Effect of inspiration of 12% O2 (balance N2) on cardiac output, respiration, oxygen saturation, and oxygen delivery.

Low arterial oxygen saturation (SaO(2)) will result in a reduced rate of arterial oxygen delivery to the tissues (DO(2)), unless there is a compensatory increase in cardiac output (CO) or haemoglobin concentration (Hb). An adequate DO(2) can therefore be maintained by increasing ventilation, CO, or both. Sustaining a tissue specific oxygen extraction is thought to play an important part in overall compensation. The present study has examined responses to acute hypoxic exposure in 8 volunteers (breathing 12% oxygen, balance nitrogen) and describes changes in CO, ventilation and the SaO(2). Aims included: examination of the extent of intersubject variations and seeing whether DO(2) was maintained. SaO(2), PCO(2), respiration (via stethograph) and Finapress (non-invasive) arterial blood pressure (BP) were recorded, firstly on air and then on 12% oxygen. CO was derived, off-line, from the BP record. CO was increased in 5 subjects (22%-45%) but was virtually unchanged in 3, and yet comparison for all 8 subjects showed that DO(2) on 12% oxygen was not significantly different from DO(2) on air (mean on air 1017 ml. min(-1); hypoxia 1080 ml. min(-1), p = 0.27). SaO(2) on 12% oxygen ranged between 85% and 93%. In conclusion, exposure to the same hypoxic gas mixture resulted in differing individual ventilatory and CO responses. However, DO(2) was well maintained.

Alveolar PCO2 oscillations and ventilation at sea level and at high altitude.

This study examines the potential for a ventilatory drive, independent of mean PCO2, but depending instead on changes in PCO2 that occur during the respiratory cycle. This responsiveness is referred to here as "dynamic ventilatory sensitivity." The normal, spontaneous, respiratory oscillations in alveolar PCO2 have been modified with inspiratory pulses approximating alveolar PCO2 concentrations, both at sea level and at high altitude (5,000 m, 16,400 ft.). All tests were conducted with subjects exercising on a cycle ergometer at 60 W. The pulses last about half the inspiratory duration and are timed to arrive in the alveoli during early or late inspiration. Differences in ventilation, which then occur in the face of similar end-tidal PCO2 values, are taken to result from dynamic ventilatory sensitivity. Highly significant ventilatory responses (early pulse response greater than late) occurred in hypoxia and normoxia at sea level and after more than 4 days at 5,000 m. The response at high altitude was eliminated by normalizing PO2 and was reduced or eliminated with acetazolamide. No response was present soon after arrival (<4 days) at base camp, 5,000 m, on either of two high-altitude expeditions (BMEME, 1994, and Kanchenjunga, 1998). The largest responses at 5,000 m were obtained in subjects returning from very high altitude (7,100-8,848 m). The present study confirms and extends previous investigations that suggest that alveolar PCO2 oscillations provide a feedback signal for respiratory control, independent of changes in mean PCO2, suggesting that natural PCO2 oscillations drive breathing in exercise.

Carotid chemoreceptor discharge during epinephrine infusion in anesthetized cats.

It is known that during exercise there is an increase in plasma epinephrine. The purpose of the present investigation was to determine whether stimulation of carotid chemoreceptors by epinephrine is a direct effect or secondary to epinephrine-induced increases in arterial plasma [K+] and whole body CO2 production (VCO2). Chemoreceptor discharge was recorded from single fiber preparations of the carotid sinus nerves in anesthetized cats ventilated to a constant arterial PCO2 (PaCO2). Infusion of epinephrine (1 microgram.kg-1 x min-1) caused arterial [K+] to increase from a mean of 2.7 to 3.8 mM. VCO2 increased so that ventilation had to be increased by 60% to maintain PaCO2 constant. Mean chemoreceptor discharge increased by 50%, but this was no greater than would be predicted on the basis of the increases in arterial [K+] and VCO2. In a further group of experiments epinephrine was infused at 0.1 microgram.kg-1 x min-1 and produced no significant increase in chemoreceptor firing. These experiments provide no evidence for epinephrine having a direct effect on the carotid chemoreceptor.

Ventilatory changes during exercise and arterial PCO2 oscillations in chronic airway obstruction patients.

Ventilatory kinetics during exercise (30 W for 6 min) were studied in 3 asthmatics, 14 patients with chronic airway obstruction (11 with bronchial or type B disease, 3 with emphysematous or type A disease), and in 5 normal age-matched controls. The measure of ventilatory increase during early exercise, alpha 1-3%, was calculated as (avg minute ventilation over 1st-3rd min of exercise--resting minute ventilation)/(avg minute ventilation over 4th-6th min of exercise--resting minute ventilation) X 100. Arterial pH, PO2, and PCO2 (PaCO2) were measured in vitro at rest and within 20 s of termination of exercise. Respiratory PaCO2 oscillations had previously been monitored at rest in the patients (indirectly as in vivo arterial pH, using a fast-response pH electrode) and quantified by upslope (delta PaCO2/delta t). alpha 1-3% was normal in asthmatics (whose respiratory oscillations as a group showed least attenuation) and in type A patients (whose respiratory oscillations as a group were most attenuated). In type B patients reduction in alpha 1-3% correlated with attenuation of delta PaCO2/delta t (r = 0.75; P less than 0.01). There was no significant correlation between delta PaCO2/delta t and change of in vitro PaCO2 from rest to the immediate postexercise period. These findings are consistent with the hypothesis that attenuation of delta PaCO2/delta t slows ventilatory kinetics during exercise in type B but not type A patients. Intact respiratory oscillations are not necessary for CO2 homeostasis after the first few minutes of exercise.

Cerebral blood flow and oxygen delivery at high altitude.

During acclimatization to moderate altitudes, a simple calculation from data of others shows that the rise in cerebral blood flow (CBF) is sufficient that oxygen delivery to brain (DaO2) is constant as arterial oxygen content (CaO2) falls. This balance occurs on average even though the hypocapnia caused by hypoxic hyperventilation causes cerebral vasoconstriction, conflicting with hypoxic cerebral vasodilation. The relative strengths of the ventilatory and cerebral vascular sensitivities may affect this balance in individual subjects. There is no evidence for a mechanism to detect or respond directly to DaO2. Hypoxic cerebral vasodilation is believed to depend upon tissue and capillary PO2 and content, not arterial. Despite these reservations it is of interest that the average resultant DO2 remains constant. I speculate here that this match may relate to the well-known local hyperemic response to neuronal activity which now has been shown to initially overcompensate, in that tissue PO2 and pH rise in the first few seconds after neural activity. Analysis of results from the paper by Severinghaus et al. (Circ. Res. 1966;19:274-282) shows that in their subjects, despite approximately 20% reductions in arterial oxygen content at 3,810 m altitude, the data does not show any significant fall in DaO2 as a result of increased cerebral blood flows.

Effect on respiration of changes in the form of the naturally occurring oscillation in arterial pH.

We have previously shorn that the respiratory control system in the cat has the requisite sensitivity and speed to respond to changes in arterial pH which are equal to, or smaller than, the normal fluctuations in pH with respiration. A respiratory response was only observed when the changes in pH were produced by alterations in PCO2 and not when they were induced by non-gaseous acids. We describe now the respiratory effect produced by various procedures which modify or abolish the naturally occurring arterial pH oscillations before they reach the peripheral chemoreceptors. The pH oscillations were abolished by a mixing chamber, whilst their phase relationship to respiration was altered by delay coils; by presenting a moving plastic surface to the arterial blood stream it was possible to distort the shape of the oscillations without increasing the transport lag between lung and peripheral chemoreceptors. All manoeuvres produced a brief period of respiratory stimulation which was greater than could occur by chance. We were particularly concerned in these experiments with the possibility of artefacts in our experimental design. We feel that we have excluded respiratory effects due to changes in arterial pressure, blood temperature and mean pH. We are less confident that we have excluded changes in ventilation resulting from the release of a substance (or substances) from the contact of blood with plastic or glass surfaces. This problem is discussed in relation to experiments on the control of breathing where blood, which is perfusing the chemoreceptors, has been in contact with artificial surfaces.

Maternal eating patterns and birth weight of Mexican American infants.

Eating patterns of 549 Mexican American mothers were identified using dietary data from the United States Hispanic Health and Nutrition Examination Survey. These eating patterns were then used to investigate the relationship between maternal diet and infant birth weight. Principle components factor analysis was used to determine the structure of the maternal eating patterns. Seven distinct eating patterns were identified: nutrient dense, traditional, transitional, nutrient dilute, protein rich, high fat dairy, and mixed dishes. Stepwise multiple regression analysis was used to identify those eating patterns associated with birth weight. In addition to eating patterns, regression variables included body mass index, hemoglobin, gestational age at delivery, maternal age, infant gender, acculturation, marital status, income, education, and smoking during pregnancy. Regression results indicated that the nutrient dense (fruits, vegetables, low fat dairy, etc.) and protein rich (low fat meats, processed meats, and dairy desserts, etc.) eating patterns were associated with increased birth weight and that the transitional eating pattern (fats and oils, breads and cereals, high fat meats, sugar, etc.) was associated with decreased birth weight. Study findings suggest that the eating pattern methodology may be an appropriate tool for analyzing food frequency data in the investigation of diet and health relationships and for targeting dietary interventions.

The effects on breathing of alternate breaths of air and a carbon dioxide rich gas mixture in anaesthetized cats.

1. An in vivo pH electrode was used to assess the effect in anaesthetized cats of the administration of 5% CO(2) (21% O(2), balance N(2)) and air as alternate inspirates upon the time course of the carotid arterial pH, and by inference, the P(CO2).2. This method of administration of CO(2) and air resulted in a lowering of the recorded pH with the production of oscillations of twice the duration seen on air alone. These larger oscillations had a period of two respiratory cycles and their amplitude was approximately twice that of normal oscillations.3. The respiratory response consisted in all cases of an increase in mean tidal volume and ventilation, and in 50-60% of recorded runs, of a highly specific sequence of tidal volume changes. The specific sequence was composed of alternately larger and smaller breaths which persisted while the larger oscillations continued.4. The use of the in vivo pH electrode made it possible to determine whether or not the tidal volume alternation was a result of sensitivity to carotid arterial P(CO2) oscillations. By diverting the carotid arterial blood through a mixing chamber the amplitude of the double (respiratory) period oscillations was, in some cases, reduced but not eliminated. In these cases the specific pattern of tidal volume changes was still present in 60% of trials. In the cases where the pH fluctuations were completely eliminated the specific respiratory pattern was never present.5. Average breath to breath differences in tidal volume seen during control runs with large oscillations present ranged in size from 3.6 to 8.6% of the mean tidal volume. When the oscillations were completely eliminated by means of the mixing chamber the breath by breath differences only ranged from 0.2 to 2.7% of mean tidal volume. The change was highly significant.6. Mean tidal volume and ventilation were not altered by eliminating the large (double period) oscillations.7. It has been shown that the tidal volume is made to change from breath to breath in a persistent manner when there are recurrent changes in carotid arterial blood chemistry. The effects on respiration involve vascular receptors above the mid carotid arterial region. It is argued that the effects involve the sensitivity of the carotid bodies to rapid (within breath) changes in P(a, CO2). There appears to be no significant effect on mean ventilation of the dynamic component of the arterial P(CO2) changes produced in these experiments.

Ventilation during carbon dioxide loading in anaesthetized women.

The mechanisms whereby arterial carbon dioxide tension (PaCO2) remains constant despite varying rates of CO2 production are poorly understood. During the gynaecological operation of laparoscopy, the abdominal cavity is filled with CO2. An increase in the rate of CO2 delivery to the lung (less than 50%) occurs as a result of venous CO2 absorption. Respiratory control in 39 anaesthetized but spontaneously breathing women was studied during such exogenous CO2 loading. End-tidal CO2 tension (PACO2 - rapid infrared analyser) and minute-ventilation (Wright respirometer) were measured before and at 5 min intervals after peritoneal insufflation. Ventilation increased and mean PACO2 remained constant in these patients. Inhalational anaesthetics depress respiration and this was confirmed by raised control PACO2 values in this study. However, it appears that mechanisms underlying PACO2 homeostasis in the presence of a CO2 load are not depressed by inhalational anaesthetic in this study. These patients were probably hyperoxic. Peripheral arterial chemoreflexes are thought to be eliminated by hyperoxia. Therefore, it is likely that neural stimuli, from exploration of the abdomen, drove breathing. Furthermore, the fact that there was not a large fall in PACO2 may have been due to feedback via the central (brainstem) chemoreceptor.

The influence of low, normal and high Pa(O2) on the respiratory effects of Pa(CO2) oscillations in anaesthetised cats.

The present study examines the influence of oxygen tension on the recurrent tidal volume changes caused by oscillations in arterial P(CO2). The oscillations have a period equal to two respiratory cycles, and are produced by giving alternately CO2 -enriched and CO2 -free gas mixtures. The results show alternation of the tidal volume with the same incidence (is greater than 50%) at low, normal and high oxygen tensions. However, the magnitudes of the breath-by-breath changes are significantly greater at low oxygen tension than at normal oxygen tension. Under high oxygen tension breath-by-breath tidal volume changes are indistinguishable from those at normal oxygen tension.

Respiratory oscillations in discharge frequency of chemoreceptor afferents in sinus nerve and anaesthetized cats at normal and low arterial oxygen tensions.

1. The discharge of chemoreceptor afferents in preparations of the sinus nerve in spontaneously breathing anaesthetized cats has been subjected to an averaging procedure in records obtained when the animals breathed (a) air and (b) a hypoxic gas mixture. 2. The mean discharge frequency was higher in hypoxia than at normal oxygen tension. 3. Oscillations in chemoreceptor discharge frequency with the same period as respiration were obtained by the averaging procedure both at normal arterial oxygen tensions and in hypoxia, but there was no significant increase in oscillation amplitude with hypoxia. 4. The carotid body response to arterial PCO2 oscillations does not therefore appear to be amplified by hypoxia. This finding is discussed in relation to the reported dependence upon hypoxia of the ventilatory effects of tube breathing in man.

Smoking, acculturation, and pregnancy outcome among Mexican Americans.

The authors present an evaluation of the role of acculturation in smoking practices and pregnancy outcome (N = 767 births) in a national sample of Mexican American women. Data employed are from the 1982-1984 Hispanic Health and Nutrition Examination Survey. The prevalence rates of smoking during pregnancy, low birth weight (< or = 2500 g), and preterm delivery (> or = 3 weeks prior to the expected date) are higher among more acculturated women compared with less acculturated women. Among the more acculturated women, the prevalence of smoking and poor birth outcomes did not increase linearly with increasing American orientation. Rather, women in the third quartile of acculturation scores, i.e., those with a moderate American orientation, experienced significantly poorer birth outcomes than women with either a stronger American orientation or a Mexican orientation. Women at this moderate level of acculturation appear to have the greatest need for public health services rather than women with the lowest level of acculturation (non-English speaking, lowest income) as a means of improving their pregnancy outcomes.

Cerebral microvascular permeability and CSF pH in anaesthetized rats.

The idea that the blood-brain barrier (BBB) may be made slightly permeable by an acid load on the brain side was tested in single pial venular capillaries of anaesthetized young rats. The fluorescent dye, Lucifer Yellow (457 Da), was used as a fluid-phase marker to measure permeability in the presence of a free radical scavenger. Tight microvessels were unresponsive to pH changes of 0.3-0.5 units. Vessels that were permeable showed small, significant increases in permeability with decreasing pH (2.19 +/- 0.562 x 10(-6) cm s-1 (pH unit)-1). This effect increased with increasing permeability.

Birth weight and smoking practices during pregnancy among Mexican-American women.

The smoking practices of a national sample of Mexican-American mothers and the resulting effects of those practices on birth weight were examined. Data were from the Hispanic Health and Nutrition Examination Survey conducted by the U.S. National Center for Health Statistics during 1983-1984. We found that 24% of the mothers had smoked during their pregnancy, with a mean of 11 cigarettes per day. Infants of these women weighed 101 g less at birth than did infants of nonsmoking mothers and had a low birth weight rate of 8.0% compared with the 5.1% low birth weight rate for the sample as a whole. Multiple regression results indicate a 7.4 g decrease in birth weight for each cigarette smoked per day during pregnancy. Cultural factors that promote a low birth weight rate for Mexican-Americans that is comparable to that of non-Hispanic whites despite increased rates of poverty and inadequate health care do not protect against the insidious effects of cigarette smoking.

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.

Respiratory arterial pH and PCO2 oscillations in patients with chronic obstructive airways disease.

1. Arterial pH oscillations have been monitored in vivo in patients with well defined chronic obstructive bronchitis, asthma and clinical emphysema. 2. The patients with clinical emphysema were shown to differ from those with chronic obstructive bronchitis on the basis of a number of clinical and physiological criteria. 3. Patients with asthma showed least attenuation of their pH oscillations as a group, in contrast to emphysematous patients who showed most attenuation. In patients with clinical emphysema the attenuation was relatively homogeneous. The patients with chronic obstructive bronchitis showed the full range from normal oscillations (zero attenuation) to zero (complete attenuation). 4. The amplitude and approximate rate of change of upslope of the PaCO2 oscillations in vivo were calculated, from measured pH oscillation amplitudes, using buffer slope values in vitro from Siggaard Anderson [(1962, 1963) Scandinavian Journal of Clinical and Laboratory Investigation, 14, 598-604; 15, 211-217], then dividing the PaCO2 amplitude by half the respiratory period. 5. Mean arterial PCO2 in vitro showed a very strong correlation with the downslope of the pH oscillation in vivo (calculated as for PaCO2 upslope) in patients without clinical emphysema. This correlation would be expected to some extent, owing to the logarithmic relationship of PaCO2 oscillations to pH oscillations. However, the mean arterial PCO2 also showed a very strong correlation with the upslope of the calculated PaCO2 oscillations, again excluding patients with clinical emphysema.

Gonorrhoea with skin and joint manifestations.

Three cases of gonorrhoea with pyrexia and lesions of the skin and joints (benign gonococcaemia) seen in one hospital group in 1969 within four months of one another are described. All three patients improved rapidly with penicillin therapy. This syndrome is commoner than is usually thought. It must therefore be borne in mind when a diagnosis is in doubt in a patient with unusual skin lesions and joint involvement. Thorough bacteriological investigation is necessary before starting treatment. The relevant literature is reviewed.