Ch. Roussos

Pulmonary endothelium in acute lung injury: from basic science to the critically ill

BackgroundPulmonary endothelium is an active organ possessing numerous physiological, immunological, and metabolic functions. These functions may be altered early in acute lung injury (ALI) and further contribute to the development of acute respiratory distress syndrome (ARDS). Pulmonary endothelium is strategically located to filter the entire blood before it enters the systemic circulation; consequently its integrity is essential for the maintenance of adequate homeostasis in both the pulmonary and systemic circulations. Noxious agents that affect pulmonary endothelium induce alterations in hemodynamics and hemofluidity, promote interactions with circulating blood cells, and lead to increased vascular permeability and pulmonary edema formation.ObjectiveWe highlight pathogenic mechanisms of pulmonary endothelial injury and their clinical implications in ALI/ARDS patients.

Respiratory muscles and weaning failure

Weaning failure is, unfortunately, a rather common phenomenon for mechanically-ventilated patients (especially those with chronic obstructive pulmonary disease (COPD)), and the respiratory muscles play a pivotal role in its development. Weaning fails whenever an imbalance exists between the ventilatory needs and the neurocardiorespiratory capacity. This can happen if there is an increase in the energy demands of the respiratory muscles, a decrease in the energy available, a decrease in neuromuscular competence, or if the respiratory muscles pose an impediment to the heart and blood flow. The imbalance created will lead to weaning failure through the development of respiratory muscle fatigue, hypercapnia, dyspnoea, anxiety and organ dysfunction.

Dynamic hyperinflation and tolerance to interval exercise in patients with advanced COPD

Dynamic hyperinflation (DH) contributes importantly to the limitation of constant-load exercise (CLE) in patients with chronic obstructive pulmonary disease (COPD). However, its role in the limitation of interval exercise (IE) remains to be explored. The change (Δ) in inspiratory capacity (IC) was measured to reflect changes in DH in 27 COPD patients (forced expiratory volume in one second mean±sem % predicted: 40±3) at the end of a symptom-limited CLE test at 80% of peak work capacity (WRmax) and an IE test at 100% WRmax (30 s of work, alternated with 30 s of unloaded pedalling). At the limit of tolerance in both IE and CLE, patients exhibited similar DH (ΔIC: 0.39±0.05 L and 0.45±0.05 L, respectively). However, exercise endurance time (tend) for IE (32.7±3.0 min) was significantly greater than for CLE (10.3±1.6 min). The IE tend correlated with resting IC, expressed as % pred normal. At 30 and 90% of total IE tend, ΔIC (0.43±0.06 and 0.39±0.05 L, respectively) and minute ventilation (31.1±1.6 and 32.7±2.2 L·min−1, respectively) were not significantly different. Resting hyperinflation helps to explain the limitation of interval exercise. Implementation of interval exercise for rehabilitation should provide important clinical benefits because it prolongs exercise endurance time and allows sustaining higher stable ventilation.

Exercise-induced flow limitation, dynamic hyperinflation and exercise capacity in patients with bronchial asthma

It is known that, in stable asthmatics at rest, tidal expiratory flow limitation (EFL) and dynamic hyperinflation (DH) are seldom present. This study investigated whether stable asthmatics develop tidal EFL and DH during exercise with concurrent limitation of maximal exercise work rate (WRmax). A total of 20 asthmatics in a stable condition and aged 32±13 yrs (mean±sd) with a forced expiratory volume in one second (FEV1) of 101±21% of the predicted value were studied. Only three patients exhibited an FEV1 below the normal limits. On a first visit, patients performed a symptom-limited incremental (20 W·min−1) bicycle exercise test. On the second visit, the occurrence of EFL (using the negative expiratory pressure technique) and DH (via reduction in inspiratory capacity) were assessed at rest and when cycling at 33, 66 and 90% of their predetermined WRmax. FEV1 was measured to detect exercise-induced asthma, 5 and 15 min after stopping exercise at 90% WRmax. Only one patient showed EFL at rest, whereas 13 showed EFL and DH during exercise. In these 13 asthmatics, exercise capacity was significantly reduced (WRmax 75±9% pred) compared to the seven non-EFL patients (WRmax 95±13% pred). Moreover, a significant correlation of WRmax (% pred) to the change in inspiratory capacity (percentage of resting value) from rest to 90% WRmax was found. Tidal EFL during exercise was not associated with exercise-induced asthma, which was detected in only three patients. In conclusion, tidal expiratory flow limitation and dynamic hyperinflation during exercise are common in stable asthmatics with normal spirometric results and without exercise-induced asthma, and may contribute to reduction in exercise capacity.

Exhaled nitric oxide in seasonal allergic rhinitis: influence of pollen season and therapy.

Exhaled nitric oxide (eNO) has been proposed as a potential indirect marker of lower airway inflammation in asthma. To investigate the existence of lower airways inflammation in allergic rhinitis eNO measurements were performed in 32 patients with symptomatic and asymptomatic seasonal allergic rhinitis early in and out of pollen seasons and in 80 healthy volunteers. To further define how exhaled NO is modified by therapy, NO levels were detected following 1‐month treatment with either inhaled steroids or non‐steroids therapy with nedocromil. Exhaled NO (mean ± SE) was significantly elevated in patients with seasonal allergic rhinitis with and without symptoms (24.2 + 2.5 and 13.9 + 2.9 ppb, respectively) as compared to healthy volunteers (4.5 + 0.3 ppb) both in and out of pollen season (21.2 + 2.1 and 9.0 + 1.4 p.p.b., respectively) with a higher increase during the allergen exposure in season. Higher levels of exhaled NO were detected in patients with symptoms, either from the upper or lower airways, and with bronchial hyperreactivity. The increased exhaled NO in symptomatic patients was reduced only by inhaled steroids and not by nedocromil. These findings possibly suggest the existence of lower airway inflammation in both symptomatic and asymptomatic patients with seasonal allergic rhinitis in and out of pollen season. Thus, exhaled NO may be used as a non‐invasive index for early detection of lower airway inflammation and for monitoring the optional treatment in patients with seasonal allergic rhinitis.

Expiratory flow limitation in morbidly obese postoperative mechanically ventilated patients

Although obesity promotes tidal expiratory flow limitation (EFL), with concurrent dynamic hyperinflation (DH), intrinsic PEEP (PEEPi) and risk of low lung volume injury, the prevalence and magnitude of EFL, DH and PEEPi have not yet been studied in mechanically ventilated morbidly obese subjects.

Echocardiographic and ambulatory electrocardiographic findings in elite water‐polo athletes

The aim of this study was to investigate the echocardiographic and electrocardiographic findings in top water‐polo athletes and test the hypothesis that their hearts exhibit dilatation associated with hypertrophy secondary to the mixed type (isotonic and isometric) of exercise they are subjected to. Eighteen athletes of the Greek national water‐polo team and 15 healthy sedentary men serving as controls were studied. All underwent an echocardiogram, a standard 12‐lead ECG and 24‐h ECG monitoring. In athletes, as compared to healthy controls, an increase was detected in the following indices: left ventricular (LV) end‐diastolic diameter index (EDDI‐LV) (by 10%; P=0.02), interventricular septal thickness (IVS) (by 32%; P<0.001), thickness of the posterior wall (PW) (by 29%; P<0.001), relative wall thickness (IVS+PW/EDD‐LV) (by 12%; P<0.001) and LV mass index (by 82%; P<0.001). Mild asymmetric thickening of the septum (IVS/PW=1.40 and 1.37) was measured in two athletes. LV fractional shortening was normal. Standard 12‐lead ECG abnormalities (LV hypertrophy or abnormal repolarization pattern) were observed in 33% of athletes. Athletes had sinus bradycardia during day and night, respiratory arrhythmia (RA) (83% vs 40% of controls; P=0.03) and sinus pauses (SP) (39% vs 0% of controls; P=0.02), with occassional arrhythmias and conduction abnormalities. We conclude that top water‐polo athletes have dilatation combined with substantial hypertrophy and normal systolic function of the LV. In addition they present bradycardia, RA and SP, with occassional arrhythmias and conduction abnormalities.

Resting respiratory variables and exercise capacity in adult patients with cystic fibrosis

INTRODUCTION Cystic fibrosis (CF) is the most common life-limiting, recessively inherited disease in the white population, associated with significantly high morbidity and mortality rates; CF pulmonary disease, assessed by pulmonary function tests, arterial blood gases and the Schwachman score, remains the most prevalent in terms of morbidity in the adult CF population. OBJECTIVES The aim of the present study was to evaluate the relationship between resting respiratory variables and exercise capacity in adult patients with CF. RESULTS Study investigations undertaken in 18 CF patients and 11 healthy volunteers showed that among the resting lung function parameters, inspiratory capacity (IC) at rest was the only significant predictor of VO(2) peak (r=0.67, p<0.007) and VO(2)/t-slope (r=0.86, p<0.0001). The percentage of predicted FEV(1) in adult CF patients was 77+/-33% pred. vs 104+/-16% pred. in healthy subjects (p<0.006); the corresponding percentage of IC at rest was 82+/-36% pred. in patients vs 116+/-20% pred. in healthy (p<0.003). CF patients presented with a significantly prolonged rapid breathing after exercise (32br per minute at recovery for CF vs 22 for healthy; p<0.001), as well as a shortened inspiratory time. CONCLUSION Adult patients with CF show a limited exercise capacity with lower peak oxygen consumption and prolonged oxygen kinetics. Interestingly, decreased IC qualified as the only significant predictor of exercise capacity in our study.

Exercise-induced skeletal muscle deoxygenation in O2-supplemented COPD patients.

This study was designed to assess quadriceps oxygenation during symptom‐limited and constant‐load exercise in patients with chronic obstructive pulmonary disease (COPD) and healthy age‐matched controls. Thirteen male COPD patients [FEV1: 43±5% predicted (mean±SEM)] and seven healthy male controls performed an incremental exercise test at peak work rate (WR) and a constant‐load test at 75% peak WR on a cycle ergometer. Quadriceps hemoglobin saturation (StO2) was measured by continuous‐wave near‐infrared spectrophotometry throughout both exercise tests. StO2 is the ratio of oxygenated hemoglobin to total hemoglobin and reflects the relative contributions of tissue O2 delivery and tissue O2 utilization. Oxygen was supplemented to all patients in order to maintain arterial O2 saturation normal (>95%). The StO2 decreased during symptom‐limited exercise, reaching the nadir at peak WR. The decrease in StO2 was greater (P<0.05) in healthy subjects (from 74±2% to 38±6%) compared with that in COPD patients (from 61±5% to 45±4%). However, when StO2 was normalized relative to the WR, the slope of change in StO2 during exercise was nearly identical between COPD patients and healthy subjects (0.47±0.10%/W and 0.51±0.04%/W, respectively). During constant‐load exercise, the kinetic time constant of StO2 desaturation after the onset of exercise (i.e., equivalent to time to reach approximately 63% of StO2 decrease) was not different between COPD patients and healthy subjects (19.0±5.2 and 15.6±2.5 s, respectively). In O2‐supplemented COPD patients, peripheral muscle oxygenation for a given work load is similar to that in healthy subjects, thus suggesting that skeletal muscle O2 consumption becomes normal for a given O2 delivery in COPD patients.

Acute myocardial infarction with normal coronary arteries during septic shock from Neisseria meningitidis.

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (▪·VA/▪·Q) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and▪·VA/▪·Qdistributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO2) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal▪·VA/▪·Qratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal▪·VA/▪·Qrelationships.