Effects of naloxone on pethidine-induced neonatal depression. Part II--Intramuscular naloxone.

Thirty full-term infants whose mothers had had pethidine during labour were given either naloxone 200 microgram or normal saline intramuscularly. The drugs were chosen blindly and administered within one minute of birth. Naloxone produced a significant reduction in mean alveolar carbon dioxide tension and an increase in carbon dioxide excretion and mean alveolar ventilation at all times up to 48 hours after birth. The mean rate of habituation to a repeated auditory stimulus, the mean sucking frequency, the sucking pressure, and the mean consumption of milk were all significantly higher in the naloxone-treated group than in the placebo-treated group up to 48 hours after birth. Intramuscular naxolone therefore seemed to reverse the undesirable effects of pethidine.     

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.     

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.     

An improved rebreathing method for measuring mixed venous carbon dioxide tension and its clinical application.

The mixed venous carbon dioxide tension (PVCO2) can be measured at the bedside by a rebreathing equilibrium technique that is quick, simple and noninvasive. Only one brief period of rebreathing is required. The technique is accurate even when the lungs are not normal, and gives a graphic record that allows verification of the accuracy of the estimate. The PVCO2 is affected mainly by changes in alveolar ventilation and cardiac output. It can be measured instead of the arterial carbon dioxide tension (PACO2) to follow changes in alveolar ventilation when the cardiac output is normal (PaCO2 = 0.8 PVCO2). When the cardiac output is abnormal, measurement of both PaCO2 and PvCO2 is useful in determining how much the cardiac output is reduced. Consideration of the relation between oxygen consumption and carbon dioxide production suggests that the equation PaCO2 = 0.8 PVCO2 - 12 indicates a reduction in cardiac output that may impair the oxygen supply to tissues. Simple corrections can be applied to allow for variations in arterial oxygen saturation and hemoglobin concentration that will affect this relationship.     

Non-invasive mechanical ventilation for acute respiratory failure.

The value of mechanical ventilation using intermittent positive pressure ventilation delivered non-invasively by nasal mask was assessed in six patients with life threatening exacerbations of chronic respiratory disease. Median (range) arterial oxygen and carbon dioxide tensions were 4.4 (3.5-7.2) kPa and 8.7 (5.5-10.9) kPa respectively, with four patients breathing air and two controlled concentrations of oxygen. The arterial oxygen tension increased with mechanical ventilation to a median (range) of 8.7 (8.0-12.6) kPa and the carbon dioxide tension fell to 8.2 (6.5-9.2) kPa. Four patients discharged after a median of 10 (8-17) days in hospital were well five to 22 months later. One died at four days of worsening sputum retention and another after five weeks using the ventilator for 12-16 hours each day while awaiting heart-lung transplantation. This technique of mechanical ventilation avoids endotracheal intubation and can be used intermittently. Hypercapnic respiratory failure can be relieved in patients with either restrictive or obstructive lung disease in whom controlled oxygen treatment results in unacceptable hypercapnia. Respiratory assistance can be tailored to individual need and undertaken without conventional intensive care facilities.     

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.     

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.     

Effect of anaesthesia on the pattern of breathing.

The pattern of breathing of male rats was studied after stimulating respiration with carbon dioxide at different levels of general anaesthesia. Anaesthesia was induced by the inhalation of halothane or by the i.p. injection of urethane. Ventilation values were measured in intubated rats in body plethysmograph. It was found that a linear relationship between minute ventilation and tidal volume was maintained during the decrease of minute ventilation due to deepening of anaesthesia. The slope of the relationship after stimulating respiration with carbon dioxide also diminished during deeper anaesthesia. The duration of inspiration did not alter significantly, despite marked changes in tidal volume. Tidal volume correlated with the duration of expiration at different anaesthesia levels. In vagotomized rats, the duration of expiration shortened as ventilation was depressed by deepening anaesthesia.     

Local regulation of pulmonary blood flow and ventilation-perfusion ratios in the coatimundi.

Small catheters (ca. 3 mm diam at tip) were wedged in subsegmental bronchi in anesthetized coatimundi (Nasua nasua) during spontaneous breathing. Mixed expired gases of a group of lobules were sampled continuously without contamination from neighboring units, and local tidal volume, frequency, carbon dioxide production, and oxygen consumption were measured, as well as mixed venous PO2 and PCO2. Local ventilation-perfusion ratio, alveolar PO2, PCO2, and blood flow were calculated. There was a 22% reduction (range 15-38) in local perfusion (as percent of flow at PAO2 100 mmHg) per 10 mmHg fall in local alveolar oxygen tension over the PAO2 range 150-36 mmHg. Local hypercapnia had little effect on local flow. Local tidal volume (ca. 1% of total tidal volume) was unaffected by changes in alveolar gas tensions. The contribution of vasoconstriction or vasodilatation, as a negative feedback system, to the stability of local PAO2 was greatest close to the physiologic range (65-85 mmHg) falloderate efficiency.     

Effects of naloxone on exercise performance

This study was designed to investigate the effects of naloxone on athletic performance in humans. Two groups of elite middle-distance runners performed a maximal or a submaximal exercise protocol following the double-blind intravenous injection of either naloxone (0.15 mg X kg body wt-1) or saline. The maximal test (group M) was comprised of a short-duration treadmill run to maximal intensity; the submaximal test (group S), a prolonged submaximal treadmill run to exhaustion. O2 uptake, heart rate, ventilation, and perceived exertion were determined during each test. Perception of pain was assessed after exercise by use of a modified McGill pain questionnaire. No significant differences between placebo and naloxone treatments were found in any of the measured variables at the usually accepted 5% (P = 0.05) confidence level; however, evidence suggesting differences (i.e., P = 0.1 to 0.05) in these important respects was observed. In group M, maximal exercise performance measured by maximal O2 consumption was not different between placebo and naloxone; results suggest that VE was increased (P = 0.08) following naloxone, but only at the final work stage. In group S, exercise performance time was reduced following naloxone (P = 0.09), whereas the affective component of pain was increased (P = 0.06); no differences in the measured physiological variables were observed. These results suggest the following: 1) the opiate receptor-endorphin system may alter the perception of pain associated with prolonged high-intensity submaximal exercise with a resultant significant effect on performance; and 2) it may play a role in the control of ventilation during maximal exercise.     

Carbonic anhydrase III inhibition in normocapnic and hypercapnic contracting mouse soleus

The physiological role of carbonic anhydrase III in slow-twitch skeletal muscle was investigated using isolated mouse soleus (N = 30) contracting once every 1.7 min for 75 min in Krebs-Henseleit solution gassed with either 95% oxygen - 5% carbon dioxide (normocapnia) or 90% oxygen - 10% carbon dioxide (hypercapnia). Each contraction was 500 ms in duration at 50 Hz. When muscles contracted in normocapnic solution (pH 7.42), the developed tension decreased an average of 6.1 +/- 0.8% over 25 min. For the next 50 min, 15 muscles remained normocapnic, while the remainder contracted in hypercapnic solution (pH 7.20). Tension decreased significantly more with hypercapnia. For the last 25 min, both normocapnic and hypercapnic muscles were divided into three treatment groups (N = 5). One group continued in the same environment, while acetazolamide (final concentration of 10(-5) M) was added to the bath of the second and sodium cyanate (final concentration of 10(-5) M) was added to the bath of the third group. Acetazolamide had no effect on tension in either carbon dioxide environment. Sodium cyanate significantly decreased tension from the hypercapnic control but had no effect in normocapnia. Thus carbonic anhydrase III inhibition with sodium cyanate increased the effect of hypercapnia implying that carbonic anhydrase III assists in the regulation of free hydrogen ion concentration in slow-twitch skeletal muscle.     

Effect of posture on regional gas exchange in pigs.

Although recent high-resolution studies demonstrate the importance of nongravitational determinants for both pulmonary blood flow and ventilation distributions, posture has a clear impact on whole lung gas exchange. Deterioration in arterial oxygenation with repositioning from prone to supine posture is caused by increased heterogeneity in the distribution of ventilation-to-perfusion ratios. This can result from increased heterogeneity in regional blood flow distribution, increased heterogeneity in regional ventilation distribution, decreased correlation between regional blood flow and ventilation, or some combination of the above (Wilson TA and Beck KC, J Appl Physiol 72: 2298-2304, 1992). We hypothesize that, although repositioning from prone to supine has relatively small effects on overall blood flow and ventilation distributions, regional changes are poorly correlated, resulting in regional ventilation-perfusion mismatch and reduction in alveolar oxygen tension. We report ventilation and perfusion distributions in seven anesthetized, mechanically ventilated pigs measured with aerosolized and injected microspheres. Total contributions of pulmonary structure and posture on ventilation and perfusion heterogeneities were quantified by using analysis of variance. Regional gradients of posture-mediated change in ventilation, perfusion, and calculated alveolar oxygen tension were examined in the caudocranial and ventrodorsal directions. We found that pulmonary structure was responsible for 74.0 +/- 4.7% of total ventilation heterogeneity and 63.3 +/- 4.2% of total blood flow heterogeneity. Posture-mediated redistribution was primarily oriented along the caudocranial axis for ventilation and along the ventrodorsal axis for blood flow. These mismatched changes reduced alveolar oxygen tension primarily in the dorsocaudal lung region.     

不同功率递增速率对正常人心肺运动试验整体功能的影响Ⅱ—亚极限运动相关指标的影响*

目的: 观察健康志愿者不同功率递增速率完成症状限制性极限心肺运动试验（CPET）对CPET亚极限运动相关核心指标的影响。方法: 选择12名健康志愿者在一周内不同工作天随机完成中等适度程度（30 W/min）及比较低（10 W/min）和比较高（60 W/min）3种不同功率递增速率CPET。按标准方法比较12名志愿者CPET亚极限运动相关核心指标：无氧阈（AT）、单位功率摄氧量（ΔVO₂/ΔWR）、摄氧通气有效性峰值平台（OUEP）、二氧化碳通气当量平均90 s最低值（Lowest VE/ VCO₂）、二氧化碳通气当量斜率（VE/ VCO₂ Slope）及截距（intercept）和无氧阈时的摄氧通气效率值（VO₂/ VE@AT）和无氧阈时的二氧化碳通气当量值（VE/ VCO₂@AT）。对三组不同功率递增速率下各个指标的差异组间两两比较。结果: 中等适度功率递增速率组与比较低和比较高功率递增速率组相比摄氧通气有效性峰值平台（42.22±4.76 vs 39.54±3.30 vs 39.29±4.29）和二氧化碳通气当量平均90 s最小值（24.13±2.88 vs 25.60±2.08 vs 26.06±3.05）明显好,差异有统计学意义（P<0.05）;比较低、比较高功率递增速率组与中等适度功率递增速率组相比,单位功率摄氧量显著升高和降低（（8.45±0.66 vs 10.04±0.58 vs 7.16±0.60）ml/（min·kg））,差异有统计学意义（P<0.05）;无氧阈值没有发生明显改变（（0.87±0.19 vs 0.87±0.19 vs 0.89±0.19）L/min）,差异无统计学意义（P>0.05）;结论: 比较低、比较高功率递增速率可以明显改变摄氧通气有效性、二氧化碳排出通气有效性、单位功率摄氧量等CPET亚极限运动相关指标;选择比较低和比较高的功率递增速率和适度功率递增速率CPET相比明显降低了健康个体的摄氧通气有效性和二氧化碳排出通气有效性。CPET规范化操作要求选择适合受试者的功率递增速率,这样得到的CPET亚极限相关指标才最能反应受试者的真实功能状态。     

Prenatal asphyxia,hyperlacticaemia, hypoglycaemia,and erythroblastosis in growth retarded fetuses.

The umbilical venous oxygen and carbon dioxide tensions, pH, lactate and glucose concentrations, nucleated red cell (erythroblast) count, and haemoglobin concentration were measured in 38 cases of intrauterine growth retardation in which fetal blood sampling was performed by cordocentesis. The oxygen tension was below the normal mean for gestational age in 33 cases; in 14 it was below the lower limit of the 95% confidence interval for normal pregnancies. The severity of fetal hypoxia correlated significantly with fetal hypercapnia, acidosis, hyperlacticaemia, hypoglycaemia, and erythroblastosis. These findings indicate that "birth asphyxia" is not necessarily due to the process of birth.     

Effects of ventilation on the surfactant system in sepsis-induced lung injury.

The present study examined the effects of mechanical ventilation, with or without positive end-expiratory pressure (PEEP), on the alveolar surfactant system in an animal model of sepsis-induced lung injury. Septic animals ventilated without PEEP had a significant deterioration in oxygenation compared with preventilated values (arterial PO(2)/inspired O(2) fraction 316 +/- 16 vs. 151 +/- 14 Torr; P < 0.05). This was associated with a significantly lower percentage of the functional large aggregates (59 +/- 3 vs. 72 +/- 4%) along with a significantly reduced function (minimum surface tension 17.7 +/- 1.8 vs. 11.8 +/- 3.8 mN/m) compared with nonventilated septic animals (P < 0.05). Sham animals similarly ventilated without PEEP maintained oxygenation, percent large aggregates and surfactant function. With the addition of PEEP, the deterioration in oxygenation was not observed in the septic animals and was associated with no alterations in the surfactant system. We conclude that animals with sepsis-induced lung injury are more susceptible to the harmful effects of mechanical ventilation, specifically lung collapse and reopening, and that alterations in alveolar surfactant may contribute to the development of lung dysfunction.     

External respiration, gas exchange and blood acid-base status in dogs with hyperthermia

Experiments on dogs have shown that hyperthermia intensifies respiration, increases oxygen consumption, induces pronounced discrepancy of the alveolar ventilation to carbon dioxide elimination, severe hypocapnia and decompensated respiratory alkalosis.     

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.     

Relation Between Personality and Ventilatory Response to Carbon Dioxide in Normal Subjects: A Role in Asthma?

Ventilatory response to carbon dioxide, as an index of respiratory centre sensitivity, was measured in 50 normal subjects. Their personality was documented in terms of extraversion and neuroticism scores by the Eysenck Personality Inventory. A significant correlation was found between extraversion score and ventilatory response to carbon dioxide in women (P < 0·005) but not in men. No correlation was found between ventilatory responsiveness and neuroticism score in either sex. It is suggested that the degree of extraversion may play some part in determining the level of ventilation adopted, and hence of arterial carbon dioxide tension, if and when women develop lung disease such as asthma.     

Pulmonary microembolism: attenuated pulmonary vasoconstriction with prostaglandin inhibitors and antihistamines.

The mechanism(s) involved in the pulmonary vascular and airway responses to pulmonary microembolism have not been clearly defined. Therefore, we determined the effects of specific prostaglandin and histamine blockade on the hemodynamic and arterial blood gas tension responses to particulate microembolism (200 mu glass beads) in intact anesthetized dogs. The marked increases in pulmonary arterial pressure and pulmonary vascular resistance observed in the untreated dogs were attenuated, but not abolished, following both prostaglandin blockade (with either meclofenamate or polyphloretin phosphate) and histamine blockade (with chlorpheniramine and metiamide) at 5 minutes, and were still attenuated 30 minutes post embolization. Combined prostaglandin and histamine blockade further attenuated, but again did not abolish, the pulmonary vascular responses. Cardiac outputs and systemic arterial pressures were unchanged from control by embolism. The alveolar hypoventilation (decreased arterial oxygen tension and increased carbon dioxide tension) observed in the untreated embolized dogs was prevented only with the prostaglandin inhibitors. Pulmonary microembolism in intact dogs, therefore, appears to induce vasoconstriction mediated partially by prostaglandin and histamine action, and alveolar hypoventilation mediated by prostaglandin, but not histamine, action.     

Effects of auditory frequency-shifts on zero and below-zero SCR habituation

The purpose of the present experiment was to test a procedure for the measurement of effects of zero- and below-zero habituation (BZH) on responding to frequency shifts in auditory stimuli. The present procedure avoided some of the drawbacks of other procedures, that is, long duration, ambiguity in the definition of BZH, and inadequate control procedures. Two groups received 18 stimulus presentations each; group 1 received first a tone of 1000 Hz 12 times, then 1400 Hz (test stimulus 1) 3 times, and 1850 Hz (test stimulus 2) 3 times. Group 2 received the same stimuli, but 3, 12, and 3 times, respectively. The procedure had the advantages of short duration of the experiment, zero habituation and BZH were operationally defined (as 3 and 12 stimulus presentations, respectively), and there were adequate control conditions since a control group that did not receive stimulus change on the relevant trial was employed. The results showed no effects of stimulus shifts on responding to the test stimuli. Group 2 responded significantly less than group 1 across trials, though, and this may be explained by an inhibitory process elicited by changes in weak stimulation during the habituation process.