Transthoracic Pressure Research Articles

Obstructive Sleep Apnea and Alzheimer’s Disease: A Two-way Street.

Background:- Obstructive sleep apnea syndrome (OSAS) and Alzheimer’s disease (AD) are really widespread chronic diseases with increasing impact on the elderly group in our society. Nowadays, many causes of obstructive sleep apnea are well identified, while Alzheimer’s disease related mechanism are still not recognized, challenging the arrival to an actual treatment. Cognitive impairment is a clinical recognized consequence of obstructive sleep apnea, which is a result of intermittent hypoxia, disruptions of sleep architecture, oxidative stress, hemodynamic and transthoracic pressure changes, all of these factors increase the Alzheimer’s disease risk in patients with obstructive sleep apnea. On the other hand, Alzheimer’s disease can aid the emergence of obstructive sleep apnea by revealing serotonin and acetylcholine deficit; which are vital neurotransmitters for upper airway patency.

Myocardial work brings a new insight into left ventricule remodelling in cardiooncology patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Serial echocardiographic assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) is the gold standard screening method for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages, as it incorporates measurements of myocardial deformation and LV pressure. Purpose To evaluate the impact of cardiotoxic treatments in MW indices. Methods Prospective study of female breast cancer patients (P) submitted to therapy (TH) who underwent serial monitoring by 2D, 3D transthoracic echocardiography (TTE) and concomitant blood pressure assessment. P were evaluated at T0, T1 and T2 (before, ≥6 and ≥12 months after starting TH). PSL analysis allowed the calculation of the following indices: Global Work Index (GWI), Global Constructive Work (GCW), Global Work Waste (GWW) and Global Work Efficiency (GWE). CTRCD was defined as an absolute decrease in 2D LVEF > 10% to a value < 54% or a relative decrease in 2D GLS > 15%, according to literature. Results 122 patients (mean age 54.7 ± 12.0 years), mostly treated with anthracyclines (77.0%, cumulative dose 268.6 ± 71.8mg/m2), anti-HER (75.4%) and radiotherapy (77.0%) were included. 2D and 3D LVEF were significantly reduced during TH, however remaining within the limits of normality (2D LVEF T0-T1 64.2 ±7.6 vs 61.1 ± 8.2%, p = 0.006 and 3D LVEF T0-T1 60.2 ± 6.7 vs 56.9 ±6.3%, p = 0.022). 2D GLS was also more impaired at T1 (-19.8 ± 2.7% vs -18.5 ± 3.0%, p = 0.003). All MW indices were significantly reduced at T1 compared to baseline (GWI 1756.9 ± 319.2 vs 1614.3 ± 338.5mmHg%, p = 0.005; GCW 2105.6 ± 352.0 vs 1970.5 ± 376.2 mmHg%, p = 0.015; GWW 121.1 ± 66.6 vs 161.1 ± 84.1 mmHg%, p = 0.001; GWE 93.5 ± 3.1 vs 91.1 ± 4.5%, p = 0.001). Between T1 and T2 no statistical difference was found but a partial recovery of parameters was observed when comparing T2 to T0 (GWI (T2) 1650.6 ± 357.5 mmHg%, p = 0.035; GCW (T2) 2013.3 ± 379.3 mmHg%, p = 0.086; GWW (T2) 148.0 ± 85.0 mmHg%, p = 0.02 and GWE (T2) 92.0 ± 4.7%, p = 0.012). During a mean follow-up of 14.9 ± 9.3 months, 36 patients (29.5%) developed CTRCD. P presenting CTRCD revealed a significant decrease in GWI and GWE at T1 comparing with women without CTRCD (GWI 1.8 ± 21.6 vs -14.2 ± 18.5%, p = 0.004 and GWE -1.0 ±3.0 vs -3.6 ±3.9%, p = 0.005). GWW had a substantially increase at T1 in P with cardiotoxicity (27.6 ± 76.3% vs 64.1 ± 68.0%, p = 0.051). Conclusion Left ventricular systolic function study with MW showed a reduction in cardiac performance with a peak at 6 months from the start of chemotherapy and partial recovery after term. Assessment of myocardial deformation parameters, namely MW, proved to be a useful tool for a better characterisation of cardiac remodelling, and could enhance patient selection for cardioprotective therapeutics. Abstract Figure. TTE parameters

Abstract 12586: Assessing Valvuloarterial Impedance in Aortic Stenosis: A Comparison of Echocardiographic- and Cardiac Magnetic Resonance-derived Methods

Introduction: Valvuloarterial impedance (Z VA ) represents the valvular and arterial factors that oppose Left Ventricular (LV) ejection and is recognised as an important index to assess global LV load in patients with Aortic Stenosis (AS). Z VA is traditionally determined by Transthoracic Echocardiogram (TTE) and brachial cuff pressure. Hypothesis: Our study sought to compare Z VA-TTE with Z VA calculated using a simultaneous Cardiac Magnetic Resonance (CMR) and Applanation Tonometry (AT) (Z VA-CMR ) technique to determine whether TTE measurement of aortic flow velocity resulted in an underestimation of Z VA. Methods: Twenty AS patients underwent a protocol of CMR/AT followed by TTE. Z VA-CMR was determined as the relationship of derived aortic pressure (radial) to CMR aortic flow velocity in the frequency domain. Z VA-TTE was determined from digitised flow velocity within the left ventricular outflow tract (LVOT) on pulsed-wave Doppler and derived central pressure waveforms. Systemic vascular resistance (SVR) was calculated from mean pressure and flow. Values from both methods were compared. Results: Our study found that Z VA-TTE values (mean±SD, 638±381 dyne.s.cm -3 ) were consistently lower (p=0.07) than Z VA-CMR values (946±318 dyne.s.cm -3 ), and attribute this to an overestimation of LVOT flow velocity on TTE. SVR calculated by CMR/AT (2215±616 dyne.s.cm -5 ) was almost four times higher than TTE (618±245 dyne.s.cm -5 ) (p<0.001). This is due to more robust axi-symmetrical sampling of aortic flow across the entire cross-section of the ascending aorta (well above the stenotic jet) during CMR, than using operator-dependent TTE. Conclusions: Whilst Z VA -TTE is commonly performed in patients with AS to assess global LV load, newer methods to assess Z VA using simultaneous CMR/AT likely represent a more accurate non-invasive assessment.

A pilot study evaluating cutting and high-pressure balloon valvuloplasty for dysplastic pulmonary valve stenosis in 7 dogs

IntroductionThis case series describes early experience and technical aspects of cutting balloon dilation followed by high-pressure balloon pulmonary valvuloplasty in dogs with dysplastic pulmonary valve stenosis. AnimalsSeven client-owned dogs were enrolled in this study. MethodsDogs were prospectively enrolled based on echocardiographic diagnosis of severe pulmonary valve dysplasia, defined as marked valve thickening with variable degrees of annular hypoplasia or subvalvar fibrous obstruction and a peak echocardiography-derived transpulmonary pressure gradient higher than 100 mmHg. Preinterventional and postinterventional hemodynamic data and transthoracic pressure gradients were obtained for all dogs. Recheck echocardiography varied in timing by client convenience, with maximum follow-up 35 months after intervention. ResultsNo intraprocedural or periprocedural mortality was observed. The only major complication was partial avulsion of a cutting blade related to exceeding recommended burst pressure of the device, which was not associated with obvious clinical consequence. Invasive hemodynamic measurements demonstrated an average reduction of 46% in peak systolic right ventricular-to-pulmonary artery pressure gradient (range, 31–77%). The echocardiographic results 24 h after procedure demonstrated an average reduction in pressure gradient of 43% (range, 20–66%), with late follow-up demonstrating an average reduction of 35% (range, 10–57%) compared with preprocedural echocardiography. ConclusionsThis procedure is a feasible therapeutic transcatheter intervention for dogs with dysplastic pulmonary valves and appears safe in this small cohort. The ideal selection criteria and rate of restenosis for this procedure is under investigation, and long-term follow-up and a large, randomized, controlled study are necessary to demonstrate efficacy.

21 Intravenous administration of puppy deciduous teeth stem cells in degenerative valve disease

Congestive heart failure is a very common complication of degenerative heart disease (DVD). Ventricular dysfunction, and ventricular remodelling may also contribute to damage the heart muscle and the progression of the disease appears to be unpredictably. To decelerate the progression and alleviate the symptoms of heart failure using standard treatment seems to be limited, stem cell therapy is a novel option for cardiovascular therapeutic approach. In this study, we examined the therapeutic effects of stem cells from puppy deciduous teeth (pDSCs) in dogs with chronic valvular heart disease. Twenty client-owned dogs with valvular heart disease underwent multiple intravenous injections of allogenic pDSCs. Dogs were assigned to two group: (i) control group with standard treatment, and (ii) group with standard treatment and multiple administrations of pDSCs. Electrocardiography, complete transthoracic echocardiography, thoracic radiography and blood pressure were recorded before and after pDSCs injections for 15, 30 and 60 days. Post pDSCs injection showed measurable improvement in left ventricular ejection fraction, American College of Veterinary Internal Medicine (ACVIM) functional class significantly improved and improved quality of life scores were observed. In the control group, there were no significant enhancements in heart function or ACVIM class. This finding suggests that pDSCs could be an alternative selection for valvular heart disease treatment. However, future studies to understand the underlying mechanism may help to proof the use of pDSCs in veterinary patients with valvular heart diseases.

Relationship Between Vitamin D Deficiency and Nondipper Hypertension

Nondipper hypertension is associated with increased cardiovascular morbidity and mortality. Vitamin D deficiency is associated with cardiovascular diseases such as coronary artery disease, heart failure, and hypertension. Vitamin D deficiency activates the renin–angiotensin–aldosterone system, which affects the cardiovascular system. For this reason, a relationship between vitamin D deficiency and nondipper hypertension could be suggested. In this study, we compared 25-OH vitamin D levels between dipper and nondipper hypertensive patients. The study included 80 hypertensive patients and they were divided into two groups: 50 dipper patients (29 male, mean age 51.5 ± 8 years) and 30 nondipper patients (17 male, mean age 50.6 ± 5.4 years). All the patients were subjected to transthoracic echocardiography and ambulatory 24-hour blood pressure monitoring. In addition to routine tests, 25-OH vitamin D and parathormone (PTH) levels were analyzed. All the patients received antihypertensive drug therapy for at least 3 months prior to the evaluations. 25-OH vitamin D and PTH levels were compared between the two groups. No statistically significant difference was found between the two groups in terms of basic characteristics. The average PTH level of hypertensive dipper patients was lower than that of nondipper patients (65.3 ± 14.2 vs. 96.9 ± 30.8 pg/mL, P < .001). The average 25-OH vitamin D level of hypertensive dipper patients was higher than that of nondipper patients (21.9 ± 7.4 vs. 12.8 ± 5.9 ng/mL, P = .001). The left ventricular mass and left ventricular mass index were lower in the dipper patients than in the nondipper patients (186.5 ± 62.1 vs. 246.3 ± 85.3 g, P = .022; and 111.6 ± 21.2 vs.147 ± 25.7 g/m2, P < .001, respectively). Other conventional echocardiographic parameters were similar between the two groups. Daytime systolic and diastolic blood pressure measurements were similar between dippers and nondippers, but there was a significant difference between the two groups with regard to nighttime measurements (nighttime systolic 118.5 ± 5.8 vs.130.2 ± 9.6 mm Hg, P < .001; and nighttime diastolic 69.3 ± 4.8 vs.78.1 ± 7.2 mm Hg, P < .001, respectively). Our results suggest that vitamin D deficiency has a positive correlation with blood pressure and vitamin D deficiency could be related to nondipper hypertension. The measurement of vitamin D may be used to indicate increased risk of hypertension-related adverse cardiovascular events.

Assessment of aortic elastic properties in patients with sarcoidosis

Background. Sarcoidosis is an inflammatory granulomatous disease of unknown etiology that involves multiple organ systems. Many studies have shown a strong relationship between inflammation and atherosclerosis. The aim of this study is to investigate the relationship between elastic properties of the aorta and the duration of the disease in patients with sarcoidosis. Method. The study population included 52 patients with sarcoidosis (22 men, mean age = 42.7 ± 10.7 years, and mean disease duration = 38.8 ± 10.8 months) and 50 healthy control subjects (18 men, and mean age = 42.0 ± 8.0 years). Aortic stiffness (β) index, aortic strain (AoS) and aortic distensibility (AoD) were calculated from the aortic diameters measured by transthoracic echocardiography and blood pressure obtained by sphygmomanometer. Cardiac functions were determined by using routine echocardiographic evaluation consist of standard two-dimensional and conventional Doppler and tissue Doppler imaging. Results. The conventional echocardiographic parameters were similar between patients and controls. There were significant differences between the control and the patient groups in β index (1.63 ± 0.55 vs 2.44 ± 1.54, p = 0.001), AoS (15.61 ± 5.69 vs 10.93 ± 4.11%, p < 0.001) and AoD (6.35 ± 2.64 vs 4.66 ± 1.98, 10 −6 cm2/dyn, p = 0.001). There were statistically significant negative correlations between the disease duration and AoD (r = −0.46, p = 0.01) and AoS (r= −0.44, p = 0.002), whereas there was a positive correlation between the disease duration and β index (r = 0.37, p = 0.01). In multivariate analysis, disease duration was significantly related with AoD, AoS and β index (respectively, RR = 3.28, p = 0.002; RR = 3.03, p = 0.004; RR = 2.39, p = 0.02). Conclusion. We observed that elastic properties of the aorta alter in patients with sarcoidosis. We also have demonstrated a statistically significant correlation between aortic elastic properties and the disease duration.

Increased echocardiographic epicardial fat thickness is related to impaired diurnal blood pressure profiles

Objective. Epicardial fat has been proposed as a new cardiometabolic risk factor. Although epicardial fat thickness (EFT) is associated with hypertension, the relationship between diurnal blood pressure profiles and EFT is still unknown. The purpose of this study is to investigate the association between the echocardiographic EFT and diurnal blood pressure profiles in hypertensive patients. Methods. After the ambulatory blood pressures of 123 patients were monitored, they were divided into three groups according to the clinical diagnoses: 41 patients (33.3%) were in the normotensive group, 40 patients (32.5%) were in the dipper hypertensive group and 42 patients (34.1%) were in the non-dipper hypertensive group. All participants underwent transthoracic echocardiography and ambulatory blood pressure monitoring to measure the EFT and blood pressure responses. Results. The mean EFT measurements of the dipper group were significantly higher than the normotensive group (6.5 ± 0.6 vs 5.8 ± 0.6; p < 0.0001). On the other hand, the mean EFTs of the non-dipper group were also significantly higher than the dipper group (7.4 ± 0.7 vs 6.5 ± 0.6, p < 0.0001). An EFT of ≥ 7 mm predicted the non-dipper profile in hypertensive patients with 74% sensitivity and 71% specificity (receiving operator characteristic area under the curve: 0.826, 95% CI 0.738–0.913; p < 0.0001). EFT was associated with both dipper (OR 8.9, 95% CI 3.03–26.3; p < 0.0001) and non-dipper blood pressure profiles (OR 12.3, 95% CI 1.75–86.31; p < 0.0001), and this relationship was also independent from all the risk factors. Conclusion. Echocardiographic EFT assessment is independently associated with impaired diurnal blood pressure profiles in the hypertensive individuals. Thus, the echocardiographic assessment of the EFT may be helpful in cardiometabolic risk stratification and therapeutic interventions.

Going to extremes of lung volume

volume changes in the lung are the basis for life-sustaining respiration, yet in many regards, the lung is overengineered and the mechanical limits are most often not approached ([11][1]). For some activities, however, the entire volume range of the thorax and lung is necessary; for example,

The physiology of forced expiration

Insight into the physiology of a forced expiration is the most important prerequisite for understanding and correctly interpreting the most common pulmonary function tests like spirometry and recording of a maximum expiratory flow-volume curve. Along the airway, intraluminal pressure falls progressively from alveolar pressure in the periphery to atmospheric pressure at the airway opening. Downstream of the equal pressure point, where intraluminal equals transthoracic pressure, the airway is dynamically compressed. Once the forced expiration is flow limited, more transthoracic pressure will rather effect more compression than a further increase in flow. It follows that the achieved maximum expiratory flow rates are then exclusively defined by the resistance of the intrathoracic airways and no longer by muscular effort. The end of a forced expiration is determined by the elastic resistance of the thoracic cage and by airway closure.

Physiotherapy for airway clearance in paediatrics.

The basic therapeutic principles in paediatric chest physiotherapy (CPT) are identical to those applied in adults. However, the child's growth and development results in continuing changes in respiratory structure and function, and the requirement for different applications of CPT in each age group. Forced expiratory manoeuvres and coughing serve as basic mechanisms for mobilization and transport of secretions, but the reduced bronchial stability after birth requires special techniques in very young patients. High externally applied transthoracic pressures have to be avoided in order to prevent interruption of airflow. In addition, airway patency is maintained by the application of back pressure and by liberal use of continuous positive airway pressure. Since sympathomimetic bronchodilators might further decrease bronchial stability, their use must be individualized in newborns and young infants. Inspiration is a basic mechanism for inflating alveolar space behind obstructing mucus plugs. Due to a highly unstable chest, the premature baby, newborn and infant cannot distend their lung parenchyma to the same extent as can older patients. Consequently all chest physiotherapy strategies applied in this age group have to incorporate appropriate techniques for raising lung volume. Positioning serves to redistribute ventilation, but the young infant's response to gravitational forces differs substantially from that of the adult, and consequently strategies used in older patients have to be modified. In addition, the therapist has to consider pathology such as bronchial instability lesions and airway hyperresponsiveness and has to adjust the therapeutic response accordingly. It is particularly important to consider the special vulnerability of newborns and young infants and to modify therapeutic interventions to avoid the harm that could otherwise be inflicted. Consideration of these differences between infant, child and adult and careful analysis of the available mucus clearance techniques allows tailoring of an individualized therapeutic approach to the paediatric patient.

Diaphragmatic and cardiac motion during suspended breathing: preliminary experience and implications for breath-hold MR imaging.

To investigate and quantify motion of the diaphragm and heart during suspended breathing at end inspiration and end expiration. In 10 healthy adult volunteers, line scanning was performed to monitor the position of the diaphragm during a breath hold at end inspiration and end expiration, with a spatial and temporal resolution of 0.25 mm and 200 msec, respectively. Electrocardiographically gated, turbo fast low-angle shot (FLASH) magnetic resonance (MR) imaging was performed to monitor movement of the diaphragm and heart. During a breath hold, the diaphragm moved upward. At end expiration, the velocity of the diaphragm during suspended breathing was constant (mean, 0.15 mm/sec). At end inspiration, motion of the diaphragm during suspended breathing was more complex (range, 0.1-7.9 mm/sec). During a 20-second breath hold, mean displacement of the diaphragm was 25% of that during normal breathing. FLASH MR imaging revealed variations in the position of the heart during a breath hold. During suspended respiration, the heart did not return to the same position on consecutive heartbeats and, consequently, the margins of the heart typically moved inward. Breath holding does not eliminate motion of the diaphragm. Changes in the motion of the diaphragm and transthoracic pressure during a breath hold result in complex movement of the heart and may cause blurring during breath-hold MR imaging.

Protective effect of cobra venom factor on pulmonary injury induced by oleic acid

The protective effect of cobra venom factor (CVF), separated from the venom of Naja naja atra, on pulmonary injury induced by oleic acid was reported. The blood gas tensions, tidal volume, transthoracic pressure and pulmonary arterial pressure in anaesthetized dogs were continually monitored. The experimental results showed that CVF, given 20 h before the dosage depleting completements exceed 95%, significantly attenuated oleic acid-induced pulmonary dysfunction, including hypoxemia, increasing veno-arterial shunt and P(A-a) o 2 and decreasing dynamic compliance and pulmonary blood flow. Histoloical examination of lung tissues after the experiment also showed improvement of hyaline membrane formation, alveolar haemprrhage and pulmonary arteriolar thrombosis. It was evident that the depletion of serum complements by CVF inhibited the development of lung injury induced by oleic acid. CVF might be a potentially useful drug for the treatment of respiratory distress syndrome in the near future.

Chest physiotherapy--the mechanical approach to antiinfective therapy in cystic fibrosis.

Chest physiotherapy is a treatment program that attempts to compensate for impaired mucociliary clearance. By removing mucopurulent secretions, it reduces airway obstruction and its consequences, such as atelectasis and hyperinflation; furthermore, physiotherapy can decrease the rate of proteolytic tissue damage by removing infected secretions. Conventional physiotherapy (clapping, vibration and compression, together with postural drainage and assisted coughing) is the most efficient physiotherapy for sick infants and young children. Later, mechanical chest percussion can reduce the patient's dependency on others. The forced expiration technique is another method of self-treatment, employing expiratory techniques to blow secretions out of the bronchi. Autogenic drainage, a special breathing technique, aims at avoiding airway compression by reducing positive expiratory transthoracic pressure. PEP-mask-physiotherapy achieves the same goal by expiring against an external airflow obstruction. Last but not least, physical exercise can clear the lungs of some CF patients and thus offers an attractive adjunct to physiotherapy.

Dynamics of chest wall in preterm infants.

The chest wall of the preterm infant has visible paradoxical movement during breathing, because of its greater flexibility than those of older children and adults. We studied the dynamics of the chest wall in 10 preterm infants to describe the interaction of the chest wall volume, as partitioned by the inductance plethysmograph, and the transthoracic and abdominal pressures. There was considerable hysteresis between the chest wall volume and the transthoracic pressure, and it had linear pressure-volume behavior during airway occlusion, late inspiration, and early expiration. The slope of this pressure-volume relationship, or the instantaneous chest wall compliance, averaged 0.89 +/- 0.16 and 0.94 +/- 0.18 ml/cmH2O for the respiratory effort during airway occlusion and early expiration, respectively. The dynamic compliance was considerably greater, averaging 7.8 +/- 2.3 ml/cmH2O. This resistive pressure-volume behavior was not related to the absolute value of or the rate of development of the esophageal or abdominal pressures. This additional degree of freedom of motion of the chest wall suggests that its linkage to the diaphragm is flexible, which provides a braking force for expiration and allows free movement of the diaphragm for breathing movements before birth.

Impedance and relative displacements of relaxed chest wall up to 4 Hz.

We measured the effective resistance (Reff) and elastance (Eeff) of the chest wall in four subjects, relaxed at functional residual capacity (FRC), during sinusoidal volume changes (5% vital capacity up to 4 Hz) delivered at the mouth. Subjects sat in a head-out body plethysmograph, and transthoracic pressure was measured with an esophageal balloon. Changes in Reff and in Eeff with frequency were nearly the same in all subjects. Reff (in cmH2O X l-1 X s) was 2.9 +/- 0.8 at 0.2 Hz and fell sharply to minimum values (0.5-0.9) at 1-4 Hz. Eeff (in cmH2O X l-1) increased from approximately 10 at the lowest frequency to a plateau of about 15 at 1-3 Hz and decreased above 3 Hz. In the same subjects, we measured the relative magnitude and phase between the displacements of different parts of the chest wall with magnetometers during identical sinusoidal forcing. Results indicate that the chest wall expands and deflates uniformly at frequencies up to 1 Hz. Thereafter the abdomen makes relatively larger excursions, and the relative magnitude and phase of displacement at different points on the chest wall show complex changes. We conclude that the frequency dependence of Reff and Eeff below 1 Hz is not due to nonuniformities in displacement of different parts of the chest wall. The frequency dependency of Reff is consistent with an increasing contribution of rate-independent plastic dissipation to the pressure difference in phase with flow as breathing frequency decreases.

1747 OPIOID EFFECTS ON LUNG MATURATION IN FETAL RABBITS

Based on the observations that the incidence of respiratory distress syndrome is less in infants of opiate-addicted mothers, and that amniotic fluid and fetal cord blood endorphins are increased during late gestation, we tested the hypothesis that endogenous opioids modulate fetal lung development. Pregnant rabbits received daily intramuscular injections, from days 18 to 28 of gestation, of either morphine sulfate (MS) (1.0 mg/kg), naloxone (NLX) (0.4 mg), or saline (C). Their fetuses, delivered prematurely on day 28 (term ∼ 31 days), were assessed for differences in their lung static pressure-volume (P-V) characteristics and morphology. The mean (± SE) deflation lung volume at transthoracic pressure (PT) = 5 cm H2O (V5), expressed as a percentage of the lung volume at PT = 40 (V40), amounted to 70.9 (± 4.3), 52.9 (± 5.8), and 33.9 (± 7.3)% in the MS, C, and NLX fetuses, respectively. Thus, relative to the C group, the MS fetuses had P-V curves displaced significantly (p < .05) upward and to the left, indicating increased alveolar stability; whereas the curves of the NLX fetuses were displaced significantly (p < .05) downward and to the right, demonstrating decreased alveolar stability. Moreover, relative to the C lungs, the MS lungs also appeared more mature histologically, having thinner alveolar septa and a greater airspace-to-tissue ratio. In contrast, the NLX lungs were less developed. These data provide evidence that opiate agonists accelerate intrauterine lung development, whereas opiate antagonists delay lung maturation. These findings suggest that lung development may be significantly modulated by endogenous opioids.

Effects of pulmonary function of whole lung irradiation for Wilm's tumour in children.

The effect of whole lung irradiation on lung function was investigated in 48 children treated for Wilm's tumour with pulmonary metastases. Lung function tests were performed before irradiation and were repeated annually for as long as possible, the length of follow-up varying from two to 17 years. A reduction in both lung volume and in dynamic compliance was clearly observed. In some patients these changes occurred in the early post-irradiation months, but in most the decrease observed progressed over longer periods of time. Static pressure volume curves, blood-gases, and carbon monoxide transfer were normal. These findings make it unlikely that post-irradiation pulmonary fibrosis was involved. Another explanation for the decreased lung volume and dynamic compliance might be failure of alveolar multiplication. Muscular injury is unlikely as the patients were able to produce normal transthoracic pressures. A failure of chest wall growth is also possible and would explain the progressive restrictive impairment but not the early lung function changes. It is suggested that the early effects detected in some patients were the result of lung injury and that later effects resulted from impaired chest wall growth.

A Pulse Method of Measuring Respiratory System Compliance in Ventilated Patients

We describe a method of measuring total static respiratory system compliance (Crs) in ventilated patients during inflation, which appears to detect relaxation of respiratory muscles and does not require an end-inspiratory pause or disconnection of a constant-flow intermittent mandatory ventilation (IMV) circuit. Flow is measured with a pneumotachometer attached to the endotracheal tube. Transthoracic pressure is taken as the difference between mouth pressure measured at the proximal pneumotachometer port and body surface (atmospheric) pressure. Flow and transthoracic pressure are displayed on separate channels of a strip chart recorder. The ventilator is adjusted to deliver a constant rule of air flow. When inflation begins, the pressure tracing shows an initial step rise related to the flow resistance of the subject followed by a section with a slower rise and a constant slope. Respiratory system compliance is calculated by dividing the flow rate in L/sec by the slope of the pressure tracing in cm H2O/sec. Pulse Crs was compared with static Crs measured with an end-inspiratory pause in nine subjects receiving mechanical ventilation. Correlation between pulse Crs and static Crs in nine ventilated patients was highly significant (4 = .997, pulse Crs = 1.00 static Crs + 0.001). We conclude that with the pulse method, one can measure static Crs during inflation without an inspiratory pause and without disconnecting an IMV circuit.

Rib cage deformation during static inspiratory efforts.

Patterns of rib cage (RC) deformation were studied in six normal subjects during moderate static inspiratory efforts such that esophageal pressure (Pes) as an index of transthoracic pressure fell to between -30 and -60 cmH2O during each maneuver. At lung volumes below 50% inspiratory capacity (IC), static inspiratory efforts deformed RC to a more elliptical shape; RC lateral diameter became smaller and RC lateral diameter became larger. However, at high lung volumes (greater than 50% IC) the opposite change in RC dimensions occurred despite similar changes in Pes, i.e., the RC became more circular. These differences in RC deformation did not appear to be a possive consequence of increased lung volume because the RC could be voluntarily deformed to a more circular shape at low lung volume when a) subjects performed static inspiratory efforts mainly with their intercostal and accessory muscles rather than their diaphragm as judged by a smaller change in transdiaphragmatic pressure for the same Pes; or b) subjects statically contracted their diaphragm with it held in a relatively flattened configuration as assessed by a large abdominal AP dimension. We suggest that deformation of the RC during static inspiratory efforts is not as predictable as has previously been suggested but depends on the pattern of contraction and configuration of the respiratory muscles.