Arterial Blood O2 Research Articles

Determinants of maximal oxygen uptake in rats acclimated to simulated altitude.

The effect of acclimation to hypoxia on maximal O2 uptake (VO2max), maximal cardiac output (Qmax), and arteriovenous O2 concentration difference (a-vCO2) was studied in male Sprague-Dawley rats acclimated for 3 wk to a barometric pressure of approximately 380 Torr (A rats). Nonacclimated control animals were pair-fed littermates maintained at an ambient barometric pressure of approximately 740 Torr (NA rats). Both A and NA rats exercised maximally on a treadmill with inspired PO2 maintained at either approximately 72 or 145 Torr. Arterial blood O2 concentration was significantly higher in A than in NA rats (16.0 +/- 0.6 vs. 12.4 +/- 0.3 ml/dl in hypoxia and 28.4 +/- 1.5 vs. 20.1 +/- 0.9 ml/dl in normoxia, respectively; both P < 0.05). During hypoxic exercise VO2max was slightly but significantly higher in A than in NA subjects (55.3 +/- 1.3 vs. 48.8 +/- 1.1 ml STPD.min-1 x kg-1; P < 0.05). In hypoxia a-vCO2 was 16.6 +/- 0.6 and 12.4 +/- 0.4 ml/dl and Qmax was 401 +/- 17 and 489 +/- 9 ml.min-1 x kg-1 in A and NA subjects, respectively (both P < 0.05). A rats showed both lower maximal heart rate and lower maximal stroke volume during hypoxic exercise. In normoxia there was no significant difference in VO2max between A and NA rats (71.8 +/- 2.7 vs. 73.9 +/- 3.1 ml.min-1 x kg-1). As with hypoxia, in normoxia a-vCO2 was significantly higher and Qmax was significantly lower in A than in NA animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic, hemodynamic, and ventilatory responses to respiratory load in sedated neonatal piglets

Some neonatal species fail to develop the expected degree of hypercapnia during hypoventilation with mechanical loads. We studied 13 spontaneously breathing, sedated piglets (1-9 days old), grouped by age as young (< or = 3 day old) or old (> 3 day old). Baseline measurements of minute ventilation, arterial blood pressure (BP), cardiac output, and O2 consumption were repeated after continuous (inspiratory and expiratory) flow-resistive loading of 330 cmH2O.l-1 x s for 10 min. Older animals [n = 6, age 6.6 +/- 1.9 (SD) days, wt 1.99 +/- 0.5 kg] increased metabolic rate (9.8 +/- 1.4 to 10.5 +/- 1.3 ml.min-1 x kg-1, P < 0.01), whereas younger animals (n = 7, 2.6 +/- 0.6 days, 1.37 +2- 0.3 kg) invariably decreased metabolic rate with loading (9.7 +/- 1.6 to 7.9 +/- 2.6 ml.min-1 x kg-1); changes were different between groups (P < 0.02). Although ventilation decreased with loading in both groups (P < 0.01), younger animals showed a relatively greater fall from baseline values (38 vs. 27%). Despite differences in the degree of hypoventilation, arterial CO2 tension increased similarly in both groups (21%). BP increased (P < 0.01) with loading in older but not younger animals. We conclude that the decreased metabolic rate and limited hemodynamic response in younger piglets reflect an accomodative response to hypoventilation in contrast to that of older animals, which display an adult pattern of increased metabolic rate and BP with loaded breathing.

Effects of Diet on Responses to Hypoxia in Sturgeon (Acipenser Naccarii)

ABSTRACT We investigated the effects of a diet enriched in omega-3 (ω3) polyunsaturated fatty acids (PUFA) and vitamin E on responses of sturgeon (Acipenser naccarii) to hypoxia. After 3 months of feeding, there were significant increases in ω3 PUFA in liver and muscle, and of vitamin E in muscle, of fish fed the enriched diet (ED) compared with fish on a standard diet (SD), indicating that tissue composition is influenced by diet. Acute exposure to hypoxia (10 min at 10.8 kPa water O2 tension, ) had no effect on oxygen consumption , increased gill ventilation frequency (fg) and reduced arterial blood O2 content in both dietary groups, but ED sturgeon exhibited a significantly smaller decrease in than did SD animals. Progressive hypoxic exposure ( decreasing gradually from 20.5 to 3.6kPa within 45–60min) led to a significant increase in at intermediate levels of in SD sturgeon that was not seen in ED animals. Furthermore, ED sturgeon showed no significant reduction in arterial plasma pH (pHa) and at levels that caused significant reductions in these variables in SD sturgeon. ED sturgeon exhibited a smaller increase in plasma lactate level than did SD fish. We suggest that PUFA and/or vitamin E contribute significantly to regulation of metabolism in hypoxia.

Relationship between blood O2 content and catecholamine levels during hypoxia in rainbow trout and American eel.

Plasma catecholamine levels and arterial blood respiratory variables were monitored in rainbow trout (Oncorhynchus mykiss) and American eel (Anguilla rostrata) acutely exposed (30 min) to graded levels of external hypoxia [water PO2 (PWO2) 20-90 Torr]. The experiments were designed to evaluate the factors controlling catecholamine mobilization in hypoxic fish and to elucidate the basis of marked interspecific differences. In trout, plasma catecholamine levels were unchanged when PWO2 remained above 50 Torr but increased markedly when PWO2 was lowered below this value; the predominant catecholamine released into the circulation was epinephrine. In eel, there was no such obvious PWO2 threshold for catecholamine release although plasma levels were consistently elevated above baseline only at PWO2 less than 35 Torr. The magnitude of the catecholamine release in eel was approximately an order of magnitude less than in trout. Unlike in trout, there was no increase in the plasma epinephrine-to-norepinephrine concentration ratio. During hypoxia, the relationship between arterial blood PO2 (PaO2) and PWO2 was similar in both species and thus could not explain the differences in the PWO2 thresholds for catecholamine release. In trout, the calculated PaO2 thresholds for catecholamine release were 25.3 (epinephrine) and 20.5 Torr (norepinephrine) whereas in eel the corresponding values were 12.5 and 11.6 Torr, respectively. These PaO2 thresholds were in good agreement with the in vivo values for PaO2 at half-maximal hemoglobin (Hb)-O2 saturation (P50) for trout and eel blood of 22.9 and 11.1 Torr, respectively. Thus both species displayed essentially equivalent catecholamine release thresholds when expressed in terms of arterial blood O2 content corresponding to approximately 45-60% Hb-O2 saturation.

Smoke aldehyde component influences pulmonary edema

The pulmonary edema of smoke inhalation is caused by the toxins of smoke and not the heat. We investigated the potential of smoke consisting of carbon in combination with either acrolein or formaldehyde (both common components of smoke) to cause pulmonary edema in anesthetized sheep. Seven animals received acrolein smoke, seven animals received a low-dose formaldehyde smoke, and five animals received a high-dose formaldehyde smoke. Pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac output were not affected by smoke in any group. Peak airway pressure increased after acrolein (14 +/- 1 to 21 +/- 2 mmHg; P less than 0.05) and after low- and high-dose formaldehyde (14 +/- 1 to 21 +/- 1 and 20 +/- 1 mmHg, respectively; both P less than 0.05). The partial pressure of O2 in arterial blood fell sharply after acrolein [219 +/- 29 to 86 +/- 9 (SE) Torr; P less than 0.05] but not after formaldehyde. Only acrolein resulted in a rise in lung lymph flow (6.5 +/- 2.2 to 17.9 +/- 2.6 ml/h; P less than 0.05). Lung lymph-to-plasma protein ratio was unchanged for all three groups, but clearance of lymph protein was increased after acrolein. After acrolein, the blood-free extravascular lung water-to-lung dry weight ratio was elevated (P less than 0.05) compared with both low- and high-dose formaldehyde groups (4.8 +/- 0.4 to 3.3 +/- 0.2 and 3.6 +/- 0.2, respectively). Lymph clearance (ng/h) of thromboxane B2, leukotriene B4, and the sulfidopeptide leukotrienes was elevated after acrolein but not formaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)

Graded Postischemic Reoxygenation Ameliorates Inhibition of Cerebral Cortical Protein Synthesis in Dogs

The purpose of this study was to determine the effect of normoxic reperfusion and graded postischemic reoxygenation on cerebral protein synthesis in a cell-free system. Ischemia alone produced a relatively small decrease (15-17%) in activity in all the subcellular systems studied. After a 15-min interval of normoxic reperfusion (75-90 mmHg O2 in arterial blood), a 40% decrease (p less than 0.01) in [14C]leucine incorporation was observed. Reoxygenation with hypoxemic blood containing 37.5 mm Hg O2 at 0-5 min and 56 mm Hg O2 at 6-10 min of recirculation followed by 5 min of normoxic reperfusion resulted in a significant increase (p less than 0.05) of polypeptide chain synthesis in vitro when compared with normoxic reperfusion. The results obtained by this experimental approach tend to show that graded postischemic reoxygenation could be used as a simple and effective neuroprotective tool that substantially diminishes the secondary postischemic damage in nervous tissue, including the newly synthesized proteins.

Ventilatory and Cardiovascular Responses to Blood pH, Plasma Pco2, Blood O2Content, and Catecholamines in an Air-Breathing Fish, the Bowfin (Amia calva)

Hydrochloric acid (HCl) infusion during aquatic normoxia increased blood pressure, gill ventilation, and air breathing in bowfin. These responses were associated with a reduction in arterial blood pH (pHa) and O2, content (Cao2) and an increase in arterial plasma CO2 tension (Paco2). Ammonium bicarbonate (NH4HCO3) infusion did not change pHa or Cao2 but increased Paco2 and had no effects on blood pressure or ventilation. In aquatic hyperoxia, HCl infusion lowered pHa and Cao2. Arterial blood O2 content, however, was maintained above normoxic levels, and there were no cardiovascular or ventilatory responses. These results indicate that cardiovascular and ventilatory responses to acid-base disturbances in bowfin are correlated with reductions in Cao2 below normoxic levels and not with decreases in pHa or increases in Cao2. Hydrochloric acid infusion in normoxia stimulated a release of endogenous catecholamines, whereas NH4HCO3 infusion and HCl infusion in hyperoxia did not. Catecholamine infusion stimulated gill ventilation but not air breathing. The correlation between increases in plasma catecholamines and gill ventilation following HCl infusion in normoxia indicates that circulating catecholamines may contribute to gill ventilatory responses to hypoxemia in bowfin.

Alveolar gas composition and exchange during deep breath-hold diving and dry breath holds in elite divers

End tidal O2 and CO2 (PETCO2) pressures, expired volume, blood lactate concentration ([Lab]), and arterial blood O2 saturation [dry breath holds (BHs) only] were assessed in three elite breath-hold divers (ED) before and after deep dives and BH and in nine control subjects (C; BH only). After the dives (depth 40-70 m, duration 88-151 s), end-tidal O2 pressure decreased from approximately 140 Torr to a minimum of 30.6 Torr, PETCO2 increased from approximately 25 Torr to a maximum of 47.0 Torr, and expired volume (BTPS) ranged from 1.32 to 2.86 liters. Pulmonary O2 exchange was 455-1,006 ml. CO2 output approached zero. [Lab] increased from approximately 1.2 mM to at most 6.46 mM. Estimated power output during dives was 513-929 ml O2/min, i.e. approximately 20-30% of maximal O2 consumption. During BH, alveolar PO2 decreased from approximately 130 to less than 30 Torr in ED and from 125 to 45 Torr in C. PETCO2 increased from approximately 30 to approximately 50 Torr in both ED and C. Contrary to C, pulmonary O2 exchange in ED was less than resting O2 consumption, whereas CO2 output approached zero in both groups. [Lab] was unchanged. Arterial blood O2 saturation decreased more in ED than in C. ED are characterized by increased anaerobic metabolism likely due to the existence of a diving reflex.

Effects of Protriptyline on Diurnal and Nocturnal Oxygenation in Patients with Chronic Obstructive Pulmonary Disease

To determine the effects of a nonsedating tricyclic antidepressant (protriptyline) on pulmonary function (lung volume, expiratory flow), arterial blood gases, sleep architecture, and sleep-induced breathing abnormalities in patients with chronic obstructive pulmonary disease. A before-and-after trial in which patients, blinded to treatment, were given a placebo for 2 weeks, followed by 2 and 10 weeks of protriptyline treatment. Referral-based pulmonology clinic in a public institution. Sixteen outpatients were enrolled in the trial. Complete results for 11 patients and partial results for 3 patients are presented. Patients were evaluated at baseline, after receiving placebo for 2 weeks, and after 2 and 10 weeks of protriptyline therapy (20 mg/d, taken at bedtime). At baseline, for the whole group, forced expiratory volume in 1 second (FEV1) was 1.0 +/- 0.08 L (mean +/- SE); the partial pressure of O2 in arterial blood (PaO2) was 59 +/- 1.2 mm Hg; and the partial pressure of CO2 in arterial blood (PaCO2) was 48.9 +/- 1.2 mm Hg. These variables remained stable after placebo. Pulmonary function test results were unchanged with protriptyline therapy. Arterial blood gas levels improved with such therapy: PaO2 levels increased by 5.1 +/- 1.4 mm Hg after 2 weeks and 6.7 +/- 2.4 mm Hg after 10 weeks (P less than 0.01); PaCO2 levels decreased by 4.2 +/- 0.9 mm Hg after 2 weeks and 2.2 +/- 1.1 mm Hg after 10 weeks (P less than 0.01). Total sleep times were similar at these visits. The only change in sleep architecture was a significant decrease in rapid eye movement (REM) sleep. The lowest value for the saturation of hemoglobin with O2 in arterial blood (SaO2) seen during sleep was 72.0% +/- 2.0% at baseline. After 2 and 10 weeks of protriptyline therapy, SaO2 values increased by 7.1% +/- 1.6% and 5.0% +/- 2.1%, respectively (P less than 0.01). With protriptyline therapy, the cumulative SaO2 curve, derived from data obtained during sleep, shifted down and to the right. Protriptyline improves diurnal and nocturnal hypoxemia in patients with chronic obstructive pulmonary disease. These changes are not related to changes in pulmonary mechanics.

Intracellular pH, lactate, and energy metabolism in neonatal brain during partial ischemia measured in vivo by 31P and 1H nuclear magnetic resonance spectroscopy.

Sequential 31P and 1H nuclear magnetic resonance spectra were measured for neonatal piglets (n = 7) to determine the relationship between brain intracellular pH (pHi), lactate, and phosphorylated energy metabolites during partial ischemia. Simultaneous determinations of arterial and cerebral venous blood gases, pH, O2 content, and plasma concentrations of glucose and lactate were also made. Ischemia, induced by bilateral carotid artery ligation plus hemorrhagic hypotension for 35 min, resulted in variable reductions in ATP, phosphocreatine, and increases in Pi, H+, and lactate relative to control levels. In four piglets, whose arterial blood glucose rose above control, brain lactate exceeded 20 mumol g-1 with corresponding decreases in pHi of greater than 0.7 units compared to control levels. The extents of brain acidosis and lactosis showed a strong linear correlation with each other (r = 0.94). Maximal changes in brain lactate, pHi, and ATP at the end of ischemia showed significant positive linear correlations with the control levels of arterial blood glucose, but did not correlate with arterial glucose or arterial cerebral-venous glucose difference values during ischemia. The relationship between pHi and buffer base deficit was comparable to results reported for adult animals up to 20 mumol ml-1. However, in contrast to models proposed for adult brain, the continued linear relationship between pH and higher buffer base levels is most consistent with a theoretical model that assumes the presence of weak acid buffers with pKa values from 6.7 to 5.2.

Lack of immediate effects of wound excision on the hyperdynamic circulation of burned patients.

The high cardiac output (CO) observed during the chronic phase in burned patients has been ascribed, among other factors, to the elevated blood flow in the burn wound. The hemodynamic effects of wound excision to fascia have been studied in eight patients with second- and third-degree burns ranging from 42% to 70% total body surface area (TBSA) undergoing debridement and skin-grafting procedures. The study was performed on the 4th to the 51st postburn day when all patients were in a hyperdynamic state. Serial hemodynamic measurements, including arterial and mixed-venous blood O2 saturation and content, were made before induction of anesthesia, during surgery both before and after wound excision, and in the recovery room a few hours after surgery. During anesthesia, the elevated CO decreased probably as a consequence of decreased metabolic requirements, but no further hemodynamic change was observed following wound excision. The size of burn wound excised to fascia averaged 24% TBSA and ranged from one-third to more than one-half of the initial burn. With discontinuation of anesthesia, CO rose rapidly above preoperative values, apparently to meet a similar increase in oxygen consumption. The excision of large areas of burned tissue did not attenuate the hyperdynamic circulation in burned patients, at least during and immediately after surgery. The data suggest that the elevated blood flow in the burn wound does not play a significant role in the pathogenesis of the hyperdynamic state.

Developmental changes in regional cerebral blood flow in fetal and newborn lambs.

Developmental changes in regional cerebral blood flow (CBF) were determined using radioactively labeled microspheres to measure flow to the cortex, brain stem, cerebellum, white matter, caudate nucleus, and choroid plexus in three groups of chronically catheterized lambs under physiological conditions: 90- to 100-day preterm fetal lambs (n = 14), 125- to 136-day near-term fetal lambs (n = 11), and newborn lambs 5-44 days old (n = 10). We continually monitored heart rate, central venous pressure, and mean arterial blood pressure (MAP) and periodically measured arterial blood O2 and CO2 tensions (PaO2, PaCO2, respectively), pH, hemoglobin, and oxygen saturation (SaO2). The regional CBF measurements (ml.100 g-1.min-1) revealed that in all three age groups the high flow areas are the choroid plexus and caudate nucleus, whereas the lowest flow area is the white matter. There is, however, a different hierarchy of regional CBF in utero (cortex less than cerebellum and brain stem) compared with extrauterine life in the newborn lamb (cortex and cerebellum greater than brain stem). Analysis of regional cerebral oxygen delivery [CBF times arterial oxygen content (CaO2)] demonstrated a progressively increasing oxygen transport to the cortex with increasing gestational maturity and after birth. Oxygen transport to the brain stem, cerebellum, and white matter increased with gestational age, but did not increase after birth. Relationships between regional CBF and natural physiological variations of cardiorespiratory parameters (PaO2, SaO2, CaO2, pH, PaCO2, and MAP) were assessed using regression analysis. Correlations of regional CBF with PaO2 and SaO2 suggest that cerebral perfusion is not primarily determined by CaO2 when variations occur within the physiological range.(ABSTRACT TRUNCATED AT 250 WORDS)

Operation Everest II: preservation of cardiac function at extreme altitude.

Hypoxia at high altitude could depress cardiac function and decrease exercise capacity. If so, impaired cardiac function should occur with the extreme, chronic hypoxemia of the 40-day simulated climb of Mt. Everest (8,840 m, barometric pressure of 240 Torr, inspiratory O2 pressure of 43 Torr). In the five of eight subjects having resting and exercise measurements at the barometric pressures of 760 Torr (sea level), 347 Torr (6,100 m), 282 Torr (7,620 m), and 240 Torr, heart rate for a given O2 uptake was higher with more severe hypoxia. Slight (6 beats/min) slowing of the heart rate occurred only during exercise at the lowest barometric pressure when arterial blood O2 saturations were less than 50%. O2 breathing reversed hypoxemia but never increased heart rate, suggesting that hypoxic depression of rate, if present, was slight. For a given O2 uptake, cardiac output was maintained. The decrease in stroke volume appeared to reflect decreased ventricular filling (i.e., decreased right atrial and wedge pressures). O2 breathing did not increase stroke volume for a given filling pressure. We concluded that extreme, chronic hypoxemia caused little or no impairment of cardiac rate and pump functions.

Ventilatory and blood gas dynamics at onset and offset of exercise in the pony.

The purpose of these experiments was to examine the temporal pattern of arterial carbon dioxide tension (PaCO2) to assess the relationship between alveolar ventilation (VA) and CO2 return to the lung at the onset and offset of submaximal treadmill exercise. Five healthy ponies exercised for 8 min at two work rates: 50 m/min 6% grade and 70 m/min 12% grade. PaCO2 decreased (P less than 0.05) below resting values within 1 min after commencement of exercise at both work rates and reached a nadir at 90 s. PaCO2 decreased maximally by 2.5 and 3.5 Torr at the low and moderate rate, respectively. After the nadir, PaCO2 increased across time during both work rates and reached values that were not significantly different (P greater than 0.05) from rest at minute 4 of exercise. Partial pressure of O2 in arterial blood and arterial pH reflected hyperventilation during the first 3 min of exercise. At the termination of exercise PaCO2 increased (1.5 Torr) above rest (P less than 0.05), reaching a zenith at 2-3 min of recovery. These data suggest that VA and CO2 flow to the lung are not tightly matched at the onset and offset of exercise in the pony and thus challenges the traditional concept of blood gas homeostasis during muscular exercise.

Cardiovascular, respiratory, and blood adjustments to hypoxia in the Japanese eel,Anguilla japonica

The cardioventilatory performance of the Japanese eel,Anguilla japonica, was evaluated during acute exposure to hypoxia. The eel became an oxygen conformer as ambient PO2 fell below the critical value of 110 mmHg. Although arterial and venous PO2 also fell progressively, the arterial O2 content remained constant down to an ambient PO2 of about 60 mmHg. Arterial blood O2 saturation was maintained at 85% even at 40 mmHg. The increase in the supply of O2 to the animal during hypoxia was due to a combination of adaptive adjustments: (1) an increase in ventilation: perfusion ratio brought about mainly be bradycardia; (2) an increase in respiratory exchange surface area which was manifested as an increase in branchial blood transit time and quantified as a rise in transfer factor, water-blood overlap coefficient and utilization (%); (3) an increase in blood O2 affinity and capacitance coefficient as a result of respiratory alkalosis and Bohr-Root shift and a decrease in haemoglobin allosteric modulator (GTP, ATP) concentrations in the RBC. These factors together helped to increase the efficiency of O2 transfer across the gills.

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)

Effects of catecholamines on lactic acid output during progressive working contractions.

Epinephrine and norepinephrine together (E + NE) and epinephrine (E) alone were infused intravenously in stepwise increasing doses during progressive isotonic tetanic contractions. The goal was to mimic, for in situ dog skeletal muscle, the concentrations of these catecholamines in the blood and the contractions during progressive exercise. The concentrations of lactate and O2 in arterial and muscle venous blood, the arterial plasma concentration of E and NE, PO2 in arterial and muscle venous blood, and the venous outflow were measured. The infusions caused a rise in plasma E and NE like those seen in progressive exercise. Compared with no-infusion controls, the E + NE infusions and the E alone infusion resulted in significant increases in maximal lactic acid output by the muscles during the contractions from 0.24 mumol X g-1 X min-1 in the controls to 0.44 and 0.54 mumol X g-1 X min-1 during E + NE and E alone infusions, respectively. The venous O2 concentrations and partial pressures were not reduced by the infusions. Both infusions resulted in a rise of arterial lactate concentration that could not be accounted for by the lactic acid output of the contracting muscles. The E alone infusions were associated with a rise in maximal O2 uptake during the contractions. Since the effects of the E + NE and E alone infusions were similar, it was suggested that E is more active than NE. It was suggested that E also increased lactic acid production in tissues other than the working muscles.

Blood respiratory properties in pigeons at high altitudes: effects of acclimation.

Many birds thrive at high altitudes where environmental temperatures are low. Previous studies have shown that tolerance of and acclimation to hypoxia involve cardiopulmonary and hematological adaptations. We investigated blood respiratory properties during exposure to simulated high altitude (hypobaric hypoxia) and low temperature in unanesthetized resting pigeons (Columbia livia, mean mass 0.38 kg). A control group (C) and a group acclimated to 7 km above sea level (ASL) in a hypobaric chamber at 25 degrees C (HA group) were used. All were acutely exposed to altitudes through 9 km ASL at 5 or 25 degrees C. Arterial and mixed venous blood gas tensions and O2 and CO2 content during steady state decreased with increased altitude, whereas blood lactate increased in both groups at both temperatures. Acute high-altitude exposure did not affect hematocrit, hemoglobin concentrations, or O2 carrying capacity, but at any altitude these were all greater in HA than in C birds. At 5 degrees C blood pH increased with altitude in controls but remained unchanged in HA birds. At 25 degrees C in both groups mean intracellular pH did not change, averaging 6.97, whereas extracellular (venous) pH increased with altitude. At the highest altitudes tissue O2 extraction was virtually complete in both groups. Acclimation changed blood O2 and CO2 combining properties in ways likely to improve gas transport at high altitudes. The previously unreported shifts in blood respiratory and acid-base properties with acclimation indicate that innate extrapulmonary adaptations contribute to avian hypoxia tolerance.

Pulmonary pathophysiological changes in sheep caused by endotoxin precursor, lipid X.

The chemical structure of the biologically active lipid A portion of Gram-negative endotoxin [lipopolysaccharide (LPS)] has recently been elucidated. This was greatly facilitated by the isolation of an Escherichia coli mutant that accumulates large quantities of lipid X, a novel monosaccharide precursor of lipid A (C. R. H. Raetz, Rev. Infect. Dis. 6: 463-471, 1984). We now report on the activity of lipid X in the lung-lymph model in sheep. We have measured the response to cumulative bolus injections of lipid X (2,3-diacylglucosamine 1-phosphate) in six chronically instrumented unanesthetized sheep. Lipid X at a total dose of 40 micrograms/kg produced a biphasic pattern of changes. The early phase was characterized by a rapid transient pulmonary arterial constrictive response that was dose dependent, accompanied by a delayed transient increase in lung-lymph flow (P less than 0.05), a significant (P less than 0.01) decrease in arterial blood O2 tension and an increase (P less than 0.05) in lung-lymph protein clearance. Protein permeability changes in the first phase are not usually seen following endotoxin injection. However, like endotoxin, lipid X also produced a late phase (3-6 h later) of increased lung vascular permeability to fluid and protein as reflected by significant (P less than 0.05) increases in both lung-lymph flow and lung-lymph protein clearance in the presence of stable pulmonary vascular pressures at or below base-line levels. We conclude that some of the pulmonary pressor activity of the endotoxin molecule can be attributed to the lipid X substructure. Furthermore, changes in vascular permeability may also be initiated by this substance.

Alpha-adrenergic-mediated reduction in coronary blood flow secondary to carotid chemoreceptor reflex activation in conscious dogs.

We examined the late coronary vascular response to carotid chemoreceptor reflex activation in normal, conscious dogs instrumented for the measurement of right main and left circumflex coronary artery blood flows, arterial and right ventricular pressures, and arterial and coronary sinus blood gases and O2 contents. With heart rate held constant by electrical stimulation, and with respiration controlled or allowed to vary spontaneously, carotid chemoreceptor reflex activation (induced by intracarotid nicotine) elicited a striking biphasic coronary vascular response characterized by an early dilation (previously described) and a late constriction. For example, with respiration controlled and with the autonomic nervous system intact, carotid chemoreceptor reflex activation resulted in a late increase in arterial pressure (19 +/- 4%; P less than 0.002), absolute reductions in right main (24 +/- 4%; P less than 0.002), and left circumflex (12 +/- 2%; P less than 0.004) coronary blood flows, and increases in right (62 +/- 13%; P less than 0.002) and left (26 +/- 3%; P less than 0.0001) coronary resistances. This carotid chemoreceptor reflex activation-induced late coronary constriction was also associated with a concomitant increase in myocardial oxygen extraction, i.e., arterial oxygen content remained constant, while coronary sinus oxygen content decreased (19 +/- 6%; P less than 0.04). Neither propranolol nor atropine had any significant effect on the magnitude of the right coronary constriction. However, both the absolute reduction in right coronary blood flow and increase in right coronary resistance were abolished by phentolamine. Furthermore, either total cardiac denervation or adrenalectomy significantly attenuated (P less than 0.01) carotid chemoreceptor reflex activation-induced reductions in right coronary blood flow and increase in right coronary resistance. We conclude that, with autonomic nervous system activity intact, carotid chemoreceptor reflex activation can elicit an absolute reflexly mediated reduction in coronary blood flow in the normal, conscious dog, despite an increase in arterial pressure. The mechanism of this vasoconstriction involves alpha-adrenergic receptor stimulation mediated by both cardiac sympathetic nerves and circulating catecholamines.