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-].     

Effects of aminophylline on hypoxemia-induced ventilatory depression in the cat

We designed experiments to evaluate changes in ventral medullary (VM) extracellular fluid (ECF) PCO2 and pH during hypoxemia-induced ventilatory depression (VD). Our aim was to investigate effects of aminophylline on VD and VM ECF acid-base variables. We used aminophylline because it inhibits adenosine, which is released within the brain during hypoxemia and could mediate VD. Experiments were performed in seven cats with acute bilateral denervation of carotid sinus nerves and vagi. Cats were anesthetized with chloralose-urethan and breathed spontaneously at a regulated and elevated arterial PCO2 (PaCO2). Measurements were made during normoxemia, hypoxemia, and recovery before (phase I) and after (phase II) aminophylline. By use of strict criteria for definition of VD, during phase II two kinds of responses were observed. Aminophylline prevented VD in five cats. In these cats in phase I, with mean arterial PO2 (PaO2) = 105 and PaCO2 = 42.2 Torr, VM ECF PCO2, [H+], and [HCO3-] were 59.5 +/- 8.6 Torr (mean +/- SD), 60.2 +/- 9.4 neq/l, and 23.1 +/- 3.7 meq/l, respectively. When mean PaO2 dropped to 49 Torr, ventilation decreased 21%, with only small changes in VM ECF acid-base variables. Studies were repeated 30 min after aminophylline (17 mg/kg iv). In phase II, during normoxemia (PaO2 = 110 Torr) VM ECF Pco2, [H+], and [HCO3-] were 55.4 +/- 8.1 Torr, 62.0 +/- 8.0 neq/l and 20.7 +/- 2.5 meq/l, respectively. During hypoxemia (PaO2 = 48 +/- 4 Torr) mean ventilation, VM ECF PCO2, [H+], and [HCO3-] did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of O2 in regulating tissue respiration in dog muscle working in situ.

This study was designed to investigate the role of tissue oxygenation in some of the factors that are thought to regulate muscle respiration and metabolism. Tissue oxygenation was altered by reductions in O2 delivery (muscle blood flow x arterial O2 content), induced by decreases in arterial PO2 (PaO2). O2 uptake (VO2) was measured in isolated in situ canine gastrocnemius at rest and while working at two stimulation intensities (isometric tetanic contractions at 0.5 and 1 contractions/s) on three separate occasions, with only the level of PaO2 (78, 30, and 21 Torr) being different for each occasion. Muscle blood flow was held constant (pump perfusion) at each work intensity for the three different levels of PaO2. Muscle biopsies were obtained at the end of each rest and work period. Muscle VO2 was significantly less (P less than 0.05) at both stimulation intensities for the hypoxemic conditions, whereas [ATP] was reduced only during the highest work intensity during both hypoxemic conditions (31% reduction at 21 Torr PaO2 and 17% at 30 Torr). For each level of PaO2, the relationships between the changes that occurred in VO2 and levels of phosphocreatine, ADP, and ATP/ADP.P(i) as the stimulation intensity was increased were significantly correlated; however, the slopes and intercepts of these lines were significantly different for each PaO2. Thus a greater change in any of the proposed regulators of tissue respiration (e.g., phosphocreatine, ADP) was required to achieve a given VO2 as PaO2 was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypoxia potentiates, oxygen attenuates deflation-induced reflex tracheal constriction

The reflex tracheomotor responses of in situ isolated segments of the extrathoracic trachea of anesthetized, paralyzed, and ventilated dogs were monitored. Reflex tracheal constriction was evoked by passive lung deflation. The purpose of this study was to determine whether the prevailing state of oxygenation altered the magnitude of this reflex. Compared with the magnitude of the response during normoxia [arterial O2 tension (PaO2) = 78 Torr], that during hypoxia (PaO2 = 44 Torr) was nearly threefold larger while that during hyperoxia (PaO2 greater than 250 Torr) was about 50% smaller. The isocapnic changes in oxygenation by themselves usually had no effect on tracheomotor tone. The deflation-induced reflex tracheal constriction was eliminated by complete denervation of the tracheal segment but usually only diminished by partial denervation. Bilateral vagotomies or bilateral carotid body denervation also usually decreased the magnitude of the reflex. It appears that the magnitude of this reflex is dependent on the prevailing state of oxygenation and that a pulmonary stretch receptor-carotid body chemoreceptor interaction accounts for the exaggerated reflex tracheal constriction during hypoxia and the attenuated response during hyperoxia.     

Forearm skin and muscle vasoconstriction during lower body negative pressure

In view of conflicting reports of skeletal muscle and skin blood flow participation in baroreceptor-mediated reflexes, we studied the effects of graded lower body negative pressure (LBNP) on cutaneous and muscular components of forearm blood flow (FBF) in seven male subjects at 28 degrees C. FBF was measured by venous occlusion plethysmography and cutaneous flow by laser-Doppler velocimetry, the difference being the muscular flow. Mean FBF decreased by 39 and 56% from control at LBNP of 20 and 50 Torr, respectively. Skin flow decreased linearly with graded LBNP contributing 32% of the decrease of total blood flow at 20 Torr and then 50% of total decrease of blood flow at 50 Torr. Conversely, the decrease in muscle flow represented 68% of the total decrease at LBNP of 20 Torr and then 50% of the total decrease at LBNP of 50 Torr. We concluded that both skin and muscle circulations participate in sustained peripheral vasoconstriction during LBNP, with muscle flow achieving near maximum vasoconstriction by 20 Torr and skin showing a graded vasoconstriction to decreases in LBNP.     

Structural basis of muscle O(2) diffusing capacity: evidence from muscle function in situ.

Although evidence for muscle O(2) diffusion limitation of maximal O(2) uptake has been found in the intact organism and isolated muscle, its relationship to diffusion distance has not been examined. Thus we studied six sets of three purpose-bred littermate dogs (aged 10-12 mo), with 1 dog per litter allocated to each of three groups: control (C), exercise trained for 8 wk (T), or left leg immobilized for 3 wk (I). The left gastrocnemius muscle from each animal was surgically isolated, pump-perfused, and electrically stimulated to peak O(2) uptake at three randomly applied levels of arterial oxygenation [normoxia, arterial PO(2) (Pa(O(2))) 77 +/- 2 (SE) Torr; moderate hypoxia, Pa(O(2)): 33 +/- 1 Torr; and severe hypoxia, Pa(O(2)): 22 +/- 1 Torr]. O(2) delivery (ml. min(-1). 100 g(-1)) was kept constant among groups for each level of oxygenation, with O(2) delivery decreasing with decreasing Pa(O(2)). O(2) extraction (%) was lower in I than T or C for each condition, but calculated muscle O(2) diffusing capacity (Dmus(O(2))) per 100 grams of muscle was not different among groups. After the experiment, the muscle was perfusion fixed in situ, and a sample from the midbelly was processed for microscopy. Immobilized muscle showed a 45% reduction of muscle fiber cross-sectional area (P < 0.05), and a resulting 59% increase in capillary density (P < 0.05) but minimal reduction in capillary-to-fiber ratio (not significant). In contrast, capillarity was not significantly different in T vs. C muscle. The results show that a dramatically increased capillary density (and reduced diffusion distance) after short-term immobilization does not improve Dmus(O(2)) in heavily working skeletal muscle.     

Relationship of venous PO2 to muscle PO2 during hypoxemia

Anesthetized mechanically ventilated rabbits were subjected to progressive hypoxemia (n = 7) to determine the relationship of venous PO2 (PvO2) to skeletal muscle PO2 (PtiO2). Measures of arterial PO2 (PaO2), right atrial PO2 [(PvO2)RA], and hindlimb PO2 [(PvO2)limb], were obtained from the carotid artery, right atrium, and inferior vena cava, just above the level of the iliac bifurcation. Biceps femoris muscle PtiO2 was measured with a surface O2 microelectrode having eight measuring points. PaO2 was decreased from 90.3 +/- 5.4 to 26.8 +/- 0.8 Torr in five consecutive steps, followed by reoxygenation to 105.6 +/- 10.5 (SE) Torr. Measurements were obtained after each decrement in PaO2. A total of 128 measures of PtiO2 were obtained per experimental stage. The mean and distribution of the muscle PtiO2 histogram were determined. Measurements were compared with analysis of variance and the Newman-Keuls post hoc method. (PvO2)limb had similar values as the average muscle PtiO2 (PtiO2) for PaO2 values greater than 52.1 +/- 4.3 Torr, where (PvO2)limb became greater than PtiO2 (P less than 0.05). The lowest measures of (PvO2)limb and PtiO2 were 15.9 +/- 0.7 and 4.0 +/- 0.1 Torr, respectively (P less than 0.01). The PtiO2 histograms showed no evidence of increased microvascular heterogeneity with hypoxemia. We conclude that in hypoxemia PvO2 is greater than muscle PtiO2. This difference may be related to the establishment of significant physicochemical O2 gradients from erythrocyte to tissue cell.     

Adaptation of laser-Doppler flowmetry to measure cerebral blood flow in the fetal sheep.

The purpose of this study was to devise a means to use laser-Doppler flowmetry to measure cerebral perfusion before birth. The method has not been used previously, largely because of intrauterine movement artifacts. To minimize movement artifacts, a probe holder was molded from epoxy putty to the contour of the fetal skull. A curved 18-gauge needle was embedded in the holder. At surgery, the holder, probe, and skull were fixed together with tissue glue. Residual signals were recorded after fetal death and after maternal death 1 h later. These averaged <5% of baseline flow signals, indicating minimal movement artifact. To test the usefulness of the method, cerebral flow responses were measured during moderate fetal hypoxia induced by giving the ewes approximately 10% oxygen in nitrogen to breathe. As fetal arterial PO(2) decreased from 21.1 +/- 0.5 to 10.7 +/- 0.4 Torr during a 30-min period, cerebral perfusion increased progressively to 56 +/- 8% above baseline. Perfusion then returned to baseline levels during a 30-min recovery period. These responses are quantitatively similar to those spot observations that have been recorded earlier using labeled microspheres. We conclude that cerebral perfusion can be successfully measured by using laser-Doppler flowmetry with the unanesthetized, chronically prepared fetal sheep as an experimental model. With this method, relative changes of perfusion from a small volume of the ovine fetal brain can be measured on a continuous basis, and movement artifacts can be reduced to 5% of measured flow values.     

Mechanism of transient nocturnal hypoxemia in hypoxic chronic bronchitis and emphysema

In five patients with hypoxic chronic bronchitis and emphysema we measured ear O2 saturation (SaO2), chest movement, oronasal airflow, arterial and mixed venous gas tensions, and cardiac output during nine hypoxemic episodes (HE; SaO2 falls greater than 10%) in rapid-eye-movement (REM) sleep and during preceding periods of stable oxygenation in non-REM sleep. All nine HE occurred with recurrent short episodes of reduced chest movement, none with sleep apnea. The arterial PO2 (PaO2) fell by 6.0 +/- 1.9 (SD) Torr during the HE (P less than 0.01), but mean arterial PCO2 (PaCO2) rose by only 1.4 +/- 2.4 Torr (P greater than 0.4). The arteriovenous O2 content difference fell by 0.64 +/- 0.43 ml/100 ml of blood during the HE (P less than 0.05), but there was no significant change in cardiac output. Changes observed in PaO2 and PaCO2 during HE were similar to those in four normal subjects during 90 s of voluntary hypoventilation, when PaO2 fell by 12.3 +/- 5.6 Torr (P less than 0.05), but mean PaCO2 rose by only 2.8 +/- 2.1 Torr (P greater than 0.4). We suggest that the transient hypoxemia which occurs during REM sleep in patients with chronic bronchitis and emphysema could be explained by hypoventilation during REM sleep but that the importance of changes in distribution of ventilation-perfusion ratios cannot be assessed by presently available techniques.     

Periodic hemodynamics in skeletal muscle during local arterial pressure reduction.

The time-dependent features of red blood cell flow were evaluated with laser-Doppler flowmetry (LDF) in the left gastrocnemius muscle of 31 anesthetized New Zealand White rabbits during stepwise arterial occlusion. During the control period with a median femoral pressure of 72 mmHg, 29 animals showed minor irregular fluctuations in LDF blood flow, and only two animals displayed periodic variations of blood flow. Lowering femoral arterial pressure induced maximal periodic blood flow variations at a median pressure of 35 mmHg in all animals with a median frequency of 1.5 cycles/min (termed "slow-wave flow motion"). The median amplitude was 48% of the corresponding average flow. These slow waves disappeared at a median femoral pressure of 20 mmHg. The median LDF flow value was 4.00 arbitrary units (AU) at control pressure and 2.05 AU at maximum slow-wave flow motion. When slow-wave flow motion was seen at several pressure levels, their frequency was identical, which supports the local pacemaker concept. This study promotes a novel concept for the role and physiological significance of periodic hemodynamics in that it is a condition not characteristic for normal control situations but is activated below a specific local arterial blood pressure and flow threshold, which is known to be the lower end of autoregulation in the microcirculation of rabbit skeletal muscle. This also suggests that slow-wave flow motion is primarily under local control mechanisms.     

Effect of acute normovolemic hemodilution on distribution of blood flow and tissue oxygenation in dog skeletal muscle.

Acute normovolemic hemodilution (ANH) is efficient in reducing allogenic blood transfusion needs during elective surgery. Tissue oxygenation is maintained by increased cardiac output and oxygen extraction and, presumably, a more homogeneous tissue perfusion. The aim of this study was to investigate blood flow distribution and oxygenation of skeletal muscle. ANH from hematocrit of 36 +/- 3 to 20 +/- 1% was performed in 22 splenectomized, anesthetized beagles (17 analyzed) ventilated with room air. Normovolemia was confirmed by measurement of blood volume. Distribution of perfusion within skeletal muscle was determined by using radioactive microspheres. Tissue oxygen partial pressure was assessed with a polarographic platinum surface electrode. Cardiac index (3.69 +/- 0.79 vs. 4.79 +/- 0.73 l. min-1. m-2) and muscle perfusion (4.07 +/- 0.44 vs. 5.18 +/- 0.36 ml. 100 g-1. min-1) were increased at hematocrit of 20%. Oxygen delivery to skeletal muscle was reduced to 74% of baseline values (0.64 +/- 0.06 vs. 0.48 +/- 0.03 ml O2. 100 g-1. min-1). Nevertheless, tissue PO2 was preserved (27.4 +/- 1.3 vs. 29.9 +/- 1. 4 Torr). Heterogeneity of muscle perfusion (relative dispersion) was reduced after ANH (20.0 +/- 2.2 vs. 13.9 +/- 1.5%). We conclude that a more homogeneous distribution of perfusion is one mechanism for the preservation of tissue oxygenation after moderate ANH, despite reduced oxygen delivery.     

Normocapnic high-frequency oscillatory ventilation affects differently extrapulmonary and pulmonary forms of acute respiratory distress syndrome in adults

The recently reported differences between pulmonary and extrapulmonary acute respiratory distress syndromes (ARDS(p), ARDS(exp)) are the main reasons of scientific discussion on potential differences in the effects of current ventilatory strategies. The aim of this study is to assess whether the presence of ARDS(p) or ARDS(exp) can differently affect the beneficial effects of high-frequency oscillatory ventilation (HFOV) upon physiological and clinical parameters. Thirty adults fulfilling the ARDS criteria were indicated for HFOV in case of failure of conventional ventilation strategy. According to the ARDS type, each patient was included either in the group of patients with ARDS(p) or ARDS(exp). Six hours after normocapnic HFOV introduction, there was no significant increase in PaO2/F(I)O2 in ARDS(p) group (from 129+/-47 to 133+/-50 Torr), but a significant improvement was found in ARDS(exp) (from 114+/-54 to 200+/-65 Torr, p<0.01). Despite the insignificant difference in the latest mean airway pressure (MAP) on conventional mechanical ventilation (CMV) between both groups, initial optimal continuous distension pressure (CDP) for the best PaO2/F(I)O2 during HFOV was 2.0+/-0.6 kPa in ARDS(p) and 2.8+/-0.6 kPa in ARDS(exp) (p<0.01). HFOV recruits and thus it is more effective in ARDS(exp). ARDS(exp) patients require higher CDP levels than ARDS(p) patients. The testing period for positive effect of HFOV is recommended not to be longer than 24 hours.     

Effect of hemoglobin concentration on maximal O2 uptake in canine gastrocnemius muscle in situ

O2 delivery to maximally working muscle was decreased by altering hemoglobin (Hb) concentration and arterial PO2 (PaO2) to investigate whether the reductions in maximal O2 uptake (VO2max) that occur with lowered [Hb] are in part related to changes in the effective muscle O2 diffusing capacity (DmO2). Two sets of experiments were conducted. In the initial set (n = 8), three levels of Hb [5.8 +/- 0.3, 9.4 +/- 0.1, and 14.4 +/- 0.6 (SE) g/100 ml] in the blood were used in random order to pump perfuse, at equal muscle blood flows and PaO2, maximally working isolated dog gastrocnemius muscle. VO2max declined with decreasing [Hb], but the relationship between VO2max and both the effluent venous PO2 (PvO2) and the calculated mean capillary PO2 (PcO2) was not linear through the origin and, therefore, not compatible with a single value of DmO2 (as calculated by Bohr integration using a model based on Fick's law of diffusion). To clarify these results, a second set of experiments (n = 6) was conducted in which two levels of Hb (14.0 +/- 0.6 and 6.9 +/- 0.6 g/100 ml) were each combined with two levels of oxygenation (PaO2 79 +/- 8 and 29 +/- 2 Torr) and applied in random sequence to again pump perfuse maximally working dog gastrocnemius muscle at constant blood flow. In these experiments, the relationship between VO2max and both PvO2 and calculated PcO2 for each [Hb] was consistent with a constant estimate of DmO2 as PaO2 was reduced, but the calculated DmO2 for the lower [Hb] was 33% less than that at the higher [Hb] (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Different responses in skin and muscle sympathetic nerve activity to static muscle contraction

We microneurographically recorded the traffic of sympathetic nerves leading to foot volar skin activity (SSA) and leg skeletal muscle activity (MSA) during isometric handgrip and simultaneously determined sweat rate by the ventilated capsule method and skin blood flow by laser-Doppler flowmetry in the innervating area of SSA. SSA increased abruptly and was almost constant during handgrip, accompanied by an increase in sweat rate, whereas skin blood flow showed no significant change during the handgrip. MSA showed a time-dependent increase during the course of handgrip. During arterial occlusion of the working forearm after handgrip, SSA decayed to the precontraction control level, whereas MSA remained at a higher level than during control. During involuntary biceps muscle contraction induced by electrical stimulation, both SSA and MSA increased. The results suggest that the SSA response during voluntary handgrip, which was demonstrated to contain mainly sudomotor activity, might be influenced by central command and input from peripheral mechanoreceptors but be influenced little by input from muscle chemoreceptors.     

Effects of acute hyperbaric oxygenation on respiratory control in cats

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.     

Ventilatory effects of acetazolamide in cats during hypoxemia.

In normoxemic cats, acetazolamide (ACTZ) has been shown to cause a large rise in ventilation (VE) but a decrease in peripheral chemoreceptor activity. The relative contribution of the peripheral chemoreceptors to ventilation is higher during hypoxemia than during normoxemia. Therefore, what are the effects of ACTZ during steady-state hypoxemia? The aims of this study in anesthetized cats were 1) to study the effect of ACTZ (50 mg/kg iv) on mean hypoxemic [arterial PO2 (PaO2) approximately 6 kPa] ventilation and 2) to study the effect of ACTZ on the isocapnic hypoxic ventilatory response. In the first study, in six cats with an inspiratory CO2 fraction of 0, ACTZ led to an insignificant rise in mean VE of 119 ml.min-1.kg-1 after 1 h. In five other cats maintained at an inspiratory CO2 fraction of 0.015, ACTZ resulted in a significantly larger response in VE (268 and 373 ml.min-1.kg-1 after 1 and 2 h, respectively). In the second study, before infusion in five cats, an isocapnic fall in mean PaO2 from 13 to 4.7 kPa led to a significant rise in mean VE of 385 ml.min-1.kg-1; 1 h later, the response (at the same mean alveolar PCO2) was reduced to an insignificant rise of 38 ml.min-1.kg-1. Before infusion four other cats showed a significant rise in mean VE of 390 ml.min-1.kg-1 when mean PaO2 was lowered isocapnically from 12.4 to 6.8 kPa; 2 h after infusion, an isocapnic fall in mean PaO2 from 13.9 to 7.2 kPa led to an insignificant rise of 112 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Operation Everest II: adaptations in human skeletal muscle

Adaptations in skeletal muscle in response to progressive hypobaria were investigated in eight male subjects [maximal O2 uptake = 51.2 +/- 3.0 (SE) ml.kg-1.min-1] over 40 days of progressive decompression to the stimulated altitude of the summit of Mt. Everest. Samples of the vastus lateralis muscle extracted before decompression (SL-1), at 380 and 282 Torr, and on return to sea level (SL-2) indicated that maximal activities of enzymes representative of the citric acid cycle, beta-oxidation, glycogenolysis, glycolysis, glucose phosphorylation, and high-energy phosphate transfer were unchanged (P greater than 0.05) at 380 and 282 Torr over initial SL-1 values. After exposure to 282 Torr, however, representing an additional period of approximately 7 days, reductions (P less than 0.05) were noted in succinic dehydrogenase (21%), citrate synthetase (37%), and hexokinase (53%) between SL-2 and 380 Torr. No changes were found in the other enzymes. Capillarization as measured by the number of capillaries per cross-sectional area (CC/FA) was increased (P less than 0.05) in both type I (0.94 +/- 0.8 vs. 1.16 +/- 0.05) and type II (0.84 +/- 0.07 vs. 1.05 +/- 0.08) fibers between SL-1 and SL-2. This increase was mediated by a reduction in fiber area. No changes were found in fiber-type distribution (type I vs. type II). These findings do not support the hypothesis, at least in humans, that, at the level of the muscle cell, extreme hypobaric hypoxia elicits adaptations directed toward maximizing oxidative function.     

Effects of hypercarbia on arterial and alveolar oxygen tensions in a model of gram-negative pneumonia

Inspired CO2 causing changes from hypo- to normocapnia has previously been shown to improve arterial O2 tension (PaO2) and to reduce alveolar-arterial O2 difference. The effect of further increases in inspired CO2 to hypercarbic levels has not been studied in inflammatory lung disease. Three days after induction of sublobar Pseudomonas pneumonia, Suffolk sheep were anesthetized and ventilated with a fixed-volume ventilator. After 2.5 h, CO2 was added to the inspired gas to raise arterial CO2 tension (PaCO2) to 60-65 Torr. Four hours later the CO2 was withdrawn and ventilation continued for an additional 2 h. Constant minute ventilation and inspired O2 fraction were maintained. Regional lung perfusion was measured by injection of radioactive microspheres. With the administration of CO2, PaO2 increased significantly from 65.5 to 77.5 Torr as did alveolar O2 tension (from 109.7 to 120.0 Torr) with no significant change in alveolar-arterial O2 difference. There were no significant changes in cardiac output, shunt fraction, O2 uptake, O2 delivery, respiratory quotient, or distribution of regional lung perfusion. We conclude that the increases in alveolar O2 tension and PaO2 with the added CO2 resulted from improved alveolar ventilation.     

A modular NIRS system for clinical measurement of impaired skeletal muscle oxygenation.

Near-infrared spectrometry (NIRS) is a well-known method used to measure in vivo tissue oxygenation and hemodynamics. This method is used to derive relative measures of hemoglobin (Hb) + myoglobin (Mb) oxygenation and total Hb (tHb) accumulation from measurements of optical attenuation at discrete wavelengths. We present the design and validation of a new NIRS oxygenation analyzer for the measurement of muscle oxygenation kinetics. This design optimizes optical sensitivity and detector wavelength flexibility while minimizing component and construction costs. Using in vitro validations, we demonstrate 1) general optical linearity, 2) system stability, and 3) measurement accuracy for isolated Hb. Using in vivo validations, we demonstrate 1) expected oxygenation changes during ischemia and reactive hyperemia, 2) expected oxygenation changes during muscle exercise, 3) a close correlation between changes in oxyhemoglobin and oxymyoglobin and changes in deoxyhemoglobin and deoxymyoglobin and limb volume by venous occlusion plethysmography, and 4) a minimal contribution from movement artifact on the detected signals. We also demonstrate the ability of this system to detect abnormal patterns of tissue oxygenation in a well-characterized patient with a deficiency of skeletal muscle coenzyme Q(10). We conclude that this is a valid system design for the precise, accurate, and sensitive detection of changes in bulk skeletal muscle oxygenation, can be constructed economically, and can be used diagnostically in patients with disorders of skeletal muscle energy metabolism.     

Effect of hypoxia on responses of respiratory smooth muscle to histamine and LTD4

The aim of the present study was to compare the effect of reduced oxygenation on the contractions of pulmonary vascular and airway smooth muscle induced by leukotriene D4 (LTD4) with those induced by histamine (an agonist with similar mechanisms of smooth muscle contraction) and KCl (a voltage-dependent stimulus). During hypoxia (PO2: 40 +/- 4 Torr) the responses of isolated porcine pulmonary artery and vein spiral strips to LTD4 increased approximately three- and two-fold, respectively, and the vein also exhibited an augmented response to histamine. The augmentation was blunted (LTD4) or reversed (histamine) during anoxia (PO2: 0 +/- 2 Torr). Responses to KCl were not systematically altered by reduced oxygenation. In contrast, the contractions of the guinea pig parenchymal lung strip by all three agonists were generally suppressed by reduced oxygenation. After reoxygenation, the contractile responses of each of the three smooth muscle preparations were generally increased compared with previous and concurrent base-line observations, particularly the LTD4-induced pulmonary vein contraction that increased approximately sevenfold after reoxygenation after anoxia. The contribution (if any) of leukotrienes to hypoxic pulmonary vasoconstriction may reflect increased vascular responsiveness to leukotrienes during hypoxia as well as (or instead of) increased leukotriene release.