Nicolás Nin

Aging increases the susceptibility to injurious mechanical ventilation

ObjectiveTo test the hypothesis that aging increases the susceptibility to organ dysfunction and systemic inflammation induced by injurious mechanical ventilation.Design and settingExperimental study in an animal model of ventilator-induced lung injury in the animal research laboratory in axa0university hospital.MethodsYoung (3–4u202fmonths old) and old (22–24u202fmonths old) anesthetized Wistar rats were ventilated for 60u202fmin with axa0protective lung strategy (VTu202f=u202f9u202fml/kg and PEEPu202f=u202f5u202fcm H2O, control) or with an injurious strategy (VTu202f=u202f35u202fml/kg and PEEPu202f=u202f0u202fcm H2O, overventilated; nu202f=u202f6 for each group).Measurements and resultsMean arterial pressure and airway pressures (PAW) were monitored. Arterial blood gases and serum AST, ALT, lactate, and IL-6 were measured. Vascular rings from the thoracic aorta were mounted in organ baths for isometric tension recording. We studied relaxations induced by acetylcholine (10u202fnM–10u202fμM) in norepinehrine-precontracted rings, and contractions induced by norepinephrine (1u202fnM–10u202fμM) in resting vessels. Lungs were examined by light microscopy. Injurious ventilation in young rats was associated with hypoxemia, lactic metabolic acidosis, increased serum AST, hypotension, impairment in norepinephrine and acetylcholine-induced vascular responses ex vivo and hyaline membrane formation. The high-VT induced hypotension, increase in mean PAW, AST, and IL-6, and the impairment in acetylcholine-induced responses were significantly more marked in aged than in young rats.ConclusionsElderly rats showed increased susceptibility to injurious mechanical ventilation-induced pulmonary injury, vascular dysfunction, and systemic inflammation.

Lung histopathological findings in fatal pandemic influenza A (H1N1)

OBJECTIVEnTo describe the lung pathological changes in influenza A (H1N1) viral pneumonia. We studied morphological changes, nitro-oxidative stress and the presence of viral proteins in lung tissue.nnnMETHODS AND PATIENTSnLight microscopy was used to examine lung tissue from 6 fatal cases of pandemic influenza A (H1N1) viral pneumonia. Fluorescence for oxidized dihydroethydium, nitrotyrosine, inducible NO synthase (NOS2) and human influenza A nucleoprotein (NP) (for analysis under confocal microscopy) was also studied in lung tissue specimens.nnnRESULTSnAge ranged from 15 to 50 years. Three patients were women, and 5 had preexisting medical conditions. Diffuse alveolar damage (DAD) was present in 5 cases (as evidenced by hyaline membrane formation, alveolo-capillary wall thickening and PMN infiltrates), and interstitial fibrosis in one case. In the fluorescence studies there were signs of oxygen radical generation, increased NOS2 protein and protein nitration in lung tissue samples, regardless of the duration of ICU admission. Viral NP was found in lung tissue samples from three patients. Type I pneumocytes and macrophages harbored viral NP, as evidenced by confocal immunofluorescence microscopy.nnnCONCLUSIONSnLung tissue from patients with pandemic influenza A (H1N1) viral pneumonia shows histological findings consistent with DAD. Prolonged nitro-oxidative stress is present despite antiviral treatment. Viral proteins may remain in lung tissue for prolonged periods of time, lodged in macrophages and type I pneumocytes.

Evidencias de la posición en decúbito prono para el tratamiento del síndrome de distrés respiratorio agudo: una puesta al día

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have high incidence and mortality rates. Most of the recently introduced treatments have failed to improve the prognosis of patients with ALI or ARDS or to reduce mortality. Several studies have shown improved oxygenation in the prone position during mechanical ventilation in patients with ARDS. However, current evidence strongly suggests that placing ARDS patients in prone position does not improve survival or reduce the duration of mechanical ventilation. Therefore, though in clinical practice this position may improve refractory hypoxemia in patients with ARDS, there is no evidence to support its systematic use.

Prone Position for the Treatment of Acute Respiratory Distress Syndrome: A Review of Current Literature

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have high incidence and mortality rates. Most of the recently introduced treatments have failed to improve the prognosis of patients with ALI or ARDS or to reduce mortality. Several studies have shown improved oxygenation in the prone position during mechanical ventilation in patients with ARDS. However, current evidence strongly suggests that placing ARDS patients in prone position does not improve survival or reduce the duration of mechanical ventilation. Therefore, though in clinical practice this position may improve refractory hypoxemia in patients with ARDS, there is no evidence to support its systematic use.

Influence of mechanical ventilation and sepsis on redox balance in diaphragm, myocardium, limb muscles, and lungs

Mechanical ventilation (MV), using high tidal volumes (V(T)), causes lung (ventilator-induced lung injury [VILI]) and distant organ injury. Additionally, sepsis is characterized by increased oxidative stress. We tested whether MV is associated with enhanced oxidative stress in sepsis, the commonest underlying condition in clinical acute lung injury. Protein carbonylation and nitration, antioxidants, and inflammation (immunoblotting) were evaluated in diaphragm, gastrocnemius, soleus, myocardium, and lungs of nonseptic and septic (cecal ligation and puncture 24 hours before MV) rats undergoing MV (n = 7 per group) for 150 minutes using 3 different strategies (low V(T) [V(T) = 9 mL/kg], moderate V(T) [V(T) = 15 mL/kg], and high V(T) [V(T) = 25 mL/kg]) and in nonventilated control animals. Compared with nonventilated control animals, in septic and nonseptic rodents (1) diaphragms, limb muscles, and myocardium of high-V(T) rats exhibited a decrease in protein oxidation and nitration levels, (2) antioxidant levels followed a specific fiber-type distribution in slow- and fast-twitch muscles, (3) tumor necrosis factor α (TNF-α) levels were higher in respiratory and limb muscles, whereas no differences were observed in myocardium, and (4) in lungs, protein oxidation was increased, antioxidants were rather decreased, and TNF-α remained unmodified. In this model of VILI, oxidative stress does not occur in distant organs or skeletal muscles of rodents after several hours of MV with moderate-to-high V(T), whereas protein oxidation levels were increased in the lungs of the animals. Inflammatory events were moderately expressed in skeletal muscles and lungs of the MV rats. Concomitant sepsis did not strongly affect the MV-induced effects on muscles, myocardium, or lungs in the rodents.

Kidney histopathological findings in fatal pandemic 2009 influenza A (H1N1)

Dear Editor, A new pandemic was originated by a novel influenza A (H1N1) virus [1– 3]. Severe cases were characterized by acute respiratory distress syndrome (ARDS), shock, and acute kidney injury (AKI) [3]. Lung histopathological changes in fatal cases showed signs of diffuse alveolar damage, necrotizing bronchiolitis, and occasional alveolar hemorrhage [2]. However, histopathological changes in organs other than the lungs are not known. Here we report kidney histopathological findings and describe for the first time the specific kidney cell type targeted by pandemic 2009 influenza A (H1N1) virus infection. With the approval of our Ethics Committee and with closest relative informed consent, renal biopsies from four patients who died in the intensive care unit (ICU) with diagnosis of confirmed influenza A (H1N1) virus infection were studied by microscopy after hematoxylin and eosin (HE), Masson’s or periodic acid-Schiff (PAS) staining. Cell nuclei were revealed by staining with 4’,6-diamidino-2-phenylindole (DAPI). Localization of viral antigen and specific kidney cells was carried out by double immunofluorescence (IF) labeling [4] using antibodies (Santa Cruz) specific for either: (1) aquaporin 1, a marker of proximal tubular cells; (2) CD10, a marker of proximal tubular cells; (3) cytokeratin 7, a marker of distal tubular cells; or (4) CD34, a marker of endothelial cells, and a rabbit antiserum specific for influenza nucleoprotein (NP). This antibody was generated by immunization of rabbits with purified recombinant NP and validated by IF, Western blotting, and immunoprecipitation of control and influenzainfected human cells [5]. This antibody is cross-reactive with several influenza A virus subtypes (data not shown). Secondary antibodies were fluorescein isothiocyanate (FITC)labeled goat anti-mouse immunoglobulin G (IgG) (Santa Cruz) and Alexa 546-conjugated goat anti-rabbit IgG. Sections were studied under confocal microscopy (Leica SP5), and single optical sections are presented. Only cases 3 and 4 were diagnosed with AKI. Cases 3 and 4 had focal changes consistent with acute tubular necrosis (ATN) in the distal tubules (epithelial cell swelling, individual cell necrosis, and shedding of

0852. Selective decontamination of the digestive tract modulates the metabolic profile in a ventilator-induced lung injury model

Acute lung injury induced by mechanical ventilation [ventilator-induced lung injury (VILI)]is characterized by a particular metabolic profile in the lung and in the systemic compartment [1]. Also, VILI has been associated with an increase in intestinal permeability [2]. We hypothesized that selective decontamination of the digestive tract (SDD) can modulate the metabolic profile associated with mechanical ventilation.

0895. Identification and validation of a mirna as a diagnostic biomarker of diffuse alveolar damage in an animal model of acute lung injury and adult respiratory distress syndrome in mechanically ventilated patients

0895. Identification and validation of a mirna as a diagnostic biomarker of diffuse alveolar damage in an animal model of acute lung injury and adult respiratory distress syndrome in mechanically ventilated patients P Cardinal-Fernandez, A Ferruelo, N Rego, Y Rojas, A Ballen-Barragan, R Granados, C Jaramillo, E Lopez-Hernandez, L Martinez-Caro, N Nin, R Herrero, MA de la Cal, A Esteban, JA Lorente