Pathophysiological and diagnostic implications of cardiac biomarkers and antidiuretic hormone release in distinguishing immersion pulmonary edema from decompression sickness

Immersion pulmonary edema (IPE) is a misdiagnosed environmental illness caused by water immersion, cold, and exertion. IPE occurs typically during SCUBA diving, snorkeling, and swimming. IPE is sometimes associated with myocardial injury and/or loss of consciousness in water, which may be fatal. IPE is thought to involve hemodynamic and cardiovascular disturbances, but its pathophysiology remains largely unclear, which makes IPE prevention difficult. This observational study aimed to document IPE pathogenesis and improve diagnostic reliability, including distinguishing in some conditions IPE from decompression sickness (DCS), another diving-related disorder. Thirty-one patients (19 IPE, 12 DCS) treated at the Hyperbaric Medicine Department (Ste-Anne hospital, Toulon, France; July 2013–June 2014) were recruited into the study. Ten healthy divers were recruited as controls. We tested: (i) copeptin, a surrogate marker for antidiuretic hormone and a stress marker; (ii) ischemia-modified albumin, an ischemia/hypoxia marker; (iii) brain-natriuretic peptide (BNP), a marker of heart failure, and (iv) ultrasensitive-cardiac troponin-I (cTnI), a marker of myocardial ischemia. We found that copeptin and cardiac biomarkers were higher in IPE versus DCS and controls: (i) copeptin: 68% of IPE patients had a high level versus 25% of DCS patients (P < 0.05) (mean ± standard-deviation: IPE: 53 ± 61 pmol/L; DCS: 15 ± 17; controls: 6 ± 3; IPE versus DCS or controls: P < 0.05); (ii) ischemia-modified albumin: 68% of IPE patients had a high level versus 16% of DCS patients (P < 0.05) (IPE: 123 ± 25 arbitrary-units; DCS: 84 ± 25; controls: 94 ± 7; IPE versus DCS or controls: P < 0.05); (iii) BNP: 53% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 383 ± 394 ng/L; DCS: 37 ± 28; controls: 19 ± 15; IPE versus DCS or controls: P < 0.01); (iv) cTnI: 63% of IPE patients had a high level, DCS patients having normal values (P < 0.05) (IPE: 0.66 ± 1.50 μg/L; DCS: 0.0061 ± 0.0040; controls: 0.0090 ± 0.01; IPE versus DCS or controls: P < 0.01). The combined “BNP-cTnI” levels provided most discrimination: all IPE patients, but none of the DCS patients, had elevated levels of either/both of these markers. We propose that antidiuretic hormone acts together with a myocardial ischemic process to promote IPE. Thus, monitoring of antidiuretic hormone and cardiac biomarkers can help to make a quick and reliable diagnosis of IPE

Eccentric exercise alters muscle sensory motor control through the release of inflammatory mediators.

Following downhill exercise, muscle damage and local inflammatory reactions, induced by lengthening contractions, are observed and voluntary muscle activation decreases. The hypothesis that feedback carried by the group IV muscle afferents could be involved has often been raised but never measured in vivo in these conditions. In this experiment, we tested the response of the group IV muscle afferents from the lower limb to injections of KCl and lactic acid in non-exercising rats and at 1, 2, and 8 days after one running session (-13 degrees, 16 m/min). At days 1 and 2, the baseline discharge of the group IV afferents increased, but further activation by test agents was absent. After 8 days, the afferent response was equivalent to the control response. Pretreatment with betamethasone before exercise abolished the effects of downhill exercise. In non-exercising rats, arachidonic acid evoked group IV afferent discharge and suppressed their further response to another stimulus. These results demonstrate that exhaustive downhill running highly activates, for at least 2 days, the sensory feedback carried by group IV afferents through the local release of inflammatory mediators. Such an altered sensori-motor control, accompanying the post-eccentric inflammatory syndrome, could play a key role in deterioration of muscle performance and of its voluntary activation

Adenosine Receptor Profiling Reveals an Association between the Presence of Spare Receptors and Cardiovascular Disorders

International audienceAdenosine and its receptors exert a potent control on the cardiovascular system. This review aims to present emerging experimental evidence supporting the existence and implication in cardiovascular disorders of specific adenosinergic pharmacological profiles, conforming to the concept of "receptor reserve", also known as "spare receptors". This kind of receptors allow agonists to achieve their maximal effect without occupying all of the relevant cell receptors. In the cardiovascular system, spare adenosine receptors appear to compensate for a low extracellular adenosine level and/or a low adenosine receptor number, such as in coronary artery disease or some kinds of neurocardiogenic syncopes. In both cases, the presence of spare receptors appears to be an attempt to overcome a weak interaction between adenosine and its receptors. The identification of adenosine spare receptors in cardiovascular disorders may be helpful for diagnostic purposes

The effects of the Fenton reaction are limited by zeolites in vitro

International audienceWe report the effects of zeolite pore systems in limiting the oxidation of ascorbic acid (vitamin C) in plasma using the mixing of FeCl2 and H2O2 (“Fenton solution”) as an oxidant. We tested three homemade zeolites and nineteen natural zeolites. Six polar zeolites were effective in restricting the oxidation of vitamin C and the majority of them acted by chelation of ferrous/ferric chloride. Faujasite (FAU13x) was the most active ROS scavenger. On the other hand, two natural zeolites, Goosecreekite and Stilbite (GOOnat and STInat), inhibited the oxidation of vitamin C by action on the reduction of hydrogen peroxide concentration to form H2O. Our hypothesis suggests that effective zeolites have the advantage of never being saturated in the time. Here, for the first time, we identified a substrate (zeolite) which acts directly on the two substrates (Fe2+/H2O2) to limit ROS formation

Ticagrelor Improves Peripheral Arterial Function in Acute Coronary Syndrome Patients: Relationship With Adenosine Plasma Level.

International audienceTicagrelor, a P2Y12 receptor antagonist, significantly reduces the incidence of major cardiovascular events in acute coronary syndrome (ACS) compared with standard treatment with clopidogrel (1). It has been suggested that this benefit effect may be accounted for by its pleiotropic properties via a purinergic mechanism. Indeed, ticagrelor increases the endogenous adenosine plasma level (APL) via red blood cell uptake inhibition in primary ACS patients compared with clopidogrel (2). However, the link between these “pleiotropic” properties and the improvement in microvascular dysfunction (MiD) remains poorly investigated. This study aimed to determine whether the increase in APL achieved with ticagrelor might improve endothelial dysfunction in primary ACS patients

Matched adaptations of electrophysiological, physiological, and histological properties of skeletal muscles in response to chronic hypoxia.

This study tried to differentiate the consequences of chronic hypoxia on the electrophysiological and physiological properties and the histological characteristics of slow and fast muscles in rats. Animals inhaled a 10% O(2) concentration for a 1-month period. Then, slow [soleus (SOL)] and fast [extensor digitorum longus (EDL)] muscles were analyzed in vitro by physiological and electrophysiological measurements and histological analyses. The results were compared to those obtained in corresponding muscles of an age-matched normoxic group. After exposure to hypoxia: (1) in SOL, there was a tendency to elevated F(max), a significant increase in twitch force and tetanic frequency and a shortening of M-wave duration, and a reduced percentage of type I fibres, whereas the proportion of type IIa fibres doubled; (2) in EDL, F(max) and tetanic frequency were lowered, the muscle became less resistant to fatigue, and the proportion of type IId/x fibres was halved. Then, after 1 month of hypoxia, in the SOL muscle, both the contractile and histological properties resemble those of a fast muscle. By contrast, the EDL became slower, despite its histology was modestly affected. Reduced muscle use in hypoxia could explain the tendency for deteriorating adaptations in EDL, and the faster properties of SOL could result from hypoxia-induced inhibition of the growth-related fast-to-slow shift in muscle fibre types

Role of proinflammatory activity contained in gastric juice from intensive care unit patients to induce lung injury in a rabbit aspiration model

OBJECTIVE: Although aspiration pneumonitis is a severe complication in patients hospitalized in intensive care units, its pathogenesis is poorly understood. The aim of this study was to determine whether the intensity of lung injury and inflammation developing after aspiration during mechanical ventilation differed depending on the inflammatory activity of intensive care unit patients' gastric fluid. DESIGN: In vitro study on human gastric juice and randomized controlled animal study. SETTING: Research laboratories of academic institutions. SUBJECTS: Male New-Zealand white rabbits. INTERVENTIONS: Proinflammatory activity of gastric juice from 17 intensive care unit patients and 12 controls undergoing elective surgery was measured based on a target cell activation assay. Two gastric juices from intensive care unit patients with similar pH but differing for their in vitro proinflammatory activity (high and low) were further instilled into the trachea of ventilated rabbits. Lung function, mechanics, pathology, leukocyte infiltration, and local cytokine levels were measured after 6 hrs. MEASUREMENTS AND MAIN RESULTS: Gastric juice from intensive care unit patients, even buffered at pH 7.4, stimulated human type II-like A549 epithelial cells to up-regulate intercellular adhesion molecule-1 and interleukin-8, significantly more than juice obtained in controls. Gastric juice from an intensive care unit patient supporting high proinflammatory activity in vitro also induced a more severe and persistent drop in PaO2/FIO2 and respiratory system compliance in ventilated rabbits, a worse histologic score, higher lung lavage concentrations of inflammatory cells, interleukin-8 (p < 0.01), and growth-related oncogene-alpha (p < 0.01) than one fluid with low proinflammatory activity. CONCLUSION: Gastric juice from critically ill patients is proinflammatory and stimulates human pulmonary cells in vitro. A human gastric juice with high proinflammatory activity is more "toxic" to the lung than one with low proinflammatory activity in a ventilated rabbit model, an effect that is independent of pH and particulate matter content

Consequences of prolonged total body immersion in cold water on muscle performance and EMG activity

The consequences of a prolonged total body immersion in cold water on the muscle function have not been documented yet, and they are the object of this French Navy research program. Ten elite divers were totally immerged and stayed immobile during 6 h in cold (18 and 10°C) water. We measured the maximal voluntary leg extension (maximal voluntary contraction, MVC) and evoked compound muscle potential (M wave) in vastus lateralis and soleus muscles at rest, after a submaximal (60% MVC) isometric extension allowing the measurement of the endurance time (Tlim). The power spectrum of surface electromyograms (EMG) was computed during 60% MVCs. MVCs and 60% MVC maneuvers were repeated four times during the immersion. Data were compared with those obtained in a control group studied in dry air condition during a 6-h session. Total body cooling did not affect MVC nor Tlim. The M wave duration increased in the coolest muscle (soleus), but only at 10°C at rest. There were no further fatigue-induced M wave alterations in both muscles. During 60% the MVCs, a time-dependant increase in the leftward shift of the EMG spectrum occurred at the two temperatures. These EMG changes were absent in the control group of subjects studied in dry air. The plasma lactate concentration was elevated throughout the 18 and mostly the 10°C immersion conditions. Throughout the 18°C immersion study, the resting potassium level did not significantly vary, whereas at 10°C, a significant potassium increase occurred soon and persisted throughout the study. Thus, total body immersion in cold water did not affect the global contractile properties of leg muscles during static efforts but elicited significant alterations in electromyographic events which may be related to the variations of interstitial fluid composition

Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome

International audienceBackground: In myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), altered membrane excitability often occurs in exercising muscles demonstrating muscle dysfunction regardless of any psychiatric disorder. Increased oxi-dative stress is also present in many ME/CFS patients and could affect the membrane excitability of resting muscles. Methods: Seventy-two patients were examined at rest, during an incremental cycling exercise and during a 10-min post-exercise recovery period. All patients had at least four criteria leading to a diagnosis of ME/CFS. To explore muscle membrane excitability, M-waves were recorded during exercise (rectus femoris (RF) muscle) and at rest (flexor digi-torum longus (FDL) muscle). Two plasma markers of oxidative stress (thiobarbituric acid reactive substance (TBARS) and oxidation-reduction potential (ORP)) were measured. Plasma potassium (K +) concentration was also measured at rest and at the end of exercise to explore K + outflow. Results: Thirty-nine patients had marked M-wave alterations in both the RF and FDL muscles during and after exercise while the resting values of plasma TBARS and ORP were increased and exercise-induced K + outflow was decreased. In contrast, 33 other patients with a diagnosis of ME/CFS had no M-wave alterations and had lower base-line levels of TBARS and ORP. M-wave changes were inversely proportional to TBARS and ORP levels. Conclusions: Resting muscles of ME/CFS patients have altered muscle membrane excitability. However, our data reveal heterogeneity in some major biomarkers in ME/CFS patients. Measurement of ORP may help to improve the diagnosis of ME/CFS