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.

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.

Effects of alcohol on respiratory variables in normal humans.

The study is designed to clarify the effect of low doses of alcohol on respiratory variables in air breathing normal subjects. Each subject was given an initial loading dose of alcohol (0.270 g/kg) followed, half an hour later, by a second dose (0.135 g/kg). Blood alcohol increased to a mean value of 52.0 +/- 3.0 (SEM) mg/100 ml at 1 hour. Resting ventilation increased significantly from a mean value of 6.25 +/- 0.41 litres min(-1) to 7.20 +/- 0.31 litres min(-1) 1 hour after alcohol (p= 0.025). Mean inspiratory flow was also increased (p= 0.045). End-tidal PCO² (PET CO²) showed a highly significant fall (1.87 +/- 0.35 mm Hg; p < 0.001) without a significant change in CO2 production rate (p > 0.05). PET CO² variability (100 x SD/mean) was low (mean 2.4%) and unaffected by alcohol. The longest end-expiratory pauses (apnoeas) observed for each subject were shortened significantly by alcohol (1.030 +/- 0.194 s and 0.690 +/- 0.138 s; p = 0.01). Moderate doses of alcohol in normal subjects, therefore lower PET CO² and shorten end-expiratory pauses (apnoeic periods) but do not affect PET CO² variability.

Effects of oral ethanol on end-tidal CO2tension in patients misusing alcohol.

This study examines the effect of oral ethanol ingestion on P(et)CO2 and other respiratory variables in alcohol-misusing subjects. Twelve patients were given a loading dose of alcohol (0.270 g/kg) followed by a second dose (0.135 g/kg) half an hour later, increasing blood alcohol to a mean of 82.0 +/- 10.3 (SEM) mg/100 ml at 1 hour. Five patients were classified as hazardous drinkers with evidence of mild alcohol dependence but no toxicity (Severity of Alcohol Dependency (SADQ) score < 15/60; serum carbohydrate-deficient transferrin < 6%). These patients showed a significant fall in mean end-tidal PCO² (P(et)CO2) on alcohol (2.08 +/- 0.61 mm Hg; p = 0.027) with slightly increased ventilation (1.76 +/- 0.94 1 min(-1), p = 0.14); responses similar to those previously reported for normal subjects. Seven patients had evidence of moderate alcohol dependency and/or recent use (SADQ > 15/60; CDT > 6%). In these patients P et CO2 did not fall after alcohol challenge (mean change + 0.61 mm Hg; p > 0.30). There were significant correlations between the changes in P et CO2 and CDT (n = 12; r(s)= 0.66, p = 0.019) and SADQ (n = 11; r(s)= 0.688, p = 0.019). The results show that P(et)CO2 control is abnormal in the alcohol dependency syndrome.

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.

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.

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.

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.

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.

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.

Arterial plasma potassium measured continuously during exercise in man.

Five continuous records of arterial plasma potassium were obtained from three normal subjects during brief periods (5-7 min) of exercise (100 W). In two of these subjects hepatic venous blood samples were withdrawn at 0.5-1.0 min intervals and analysed in vitro for plasma potassium. Arterial plasma potassium rose rapidly at the start of exercise from 3.8 +/- 0.3 mmol/l (mean +/- SD) to plateau levels of 5.4 +/- 0.1 mmol/l. One of the above subjects and a further subject were studied after beta-blockade with propranolol. This resulted in an exaggerated rise in arterial plasma potassium during exercise. Hepatic venous potassium measurements indicated that the liver probably had little effect on potassium changes during exercise. The changes in arterial plasma potassium during exercise are rapid and substantial. If transmitted to the extracellular fluid these changes would alter cell transmembrane potential and might as a result alter receptor sensitivity.

The effect of increased lung volume on the expiratory rate of rise of alveolar carbon dioxide tension in normal man.

The rate at which alveolar PCO2 (PA, CO2) rises during expiration has been measured in seven healthy medical students. PA, CO2 rate of rise [delta PA, CO2/delta t] was measured by a method utilizing constant expiratory flow rates in individual breaths in two subjects, and was calculated from airway PCO2 and expiratory tidal volume in the remaining five subjects. Steady-state runs were recorded at two or more metabolic rates with the subject making no special effort to control mean lung volume. This was done to establish the relationship between delta PA, CO2/delta t and the rate of CO2 production (VCO2) at normal lung volume in individual subjects. Steady-state runs were also recorded at high lung volume. In each subject delta PA, CO2/delta t was less than would have been obtained at normal lung volume. Inversion of a hypothetical relation between delta PA, CO2/delta t, VCO2 and average lung volume (VLa; DuBois, Britt & Fenn, 1952) yielded calculated values of VLa for both the normal and the high lung volume states. Lung gas volume was measured in a whole body plethysmograph, ('box volume') both for the normal and high lung volume states, in each subject. Mean VLa and 'box volume' estimates showed only moderately good agreement, whereas the estimated differences between normal and high lung volume obtained by the two methods were virtually identical. These experiments suggest that the expiratory PA, CO2 rate of rise is determined, in the steady state, partly by the rate of CO2 production (a directly proportional relationship) and partly by the mean lung volume (an inversely proportional relationship).

The rate of rise of alveolar carbon dioxide pressure during expiration in man.

1. The purpose of the study was to see whether the rate of rise of alveolar PCO2 (PA, CO2) in expiration was directly proportional to the rate of pulmonary elimination of CO2 (VCO2) in man in the steady state. 2. Alveolar ventilation at rest and during exercise in man was calculated from the difference between total ventilation and dead space ventilation, and from the ratio of the rate of pulmonary CO2 elimination to the mean expired alveolar CO2 (total) fraction. The results were indistinguishable. In agreement with other workers' findings alveolar ventilation changed in direct proportion to the rate of carbon dioxide elimination, confirming the isocapnia of exercise ventilation in man. 3. The rate of rise of expiratory alveolar PCO2 in individual breaths has been obtained by two methods. In the first, a pattern of respiration with constant expiratory flow in each breath brought expiratory alveolar profiles to the outermost end of the airway. In the second method, the early part of the alveolar PCO2 during normal expiration was calculated from airway PCO2 and expired volume. 4. The data obtained with both methods show that, in the steady state, expiratory alveolar PCO2 rises at a rate which is directly proportional to the rate of CO2 production.

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.