Experimental acid-aspiration pneumonia in the rabbit. A pathologic and morphometric study.
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Four anesthetized rabbits given intratracheal injections of hydrochloric acid, pH 1.5, 2 ml/kg, were killed 4 h later. A fifth rabbit was an untreated control. Each lung had a few red-brown patches of compression atelectasis. Microscopically, treated lungs had a severe exudative necrotizing bronchitis, bronchiolitis, and alveolitis. There was also intra-alveolar hemorrhage and edema. Electron microscopy showed folds, projections and focal swellings of type I cells lining affected alveoli. A morphometric study showed 69% of parenchyma to be normal, 26% edematous and 5% hemorrhagic. In the airways 58% of the epithelium was damaged. (+info)
Acute lung injury after instillation of human breast milk into rabbits' lungs: effects of pH and gastric juice.
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BACKGROUND: The authors compared the lung injury in rabbits that occurred after tracheal instillation of human breast milk (HBM) acidified to pH 1.8 with hydrochloric acid (HCl), HBM at its native pH (7.0), and HBM acidified with gastric juice to pH 1.8 and 3.0. METHODS: The alveolar-to-arterial oxygen tension gradient and dynamic compliance were recorded before and hourly for 4 h after intratracheal instillation of 0.8 ml/kg HBM acidified with HCI (pH 1.8), HBM at its native pH (7.0), HBM acidified with gastric juice (pH 1.8 or 3.0), or 5% dextrose solution acidified with gastric juice (pH 1.8) as a control in 30 adult rabbits. The circulating neutrophil count and phagocyte oxidant activity were determined before and 1 and 4 h after instillation. RESULTS: The alveolar-to-arterial oxygen tension gradient increased and dynamic compliance decreased significantly in all groups after instillation of HBM compared with baseline values and those in the control group. The severity of the lung injury after instillation of HBM at all pH values (1.8, 3.0, and 7.0) and after acidification with gastric juice or HCl was similar. The circulating neutrophil count increased steadily for 4 h after instillation (P < 0.013), whereas spontaneous phagocyte oxidant burst activity peaked at 1 h (P < 0.007) and returned to baseline by 4 h after instillation. CONCLUSIONS: The severity of the lung injury after tracheal instillation of 0.8 ml/kg HBM in rabbits is similar at pH values between 1.8 and 7.0 after acidification with HCl or gastric juice. Tracheal instillation of HBM increases the circulating neutrophil count and phagocyte oxidant burst activity. (+info)
Assessing the laryngeal cough reflex and the risk of developing pneumonia after stroke: an interhospital comparison.
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BACKGROUND AND PURPOSE: We sought to evaluate the efficacy of testing the laryngeal cough reflex in identifying pneumonia risk in acute stroke patients. METHODS: We performed a prospective study of 400 consecutive acute stroke patients examined using the reflex cough test (RCT) compared with 204 consecutive acute stroke patients from a sister facility examined without using the RCT. The binary end point for the study outcome was the development of pneumonia. RESULTS: Of the 400 patients examined with the RCT, 5 developed pneumonia. Of the 204 patients examined without the RCT, 27 developed pneumonia (P<0.001). Three of the 27 patients died in the rehabilitation hospital of respiratory failure secondary to pneumonia. Seven others were transferred to the emergency department with acute respiratory distress. Power analysis for this comparison was 0.99. There were no other significant differences between the 2 groups. CONCLUSIONS: A normal RCT after an acute stroke indicates a neurologically intact laryngeal cough reflex, a protected airway, and a low risk for developing aspiration pneumonia with oral feeding. An abnormal RCT indicates risk of an unprotected airway and an increased incidence of aspiration pneumonia. Alternate feeding strategies and preventive measures are necessary with an abnormal RCT. Clinical treatment algorithm and prescription of food, fluids, and medications are discussed on the basis of RCT results. (+info)
Midazolam/ketamine sedative combination compared with fentanyl/propofol/isoflurane anaesthesia for oocyte retrieval.
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Assisted reproduction may be associated with repeated occasions of surgical intervention. Propofol, which is frequently used for induction of anaesthesia in such procedures, has been suspected of damaging oocytes. We compared in a randomized prospective design the use of general anaesthesia with fentanyl 0.017 mg/kg, propofol 2.5 mg/kg and isoflurane to that of sedation with midazolam 0.06 mg/kg and ketamine 0.75 mg/kg for transvaginal oocyte retrieval in 50 patients with no premedication. Overall, patient satisfaction was not different between the groups. Sedated patients were more arousable than anaesthetized patients during the procedure and experienced less postoperative abdominal pain at 30 min. Despite some movement in response to pain, oocyte retrieval was conveniently feasible in all sedated patients, of which none required a switch to general anaesthesia. A comparable number of oocytes was retrieved per cycle, 10.8 (+/-7.8) versus 9.6 (+/-10.9) with sedation and anaesthesia respectively. No patient recalled any pain sensation during the procedure. The rate of embryo transfers and pregnancies were not different between the two groups. We conclude that the sedative combination of midazolam and ketamine for oocyte retrieval may serve as an alternative for general anaesthesia. (+info)
The role of tumor necrosis factor-alpha in the pathogenesis of aspiration pneumonitis in rats.
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BACKGROUND: Aspiration pneumonitis is characterized by proteinaceous pulmonary edema and acute infiltration of neutrophils into the alveolar space. This study examined the role of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), on the pathogenesis of the injury produced by the different components that may be present in the aspirate, acid, or gastric particles. METHODS: Rats were injured by intratracheal instillation of a vehicle containing acid or gastric particles. TNF-alpha concentration of bronchoalveolar lavage fluid was determined using a bioassay. upregulation of lung TNF-alpha mRNA was also measured. The effect of intratracheal anti-rat TNF-alpha treatment was assessed by lung protein permeability, blood gases, and lung myeloperoxidase activity. RESULTS: Injury vehicle alone and acid injury resulted in a small TNF-alpha peak 1-2 h after injury in the lavage fluid. Both particulate and acidic particulate groups produced a much more robust TNF-alpha signal that reached a plateau at 2-4 h after injury and declined at 8 h. Upregulation of TNF-alpha mRNA was only detected in the particulate-containing groups. Acidic particulate exposure yielded a synergistic increase in protein permeability and decrease in blood oxygenation. Anti-TNF-alpha treatment reduced protein permeability and myeloperoxidase activity and increased blood oxygenation in the groups exposed to only acid. Such treatment had no effect on either of the particulate containing injuries. CONCLUSIONS: TNF-alpha is differentially manifested according to the components that make up the aspirate but the levels of TNF-alpha expression do not correlate with the severity of the resultant injury. However, the reduction in acid-induced lung injury by anti-TNF-alpha treatment indicates that TNF-alpha plays a role in the pathogenesis of aspiration pneumonitis. (+info)
BACKGROUND: Inhaled nitric oxide is often used in patients with adult respiratory distress syndrome. However, nitric oxide also may be significantly toxic, especially if administered concurrently with hyperoxia. The authors evaluated the isolated effect of nitric oxide and the combined effects of nitric oxide and hyperoxia on lung injury in rats after acid aspiration. METHODS: Animals were injured by instillation of 1.2 ml/kg hydrogen chloride in low-pH saline (the acid group) or acidified gastric particles (the casp group) into the lungs under halothane anesthesia via a tracheal catheter. Controls received no injury vehicle but rather underwent the surgical process. After recovery from anesthesia, the animals were exposed to 20% or 90% oxygen with or without 20, 40, or 80 ppm nitric oxide for 5 h. The permeability index, alveolar-arterial oxygen difference, the ratio of oxygen pressure to the inspired fraction of oxygen, and the ratio of wet to dry weight were assessed 5 h after injury as indices of lung injury. Data were assessed using analysis of variance. RESULTS: Each group included 6-10 rats. Exposure to nitric oxide (80 ppm) in air increased protein permeability in the lungs to a permeability index of 1.42+/-0.12 after acid aspiration. The combination of nitric oxide (80 ppm) and hyperoxia further increased protein leakage to a permeability index of 2.1+/-0.25. Exposure to lower concentrations of nitric oxide (e.g., 20 and 40 ppm) increased the permeability index of the lungs (1.44+/-0.21, 1.75+/-0.29, respectively) in the presence of hyperoxia, although it did not affect the permeability index of the lungs during exposure to air. Pretreatment of animals with deferoxamine and methylene blue partially inhibited the adverse effect of hyperoxia and nitric oxide, which suggested a complex underlying mechanism involving both reactive-species generation and pulmonary vasomotor changes. CONCLUSIONS: These results show that inhaled nitric oxide at 80 ppm for a short duration (5 h) increases the severity of the inflammatory microvascular lung injury after acid aspiration. The pulmonary damage is exacerbated further in the presence of high oxygen concentrations. Although lower concentrations of nitric oxide did not increase the extent of lung injury, longer exposure times need to be assessed. (+info)
Membrane attack complex of complement and neutrophils mediate the injury of acid aspiration.
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A significant role for the alternative complement pathway in acid aspiration has been demonstrated by the observation that C3 genetic knockout mice are protected from injury. Utilizing C5-deficient mice, we now test the role of the terminal complement components in mediating injury. Lung permeability in C5-deficient mice was 64% less than in wild-type animals and was similar to wild-type mice treated with soluble complement receptor type 1, which gave a 67% protection. Injury was fully restored in C5-deficient mice reconstituted with wild-type serum. The role of neutrophils was established in immunodepleted wild-type animals that showed a 58% protection. Injury was further reduced (90%) with the addition of soluble complement receptor type 1, indicating an additive effect of neutrophils and complement. Similarly, an additional protection was noted in C5-deficient neutropenic mice, indicating that neutrophil-mediated injury does not require C5a. Thus acid aspiration injury is mediated by the membrane attack complex and neutrophils. Neutrophil activity is independent of C5a. (+info)
A novel model of aspiration in young and old guinea-pigs using LacZ gene transduction of adenovirus vector.
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The effects of anaesthesia on upper airway reflexes in older animals have not been elucidated fully. We studied young (4-month-old) and old (28-month-old) guinea-pigs to examine the relationship between aspiration and altered upper airway reflexes during anaesthesia. We administered an adenovirus vector carrying Escherichia coli LacZ gene (Ad vector) intranasally to guinea-pigs with or without anaesthesia. LacZ gene expression was investigated in the nostrils and lungs of each animal under anaesthesia. No LacZ gene expression was found in the lungs of unanaesthetized animals given Ad vector. Thus intranasal administration of Ad vector was aspirated into the lower airways under anaesthesia. Next we examined the effect of age on anaesthesia-induced aspiration. At a lower concentration of halothane in 100% oxygen, greater LacZ gene expression in the lungs was measured in older than in younger animals, suggesting that older animals are liable to aspirate oropharyngeal contents into the lower airways during light anaesthesia. This novel animal model of aspiration using Ad vector may be useful to explore the mechanism of aspiration during and after anaesthesia in young and old animals. (+info)