Yves Jammes

Mechanical ventilation affects lung function and cytokine production in an experimental model of endotoxemia.

Background:Mechanical ventilation using tidal volumes around 10 ml/kg and zero positive end-expiratory pressure is still commonly used in anesthesia. This strategy has been shown to aggravate lung injury and inflammation in preinjured lungs but not in healthy lungs. In this study, the authors investigated whether this strategy would result in lung injury during transient endotoxemia in the lungs of healthy animals. Methods:Volume-controlled ventilation with a tidal volume of 10 ml/kg and zero positive end-expiratory pressure was applied in two groups of anesthetized–paralyzed rabbits receiving either intravenous injection of 5 &mgr;g/kg Escherichia coli lipopolysaccharide (n = 10) or saline (n = 10) 2 h after the start of mechanical ventilation. The third group consisted of 10 spontaneously breathing anesthetized animals receiving lipopolysaccharide. Anesthesia was then continued for 4 h in the three groups while the ventilatory modes were maintained unchanged. Lung injury was studied using blood gases, respiratory physiologic variables, analysis of the bronchoalveolar lavage cell counts, and cytokine concentrations and lung pathologic examination. Results:Significant histologic lung alterations, hypoxemia, and altered lung mechanics were observed in rabbits treated with mechanical ventilation and intravenous lipopolysaccharide but not in the mechanically ventilated animals injected with saline or in spontaneously breathing animals treated with lipopolysaccharide. Endotoxemic ventilated animals also had significantly more lung inflammation as assessed by the alveolar concentration of neutrophils, and the concentrations of the chemokines interleukin 8 and growth-related oncogen &agr;. Conclusions:These results showed that positive-pressure mechanical ventilation using a tidal volume of 10 ml/kg and zero positive end-expiratory pressure was harmful in the setting of endotoxemia, suggesting that the use of this ventilator strategy in the operating room may predispose to lung injury when endotoxemia occurs.

Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins

Abstract.  Jammes Y, Steinberg JG, Delliaux S (Aix‐Marseille University, Marseille, France). Chronic fatigue syndrome: acute infection and history of physical activity affect resting levels and response to exercise of plasma oxidant/antioxidant status and heat shock proteins. J Intern Med 2012; 272: 74–84.

Long-term outcome in chest trauma.

Background: Currently, there are limited data available describing the long-term outcomes of chest trauma survivors. Here, the authors sought to describe chest trauma survivor outcomes 6 months and 1 yr after discharge from the intensive care unit, paying special attention to pulmonary outcomes. Methods: A cohort of 105 multiple trauma patients with blunt chest trauma admitted to the intensive care unit was longitudinally evaluated. After 6 months, a chest computed tomography scan, pulmonary function testing (PFT), and quality of life were collected in 55 of these patients. A subgroup of 38 patients was followed up for 1 yr. Results: At least one abnormal PFT result was found in 39 patients (71%). Compared with normalized data of the age- and sex-matched population, physical function was decreased in 38 patients (70%). The 6-min walk distance was reduced for 29 patients (72%). Although pathologic images were observed on the chest computed tomography scan from 33 patients (60%), no relation was found between PFT and computed tomography. A ratio of arterial oxygen pressure to inspired oxygen fraction less than 200 at admission to the intensive care unit predicted an abnormal PFT result at 6 months. One year after discharge from the intensive care unit, paired comparisons showed a significant increase in forced vital capacity (P = 0.02) and Karnofsky Performance Status (P < 0.001). Conclusions: Survivors of multiple traumas including chest trauma demonstrate a persistent decrease in the 6-min walk distance, impairment on PFT, and reduced pulmonary-specific quality of life.

Respiratory and cardiovascular responses evoked by tibialis anterior muscle afferent fibers in rats

The muscle metaboreflex is thought to be one of the neural mechanisms involved in the cardiovascular and respiratory adjustments to muscular activity. The afferent arm of the reflex is composed of thinly myelinated group III and unmyelinated group IV sensitive fibers. Such reflex arc had been extensively described in cats, dogs, rabbits and humans. However, results obtained in rats are controversial and the role of the afferent fibers from the tibialis anterior skeletal muscle has never been shown. The purpose of the present experiments was to study the responses of both respiratory and cardiovascular systems following activation of the metabosensitive fibers originating from tibialis anterior muscle in non decerebrated and non vagotomized barbituric anesthetized adult rats. Mean arterial blood pressure, mean arterial blood flow, heart rate and phrenic nerve activity (frequency and amplitude) were monitored during electrically induced fatigue or after intramuscular injection of potassium chloride or lactic acid (specific stimuli of the group III and IV afferent fibers). The experiments were performed under normal condition, then after regional circulatory occlusion, which isolated and maintained the neural drive and abolished humoral communication and after section of the peroneal nerve innervating the tibialis anterior muscle. We showed that cardiorespiratory parameters were increased significantly in response to stimuli under normal conditions and after venous outflow occlusion excluding any participation of central chemoception. No change was observed after nerve section. Our data indicate that changes occurring in rat hindlimb muscle such as the tibialis anterior are sufficient to regulate the cardiorespiratory function via metabosensitive fiber activation.

Haemodynamic changes after prolonged water immersion

Abstract Thermoneutral water immersion increases cardiac preload and changes the neuroendocrine settings of blood volume regulation. The resulting marked diuresis may lead to significant haemodynamic changes after the end of a prolonged water immersion. Ten volunteers underwent 6 h of complete thermoneutral water immersion. Changes in cardiovascular status were assessed 1 h and 16 h after water immersion. Haemodynamic changes were assessed by Doppler echocardiography. Arterial wall distensibility was estimated by pulse wave velocity analysis. One hour after water immersion, mean weight loss was 1.78 kg and urine volume amounted to 1.5 litres. Echocardiographic measurements evidenced a significant decrease in dimensions of the left cardiac chambers and inferior vena cava. The decreased cardiac preload was paralleled by a lower stroke volume and cardiac output. A peripheral vasoconstriction associated with a relative decrease in the lower limb blood flow was evidenced by an increase in carotid-pedal pulse wave velocity and by a decrease in ankle brachial index. Sixteen hours after water immersion, cardiac preload and cardiac output remained below baseline values and peripheral vascular tone was still higher than at baseline. Marked haemodynamic changes had not returned to baseline 16 h after water immersion. There is a need to design fluid-replacement protocols to improve this recovery.

Does Norepinephrine Modify the Effects of Inhaled Nitric Oxide in Septic Patients with Acute Respiratory Distress Syndrome

Background Hypoxia‐related pulmonary vasoconstriction enhanced by norepinephrine could be deleterious in patients with the acute respiratory distress syndrome (ARDS) and sepsis. A prospective study compared the effects of nitric oxide on cardiorespiratory parameters, including the evaluation of right ventricular function in patients with ARDS and sepsis who were receiving or not receiving norepinephrine. Methods During a 15‐month period, 27 patients with ARDS and sepsis were prospectively investigated (group 1: 15 patients not receiving norepinephrine; group 2: 12 patients receiving norepinephrine). Right ventricular ejection fraction was measured by thermodilution. After baseline measurements, nitric oxide was administered at increasing inspiratory concentrations. Results The ratio of oxygen tension in arterial blood to the fractional concentration of oxygen in inspired gas increased in the two groups. After logarithmic transformation of the data, an analysis of variance was performed that did not show any difference between the two groups. A dose‐dependent decrease in mean pulmonary arterial pressure was observed in the two groups. This decrease and the increase in right ventricular ejection fraction induced by inhaled nitric oxide were more marked when patients received norepinephrine (P < 0.0001). Conclusion Norepinephrine did not influence the beneficial effects of inhaled nitric oxide administered to patients with ARDS and sepsis on oxygenation.

Combination of two oxidant stressors suppresses the oxidative stress and enhances the heat shock protein 27 response in healthy humans

We tested the hypothesis that the combination of 2 oxidant stressors (hyperoxia and fatiguing exercise) might reduce or suppress the oxidative stress. We concomitantly measured the plasma concentration of heat shock proteins (Hsp) that protect the cells against the deleterious effects of reactive oxygen species. Healthy humans breathed pure oxygen under normobaric condition for 50-minute periods during which they stayed at rest or executed maximal static handgrip sustained until exhaustion. They also repeated handgrip bouts in normoxic condition. We performed venous blood measurements of 2 markers of the oxidative stress (thiobarbituric acid reactive substances and reduced ascorbic acid) and Hsp27. Under normoxic condition, the handgrip elicited an oxidative stress and a modest increase in plasma Hsp27 level (+7.1 +/- 5.4 ng/mL). Under hyperoxic condition, (1) at rest, compared with the same time schedule in normoxic condition, we measured an oxidative stress (increased thiobarbituric acid reactive substances and decreased reduced ascorbic acid levels) and the plasma Hsp27 level increased (maximal variation, +12.5 +/- 6.0 ng/mL); and (2) after the handgrip, the oxidative stress rapidly disappeared. The combination of both hyperoxia and handgrip bout doubled the Hsp27 response (maximal variation, +24.8 +/- 9.2 ng/mL). Thus, the combination of 2 hits eliciting an oxidative stress seems to induce an adaptive Hsp27 response that might counterbalance an excessive production of reactive oxygen species.

A Three-Dimensional Human Trunk Model for the Analysis of Respiratory Mechanics

Over the past decade, road safety research and impact biomechanics have strongly stimulated the development of anatomical human numerical models using the finite element (FE) approach. The good accuracy of these models, in terms of geometric definition and mechanical response, should now find new areas of application. We focus here on the use of such a model to investigate its potential when studying respiratory mechanics. The human body FE model used in this study was derived from the RADIOSS HUMOS model. Modifications first concerned the integration and interfacing of a user-controlled respiratory muscular system including intercostal muscles, scalene muscles, the sternocleidomastoid muscle, and the diaphragm and abdominal wall muscles. Volumetric and pressure measurement procedures for the lungs and both the thoracic and abdominal chambers were also implemented. Validation of the respiratory module was assessed by comparing a simulated maximum inspiration maneuver to volunteer studies in the literature. Validation parameters included lung volume changes, rib rotations, diaphragm shape and vertical deflexion, and intra-abdominal pressure variation. The HUMOS model, initially dedicated to road safety research, could be turned into a promising, realistic 3D model of respiration with only minor modifications.

Effects of endogenous nitric oxide in activation of group IV muscle afferents.

Based on previous observations that acute hypoxemia, which enhances nitric oxide (NO) production, depresses the activation of group IV afferents after repetitive low‐frequency muscle stimulation (MS), we hypothesized that endogenous NO modulates the response of these nerve endings to their specific stimuli. The present study in rabbits examined the effects of a blocker of NO synthase (NG‐nitro‐L‐arginine methyl ester L, L‐NAME) and an exogenous NO donor (3‐morpholinosydnonimine, SIN‐1) on the group IV afferents of tibialis anterior. The efficacy of the two test agents was judged by their effects on systemic blood pressure. L‐NAME markedly elevated (+46%) the resting discharge rate of group IV afferents but abolished their activation after repetitive MS. After SIN‐1 injection, there was a transient decrease in blood pressure, which correlated well with a lowered resting discharge rate of group IV afferents. SIN‐1 infusion caused a stable reduction of blood pressure; the resting afferent nerve discharge rate began first to decrease but then recovered control mean values. SIN‐1 infusion abolished the activation of group IV afferents after MS. This study indicates that endogenous NO production in a resting or contracting muscle attenuates the baseline activity of group IV muscle afferents and their activation after repetitive muscle contractions.

The changes in neuromuscular excitability with normobaric hyperoxia in humans.

Based on previous observations in hyperbaric hyperoxia, we hypothesized that normobaric hyperoxia, often used during general anaesthesia and resuscitation, might also induce a neuromuscular excitability. In heathy volunteers, we studied the consequences of a 50 min period of pure oxygen breathing on the neuromuscular conduction time (CT), the amplitude of the compound evoked muscle potential (M‐wave), the latency and amplitude of the Hoffman reflex (H reflex) and the electromyographic tonic vibratory response (TVR) of the flexor digitorum superficialis muscle to explore the proprioceptive reflex loop. Hyperoxia‐induced oxidative stress was measured by the changes in blood markers of lipid peroxidation (thiobarbituric acid reactive substances, TBARS) and antioxidant response (reduced ascorbic acid, RAA). During hyperoxia, the M‐wave amplitude increased, both CT and H reflex latency were shortened, and the H reflex amplitude increased. By contrast, TVR significantly decreased. Concomitantly, an oxidative stress was assessed by increased TBARS and decreased RAA levels. This study shows the existence of dual effects of hyperoxia, which facilitates the muscle membrane excitability, nerve conduction and spinal reflexes, but reduces the gain of the proprioceptive reflex loop. The activation of the group IV muscle afferents by hyperoxia and the resulting oxidative stress might explain the TVR depression.