Tissue carbon dioxide tension: a putative specific indicator of ischemia in porcine latissimus dorsi flaps

Free flap surgical procedures are technically challenging, and anastomosis failure may lead to arterial or venous occlusion and flap necrosis. To improve myocutaneous flap survival rates, more reliable methods to detect ischemia are needed. On the basis of theoretical considerations, carbon dioxide tension, reflecting intracellular acidosis, may be suitable indicators of early ischemia. It was hypothesized that tissue carbon dioxide tension increased rapidly when metabolism became anaerobic and would be correlated with acute venoarterial differences in lactate levels, potassium levels, and acid-base parameters. Because metabolic disturbances have been observed to be less pronounced in flaps with venous occlusion, it was hypothesized that tissue carbon dioxide tension and venoarterial differences in lactate and potassium levels and acid-base parameters would increase less during venous occlusion than during arterial occlusion. In 14 pigs, latissimus dorsi myocutaneous flaps were surgically isolated, exposed to acute ischemia for 150 minutes with complete arterial occlusion (seven subjects) or venous occlusion (seven subjects), and reperfused for 30 minutes. After arterial occlusion, pedicle blood flow decreased immediately to less than 10 percent of baseline flow. Blood flow decreased more slowly after venous occlusion but within 3 minutes reached almost the same low levels as observed during arterial occlusion. Venous oxygen saturation decreased from approximately 70 percent to approximately 20 percent, whereas oxygen uptake was almost arrested. Tissue carbon dioxide tension increased to two times baseline values in both groups (p < 0.01). The venoarterial differences in carbon dioxide tension, pH, base excess, glucose levels, lactate levels, and potassium levels increased significantly (p < 0.01). Tissue carbon dioxide tension measured during the occlusion period were closely correlated with venoarterial differences in pH, base excess, glucose levels, lactate levels, and potassium levels (median r2, 0.67 to 0.92). After termination of arterial or venous occlusion, more pronounced hyperemia was observed in the arterial occlusion group than in the venous occlusion group (p < 0.05). Oxygen uptake (p < 0.05) and venoarterial differences in lactate and potassium levels (p < 0.05) were significantly more pronounced in the arterial occlusion group. In the venous occlusion group, with less pronounced hyperemia, venoarterial differences in acid-base parameters remained significantly different from baseline values before occlusion (p < 0.01). The data indicate that tissue carbon dioxide tension can be used to detect anaerobic metabolism, caused by arterial or venous occlusion, in myocutaneous flaps. The correlations between carbon dioxide tension and venoarterial differences in acid-base parameters were excellent. Because carbon dioxide tension can be measured continuously in real time, such measurements are more likely to represent a clinically useful parameter than are venoarterial differences.     

Ventilatory responses to carbon dioxide at low and high levels of oxygen are elevated after episodic hypoxia in men compared with women.

We hypothesized that the acute ventilatory response to carbon dioxide in the presence of low and high levels of oxygen would increase to a greater extent in men compared with women after exposure to episodic hypoxia. Eleven healthy men and women of similar race, age, and body mass index completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the end-tidal partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr), or high oxygen gas mixture (150 Torr). During the trials, PetCO2 increased while the selected level of oxygen was maintained. The point at which minute ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the carbon dioxide set point. The ventilatory response below and above this point was determined. The results showed that the ventilatory response to carbon dioxide above the set point was increased in men compared with women before exposure to episodic hypoxia, independent of the oxygen level that was maintained during the rebreathing trials (50 Torr: men, 5.19 +/- 0.82 vs. women, 4.70 +/- 0.77 l x min(-1) x Torr(-1); 150 Torr: men, 4.33 +/- 1.15 vs. women, 3.21 +/- 0.58 l x min(-1) x Torr(-1)). Moreover, relative to baseline measures, the ventilatory response to carbon dioxide in the presence of low and high oxygen levels increased to a greater extent in men compared with women after exposure to episodic hypoxia (50 Torr: men, 9.52 +/- 1.40 vs. women, 5.97 +/- 0.71 l x min(-1) x Torr(-1); 150 Torr: men, 5.73 +/- 0.81 vs. women, 3.83 +/- 0.56 l x min(-1) x Torr(-1)). Thus we conclude that enhancement of the acute ventilatory response to carbon dioxide after episodic hypoxia is sex dependent.     

Effect of increased gas density on pulmonary gas exchange in man.

Pulmonary gas exchange was measured in seven resting supine subjects breathing air or a dense gas mixture containing 21% O2 in sulfur hexafluoride (SF6). The mean value of the alveolar-arterial oxygen difference (AaDO2) decreased from 12.4 on air to 7.0 on SF6 (P less than 0.01), and increased again to 13.4 when air breathing resumed (P less than 0.01). No differences occurred between gas mixtures for O2 consumption, respiratory quotient, minute ventilation, breathing frequency, heart rate, or blood pressure, and the improved oxygen transfer could not be attributed to changes in cardiac output or mixed venous oxygen content in the one subject in which they were measured. These results are best explained by an altered distribution of ventilation during dense gas breathing, so that the ventilation-perfusion ratio (VA/Q) variance was reduced. Of several considered mechanisms, we favor one in which SF6 promotes cardiogenic gas mixing between peripheral parallel units having different alveolar gas concentrations. This mechanism allows for observed increases in arterial carbon dioxide tension and dead space-to-tidal volume ratio during dense gas breathing, and suggests that intraregional VA/Q variance accounts for at least one-half of the resting AaDO2 in healthy supine young men.     

Metabolic and respiratory effects of flow-resistive loading in preterm infants

Oxygen consumption (VO2) was measured during hypoventilation induced by moderate-sized flow-resistive loading in 12 preterm infants, and the results were compared with those obtained under basal conditions immediately before and after the loaded run, each of which lasted for 7-10 min. Loading was performed with a continuous flow-resistive load (inspiratory and expiratory), which was approximately threefold greater in magnitude than the intrinsic resistance of preterm infants. VO2, minute ventilation (VE), transcutaneous oxygen tension (PtCO2), and transcutaneous carbon dioxide tension (PtcCO2) were continuously monitored. Results revealed that VE decreased significantly with loading, from 336 +/- 103 to 231 +/- 58 (SD) ml.min-1.kg-1 (P less than 0.001), while returning to basal levels of 342 +/- 59 ml.min-1.kg-1 after discontinuation of the load. VO2 decreased from 7.2 +/- 1.2 to 5.9 +/- 0.9 ml.min-1.kg-1 with loading (P less than 0.001) and returned to 7.2 +/- 1.2 ml.min-1.kg-1 at the second basal measurement. PtcCO2 remained unchanged with loading, and PtcCO2 only increased from 39 +/- 8 to 41 +/- 9 Torr (P less than 0.05) with loading, while returning to 40 +/- 9 Torr at the second basal measurement. Results indicate a decrease in the metabolic rate and ventilation with loading, with relatively little increase in PtcCO2. These data can explain prior observations that minimal disturbances in oxygen and carbon dioxide tensions occur with hypoventilation during flow-resistive loading in neonates, although the precise mechanism for this reduction remains to be determined.     

Arterial hypoxia does not affect subchondral pressure and regional blood flow

The influence of arterial hypoxia on bone marrow pressure, regional blood flow and oxygen and carbon dioxide tensions was investigated by simultaneous and continuous measurements in the femoral condyles of 8 rabbits. Arterial hypoxia was obtained by hypoventilation. The subchondral gas tensions and regional blood flow were measured by a previously described technique based on mass spectrometry. Arterial hypoxia caused a significant decrease in subchondral oxygen tension and an increase in subchondral carbon dioxide tension. There was no significant change in bone marrow pressure and regional blood flow.     

Metabolic changes during phosphate deprivation in Englena in air and in oxygen

1. Euglena cells were grown in culture media containing either 20mm-phosphate or 20mum-phosphate, with ethanol or glucose as the sole source of carbon, and gassed with either air+carbon dioxide (95:5) or oxygen+carbon dioxide (95:5) at atmospheric pressure. 2. After growth in low-phosphate medium with ethanol as substrate, the cells developed signs of oxygen toxicity, as indicated by a decreased rate of respiration, a decreased net synthesis of paramylum and a failure to resume growth on replenishment of phosphate. 3. After growth in low-phosphate medium with glucose as substrate, the signs of oxygen toxicity were less apparent. 4. During phosphate deprivation the carotenoid content of Euglena increased more than threefold. This increase was largely prevented by exposure of the cells to oxygen+carbon dioxide (95:5) during growth. Oxygenation appears to interfere with ring closure of the common carotenoid precursor. 5. Mitochondria obtained from Euglena exposed to oxygen during phosphate deprivation, i.e. when signs of oxygen toxicity were evident, had greatly decreased activities of succinate dehydrogenase, succinate-cytochrome c oxidoreductase and NADH-cytochrome c oxidoreductase, compared with mitochondria obtained from Euglena exposed to oxygen in medium containing 20mm-phosphate.     

Arterial Blood Gas Tensions and pH in Acute Asthma in Childhood

Studies of the arterial blood gas tensions and pH in 21 children during 24 acute attacks of asthma showed that all were hypoxic on admission to hospital, and in 10 there was evidence of carbon dioxide retention. Cyanosis, invariably present when the So₂ was below 85%, and restlessness in patients breathing air were the most reliable indices of the severity of hypoxia. There were no reliable clinical guides to the Pco₂ level. Conventional oxygen therapy in tents (25–40%) did not always relieve hypoxia, and in three cases the administration of oxygen at a concentration of 40% or over failed to produce a normal arterial oxygen tension. Uncontrolled oxygen therapy may aggravate respiratory acidosis, and three of our patients developed carbon dioxide narcosis while breathing oxygen. The necessity for blood gas measurements in the management of severe acute asthma in childhood is emphasized.     

Instability of the Middle Cerebral Artery Blood Flow in Response to CO2

Background

The middle cerebral artery supplies long end-artery branches to perfuse the deep white matter and shorter peripheral branches to perfuse cortical and subcortical tissues. A generalized vasodilatory stimulus such as carbon dioxide not only results in an increase in flow to these various tissue beds but also redistribution among them. We employed a fast step increase in carbon dioxide to detect the dynamics of the cerebral blood flow response.

Methodology/Principal Findings

The study was approved by the Research Ethics Board of the University Health Network at the University of Toronto. We used transcranial ultrasound to measure the time course of middle cerebral artery blood flow velocity in 28 healthy adults. Normoxic, isoxic step increases in arterial carbon dioxide tension of 10 mmHg from both hypocapnic and normocapnic baselines were produced using a new prospective targeting system that enabled a more rapid step change than has been previously achievable. In most of the 28 subjects the responses at both carbon dioxide ranges were characterised by more complex responses than a single exponential rise. Most responses were characterised by a fast initial response which then declined rapidly to a nadir, followed by a slower secondary response, with some showing oscillations before stabilising.

Conclusions/Significance

A rapid step increase in carbon dioxide tension is capable of inducing instability in the cerebral blood flow control system. These dynamic aspects of the cerebral blood flow responses to rapid changes in carbon dioxide must be taken into account when using transcranial blood flow velocity in a single artery segment to measure cerebrovascular reactivity.     

祁连山东段高原鼢鼠采食洞道气体研究

研究高原鼢鼠（Myospalax baileyi）洞道气体环境对了解其低氧适应机制具有重要作用。本试验在祁连山东段高寒草甸利用土壤原位气体测定仪,对高原鼢鼠采食活动洞道、非活动洞道、地表空气及无洞道土壤内的温度、氧气、二氧化碳、甲烷含量进行了连续12个月的监测。通过One-Way ANOVA检验、重复测量方差分析以及Pearson相关性分析发现,（1）高原鼢鼠活动洞道氧气含量,除10月、11月与非活动洞道无显著性差异外（P>0.05）,均显著小于非活动洞道、地表空气和无洞道土壤（P<0.05）;活动洞道二氧化碳含量,除7月、8月份与非活动洞道无显著性差异外（P>0.05）,均显著大于非活动洞道、地表空气和无洞道土壤（P<0.05）;活动洞道内甲烷含量各月均显著高于地表空气甲烷含量（P<0.05）,与非活动洞道、无洞道土壤的月季差异各异。（2）高原鼢鼠活动洞道内氧气含量的最小值和二氧化碳的最大值均出现在5月和9月,其它处理下氧气最小值和二氧化碳最大值均出现在6-8月;4个处理下甲烷含量最小值在1月与12月出现,最大值出现在5月和9月。（3）月份、处理以及月份和处理间的交互作用均对氧气、二氧化碳、甲烷含量有显著影响（P<0.05）。可见,高原鼢鼠生存在低氧、高二氧化碳和较高甲烷含量的环境中,且洞道内部的气体环境会受季节和高原鼢鼠活动的影响。     

Cerebral Oxygen Saturation: Graded Response to Carbon Dioxide with Isoxia and Graded Response to Oxygen with Isocapnia

Background

Monitoring cerebral saturation is increasingly seen as an aid to management of patients in the operating room and in neurocritical care. How best to manipulate cerebral saturation is not fully known. We examined cerebral saturation with graded changes in carbon dioxide tension while isoxic and with graded changes in oxygen tension while isocapnic.

Methodology/Principal Findings

The study was approved by the Research Ethics Board of the University Health Network at the University of Toronto. Thirteen studies were undertaken in healthy adults with cerebral oximetry by near infrared spectroscopy. End-tidal gas concentrations were manipulated using a model-based prospective end-tidal targeting device. End-tidal carbon dioxide was altered ±15 mmHg from baseline in 5 mmHg increments with isoxia (clamped at 110±4 mmHg). End-tidal oxygen was changed to 300, 400, 500, 80, 60 and 50 mmHg under isocapnia (37±2 mmHg). Twelve studies were completed. The end-tidal carbon dioxide versus cerebral saturation fit a linear relationship (R² = 0.92±0.06). The end-tidal oxygen versus cerebral saturation followed log-linear behaviour and best fit a hyperbolic relationship (R² = 0.85±0.10). Cerebral saturation was maximized in isoxia at end-tidal carbon dioxide of baseline +15 mmHg (77±3 percent). Cerebral saturation was minimal in isocapnia at an end-tidal oxygen tension of 50 mmHg (61±3 percent). The cerebral saturation during normoxic hypocapnia was equivalent to normocapnic hypoxia of 60 mmHg.

Conclusions/Significance

Hypocapnia reduces cerebral saturation to an extent equivalent to moderate hypoxia.     

Characteristics of ventilatory control during exercise in coronary heart disease patients

The relationship between the carbon dioxide ventilatory equivalent and hemodynamic parameters during exercise was studied in healthy subjects and coronary heart disease (CHD) patients. Gas exchange, ventilatory control, and central hemodynamics during graded exercise were analyzed in 85 subjects, including 32 healthy subjects and 53 CHD patients. Twenty-seven CHD patients had coronary insufficiency but not heart failure and had a left ventricle ejection fraction of ≥50%; 26 patients had chronic heart failure and an ejection fraction of <40%. A high carbon dioxide ventilatory equivalent and its disturbed response (a decrease below 20%) with an increase in physical load, which reflects an imbalance of ventilatory control with decreased parameters of maximum oxygen consumption and hemodynamics, allows the ventilatory equivalent to be used as a marker for stratifying CHD patients with chronic heart failure.     

The effects of acute hypoxia and hypercapnia on oxygen consumption of the freshwater European eel

When exposed to hypoxia, eels Anguilla anguilla were able to regulate and maintain Vo₂ down to a water oxygen tension ( Pwo₂ ) of about 25 mmHg, a value far below those reported in other studies. When exposed to hypercapnia, eels showed a depression in Vo₂ as water carbon dioxide tension ( Pwco₂ ) increased. Faced with combined hypoxia-hypercapnia, eels showed an increase in their sensitivity to hypoxia, and the critical oxygen tension increased to 40–45 mmHg. The possible mechanisms underlying these responses were discussed, and the implications of such findings for extensive culture of eels were highlighted.     

Adrenergic involvement in blood oxygen transport and acid-base balance during hypercapnic acidosis in the Rainbow Trout,Salmo gairdneri

Summary Rainbow trout (Salmo gairdneri) were subjected to 12 h of external hypercapnia (1% CO₂ in air) during - and/or -adrenoceptor blockade in order to assess the importance of adrenergic responses in modulating blood oxygen transport and acid-base balance during an acute acidotic stress. External hypercapnia caused an elevation of blood carbon dioxide tension and a reciprocal decrease in whole blood pH. A gradual elevation of blood bicarbonate levels caused whole blood pH to increase toward pre-hypercapnic values throughout the hypercapnic period. Pre-treatment of fish with propranolol (a -adrenoceptor antagonist) or phentolamine (an -adrenoceptor antagonist) did not affect their ability to regulate extracellular acid-base status during hypercapnia. On the other hand, adrenergic responses were essential in the maintenance of arterial blood oxygen content during hypercapnia despite the severe extracellular acidosis and a marked Root effect in trout blood, in vitro. Important adrenergic responses included pronounced increases in haematocrit (an -adrenergic effect) and arterial oxygen tension (- and -adrenergic effects) as well as partial regulation of red blood cell pH (a -adrenergic effect). Although pre-treatment of fish with either propranolol or phentolamine caused a reduction in blood oxygen content during hypercapnia, fish died only during complete adrenoceptor blockade, presumably due to severe hypoxemia.Symbols and abbreviations total concentration of oxygen or carbon dioxide, respectively - hct haemotocrit - rbc red blood cell     

Negative arterial-mixed expired PC02 gradient during acute and chronic hypercapnia.

In resting conscious dogs physiological dead space was calculated using the Bohr equation and measurements of arterial and mixed expired carbon dioxide tension. Whenever dogs inhaled carbon dioxide mixtures (5-10%) that had normal or low oxygen concentrations, the calculated dead space became negative. This paradox was based on the fact that the mixed expired carbon dioxide tension in resting hypercapnic dogs. Under these circumstances carbon dioxide was produced from the lung as measured by gas analyses and blood analyses. By the lung as measured by gas analyses and blood analyses. By reasoning this implies that "alveolar" carbon dioxide tension was higher than pulmonary venous carbon dioxide tension. The negative carbon dioxide gradient persisted at 14 days of chronic hypercapnia and reverted to normal within 10 min of breathing air after chronic hypercapnia. These findings suggest that the exchange of carbon dioxide in the lung cannot be explained solely on the basis of passive diffusion.     

THE SURVIVAL OF RAINBOW TROUT (SALMO GAIRDNERII RICHARDSON) AND PERCH (PERCA FLUVIATILIS L.) AT VARIOUS CONCENTRATIONS OF DISSOLVED OXYGEN AND CARBON DIOXIDE

The relative importance of dissolved oxygen and dissolved carbon dioxide in determining the lethal effect of an environment for rainbow trout and perch has been investigated with an apparatus which controls the concentrations of these gases in a body of water. It is shown that concentrations of carbon dioxide which sometimes occur in polluted streams can more than double the minimum concentration of dissolved oxygen necessary for the survival of half a population of rainbow trout fingerlings for 24 hr. Increase in temperature between 12·5 and 19·5°C. shortens period of survival in solutions containing up to 67 p. p. m. CO₂. Within the range of dissolved oxygen concentration which is lethal in the presence of 59 p. p. m. CO₂ or more, perch are more resistant than rainbow trout in the lower, but less resistant in the higher, oxygen concentrations. The relation between carbon dioxide concentration and the oxygen tension at which rainbow trout blood is half saturated with oxygen is similar to the relation between carbon dioxide concentration and the oxygen tension at which the median period of survival of this species is I hr.     

Participations of Iron and Flavin Adenine Dinucleotide on the Enzymatic Hydroxylation of p-Hydroxybenzoate.

The effects of oxygen and carbon dioxide in inosine fermentation were investigated from the industrial viewpoint. Oxygen supply at the rate of more than 5 × 10^-7 mole/ml-min was indispensable for maintaining the high productivity of inosine in jar fermentors as well as in shaking flasks. Oxygen deficiency due to insufficient oxygen supply, on the other hand, resulted in the inhibition of inosine production, even though glucose added to the medium was entirely assimilated. In addition to sufficient oxygen supply ventilation was also indispensable since an increased tension of carbon dioxide reduced the inosine-producing capability of the cells.     

Middle cerebral artery flow velocity and blood flow during exercise and muscle ischemia in humans.

Changes in middle cerebral artery flow velocity (Vmean), measured by transcranial Doppler ultrasound, were used to determine whether increases in mean arterial pressure (MAP) or brain activation enhance cerebral perfusion during exercise. We also evaluated the role of "central command," mechanoreceptors, and/or muscle "metaboreceptors" on cerebral perfusion. Ten healthy subjects performed two levels of dynamic exercise corresponding to a heart rate of 110 (range 89-134) and 148 (129-170) beats/min, respectively, and exhaustive one-legged static knee extension. Measurements were continued during 2-2.5 min of muscle ischemia. MAP increased similarly during static [114 (102-133) mmHg] and heavy dynamic exercise [121 (104-136) mmHg] and increased during muscle ischemia after dynamic exercise. During heavy dynamic exercise, Vmean increased 24% (10-47%; P less than 0.01) over approximately 3 min despite constant arterial carbon dioxide tension. In contrast, static exercise with a higher rate of perceived exertion [18 (13-20) vs. 15 (12-18) units; P less than 0.01] was associated with no significant change in Vmean. Muscle ischemia after exercise was not associated with an elevation in Vmean, and it did not provoke an increase in Vmean after static exercise. Changes in Vmean during exercise were similar to those recorded with the initial slope index of the 133Xe clearance method. The data show that middle cerebral artery mean flow velocity reflects changes in cerebral perfusion during exercise. Furthermore, they support the hypothesis that cerebral perfusion during exercise reflects an increase in brain activation that is independent of MAP, central command, and muscle metaboreceptors but is likely to depend on influence of mechanoreceptors.     

Effect of Oxygen on the Rate of Photorespiration in Detached Tobacco Leaves

The rate of carbon dioxide exchange in both light and darkness by detached tobacco leaves placed at various oxygen concentrations was measured by an Infra-Red CO₂ Analyzer and a Clark oxygen electrode. It was observed that during illumination oxygen had two different effects. One was to stimulate carbon dioxide evolution and the other to inhibit carbon dioxide absorption. Concentration of carbon dioxide at compensation point was found to be a linear function of oxygen concentration and this has been explained as due mainly to an increased evolution of carbon dioxide. Such an evolution during illumination has been called photorespiration. Increased concentrations of oxygen also had a stimulating effect on the magnitude of the initial post-illumination burst of carbon dioxide in darkness, but no effect on the subsequent steady rates. These data have been explained as due to the suspension of regular respiration in darkness and its replacement by a different process, tentatively called photorespiration. A second effect of oxygen was to reduce the efficiency (called “carboxylation efficiency”) with which a leaf was able to remove carbon dioxide from the atmosphere.     

Serum glucose level in severe acute exogenous normobaric hypoxia in humans at rest

The study of the effect of acute normobaric hypoxia, which was simulated by inhalation of the oxygen-nitrogen mixture containing 8% of oxygen, which corresponds to its partial pressure at an altitude of 7000 m above sea level, was conducted in a group of apparently healthy men (aged 19–23 years, n = 10). The biochemical analysis during the test included determining the glucose, pyruvate, and lactate levels in venous blood; the hemoglobin content, pH, hematocrit, partial oxygen and carbon dioxide pressures, and hemoglobin saturation with oxygen. It was shown that, at the fifth minute of hypoxia, the serum glucose level decreased significantly (p < 0.05) compared to the background. However, on the whole, the maximal glucose level decrease was 0.76 mM, and the lowest individual parameter values did not decrease below 4.0 mM. The serum glucose level was restored to the background values at the tenth minute of testing. It was suggested that the syncopal form of altitude hypoxia in humans is unlikely to be linked to the development of hypoglycemia.     

Chronic stable asthma and the normal arterial pressure of carbon dioxide in hypoxia.

Arterial blood-gas tensions, pH, and peak expiratory flow rate were measured in 29 patients with chronic asthma in a stable state. The hypoxia in these patients was found to be comparable with the hypoxia seen in normal subjects at high altitude in its effects on arterial pressure of carbon dioxide (PaCO2). These results suggest that in patients with asthma the PaCO2 taken as normal should be related to the arterial oxygen tension. Any increase in the observed value compared with this predicted value indicates impaired respiratory control. This may well help in assessing the patients at greatest risk during an attack of asthma.