Ventral medullary extracellular fluid pH and PCO2 during hypoxemia

We designed experiments to study changes in ventral medullary extracellular fluid (ECF) PCO2 and pH during hypoxemia. Measurements were made in chloralose-urethan-anesthetized spontaneously breathing cats (n = 12) with peripherial chemodenervation. Steady-state measurements were made during normoxemia [arterial PO2 (PaO2) = 106 Torr], hypoxemia (PaO2 = 46 Torr), and recovery (PaO2 = 105 Torr), with relatively constant arterial PCO2 (approximately 44 Torr). Mean values of ventilation were 945, 683, and 1,037 ml/min during normoxemia, hypoxemia, and recovery from hypoxemia, respectively. Ventilatory depression occurred in each cat during hypoxemia. Mean values of medullary ECF PCO2 were 57.7 +/- 7.2 (SD), 59.4 +/- 9.7, and 57.4 +/- 7.2 Torr during normoxemia, hypoxemia, and recovery to normoxemia, respectively; respective values for ECF [H+] were 60.9 +/- 8.0, 64.4 +/- 11.6, and 62.9 +/- 9.2 neq/l. Mean values of calculated ECF [HCO3-] were 22.8 +/- 3.0, 21.7 +/- 3.3, and 21.4 +/- 3.1 meq/l during normoxemia, hypoxemia, and recovery, respectively. Changes in medullary ECF PCO2 and [H+] were not statistically significant. Therefore hypoxemia caused ventilatory depression independent of changes in ECF acid-base variables. Furthermore, on return to normoxemia, ventilation rose considerably, still independent of changes in ECF PCO2, [H+], and [HCO3-].     

Hemodynamic effects of rapidly evacuating prolonged pneumothorax in rabbits

Clinical observations suggest that systemic hypotension may be caused by rapid evacuation of persistent pneumothorax. This observation has not been substantiated experimentally and the mechanism(s) are unknown. In this study, we measured systemic hemodynamic parameters in rabbits before and for 2 h during negative pressure evacuation of a right-sided pneumothorax of 7-9 days duration. Three groups of animals were studied: 10 rabbits breathed room air and were hypoxemic during pneumothorax (hypoxemic pneumothorax = HP); 10 rabbits breathed 40% O2-60% N2, which prevented arterial hypoxemia during pneumothorax (supraoxemic pneumothorax = SP); seven normal control animals were untreated during this time period (NC). Pneumothoraces in HP and SP were evacuated by negative pressure applied to the right pleural space for 2 h while animals were anesthetized and mechanically ventilated. The NC group was anesthetized and ventilated without prior pneumothorax. Serial hemodynamic measurements were made before and during pleural suction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Aminopeptidases in visceral organs during alterations in body fluid volume and osmolality

Enzymatic cleavage of some peptides in the local environment could be included among the mechanisms related to the regulation of hydrosaline balance. In order to examine this hypothesis, we measured representative aminopeptidase activities in visceral organs of rats after applying certain hydrosaline challenges. Decreased levels (about 30%) of particulate puromycin-insensitive-neutral aminopeptidase in the renal medulla and of soluble acid aminopeptidase in the lung were observed under hyperosmolality and hypovolemia. Decreased levels (more than 45%) of particulate type-I-pyroglutamyl aminopeptidase in the heart were observed under altered volemia. These results indicate that aminopeptidases at these anatomical locations might be involved in the regulation of body fluid volume and osmolality.     

Arterial hypoxemia and performance during intense exercise

In order to determine the level of hypoxemia which is sufficient to impair maximal performance, seven well-trained male cyclists [maximum oxygen consumption (VO_2max)51·min^–1 or 60 ml·kg^–1·min^–1] performed a 5-min performance cycle test to exhaustion at maximal intensity as controlled by the subject, under three experimental conditions: normoxemia [percentage of arterial oxyhemoglobin saturation (%S _a O₂)>94%], and artificially induced mild (%S _aO₂=90±1%) and moderate (%S _aO₂=87±1%) hypoxemia. Performance, evaluated as the total work output (Work_tot) performed in the 5-min cycle test, progressively decreased with decreasing %S _aO₂ [mean (SE) Work_tot=107.40 (4.5) kJ, 104.07 (5.6) kJ, and 102.52 (4.7) kJ, under normoxemia, mild, and moderate hypoxemia, respectively]. However, only performance in the moderate hypoxemia condition was significantly different than in normoxemia (P=0.02). Mean oxygen consumption and heart rate were similar in the three conditions (P=0.18 andP=0.95, respectively). End-tidal partial pressure of CO₂ was significantly lower (P=0.005) during moderate hypoxemia compared with normoxemia, and ventilatory equivalent of CO₂ was significantly higher (P=0.005) in both hypoxemic conditions when compared with normoxemia. It is concluded that maximal performance capacity is significantly impaired in highly trained cyclists working under an %S _aO₂ level of 87% but not under a milder desaturation level of 90%.     

Extracellular mechanical forces drive endocardial cell volume decrease during zebrafish cardiac valve morphogenesis

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CO2 elimination as a function of frequency and tidal volume in rabbits during HFO

CO2 elimination (VCO2) was monitored during high-frequency oscillation (HFO) over a frequency (f) range of 2-30 Hz in anesthetized and paralyzed rabbits to determine whether effective gas exchange could be achieved in this species, to determine the f and tidal volume (VT) dependence of gas exchange in this species, and to compare these results with those from dog and human studies. We were able to produce VCO2 levels during HFO that exceeded normal steady-state levels of CO2 production with VT's less than the total dead space volume. VCO2 was related to f in a curvilinear fashion, whereas in some rabbits VCO2 became independent of f at higher frequencies. This curvilinear relationship between f and VCO2 is similar to data from humans but contrasts with the linear relationship found in dogs. Evidence is presented indicating frequency-dependent behavior of gas exchange is correlated with a frequency-dependent decrease in respiratory system resistance. We propose that the frequency-dependent mechanical properties of the rabbit lung may also account for the species differences in HFO gas exchange.     

Fractional changes in lung capillary blood volume and oxygen saturation during the cardiac cycle in rabbits

Topulos, George P., Nina R. Lipsky, John L. Lehr, Rick A. Rogers, and James P. Butler. Fractional changes in lung capillary blood volume and oxygen saturation during the cardiac cycle in rabbits.J. Appl. Physiol. 82(5):1668-1676, 1997.Changes in local pulmonary capillary bloodvolume (Vc) and oxygen saturation (S) have been difficult to measure inlive animals. By utilizing the differences in absorptionof light at two wavelengths (650 and 800 nm), we estimated thefractional change in Vc and S during the course of the cardiac cycle ineight anesthetized, ventilated rabbits at low and high lung volumes.Observations were made of the pattern of diffusely backscattered light,from an ~1-cm³ volume of lungilluminated with a point source placed on the pleural surface through athoracotomy. At low lung volume, the fractional change in Vc was~13%, the change in S was ~4.6%, and the mean S was close to77%. The fluctuations in Vc and S lagged behind peaksystemic blood pressure by about one-fifth and three-fifths of a cycle,respectively. At high lung volume, there were no important fluctuationsin Vc or S, and the mean S was ~82%. These results areconsistent with fluctuations in pulmonary capillary pressure and gasexchange over the cardiac cycle, and with decreasing capillary compliance with increasing lung volume.

     

Age-dependent core temperature responses of conscious rabbits to acute hypoxemia.

Experiments were carried out on chronically instrumented newborn and older rabbits to characterize their core temperature (T(c)) responses to acute hypoxemia and to differentiate "forced" vs. "regulated" thermoregulatory responses. Three age ranges of kits were studied: 4-6, 9-11, and 28-30 days of age. During an experiment, T(c), selected ambient temperature (T(a)), and oxygen consumption were measured from kits studied in a thermocline during a control period of normoxemia, an experimental period of normoxemia or hypoxemia (fraction of inspired oxygen 0.10), and a recovery period of normoxemia. We reasoned that no change or a decrease in T(a) while T(c) decreased during hypoxemia would indicate a regulated thermoregulatory response, whereas an increase in T(a) while T(c) decreased during hypoxemia would indicate a forced thermoregulatory response. T(c) decreased during acute hypoxemia in the older kits but not in the 4- to 6-day-old kits; the decrease in T(c) was accentuated on postnatal days 28-30 compared with postnatal days 9-11. T(a) decreased or stayed the same during exposure to acute hypoxemia. Our data provide evidence that postnatal maturation influences the T(c) response of rabbits to acute hypoxemia and that the decrease in T(c) during hypoxemia in the older kits results from a regulated thermoregulatory response.     

Behavioral activity during prolonged hypoxemia in fetal sheep

Experiments were conducted in unanesthetized, chronically catheterized pregnant sheep to determine the fetal behavioral response to prolonged hypoxemia produced by restricting uterine blood flow. Uterine blood flow was reduced by adjusting a vascular occluder placed around the maternal common internal iliac artery to decrease fetal arterial O2 content from 6.1 +/- 0.3 to 4.1 +/- 0.3 ml/dl for 48 h. Associated with the decrease in fetal O2 content, there was a slight increase in fetal arterial PCO2 and decrease in pH, which were both transient. There was an initial inhibition of both fetal breathing movements and eye movements but no change in the pattern of electrocortical activity. After this initial inhibition there was a return to normal incidence of both fetal breathing movements and eye movements by 16 h of the prolonged hypoxemia. These studies indicate that the chronically catheterized sheep fetus is able to adapt behaviorally to a prolonged decrease in arterial O2 content secondary to the restriction of uterine blood flow.     

Development of cerebrospinal fluid and the blood-cerebrospinal fluid barrier in rabbits.

Blood plasma and cerebrospinal fluid (CSF) samples were collected from adult female rabbits (New Zealand White), newborn, and embryos at 18, 20, 24, and 28 days of gestation. Samples were analyzed for total protein using the Folin phenol reagent. During development, mean total protein of blood plasma rose sharply from 12.45 to 12.51 mg/ml at 18 to 20 days to 37.56 mg/ml at 28 days. Levels further increased to 54.06 mg/ml in the newborn and to 66.18 mg/ml in the adult. The protein concentration of cerebrospinal fluid was constant at 5.20 to 5.29 mg/ml between 18 and 20 days of gestation, but steadily decreased to 3.53 mg/ml at 28 days. By birth, the CSF protein concentration was further reduced to 2.08 mg/ml, and this level differed only slightly (P < 0.05) from CSF protein values determined for adults. These data indicate that the blood-cerebrospinal fluid barrier to proteins begins to function by 18 to 20 days of gestation, and the protein concentration of cerebrospinal fluid approaches the normal adult value soon after birth.     

Baroreceptor control of pressure-flow relationships during hypoxemia

In the absence of peripheral chemoreceptors, the effects of graded hypoxemia on the carotid sinus control of central and regional hemodynamics were studied in anesthetized mongrel dogs. Baroreceptor stimulation was effected by carotid sinus isolation and perfusion under controlled pressure. Blood flows were measured in the aorta and the celiac, mesenteric, left renal, and right iliac arteries. Carotid sinus reflex set-point pressures were well maintained until hypoxemia was severe. Carotid sinus reflex set-point gain was maximal during mild hypoxemia. Reflex operating point regional flows were unaffected by hypoxemia. A factorial analysis of overall reflex increases in mean aortic pressure, flow, and power during reduced baroreceptor stimulation showed potentiation by increasing hypoxemia. Corresponding effects of baroreceptor stimulation and hypoxemia on aortic resistance and heart rate were additive. Celiac, renal, and iliac blood flows increased during both hypoxemia and reduced baroreceptor stimulation. Only in the celiac bed were blood flow changes independent of concomitant changes in cardiac output. Thus, at maximum sympathetic stimulation (low carotid sinus pressure) during hypoxemia, the cardiovascular system maintained both central and regional blood flows at high systemic blood pressures independent of the peripheral chemoreceptors.     

Cerebral blood flow velocity and cranial fluid volume decrease during +Gz acceleration

Cerebral blood flow (CBF) velocity and cranial fluid volume, which is defined as the total volume of intra- and extracranial fluid, were measured using transcranial Doppler ultrasonography and rheoencephalography, respectively, in humans during graded increase of +Gz acceleration (onset rate: 0.1 G/s) without straining maneuvers. Gz acceleration was terminated when subjects' vision decreased to an angle of less than or equal to 60 degrees, which was defined as the physiological end point. In five subjects, mean CBF velocity decreased 48% from a baseline value of 59.4 +/- 11.2 cm/s to 31.0 +/- 5.6 cm/s (p<0.01) with initial loss of peripheral vision at 5.7 +/- 0.9 Gz. On the other hand, systolic CBF velocity did not change significantly during increasing +Gz acceleration. Cranial impedance, which is proportional to loss of cranial fluid volume, increased by 2.0 +/- 0.8% above the baseline value at the physiological end point (p<0.05). Both the decrease of CBF velocity and the increase of cranial impedance correlated significantly with Gz. These results suggest that +Gz acceleration without straining maneuvers decreases CBF velocity to half normal and probably causes a caudal fluid shift from both intra- and extracranial tissues.