R. H. Ingram

Arterial Oxygenation during Hemodialysis

A FALL in partial pressure of arterial oxygen, or oxygen tension (Pao2), occurring during hemodialysis is a well described phenomenon.1 , 2 The published data, however, are disparate over its cause...

Effects of frequency, tidal volume, and lung volume on CO2 elimination in dogs by high frequency (2-30 Hz), low tidal volume ventilation.

Recent studies have shown that effective pulmonary ventilation is possible with tidal volumes (VT) less than the anatomic dead-space if the oscillatory frequency (f) is sufficiently large. We systematically studied the effect on pulmonary CO2 elimination (VCO2) of varying f (2-30 Hz) and VT (1-7 ml/kg) as well as lung volume (VL) in 13 anesthetized, paralyzed dogs in order to examine the contribution of those variables that are thought to be important in determining gas exchange by high frequency ventilation. All experiments were performed when the alveolar PCO2 was 40 +/- 1.5 mm Hg. In all studies, VCO2 increased monotonically with f at constant VT. We quantitated the effects of f and VT on VCO2 by using the dimensionless equation VCO2/VOSC = a(VT/VTo)b(f/fo)c where: VOSC = f X VT, VTo = mean VT, fo = mean f and a, b, c, are constants obtained by multiple regression. The mean values of a, b, and c for all dogs were 2.12 X 10(-3), 0.49, and 0.08, respectively. The most important variable in determining VCO2 was VOSC; however, there was considerable variability among dogs in the independent effect of VT and f on VCO2, with a doubling of VT at a constant VOSC causing changes in VCO2 ranging from -13 to +110% (mean = +35%). Increasing VL from functional residual capacity (FRC) to the lung volume at an airway opening minus body surface pressure of 25 cm H2O had no significant effect on VCO2.

Evaluation of Role Played by Mediators of Immediate Hypersensitivity in Exercise-induced Asthma

To determine whether mediators of immediate hypersensitivity played a role in the pathogenesis of exercise-induced asthma, we measured the concentration of histamine and neutrophil-chemotactic activity present in systemic arterial blood during thermal challenges in five asymptomatic asthmatics. Because exercise-induced asthma has been shown to be a result of respiratory heat loss and because respiratory heat loss during isocapnic hyperventilation has been shown to give identical responses, we chose the latter provocational method in order to minimize increases in cardiac output that might interfere with the interpretation of mediator concentrations in arterial blood. Multiple aspects of pulmonary mechanics were also recorded before and after provocation. The results of these studies were then compared with the effects observed when the same subjects inhaled aerosols of specific antigens on the same day. Each challenge produced identical alterations in lung function, and neither was associated with consistent changes in arterial histamine. However, antigen provocation evoked a sustained and prolonged release of neutrophil chemotactic activity in each subject, whereas isocapnic hyperventilation with cold air was without effect. These data strongly suggest that mast-cell derived mediators are not involved in the development or maintenance of the bronchial obstruction that follows exercise in asthmatics.

Relative contributions of large and small airways to flow limitation in normal subjects before and after atropine and isoproterenol.

Bronchodilatation was produced in normal subjects by the inhalation of atropine, a parasympatholytic agent, and isoproterenol, a beta adrenergic stimulator. Density dependence of maximal expiratory flow (Vmax), expressed as a ratio of Vmax with an 80% helium-20% oxygen gas mixture to Vmax with air at isolung volumes, indicated that the predominant flow regimes across upstream airways changed differently after each agent was given separately. After atropine Vmax increased, elastic recoil pressure did not change, and density dependence decreased. Utilizing the equal pressure points analysis which defines upstream and downstream segments of the intrathoracic airways at flow limitation, these results suggest a greater relative dilatation of the larger upstream airways such that more of the driving pressure is dissipated across the smaller airways in which flow is less dependent upon gas density. After isoproterenol Vmax increased, elastic recoil pressure did not change, and density dependence increased. This suggests a preferential dilatation of the smaller and more peripheral airways with less density-dependent flow regimes such that more of the driving pressure would be dissipated in the larger airways in which flow is more dependent upon gas density. Systematic decreases after isoproterenol lead independently to the same conclusion. After both agents together, Vmax increased and density dependence and critical alveolar pressures did not change from control, suggesting a relatively uniform dilatation of all the airways comprising the upstream segment.

Airway cooling in asthmatic and nonasthmatic subjects during nasal and oral breathing

It has been suggested that nasal breathing attenuates the airway obstruction that follows physical exertion in asthmatics. In an effort to determine the reason for this protection, we had nine asymptomatic asthmatics and five normal subjects inhale subfreezing air at equal ventilations through either their noses or mouths in a random fashion while we measured the temperature in the retrotracheal esophagus (Trt). Pulmonary mechanics recorded before and after voluntary eucapnic hyperventilation simulating moderately heavy workloads demonstrated a mean fall in forced expiratory volume in one second (as a representative variable) of 28.6% +/- 4.8% (SEM) and 7.5% +/- 1.9% from control in the oral and nasal challenges, respectively, in the asthmatic subjects (p less than 0.001). Measurement of Trt during hyperventilation showed a mean fall of 2.7 degrees +/- 0.05 degree C with nasal breathing in this group (p less than 0.0001) and a linear relationship between the degree of airway cooling and the severity of subsequent bronchoconstriction (r=0.81). The normal subject showed similar changes in temperature but did not change their lung function. These data demonstrate that nasal ventilation minimizes airway cooling in both normal and asthmatic individuals through more efficient conditioning of inspired air, and it is through this mechanism that this form of respiration protects against exercise-induced bronchospasm.

Changes in canine left ventricular size and configuration with positive end-expiratory pressure.

Previous studies have shown that left atrial pressure increases when measured relative to pleura! pressure during positive end-expiratory pressure (PEEP). We studied the factors leading to this increase in anesthetized mechanically ventilated dogs. Cardiac output was maintained nearly constant before and during PEEP, and heart rate did not change. Left atrial pressure measured relative to pleura! pressure rose by 2.5 ± 0.5 mm Hg (mean ± SB) during PEEP. Pericardial pressure did not rise more during PEEP than did pleural pressure, indications that there was a true increase in transmural left atrial pressure. With PEEP there was no change in left ventricular diastolic volume as measured by cineangiography and cinefluorography of lead markers implanted in the subendocardium. Left ventricular contractile function, as measured by ejection fraction, also was unchanged. Analysis of the ventricular axes showed an increase in the ratio of septal-lateral to apex-base and anterior-posterior axes with PEEP, indicating a shape change in the left ventricle. Plots of left ventricular volume against left atrial transmural pressure confirmed that there was a shift in the left ventricular pressure-volume curve during PEEP. Thus, the rise in left atrial transmural pressure during PEEP appears to have been caused by a change in left ventricular diastolic pressure-volume properties. We suggest that these changes in the left ventricle may be related to the effects of PEEP on the right ventricle which, in turn, influence the left ventricle. Ore Re* 44: 67S-678, 1979

Bilateral diaphragmatic paralysis with hypercapnic respiratory failure: A physiologic assessment

Bilateral diaphragmatic paralysis was suspected in a patient presenting with hypercapnic respiratory failure who exhibited paradoxic (i.e., inward) abdominal movement on inspiration during tidal breathing in the supine posture; no paradoxic abdominal motion was observed at the bedside with the patient upright. Transdiaphragmatic pressure measurements established the diagnosis of diaphragmatic paralysis, although 20 cm H2O pressure developed across the diaphragm during the latter part of a forced expiration, presumably due to the development of passive tension in the diaphragm as it was stretched near residual volume. Analysis of the relative motion of the rib cage and abdomen during breathing by the use of magnetometers confirmed the presence of abdominal paradox throughout the breathing cycle when the patient was supine, and established that paradoxic motion of the abdomen also occurred when the patient was in the erect posture but only in the latter half of inspiration. Our findings confirm that the use of transdiaphragmatic pressure measurements and magnetometry will help to quantify diaphragmatic function, that passive tension develops in the paralyzed diaphragm near residual volume and should not be confused with active contraction, and that paradoxic motion of the abdomen may be masked from the clinician when the patient is erect.

Relationship between bronchial responsiveness to hyperventilation with cold and methacholine in asthma

Twenty-seven subjects with asthma and normal baseline lung function were challenged with aerosols of methacholine (M) and by isocapnic hyperventilation with cold air (HV). Stimulus-effect relationships were determined for each provocational technique on separate days and were expressed as the dose required to produce a 20% fall in forced expired volume in 1 sec (FEV1) obtained by linear interpolation from log stimulus vs. response curves (PD20). Each stimulus was applied with a sufficient intensity to produce a 20% or greater fall in FEV1 in each subject. The PD20 for M correlated significantly with the PD20 for HV (p less than 0.001) when the latter was expressed in liters per minute. The correlation between cumulative M PD20 and HV PD20 expressed as a percent of maximal voluntary ventilation was significant but less strong. We conclude that the airway response to HV reflects nonspecific bronchial hyperresponsiveness and that the dose of HV is best determined as the absolute level of ventilation.

Magnitude and site of airway response to exercise in asthmatics in relation to arterial histamine levels

In order to determine if there is a relationship among arterial histamine levels, state of disease activity, and the magnitude and site of obstruction in exercise-induced asthma, we recorded airway resistance, lung volumes, spirometry, and density dependence of maximum expiratory flow before and after an exercise challenge in 17 asymptomatic individuals. These observations were then related to the concentration of histamine in systemic arterial blood. This study demonstrates that those individuals whose disease process was the most active at the time of investigation had more depressed lung function and higher baseline histamine levels, and responded to the challenge with severe obstruction that involved the airways in the periphery of the lung. In contrast, those subjects whose underlying disease was more quiescent had lower histamine values and the response to provocation was less severe and predominated in the larger airways. In neither group did the postchallenge values for histamine increase. It is suggested that the factor that determines these patterns of response is the state of inflammation of the airways, for which histamine may serve as a marker.

Respiratory Changes During Exercise in Patients With Pulmonary Venous Hypertension

HE acute* physiologic responses of the respiratory and cardiovascular systems to physical exercise have been well studied in normal human subjects and in patients with obstructive airway disease. In patients with primary heart disease acute cardiovascular responses to exercise have been more completely characterized than have the respiratory ones. It is logical to have mainly studied circulatory factors in patients with heart disease, since it is the circulation, possibly the work of the heart, which limits exercise performance in normal subjects. 1,2 However, due to the integrated nature of the heart-lung system it is difficult for one component to be compromised without altering the function of the other.3 It is now well understood that increases in left atrial pressure produce both pulmonary mechanical and gas exchange abnormalities. Thus as heart failure increases during exercise, lung function would be expected to become more compromised. Exploration of the potential role of this progressively parallel heart and lung dysfunction during exercise is the purpose of this brief review. In order to accomplish this goal we will describe the quantitative and qualitative aspects of the normal respiratory physiologic response to exercise, then outline the demonstrated respiratory pathophysiologic abnormalities found at rest in patients with primary cardiac disease, and, finally, attempt a synthesis of the many respiratory pathophysiologic changes that have been either demonstrated or that are to be reasonably expected during exercise in such patients.