43 Torr. This was associated with profound hypoxemia and hypocapnia; at 60 W of exercise at PIO2 43 Torr, arterial PO2 = 28 +/- 1 Torr and PCO2 = 11 +/- 1 Torr, with a marked reduction in mixed venous PO2 [14.8 +/- 1 (SE) Torr]. Considering the major factors responsible for transfer of O2 from the atmosphere to the tissues, the most important adaptations occurred in ventilation where a fourfold increase in alveolar ventilation was observed. Diffusion from alveolus to end-capillary blood was unchanged with altitude. The mass circulatory transport of O2 to the tissue capillaries was also unaffected by altitude except at PIO2 43 Torr where cardiac output was increased for a given O2 uptake. Diffusion from the capillary to the tissue mitochondria, reflected by mixed venous PO2, was also increased with altitude. With increasing altitude, blood lactate was progressively reduced at maximal exercise, whereas at any absolute and relative submaximal work load, blood lactate was higher. These findings suggest that although glycogenolysis may be accentuated at low work loads, it may not be maximally activated at exhaustion.     

Pulmonary and circulatory changes in conscious sheep exposed to 100% O2 at 1 ATA

We have measured the effects of normobaric hyperoxia on arterial and mixed venous gas tensions, cardiac output, heart rate, right atrial, pulmonary, and aortic pressures in 12 conscious chronically instrumented sheep. Regional blood flow to brain, heart, kidney, intestines, and respiratory muscles was assessed in five sheep by injecting 15-micrometers microspheres labeled with gamma-emitting isotopes. Survival time ranged from 60 to 120 h (mean = 80 h). All variables except arterial O2 partial pressure (PaO2) and mixed venous O2 partial pressure remained at base-line level during the first 40 h of exposure, after which PaO2 decreased gradually but remained above 200 Torr at death. After this there was a progressive uncompensated respiratory acidosis with terminal arterial CO2 partial pressure values exceeding 90 Torr. There was a considerable rise in the brain blood flow, whereas flow to the other organs either remained unchanged or increased in proportion to cardiac output. Our experiments also showed that systemic hyperoxic vasoconstriction did not occur, and any local changes were not of sufficient magnitude to affect perfusion.     

Pulmonary vasoconstrictor response to acute decrease in blood P50

The O2 sensor that triggers hypoxic pulmonary vasoconstriction may be sensitive not only to alveolar hypoxia but also to hypoxia in mixed venous blood. A specific test of the blood contribution would be to lower mixed venous PO2 (PvO2), which can be accomplished by increasing hemoglobin-O2 affinity. When we exchanged transfused rats with cyanate-treated erythrocytes [PO2 at 50% hemoglobin saturation (P50) = 21 Torr] or with Créteil erythrocytes (P50 = 13.1 Torr), we lowered PvO2 from 39 +/- 5 to 25 +/- 4 and to 14 +/- 4 Torr, respectively, without altering arterial blood gases or hemoglobin concentration. Right ventricular systolic pressure increased from 32 +/- 2 to 36 +/- 3 Torr with cyanate erythrocytes and to 44 +/- 5 Torr with Créteil erythrocytes. Cardiac output was unchanged. Control exchange transfusions with normal rat or 2,3-diphosphoglycerate-enriched human erythrocytes had no effect on PvO2 or right ventricular pressure. Alveolar hypoxia plus high O2 affinity blood caused a greater increase in right ventricular systolic pressure than either stimulus alone. We concluded that PvO2 is an important determinant of pulmonary vascular tone in the rat.     

Sex differences in the respiratory response to hemorrhage in the conscious, New Zealand white rabbit

In conscious animals, the response to hemorrhage is biphasic. During phase 1, arterial pressure is maintained. Phase 2 is characterized by profound hypotension. Despite allied roles, less is known about the integrated cardiovascular and respiratory response to blood loss in conscious animals. We evaluated cardiorespiratory changes during hemorrhage to test the hypotheses that 1) respiratory rate (RR) and blood gases do not change during phase 1; 2) RR increases during phase 2; and 3) RR and blood gas changes during hemorrhage are similar in males and females. We measured mean arterial pressure, RR, and blood gases during hemorrhage in 16 conscious, chronically prepared, male and female New Zealand white rabbits. We removed venous blood until mean arterial pressure was < or =40 mmHg. Sex did not affect mean arterial pressure, heart rate, Pa(O(2)), Pa(CO(2)), or pH during hemorrhage or the blood loss required to induce phase 2. Pa(CO(2)) decreased significantly from 37 +/- 1 to 33 +/- 1 and 29 +/- 1 mmHg (P < 0.001) during phase 1 and 2, respectively. Before hemorrhage, Pa(O(2)) was 87 +/- 2 mmHg. Pa(O(2)) was unchanged in phase 1 (92 +/- 2 mmHg) but increased in phase 2 (101 +/- 2 mmHg; P < 0.001). Body temperature, Pv(CO(2)) (thoracic vena cava), and ventilation-perfusion mismatch (A-a gradient) were unchanged during phases 1 and 2. Neither sex increased RR during phase 1. While males doubled RR during phase 2, RR in females did not change (P < 0.001). Thus, while Pa(CO(2)) decreases in phase 1 and phase 2, the decreases are achieved in different ways across the two phases and in the two sexes.     

In vivo regulation of plasma [H+] in ponies during acute changes in PCO2

The major objective of this study was to test the hypothesis that in ponies the change in plasma [H+] resulting from a change in PCO2 (delta H+/delta PCO2) is less under acute in vivo conditions than under in vitro conditions. Elevation of inspired CO2 and lowering of inspired O2 (causing hyperventilation) were used to respectively increase and decrease arterial PCO2 (Paco2) by 5-8 Torr from normal. Arterial and mixed venous blood were simultaneously sampled in 12 ponies during eucapnia and 5-60 min after Paco2 had changed. In vitro data were obtained by equilibrating blood in a tonometer at five different levels of PCO2. The in vitro slopes of the H+ vs. PCO2 relationships were 0.73 +/- 0.01 and 0.69 +/- 0.01 neq.1-1.Torr-1 for oxygenated and partially deoxygenated blood, respectively. These slopes were greater (P less than 0.001) than the in vivo H+ vs. PCO2 slopes of 0.61 +/- 0.03 and 0.57 +/- 0.03 for arterial and mixed venous blood, respectively. The delta HCO3-/delta pH (Slykes) was 15.4 +/- 1.1 and 17.0 +/- 1.1 for in vitro oxygenated and partially deoxygenated blood, respectively. These values were lower (P less than 0.001) than the in vivo values of 23.3 +/- 2.7 and 25.2 +/- 4.7 Slykes for arterial and mixed venous blood, respectively. In vitro, plasma strong ion difference (SID) increased 4.5 +/- 0.2 meq/l (P less than 0.001) when Pco2 was increased from 25 to 55 Torr. A 3.5-meq/l decrease in [Cl-] (P less than 0.001) and a 1.3 +/- 0.1 meq/l increase in [Na+] (P less than 0.001) accounted for the SID change.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemoglobin concentrations and blood gas tensions of free-diving Weddell seals

Arterial blood gas tensions, pH, and hemoglobin concentrations were measured in four free-diving Weddell seals Leptonychotes weddelli. A microprocessor-controlled sampling system enabled us to obtain 24 single and 31 serial aortic blood samples. The arterial O2 tension (PaO2) at rest [78 +/- 13 (SD) Torr] increased with diving compression to a maximum measured value of 232 Torr and then rapidly decreased to 25-35 Torr. The lowest diving PaO2 we measured was 18 Torr just before the seal surfaced from a 27-min dive. A consistent increase of arterial hemoglobin concentrations from 15.1 +/- 1.10 to 22.4 +/- 1.41 g/100 ml (dives less than 17 min) and to 25.4 +/- 0.79 g/100 ml (dives greater than 17 min) occurred during each dive. We suggest that an extension of the sympathetic outflow of the diving reflex possibly caused profound contraction of the Weddell seal's very large spleen (0.89% of body wt at autopsy), although we have no direct evidence. This contraction may have injected large quantities of red blood cells (2/3 of the total) into the seal's central circulation during diving and allowed arterial O2 content to remain constant for the first 15-18 min of long dives. The increase of arterial CO2 tensions during the dive and the compression increase of arterial N2 tensions were also moderated by injecting red blood cells sequestered at ambient pressure. After each dive circulating red blood cells are oxygenated and rapidly sequestered, possibly in the spleen during the first 15 min of recovery.     

Temporal pattern of arterial CO2 partial pressure during exercise in humans

The major objective of this study was to test the hypothesis that arterial CO2 partial pressure (PaCO2) does not change in transitions from rest to steady-state exercise and between two levels of exercise. Nine young adults exercised on a treadmill or a bicycle (sit or supine) for 5 min at a mild work load (heart rate = 90 beats X min-1) and then 3 min at a moderate work load (heart rate = 150 beats X min-1). In some studies the moderate work load preceded the mild work load. Arterial blood was sampled from a catheterized artery. During all exercise tasks isocapnia was not strictly maintained (F greater than 4.0, P less than 0.001). For example, a 1-to 2-Torr hypocapnia was the dominant trend during the first 15-45 s after increasing treadmill speed, and a transient hypercapnia was most prevalent when treadmill speed was decreased. During steady-state exercise PaCO2 did not deviate by more than 1-3 Torr from PaCO2 during any resting posture, and PaCO2 differences between exercise intensities and conditions did not exceed 1-2 Torr. A mouthpiece-breathing valve system was not used in most studies, but when this system was used, it did not consistently affect exercise PaCO2. Increasing inspired O2 to 40% likewise did not consistently alter exercise PaCO2. Failure to maintain isocapnia throughout exercise indicates that the matching of alveolar ventilation (VA) to lung CO2 delivery is not exquisitely precise. Accordingly it is inappropriate to base theories of the exercise hyperpnea on the heretofore contention of precise matching.(ABSTRACT TRUNCATED AT 250 WORDS)