Effects of theophylline on diaphragmatic strength and fatigue in patients with chronic obstructive pulmonary disease

We studied the effects of theophylline on diaphragmatic strength and fatigue in 15 patients with severe chronic obstructive pulmonary disease. Diaphragmatic strength was assessed by measurement of the transdiaphragmatic pressure generated at functional residual capacity during a maximal inspiratory effort against closed airways. Diaphragmatic fatigue was induced by resistive loaded breathing. The electrical activity of the diaphragm was recorded with an esophageal electrode during the fatigue runs, and the high-low ratio of the electrical signal was analyzed to assess diaphragmatic fatigue. Studies were performed before and after 7 and 30 days of theophylline administration (mean plasma level, 13 +/- 2 mg per liter). A control group received a placebo instead of theophylline. Theophylline increased maximal transdiaphragmatic pressure by 16 per cent after 7 days of administration (P less than 0.01), and this increase persisted after 30 days. No significant change in maximal transdiaphragmatic pressure was observed in the group given the placebo. Theophylline also suppressed diaphragmatic fatigue in all patients who received it. We conclude that theophylline has a potent and long-lasting effect on diaphragmatic strength and fatigue in patients with fixed airway obstruction.     

Task failure from inspiratory resistive loaded breathing: a role for inspiratory muscle fatigue?

The use of non-invasive resistive breathing to task failure to assess inspiratory muscle performance remains a matter of debate. CO₂ retention rather than diaphragmatic fatigue was suggested to limit endurance during inspiratory resistive breathing. Cervical magnetic stimulation (CMS) allows discrimination between diaphragmatic and rib cage muscle fatigue. We tested a new protocol with respect to the extent and the partitioning of inspiratory muscle fatigue at task failure. Nine healthy subjects performed two runs of inspiratory resistive breathing at 67 (12)% of their maximal inspiratory mouth pressure, respiratory rate ( f_R), paced at 18 min^–1, with a 15-min pause between runs. Diaphragm and rib cage muscle contractility were assessed from CMS-induced esophageal (P_es,tw), gastric (P_ga,tw), and transdiaphragmatic (P_di,tw) twitch pressures. Average endurance times of the first and second runs were similar [9.1 (6.7) and 8.4 (3.5) min]. P_di,tw significantly decreased from 33.1 to 25.9 cmH₂O in the first run, partially recovered (27.6 cmH₂O), and decreased further in the second run (23.4 cmH₂O). P_es,tw also decreased significantly (–5.1 and –2.4 cmH₂O), while P_ga,tw did not change significantly (–2.0 and –1.9 cmH₂O), indicating more pronounced rib cage rather than diaphragmatic fatigue. End-tidal partial pressure of CO₂ (P_ETCO₂) rose from 37.2 to 44.0 and 45.3 mmHg, and arterial oxygen saturation (S_aO₂) decreased in both runs from 98% to 94%. Thus, task failure in mouth-pressure-targeted, inspiratory resistive breathing is associated with both diaphragmatic and rib cage muscle fatigue. Similar endurance times despite different degrees of muscle fatigue at the start of the runs indicate that other factors, e.g. increases in P_ETCO₂, and/or decreases in S_aO₂, probably contributed to task-failure.     

Characteristics of diaphragmatic fatigue during exhaustive exercise until task failure

The diaphragm was postulated to fatigue relatively early during exhaustive whole body exercise without further loss in contractility as exercise proceeds towards task failure. Diaphragmatic contractility was investigated prior/during/after exhaustive whole body exercise until task failure by using lung volume corrected twitch transdiaphragmatic pressure (TwPdi(c)) during magnetic phrenic nerve stimulation (every 45s). Eleven cyclists exercised to exhaustion (workloads ≥85% maximal oxygen uptake; 20.7±9.8min). Individual post hoc calculation of TwPdi(c) was conducted (diaphragmatic contractility versus lung volume). Diaphragmatic fatigue (i.e. TwPdi reduction baseline/recovery ≥10%) occurred in 9/11 subjects (82% "fatiguers"; baseline/recovery TwPdi(c) -16±13%, p<0.01). Fatiguers TwPdi(c) was: baseline: 2.99±0.40kPa, exercise-onset: 2.98±0.41kPa, initial third: 2.80±0.67kPa, second third: 2.54±0.55kPa, final third-task failure: 2.51±0.44kPa, recovery: 2.50±0.52kPa. Diaphragmatic contractility and lung volume (rest) were strongly related (r(2)=0.98, mean TwPdi(c) gradient 0.78kPa/l). To conclude, diaphragmatic contractility (lung volume corrected) decreases relatively early (initial two thirds) during exhaustive exercise and remains preserved towards task failure. This confirms previous assumptions postulating that respiratory performance is sustained without further fatigue of the primary inspiratory muscle.     

Electrical activity of the human respiratory muscles during the action of various humoral influences on the respiratory center

Summary The electrical activity of human inspiratory and expiratory muscles was studied in hypoxia, hyperoxia, and hypercapnia during added resistance to respiration. The results obtained confirmed that in man the inspiratory and expiratory zones are reciprocally related. This condition was distinctly demonstrated during changes of the arterial blood oxygen and carbon dioxide tensions. In hypoxic hypoxia and hypercapnia electrical activity of the inspiratory muscles was enhanced, and that of the expiratory muscles reduced. The reverse effect was obtained during the inhalation of pure oxygen.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 54, No. 7, pp. 3–6, July, 1962     

Contractile properties of the human diaphragm during chronic hyperinflation

BACKGROUND. In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation. We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm. METHODS. In eight patients with COPD and five control subjects of similar age, the transdiaphragmatic pressure generated by the twitch response to phrenic-nerve stimulation was recorded at various base-line lung volumes, from functional residual capacity to total lung capacity, and during relaxation and graded voluntary efforts at functional residual capacity (twitch occlusion). RESULTS. At functional residual capacity, the twitch transdiaphragmatic pressure ranged from 10.9 to 26.6 cm of water (1.07 to 2.60 kPa) in the patients and from 19.8 to 37.1 cm of water (1.94 to 3.64 kPa) in the controls, indicating considerable overlap between the two groups. The ratio of esophageal pressure to twitch transdiaphragmatic pressure, an index of the inspiratory action of the diaphragm, was -0.50 +/- 0.05 in the patients, as compared with -0.43 +/- 0.02 in the controls (indicating more efficient inspiratory action in the patients than in the controls). At comparable volumes, the twitch transdiaphragmatic pressure and esophageal-to-transdiaphragmatic pressure ratio were higher in the patients than in normal subjects, indicating that the strength and inspiratory action of the diaphragm in the patients were actually better than in the controls. Twitch occlusion (a measure of the maximal activation of the diaphragm) indicated near-maximal activation in the patients with COPD, and the maximal transdiaphragmatic pressure was 106.9 +/- 13.8 cm of water (10.48 +/- 1.35 kPa). CONCLUSIONS. The functioning of the diaphragms of the patients with stable COPD is as good as in normal subjects at the same lung volume. Compensatory phenomena appear to counterbalance the deleterious effects of hyperinflation on the contractility and inspiratory action of the diaphragm in patients with COPD. Our findings cast doubt on the existence of chronic fatigue of the diaphragm in such patients and therefore on the need for therapeutic interventions aimed at improving diaphragm function.     

Schlafbezogene Hypoventilation

In healthy subjects, respiratory regulation adapts alveolar ventilation to metabolic carbon dioxide production. A dysproportional decrease in alveolar ventilation after sleep onset with a consecutive rise in arterial carbon dioxide partial pressure is called sleep-related hypoventilation, which usually coincides with longer lasting arterial oxygen desaturation. Limits of normal pCO₂ values during sleep in the literature are inconsistent. The International Classification of Sleep Disorders (ICSD-2) distinguishes five types of sleep-related hypoventilation. As pathophysiological mechanisms, ??central?? mechanisms, caused by impairment of central nervous regulation of respiration are differentiated from ??peripheral?? mechanisms, caused by medical or neurological conditions. The diagnosis is based on the detection of hypercapnia. Taking into account the methodological limitations, this can be done using transcutaneous or end-tidal pCO₂ measurements.     

腹膜后腔镜手术并发高二氧化碳血症的临床观察

目的观察腹膜后腔镜手术高二氧化碳血症的发生情况,分析其相关因素,为麻醉管理提供指导。方法选取择期腹膜后腔镜手术患者40例,观测并记录气腹前（T0）、气腹后30min（T1）、气腹后60min（T2）、气腹后90min（T3）、停气腹后30min（T4）各时点的心率（HR）、收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP）、呼气末二氧化碳分压（PETCO2）、血氧饱和度（SpO2）;并同时行动脉血气分析,观察PH值、动脉血氧分压（PaO2）和动脉血二氧化碳分压（PaCO2）的变化;如患者合并皮下气肿,对其严重程度进行分级。结果全手术过程中所有患者的PaO2均〉100mmHg,SpO2均为100%,患者的HR、SBP、DBP和MAP基本平稳。与T0相比,T1、T2、T3患者PaCO2和PETCO2呈进行性升高,pH明显降低（P〈0.05）,T1、T2、T3高二氧化碳血症（PaCO2〉50mmHg）发生率分别为10%、41%、75%;30例发生皮下气肿,其中轻度13例、中度12例、重度5例,5例重度皮气肿患者PaCO2最高超过80mmHg,PETCO2最高超过50mmHg;另有1例术中出现气胸。结论腹膜后腔镜手术易发生高二氧化碳血症,气腹时间、皮下气肿严重程度等都为相关因素,提示麻醉期间应警惕高二氧化碳血症,以早期发现、及时处理。     

Mapping of the cerebral vascular response to hypoxia and hypercapnia using quantitative perfusion MRI at 3 T

Changes in breathing change the concentration of oxygen and carbon dioxide in arterial blood resulting in changes in cerebral blood flow (CBF). This mechanism can be described by the cerebral vascular response (CVR), which has been shown to be altered in different physiological and pathophysiological states. CBF maps of grey matter (GM) were determined with a pulsed arterial spin labelling technique at 3 T in a group of 19 subjects under baseline conditions, hypoxia, and hypercapnia. Experimental conditions allowed a change in either arterial oxygen (hypoxia) or carbon dioxide (hypercapnia) concentration compared with the baseline, leaving the other variable constant, in order to separate the effects of these two variables. From these results, maps were calculated showing the regional distribution of the CVR to hypoxia and hypercapnia in GM. Maps of CVR to hypoxia showed very high intra-subject variations, with some GM regions exhibiting a positive response and others a negative response. Per 10% decrease in arterial oxygen saturation, there was a statistically significant 7.0 +/- 2.9% (mean +/- SEM) increase in GM-CBF for the group. However, 70% of subjects showed an overall positive CVR (positive responders), and the remaining 30% an overall negative CVR (negative responders). Maps of CVR to hypercapnia showed less intra-subject variation. Per 1 mm Hg increase in partial pressure of end-tidal carbon dioxide, there was a statistically significant 5.8 +/- 0.9% increase in GM-CBF, all subjects showing an overall positive CVR. As the brain is particularly vulnerable to hypoxia, a condition associated with cardiorespiratory diseases, CVR maps may help in the clinic to identify the areas most prone to damage because of a reduced CVR.     

Differences in mouth occlusion pressure and breathing pattern between arm and leg incremental exercise

The aim of the study was to compare breathing pattern, mouth occlusion pressure, mean inspiratory flow and the ratio of mouth occlusion pressure to mean inspiratory flow at the same power output and carbon dioxide output during arm and leg incremental exercise. Mouth occlusion pressure was used as an index of inspiratory neuromuscular activity and its ratio to mean inspiratory flow as an index of the ‘effective’ impedance of the respiratory system. Eight normal subjects performed two incremental exercise tests, one with arms, the other with legs, on different weeks and in randomized order, and on two identical cycle ergometers. The power output was increased by steps of 25 W for arms and 50 W for legs every 4 min until exhaustion. At the same power output, oxygen consumption, carbon dioxide output, ventilation, mean inspiratory flow, mouth occlusion pressure, ‘effective’ impedance (P<0.001) and respiratory frequency (P<0.01) were higher during arm exercise than during leg exercise, whereas inspiratory time (P<0.05) and expiratory time (P<0.01) were lower. At the same carbon dioxide output, mouth occlusion pressure, ventilation, ‘effective’ impedance (P<0.001) and respiratory frequency (P<0.01) were higher and expiratory time (P<0.05) was lower during arm exercise. In conclusion, the higher inspiratory neuromuscular activity and impedance of the respiratory system during arm exercise and the differences observed in ventilation and breathing pattern at equal carbon dioxide output seem related to the differences in exercising muscle afferents and the presence of an increased load due to contraction of rib cage muscles to stabilize posture.     

Central and peripheral components of diaphragmatic fatigue during inspiratory resistive load in cats

The development of fatigue was investigated in the diaphragm of anaesthetized, tracheostomized, spontaneously breathing cats during restricted air flow. Ventilation, transdiaphragmatic pressure (P_di), integrated electrical activity of diaphragm (E_di) and phrenic nerve (E_ph) were measured simultaneously and expressed as a percentage of values at unloaded breathing. Inspiratory loads were 60, 70 and 80% of P_{di max}. The P_{di max} was measured by airway occlusion at functional residual capacity. The duration of loads was 40–60 min. The diaphragmatic fatigue developed only during heavy inspiratory loading (80% P_{di max}). During the first 10 min of heavy load P_di, E_di and E_ph increased to 905 ± 60%, 248 ± 20% and 229 ± 24%, respectively (P < 0.01), and then began to fall gradually. Ventilation declined to 39 ± 3% after 60 min of heavy load (P < 0.01), resulting in acute hypercapnia and hypoxia. Initial fatigue appeared as a decrease in P_di (to 781 ± 63%) and parallel decline in E_di (to 233 ± 21%) after 30 min of load (P < 0.05). Phrenic nerve activity did not change during this stage. These data suggest a peripheral basis of diaphragmatic fatigue, related to disorders in neuromuscular transmission. After 60 min of heavy load, P_di fell to 675 ± 49%, E_di declined to 209 ± 28% and E_ph decreased to 189 ± 25%. We interpret the decrease in phrenic nerve activity as a weakening of central inspiratory drive and development of the central component of diaphragmatic fatigue in the last stage.     

The effect of bronchodilator drugs on breath-holding capability in asthma

A method of assessing the relationship between maximum voluntary breath-holding time (BHT) and the partial pressure of end-tidal carbon dioxide (PETCO2) during hyperoxic carbon dioxide rebreathing is described. The resulting index is referred to as the breath-holding capability (BHC). BHC and the maximum rate of early inspiratory pressure fall at the mouth while breathing oxygen at rest (RHdP/dtmax) were measured in normal and asthmatic subjects before and after treatment with nebulized solutions of salbutamol and ipratropium bromide. BHC was low in asthmatics when their airflow resistance was high and rose when the airflow resistance fell as the result of treatment; RHdp/dtmax was high in the asthmatics before treatment and fell after bronchodilator drugs were administered. The fall in respiratory drive which followed bronchodilatation in the asthmatic subjects cannot be solely explained in terms of the resulting fall in viscous and elastic work of breathing. Vagal afferent signals arising in the airways might play a part in modifying respiratory drive in such circumstances.     

Relation of oxygen delivery, mixed venous oxygenation, and pulmonary hemodynamics to prognosis in chronic obstructive pulmonary disease

We studied the relation of oxygen delivery, mixed venous oxygenation, and pulmonary hemodynamics to prognosis in 50 randomly selected patients with chronic obstructive pulmonary disease. Cardiac catheterization was performed when the patients were clinically stable. Four years later, 27 patients (54 per cent) had died of respiratory failure. At the time of catheterization, patients who subsequently lived were similar to those who died in age, physical characteristics, and hematocrit. Nonsurvivors had significantly lower arterial and mixed venous oxygen tension and significantly higher arterial and mixed venous carbon dioxide tension. The mean pulmonary arterial pressure, pulmonary arteriolar resistance, right ventricular work, coefficient of oxygen delivery, and cardiac index did not differ between the two groups. After inhalation of 100 per cent oxygen for one hour, the mixed venous oxygen tension of nonsurvivors rose to a level equivalent to that of survivors, and their mean pulmonary arterial pressure fell significantly. These results indicate that, with respect to oxygen supply to the tissues, mixed venous oxygenation is one of the important prognostic factors in chronic obstructive pulmonary disease. Pulmonary and right ventricular hemodynamics measured during periods of clinical stability do not differentiate nonsurvivors from survivors.     

Low-concentration carbon dioxide is an effective adjunct to positive airway pressure in the treatment of refractory mixed central and obstructive sleep-disordered breathing

OBJECTIVES: To assess the efficacy of added carbon dioxide as adjunctive therapy to positive airway pressure-refractory mixed obstructive and central sleep-disordered breathing, using a prototype device-the positive airway pressure gas modulator. DESIGN: Open-label evaluation of low concentrations of carbon dioxide added to a positive airway pressure circuit. SETTING: Physician-attended polysomnographic titration in a free-standing sleep laboratory with end-tidal and transcutaneous carbon-dioxide monitoring. PATIENTS: Six adult men (age 54 +/- 5.7 years) with severe poorly controlled mixed sleep-disordered breathing in the absence of renal or heart failure. INTERVENTIONS: Flow-independent addition of incremental concentrations of carbon dioxide during sleep. MEASUREMENTS AND RESULTS: The respiratory disturbance index before treatment was 66 +/- 14.5 events per hour of sleep, with a nocturnal desaturation low of 84.6% +/- 10.1%. Residual respiratory disturbance index on best treatment was 43 +/- 9 events per hour of sleep. There was an immediate (<1 minute) response to the addition of 0.5% to 1% carbon dioxide, and minimal changes were required to be made across the night. There was no discomfort, shortness of breath, palpitations, headache, or significant increase in respiratory or heart rate. The residual respiratory disturbance index on carbon dioxide, scored irrespective of desaturations, was in the normal range (< 5 / hour of sleep). Two subjects had a second night at the concentration of carbon dioxide determined to be efficacious, with no required concentration change. No adverse effects on overall sleep architecture were noted. CONCLUSIONS: Low concentrations of carbon dioxide added to conventional positive airway pressure effectively control severe treatment-resistant mixed obstructive and central sleep-disordered breathing.     

Respiratory muscle injury, fatigue and serum skeletal troponin I in rat

To evaluate injury to respiratory muscles of rats breathing against an inspiratory resistive load, we measured the release into blood of a myofilament protein, skeletal troponin I (sTnI), and related this release to the time course of changes in arterial blood gases, respiratory drive (phrenic activity), and pressure generation. After ∼1.5 h of loading, hypercapnic ventilatory failure occurred, coincident with a decrease in the ratio of transdiaphragmatic pressure to integrated phrenic activity ( P _di /∫Phr) during sighs. This was followed at ∼1.9 h by a decrease in the P _di /∫Phr ratio during normal loaded breaths (diaphragmatic fatigue). Loading was terminated at pump failure (a decline of P _di to half of steady-state loaded values), ∼2.4 h after load onset. During 30 s occlusions post loading, rats generated pressure profiles similar to those during occlusions before loading, with comparable blood gases, but at a higher neural drive. In a second series of rats, we tested for sTnI release using Western blot–direct serum analysis of blood samples taken before and during loading to pump failure. We detected only the fast isoform of sTnI, release beginning midway through loading. Differential detection with various monoclonal antibodies indicated the presence of modified forms of fast sTnI. The release of fast sTnI is consistent with load-induced injury of fast glycolytic fibres of inspiratory muscles, probably the diaphragm. Characterization of released fast sTnI may provide insights into the molecular basis of respiratory muscle dysfunction; fast sTnI may also prove useful as a marker of impending respiratory muscle fatigue.     

Abdominal expiratory muscle activity in anesthetized vagotomized neonatal rats

The pattern of respiratory activity in abdominal muscles was studied in anesthetized, spontaneously breathing, vagotomized neonatal rats at postnatal days 0–3. Anesthesia (2.0% isoflurane, 50% O₂) depressed breathing and resulted in hypercapnia. Under this condition, abdominal muscles showed discharge late in the expiratory phase (E2 activity) in most rats. As the depth of anesthesia decreased, the amplitude of discharges in the diaphragm and abdominal muscles increased. A small additional burst frequently occurred in abdominal muscles just after the termination of diaphragmatic inspiratory activity (E1 or postinspiratory activity). Since this E1 activity is not often observed in adult rats, the abdominal respiratory pattern likely changes during postnatal development. Anoxia-induced gasping after periodic expiratory activity without inspiratory activity, and in most rats, abdominal expiratory activity disappeared before terminal apnea. These results suggest that a biphasic abdominal motor pattern (a combination of E2 and E1 activity) is a characteristic of vagotomized neonatal rats during normal respiration.     

A mechanism of central sleep apnea in patients with heart failure.

BACKGROUND: Breathing is controlled by a negative-feedback system in which an increase in the partial pressure of arterial carbon dioxide stimulates breathing and a decrease inhibits it. Although enhanced sensitivity to carbon dioxide helps maintain the partial pressure of arterial carbon dioxide within a narrow range during waking hours, in some persons a large hyperventilatory response during sleep may lower the value below the apneic threshold, thereby resulting in central apnea. I tested the hypothesis that enhanced sensitivity to carbon dioxide contributes to the development of central sleep apnea in some patients with heart failure. METHODS: This prospective study included 20 men who had treated, stable heart failure with left ventricular systolic dysfunction. Ten had central sleep apnea, and 10 did not. The patients underwent polysomnography and studies of their ventilatory response to carbon dioxide. RESULTS: Patients who met the criteria for central sleep apnea had significantly more episodes of central apnea per hour than those without central sleep apnea (mean [+/-SD], 35+/-24 vs. 0.5+/-1.0 episodes per hour). Those with sleep apnea also had a significantly larger ventilatory response to carbon dioxide than those without central sleep apnea (5.1+/-3.1 vs. 2.1+/-1.0 liters per minute per millimeter of mercury, P=0.007), and there was a significant positive correlation between ventilatory response and the number of episodes of apnea and hypopnea per hour during sleep (r=0.6, P=0.01). CONCLUSIONS: Enhanced sensitivity to carbon dioxide may predispose some patients with heart failure to the development of central sleep apnea.     

124例健康成人吸气肌强度和耐力测定

本文测定了124例健康成人最大吸气压和最大持续吸气压,探讨吸气肌强度和耐力的分布及影响因素。发现最大吸气压和最大持续吸气压受年龄、体重和性别响影,吸气肌张力时间指数0.30可作为检测吸气肌疲劳的临界阈值。     

Separate resistive loading of the respiratory phases during mild hypercapnia in man

Eleven human subjects were studied during steady state, controlled mild hypercapnia with resistive loading of either inspiration (RI) or expiration (RE). Minute ventilation and frequency were significantly reduced by RI (P = less than 0.01) and even more so by RE (P = less than 0.001). Tidal volume was unchanged. Both RI and RE reduced mean flow in the loaded phase - an effect relatively greater with RE. Neither RI nor RE altered mean flow in the unloaded phase. Although mean inspiratory flow was unchanged with RE, mouth occlusion pressure (P0.1) was increased (P = less than 0.01). Functional residual capacity (seven subjects) was increased with RE, but not with RI (P = less than 0.05). Five additional subjects were similarly studied with and without RE in whom transdiaphragmatic pressure (PDi) and peak diaphragmatic EMG (EMGDi) were examined. Changes in ventilation, breathing pattern and P0.1 were similar to those described above. Neither PDi nor EMGDi were significantly altered by RE, but with RE, diaphragmatic EMG activity began 50-190 ms before inspiratory flow. In conclusion, ventilation is reduced more by RE than by RI due to greater respiratory phase time. Moderately heavy RE does not augment inspiratory drive as reflected by mean flow, PDi or EMGDi. With RE and increased FRC, P0.1 does not accurately reflect inspiratory drive because of dissociation between EMG and flow.     

P pulmonale in status asthmaticus.

We studied 129 patients during acute, severe asthmatic attacks. Electrocardiograms showed P pulmonale in 49% of patients who had an arterial carbon dioxide tension (PaCo2) greater than or equal to 45 mm Hg and an arterial pH less than or equal to 7.37, whereas P pulmonale was present in only 2.5% of asthmatics who had a PaCO2 less than or equal to 44 mm Hg and a pH greater than or equal to 7.38 (p less than 0.001). P wave and QRS axes were 79 +/- 8 degrees and 80 +/- 20 degrees, respectively, in the presence of P pulmonale. When P pulmonale disappeared, the P wave and QRS axes shifted significantly to the left (p less than 0.001). Electrocardiographic P pulmonale persisted 12 to 60 hr after correction of hypoxemia, hypercapnia, and acidosis. In 7 patients with P pulmonale and respiratory acidosis, cardiac catheterization demonstrated normal artery pressures (PAPs) measured relative to atmospheric pressure. In 12 of these peak inspiratory pulmonary artery transmural pressures (PATPs) were increased. Since increased right heart transumural pressures could result in chamber distention, these data are consistent with the hypothesis that reversible P pulmonale in status asthmaticus is explainable on the basis of markedly negative tidal pleural pressures and increased right heart transmural pressures.     

Characteristics of inspiratory inhibition by occlusion of both external carotid and basilar arteries in cats.

Effects of the occlusion of both the external carotid and basilar arteries on the inspiratory activity were studied in anesthetized, vagotomized, paralyzed, and artificially ventilated cats. Integrated phrenic nerve activity was used as an index of the inspiratory activity. Blood pressure in the lingual artery, located downstream from the occluded external carotid arteries, was measured as the arterial pressure of the upper brain stem during occlusion. The basilar artery was occluded at the boundary between the medulla and pons. Occlusions of the external carotid arteries and basilar artery suppressed the phrenic nerve activity to finally disappear within 1 min (phrenic nerve apnea, 45 out of 50 occlusions in 6 cats). The blood pressure in the upper brain stem was 16.6 +/- 5.7 mmHg (mean +/- S.D.) during occlusions. These effects of occlusion on the phrenic nerve activity were also observed during hypercapnia and hypoxia, although they were not so remarkable as those during normocapnia and normoxia. The results indicate that the upper part of the brain stem operates a profound facilitatory mechanism on the medullary inspiratory activity.