Decrease In Ventilation Research Articles

Ventilatory response to spontaneous resistive load variations during sleep

We investigated the ventilatory response to spontaneous changes in resistive load during sleep in nine adult asthmatic patients, four of whom were snorers. All patients had a history of nocturnal worsening of respiratory symptoms and were submitted to a nocturnal polysomnographic study in a sleep laboratory. During the night, all patients showed spontaneous increases in pulmonary resistance due to bronchoconstriction. A temporary additional increase in inspiratory resistance (RI) was observed as a result of snoring. In all patients, a highly significant inverse linear relationship was found between ventilation (VE) and RI, but the slopes of the regressions varied considerably among patients; the decrease in VE was due to a reduced mean inspiratory flow. The most effective ventilatory compensation to increasing resistive load (lowest absolute values in the VE/RI slopes) was observed in two patients: one nonsnorer and one snorer. Effective VE compensation appeared to be dependent on the individual's combined adjustments of transpulmonary pressure (Ptp) and duty cycle (TI/TT). In fact, an increase in Ptp, linearly related to RI, was observed in all patients except one (a snorer during nonsnoring breathing); however, the Ptp increase was able to compensate VE only when TI/TT increased. We conclude that, in sleeping asthmatic patients, VE adaptation to increased spontaneous load is highly variable among patients and its effectiveness is related to individual strategies on the basis of adequate adjustments of neuromuscular output and timing of the breathing cycle.

Effect of physical training on exercise-induced hyperkalemia in chronic heart failure. Relation with ventilation and catecholamines.

The exercise-induced rise in arterial potassium concentration ([K+]a) may contribute to exercise hyperpnea and could play a role in exertional fatigue. This study was designed to determine whether the exercise-induced rise in [K+]a is altered in patients with chronic heart failure (CHF) and whether physical training affects K+ homeostasis. We evaluated 10 subjects with CHF (ejection fraction, 23 +/- 3.9%) and 10 subjects with normal left ventricular function (NLVF) who had undergone previous coronary artery graft surgery (ejection fraction, 63 +/- 8.6%). Subjects performed an incremental cycle ergometer exercise test before and after a physical training or detraining program. Changes in [K+]a and ventilation (VE) during exercise were closely related in both groups. Subjects with CHF did less absolute work and had reduced maximal oxygen consumption (VO2max) compared with subjects with NLVF (P < .01). Exercise-induced rises in [K+]a, VE, norepinephrine, lactate, and heart rate were greater at matched absolute work rates in subjects with CHF than in subjects with NLVF (P < .01). However, when the rise in [K+]a was plotted against percentage of VO2max to match for relative submaximal effort, there were no differences between the two groups. Physical training resulted in reduced exercise-induced hyperkalemia at matched submaximal work rates in both groups (P < .01) despite no associated change in the concentration of arterial catecholamines. At maximal exercise when trained, peak increases in [K+]a were unaltered, but peak concentrations of catecholamines were raised (P < .05). The decrease in VE at submaximal work rates after training was not significant with this incremental exercise protocol, but both groups had an increased peak VE when trained (P < .01). Exercise-induced rises in [K+]a, catecholamines, and VE are greater at submaximal work rates in subjects with CHF than in subjects with NLVF. Physical training reduces the exercise-induced rise in [K+]a but does not significantly decrease VE during submaximal exercise with this incremental cycle ergometry protocol. The reduction in exercise-induced hyperkalemia after training is not the result of altered concentrations of arterial catecholamines. The pathophysiological significance of the increased exercise-induced hyperkalemia in CHF and the mechanisms of improved K+ homeostasis with training have yet to be established.

Ventilatory pattern after hypoxic stimulation during wakefulness and NREM sleep.

The ventilatory after-discharge mechanism (VAD) may stabilize ventilation (VE) after hyperventilation but has not been studied in detail in humans. Several studies conducted during wakefulness suggest that VAD is present, although none has been conducted during sleep, when disordered ventilation is most common. We conducted two experiments during wakefulness and non-rapid-eye-movement (NREM) sleep in 14 healthy young men to characterize the ventilatory response after termination of a 45- to 60-s 10-12% O2 hypoxic stimulus. Eight subjects had triplicate hypoxic trials terminated by 100% O2 during wakefulness and NREM sleep. Hypoxia caused a drop in arterial O2 saturation to 78.5 +/- 0.5%, an increase in VE of 4.4 +/- 0.6 l/min, and a decrease in end-tidal PCO2 of 4.4 +/- 0.4 Torr during wakefulness, with no significant differences during sleep. When the hypoxia was terminated with 100% O2, VE was variable within and between subjects during wakefulness. During sleep, all subjects developed hypopnea (VE < 67% baseline) with a mean decrease of 65.5 +/- 7.8% at the onset of hyperoxia (P < 0.05 compared with baseline VE). We hypothesized that this uniform decrease in VE might be due to the nonphysiological hyperoxia employed. We therefore studied six additional subjects, all during NREM sleep, with identical hypoxic stimulation of breathing terminated by 100% O2 or room air. We again found that termination of hypoxia with 100% O2 produced uniform hypoventilation. However, when the identical stimulus was terminated with room air, no hypoventilation occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Does the Hypoxic Ventilatory Response Predict the Oxygen-induced Falls in Ventilation in COPD?

The purpose of this study was to determine whether supplemental oxygen-induced decreases in ventilation (VE) and mouth occlusion pressure (P0.1) in patients with COPD are related to the ventilatory or P0.1 responses to hypoxia (delta VE/delta SaO2, delta P0.1/delta SaO2). We measured these responses in 14 patients with a (mean +/- SD) FEV1 of 0.95 +/- .41 L. The VE and P0.1 were also measured while the patients sequentially breathed either room air or supplemental oxygen (1-2 L/min) for 10 min in a randomized single blind fashion. The mean (+/- SEM) SaO2 increased from 90.8 +/- 0.99 percent to 95.2 +/- 0.46 percent and the VE decreased during oxygen breathing from 12.3 +/- 0.46 to 11.6 +/- 0.47 L/min (p < 0.03). However, the individual changes in VE were not significantly related to the corresponding changes in SaO2 (CHG SaO2), (delta VE/delta SaO2), or (delta VE/SaO2) (CHG SaO2). Similarly, the P0.1 decreased from 2.50 +/- 0.27 to 2.26 +/- 0.20 cm H2O (p < 0.05), but the individual changes in P0.1 were not significantly related to (CHG SaO2), (delta P0.1/delta SaO2), or (delta PO.1/delta SaO2) (CHG SaO2).

Plasma potassium and ventilation during incremental exercise in humans: modulation by sodium bicarbonate and substrate availability.

It has recently been demonstrated that, compared to normal conditions, ventilation (VE) was increased during exercise after glycogen depletion, in spite of a marked increase in plasma pH (pHP). It was further demonstrated that VE in patients with McArdle's syndrome was reduced when substrate availability was improved. In the present experiments, six endurance trained men performed two successive cyclo-ergometric incremental exercise tests (tests A, B) after normal nutrition (N) and after a fatty meal in conjunction with a sodium bicarbonate (NaHCO3) solution (FSB) or without NaHCO3 (F), and the relationship between VE, plasma potassium concentration ([K+]P), and pHP was checked. Plasma free fatty acid concentration ([FFA]P) was markedly increased in the F and FSB trials (P < 0.001). In FSB pHP was significantly increased, compared to N and F (P < 0.001). In all the B tests, pHP increased during moderate and intense exercise and in FSB, remained alkalotic even during maximal exercise intensity. In contrast, VE and [K+]P changes were almost equal in all the trials and in tests A and B. It was found that exercise-induced changes of VE and [K+]P in the present experiments were not markedly affected by [FFA]P or pHP values and that these changes also occurred independently of changes in pHP or plasma bicarbonate concentration. The often used glycogen depletion strategy may have slightly increased VE but apparently did not overcompensate for a possible decrease in VE due to increased pHP.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Insufflation: Increasing Flow Rates Progressively Reduce Dead Space in Respiratory Failure

We have previously shown that airway insufflation (AI) reduces dead space (VD) and minute ventilation (VL) in patients with respiratory failure, and when used chronically leads to lowered and more stable arterial PCO2. The present study was designed to measure the effect of increasing AI flow rate on VD and other aspects of gas exchange in respiratory failure in order to examine the hypothesis that AI exerts its main physiologic effect by progressive reductions of VD. Five patients with varying degrees of respiratory failure caused by either restrictive or obstructive lung disease were studied by means of the specialized techniques we developed to analyze gas exchange during AI. At 1 L/min (as in transtracheal oxygenation), at 5 L/min, and 8 L/min, AI produced progressive reductions in VD, tidal volume, and VL. Contrary to our previous study, some of these patients accompanied the decrease in VD with not only decreases in VL but with slight rises in alveolar ventilation (VA) and decrements in arterial PCO2. The greatest percentile decreases in VD and VL occurred in those with the smallest initial control values for each of these parameters. In summary, AI exerts its main effects on gas exchange through the reductions in VD that it produces, and the accompanying decreases in VL and/or slight increases in VA seem to stem from the latter.

Target-flow inspiratory muscle training

In target-flow inspiratory muscle training (TF-IMT), the generated inspiratory mouth pressure and the duration of the inspiration and expiration are standardized to given an adequate training stimulus to the inspiratory muscles. The acute effects of TF-IMT on the efficiency of breathing were studied in a group of 12 COPD patients with a ventilatory limitation of their exercise capacity (mean age 58, mean FEV1 46.2% of predicted) and in 15 normal subjects (mean age 30). Also, the effect of a 10 week period of TF-IMT on the maximal inspiratory mouth pressure (PImax) in the COPD patients was measured. After an unloaded baseline period, the subjects started to inspire through a target-flow device during 15 min, followed by a recovery phase of 5 min. During TF-IMT minute ventilation (VE) decreased only in the COPD group. The ventilatory equivalent for O2 (VE/VO2) and the dead space to tidal volume ratio (VD/VT) decreased in both groups. During recovery, VE, VE/VO2 and VD/VT remained below baseline values in the COPD group, but not in the control group. PCO2 and lactate concentrations did not change during TF-IMT. After the 10 week training period, PImax [means) (SD] increased from 5.7(2.2) to 8.2(2.7) kPa (p less than 0.05). The results indicate that with standardized TF-IMT, the inspiratory muscles can be trained effectively in COPD patients with a ventilatory limitation. The persistence of the decrease in VE, VE/VO2 and VD/VT after a training session may be an additional beneficial effect of TF-IMT.

Reductions in Exercise Lactic Acidosis and Ventilation as a Result of Exercise Training in Patients with Obstructive Lung Disease

Though exercise training is part of most pulmonary rehabilitation programs, whether there is a physiologic basis for increased exercise tolerance is unclear. We sought to determine whether patients with chronic obstructive pulmonary disease (COPD) are capable of obtaining a physiologic training effect, as manifested by a reduction in blood lactate and ventilation (VE) at a given level of exercise. We also sought to determine whether training work rate determines the size of the training effect. Nineteen participants with COPD of predominantly moderate severity in an inpatient rehabilitation program performed two cycle ergometer exercise tests at a low and a high work rate for 15 min or to tolerance and also an incremental exercise test to tolerance. Arterial blood was sampled for blood gas and lactate analyses. Identical tests were performed before and after 5-day-per-week cycle ergometer training for 8 wk either for 45 min/day at a high work rate (average, 71 W) or for a proportionally longer time at a low work rate (average, 30 W). Average FEV1 was 56 +/- 12% predicted and did not change with training. Peak exercise lactate (average, 6.5 mEq/L) was not correlated with FEV1. For the high work rate training group, identical work rates engendered less lactate (4.5 versus 7.2 mEq/L) and less VE (48 versus 55 L/min) after training; the low work rate training group had significantly less lactate and VE decrease (p less than 0.01). Further, endurance time for the high constant work rate increased 73% in the high work rate training group but only 9% in the low work rate training group. At identical work rates, VE decrease average 2.5 L/min per mEq/L decrease in lactate (r = 0.75). We conclude that most COPD subjects studied increased blood lactate at low work rates. Many of these patients were able to achieve a physiologic training effect. Though total work was the same, training at a high work rate was more effective than was training at a low work rate. The lower VE requirement to perform exercise was in proportion to the lower lactate level, but the VE decrease for a given decrease in lactate was smaller than that seen in normal subjects (7.2 L/min/mEq/L), apparently because patients with COPD fall to hyperventilate in response to lactic acidosis (PaCO2 does not drop). These findings provide a physiologic rationale for exercise training of patients with COPD.

Ketamine in hypovolemic dogs

The cardiopulmonary consequences of hemorrhagic hypovolemia and the subsequent administration of ketamine were evaluated in eight dogs; five additional dogs served as controls. Heart rate (HR), systemic vascular resistance, breathing rate, minute ventilation (VE), PaO2, alveolar-arterial oxygen tension gradient, and oxygen extraction ratio increased, while arterial and pulmonary pressures, CVP, cardiac output, oxygen transport, PVO2 PaCO2, mixed venous oxygen content, bicarbonate, and base deficit decreased in response to hypovolemia. Ketamine administration was associated with a significant increase in HR, arterial and pulmonary BP, and PaCO2, and a significant decrease in VE (transient), PaO2 (transient), and pH. Ketamine supported cardiovascular function well, did not impair tissue oxygenation, and caused only transient respiratory depression in these hypovolemic dogs.

Effect of aortic balloon inflation on ventilation and brain stem blood flow in piglets

Increases in brain stem blood flow (BBF) during hypoxia may decrease tissue PCO2/[H+], causing minute ventilation (VE) to decrease. To determine whether an increase in BBF, isolated from changes in arterial PO2 and PCO2, can affect respiration, we obstructed the thoracic aorta with a balloon in 31 intact and 24 peripherally chemobarodenervated, anesthetized, spontaneously breathing newborn piglets. Continuous measurements of cardiorespiratory variables were made before and during 2 min of aortic obstruction. Radiolabeled microspheres were used to measure BBF before and approximately 30 s after balloon inflation in eight intact and five denervated animals. After balloon inflation, there was a rapid increase in mean blood pressure in both the intact and denervated animals, followed within 10 s by a decrease in tidal volume and VE. In the intact animals, the decrease in VE after acute hypertension can be ascribed to a baroreceptor-mediated reflex. After peripheral chemobarodenervation, however, acute hypertension continued to produce a decrease in VE, which cannot be explained by baroreceptor stimulation. In these denervated animals, aortic balloon inflation was associated with an increase in BBF (13.1 +/- 2.7%; P less than 0.05). We speculate that the increase in BBF during hypoxia may contribute to the decrease in ventilation observed after carotid body denervation.

No effect of brain blood flow on ventilatory depression during sustained hypoxia

Minute ventilation (VE) during sustained hypoxia is not constant but begins to decline within 10-25 min in adult humans. The decrease in brain tissue PCO2 may be related to this decline in VE, because hypoxia causes an increase in brain blood flow, thus resulting in enhanced clearance of CO2 from the brain tissue. To examine the validity of this hypothesis, we measured VE and arterial and internal jugular venous blood gases simultaneously and repeatedly in 15 healthy male volunteers during progressive and subsequent sustained isocapnic hypoxia (arterial PO2 = 45 Torr) for 20 min. It was assumed that jugular venous PCO2 was an index of brain tissue PCO2. Mean VE declined significantly from the initial (16.5 l/min) to the final phase (14.1 l/min) of sustained hypoxia (P less than 0.05). Compared with the control (50.9 Torr), jugular venous PCO2 significantly decreased to 47.4 Torr at the initial phase of hypoxia but did not differ among the phases of hypoxia (47.2 Torr for the intermediate phase and 47.7 Torr for the final phase). We classified the subjects into two groups by hypoxic ventilatory response during progressive hypoxia at the mean value. The decrease in VE during sustained hypoxia was significant in the low responders (n = 9) [13.2 (initial phase) to 9.3 l/min (final phase of hypoxia), P less than 0.01], but not in the high responders (n = 6) (20.9-21.3 l/min, NS). This finding could not be explained by the change of arterial or jugular venous gases, which did not significantly change during sustained hypoxia in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory and neuroendocrine responses of piglets to hypoxia during postnatal development.

Breathing response to 12% and 6% O2 in N2 (at isocapnia) was measured in anaesthetized piglets, 1-5 and 19-25 days old, before and after 3 mg kg-1 i.v. naltrexone. The degree of interaction between the anaesthetic and naltrexone was assessed. At the end of each hypoxic trial, arterial blood was sampled for measurements of pH and gas tensions, (Met)enkephalin-Arg6-Phe7, adenosine, noradrenaline and adrenalin. Whereas respiration in older animals was stimulated by hypoxia, young piglets had a biphasic response with a pronounced ventilatory decrease in response to severe hypoxia (6% O2/N2). In young animals there was a greater ventilatory response with naltrexone than without the drug, and the biphasic hypoxic response was ameliorated or reversed by naltrexone. Levels of adrenalin increased and those of encephalin, adenosine and noradrenaline tended to increase during hypoxia in the younger age group. Levels of adenosine showed significant increase when data from both age groups and levels of hypoxia were pooled. Combined with previously reported physiological evidence regarding adenosine in hypoxic depression, we conclude that the present results are compatible with a role of opioid peptides and adenosine in the early postnatal response to hypoxia.

The pathophysiology of septic ventilatory depression and apnea in infancy

Ventilatory depression and apnea are well-known early pulmonary responses to sepsis in infants, yet their underlying mechanisms are not understood. To further elucidate the pathophysiology, we induced Escherichia coli septicemia in young piglets and studied sequential changes in intrapulmonary shunt (QS/QT), physiological dead space (VD/VT), minute ventilation (VE), and blood gases for up to 6 h of lethal sepsis. Lung lymph was also collected by cannulating the right lymphatic duct and extravascular lung water (EVLW) was measured. Compared to the controls, QS/QT increased and PaO2 decreased significantly by 30 min after E. coli infusion, followed by a significant increase in PaCO2 by 45 min and a decrease in VE or apnea in 9 of the 13 septic piglets within 1 h. Lymph flow increased to 250% over baseline after 30 min of septicemia. EVLW and dry weight of the bloodless lung (EVLW/DWL) in the septic group also increased significantly within 1 h. Histology confirmed that interstitial edema developed by 1 h after E. coli infusion. These sequential data suggest that high-permeability pulmonary edema is a contributing factor in early ventilation-perfusion maldistribution in spontaneously breathing, young septic piglets. The latter in turn appears to be responsible for hypoxemia and subsequent ventilatory depression and apnea.

Effect of halothane on diaphragmatic muscle function in pentobarbital-anesthetized dogs.

The mechanism underlying the decrease in minute ventilation (VE) observed under halothane anesthesia was investigated in nine spontaneously breathing dogs. Anesthesia was induced with pentobarbital sodium and was maintained with halothane. Inspired fraction of halothane (FIhal) was increased every 30 min, from 0.005 to 0.02. VE decreased from 8.1 +/- 0.9 to 4.8 +/- 0.4 l . min-1 (P less than 0.001), as FIhal increased from 0 to 0.02. This resulted from a decrease in both mean inspiratory flow (VT/TI) and the duty ratio (TI/TTOT). Transdiaphragmatic pressure (Pdi) and the integrated electrical activity of both hemidiaphragms (Edi) were measured during normal breathing, and during breathing against closed airways (P0di, E0di), in order to obtain an index of the inspiratory neuromuscular output of the diaphragm. With increasing FIhal, there was a significant decrease in Pdi, P0di, Edi, and E0di. The authors measured Pdi and Edi generated during supramaximal stimulation of the two phrenic nerves (PSdi, Esdi) at frequencies of 10, 20, 50, and 100 Hz, in order to eliminate in this decrease the role played by a decrease in the neural drive to breathing. PSdi and ESdi decreased significantly with increasing FIhal, and had not returned to the control values 30 min after discontinuation of halothane administration. The authors conclude that, in pentobarbital-anesthetized dogs, halothane is responsible for a diaphragmatic dysfunction, which may be located either at the neuromuscular junction, on the contractile processes of the muscle, or on both, and for a decrease in the activation time of the inspiratory muscles. Both of these effects contribute to the decrease in VE observed under halothane anesthesia.

VENTILATORY RESPONSES TO CARBON DIOXIDE IN CHILDREN DURING NITROUS OXIDE-HALOTHANE ANAESTHESIA

The ventilatory response to carbon dioxide was studied in 12 unpremedicated children, aged 20-68 months, weighing between 10 and 20 kg, under nitrous oxide-halothane anaesthesia. Tidal volume (VT) and end-tidal carbon dioxide tension (PE'CO2) were continuously measured by pneumotachograph and capnograph. Minute ventilation (VE), respiratory rate (f), mean inspiratory flow (Vl) and effective inspiratory cycle (Tl/Ttot) were calculated during anaesthesia at three different inspired halothane concentrations (0.5, 1 and 1.5%). The ventilatory response to carbon dioxide was determined by relating the increase in ventilation during exposure to 2% carbon dioxide to the change in end-tidal carbon dioxide concentration. When the inspired concentration of halothane increased, there were significant decreases in VE, VT, Vl, and a significant increase in PE' CO2. The slope of the carbon dioxide response under light nitrous oxide-halothane anaesthesia (0.5% halothane) was relatively flat (18.64 ml min-1 kg-1 mm Hg-1) when compared with the mean values published for anaesthetized adults, children or neonates. When the inspired concentration of halothane was increased, the slope decreased significantly (39% of initial value at 1% inspired halothane, 26% at 1.5%). The addition of carbon dioxide produced significant increases in VE, VT and Vl but no change in respiratory rate. No statistical difference was observed in the slope of carbon dioxide response between the initial and "control" periods which were measured at the same inspired halothane concentration (0.5%).

Effects of altered ambient temperature on metabolic rate during CO2 inhalation.

The purpose of this study was to determine if the changes in O2 consumption (VO2) during CO2 inhalation could in part be due to stimulation of thermogenesis for homeothermy. Twelve ponies were exposed for 30-min periods to inspired CO2 (PIco2) levels of less than 0.7, 14, 28, and 42 Torr during the winter at 5 (neutral) and 23 degrees C ambient temperatures (TA) and during the summer at 21 (neutral TA), 30, and 12 degrees C. Elevating TA in both seasons resulted in an increased pulmonary ventilation (VE) and breathing frequency (f) (P less than 0.01) but no significant increase in VO2 (P greater than 0.05). Decreasing TA in the summer resulted in a decrease in VE and f (P less than 0.01) but no significant change in VO2 (P greater than 0.05). At neutral TA in both seasons, VO2 increased progressively (P less than 0.05) as PIco2 was increased from 14 to 28 and 42 Torr. The increases in VO2 during CO2 inhalation were attenuated (P less than 0.05) at elevated TA and accentuated at the relatively cold TA in the summer (P less than 0.05). Respiratory heat loss (RHL) during CO2 inhalation was inversely related to TA. Above a threshold RHL of 2 cal X min-1 X m-2, metabolic heat production (MHP) increased 0.3 cal X min-1 X m-2 for each unit increase in RHL during CO2 inhalation at the neutral and elevated TA. However, during cold stress in the summer, the slope of the MHP-RHL relationship was 1.6, indicating an increased MHP response to RHL.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of a single breath of 100% oxygen on respiration in neonates during sleep

To determine the effect of a single breath of 100% O2 on ventilation, 10 full-term [body wt 3,360 +/- 110 (SE) g, gestational age 39 +/- 0.4 wk, postnatal age 3 +/- 0.6 days] and 10 preterm neonates (body wt 2,020 +/- 60 g, gestational age 34 +/- 2 wk, postnatal age 9 +/- 2 days) were studied during active and quiet sleep states. The single-breath method was used to measure peripheral chemoreceptor response. To enhance response and standardize the control period for all infants, fractional inspired O2 concentration was adjusted to 16 +/- 0.6% for a control O2 saturation of 83 +/- 1%. After 1 min of control in each sleep state, each infant was given a single breath of O2 followed by 21% O2. Minute ventilation (VE), tidal volume (VT), breathing frequency (f), alveolar O2 and CO2 tension, O2 saturation (ear oximeter), and transcutaneous O2 tension were measured. VE always decreased with inhalation of O2 (P less than 0.01). In quiet sleep, the decrease in VE was less in full-term (14%) than in preterm (40%) infants (P less than 0.001). Decrease in VE was due primarily to a drop in VT in full-term infants as opposed to a fall in f and VT in preterm infants (P less than 0.05). Apnea, as part of the response, was more prevalent in preterm than in full-term infants. In active sleep the decrease in VE was similar both among full-term (19%) and preterm (21%) infants (P greater than 0.5). These results suggest greater peripheral chemoreceptor response in preterm than in full-term infants, reflected by a more pronounced decrease in VE with O2. The results are compatible with a more powerful peripheral chemoreceptor contribution to breathing in preterm than in full-term infants.

Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure.

The effects of the administration of 100% oxygen on minute ventilation (VE) and arterial blood gases were studied in patients with chronic obstructive pulmonary disease during acute respiratory failure. The administration of O2 resulted in an early decrease in VE, which averaged 18% +/- 2 SE of the control VE, and was due to a decrease in both tidal volume (VT) and respiratory frequency (f). This was followed by a slow increase in VE, such that after 15 min of breathing O2, VE rose to 93 +/- 6% of the control room air value, with both VT and f similar to control values. Despite the small difference between VE while breathing room air and that at the fifteenth minute of O2 inhalation, PaCO2 increased by 23 +/- 5 mmHg, and no significant correlation was found between the changes in VE and PaCO2. By the fifteenth minute of O2 inhalation the PaO2 averaged 225 +/- 23 mmHg, and it was concluded that despite the removal of the hypoxic stimulus of O2 inhalation, the activity of the respiratory muscles remained great enough to maintain VE at nearly the same degree as that while breathing room air. Consequently, the changes in PaCO2 after the administration of O2 were mainly due to increased inhomogeneity of VA/Q distribution within the lungs.

Thyrotoxicosis: Comparison of Effects of Thyroid Ablation and Beta-Adrenergic Blockade on Metabolic Rate and Ventilatory Control*

To elucidate the role of the beta-sympathetic system in thyrotoxicosis (THY), we examined cardiac sensitivity to infused beta-agonist and compared the effect of beta-blockade with that of resolution of the hyperthyroid state. Beta-sympathetic (beta-SYM) sensitivity was measured as the heart rate response to isoproterenol in THY patients and in normal subjects. The patients with THY showed both lower threshold (P less than 0.05) and increased slope (P less than 0.05) of the heart rate-isoproterenol response, suggesting beta-SYM hypersensitivity. The beta-SYM like features of THY were measured in 7 patients before and 7 days after beta-SYM blockade with propranolol (mean dose 411 +/- 32 mg/day [SEM]) which was shown to block the heart rate response to isoproterenol. These results were compared with those in a similar group of thyrotoxic patients rendered euthyroid with 131I. During beta-SYM blockade, heart rate decreased from 101 +/- 6.3 to 78 +/- 4.6 (P less than 0.01), but the elevated metabolic rate (V02), resting ventilation (VE), and increased hypoxic and hypercapnic ventilatory responses were not significantly affected. In the group rendered euthyroid with 131I, heart rate decreased from 110 +/- 3.5 to 76 +/- 7.8 (P less than 0.02), but in contrast to the result of beta-SYM blockade, a 28% decrease in VO2 (P less than 0.01), 41% decrease in VE (P less than 0.05), a 38% decrease in hypercapnic ventilatory response (P less than 0.05), and a 66% decrease in hypoxic response (P less than 0.03) occurred. During THY, beta-SYM mechanisms are responsible for part of the tachycardia, but the metabolic and ventilatory abnormalities are not beta-SYM mediated.

Regional Functional Decrease in Bronchial Carcinoma

Preoperative regional functional analysis with bronchospirometry was done in 180 patients operated on for bronchial carcinoma during the years 1954 to 1964. Ventilatory decrease in the cancerous lung seems to occur earlier than circulatory decrease. With higher functional decrease, circulation becomes more impaired than ventilation. Evaluation of the regional circulatory decrease yields better preoperative information on operability than does regional ventilatory decrease. A close correlation exists between regional circulatory decrease and the survival rate. Gross vascular involvement goes hand in hand with extensive lymph node metastases. Analysis of the regional function should always be done preoperatively either by bronchospirometry or by xenon 133 radiospirometry. Classification on the basis of the regional functional decrease in the cancerous lung has proved to be simple and of great practical value in determining operability.