Pathophysiological responses following phosgene exposure in the anaesthetized pig

Abstract

This study aimed to develop a reproducible model of phosgene-induced lung injury in the pig to facilitate the future development of therapeutic strategies. Ten female young adult large white pigs were used. Following induction of anaesthesia using a halothane/oxygen/nitrous oxide mixture, arterial and venous catheters were inserted together with a pulmonary artery thermodilution catheter, and a suprapubic urinary catheter by laparotomy. Anaesthesia was maintained throughout the experiment by intravenous infusion of ketamine, midazolam and alfentanil. On completion of surgery the animals were allowed to equilibrate for 1 h and then were divided into two groups. Group 1 (n = 5) was exposed to phosgene for 10 min (mean Ct = 2443 +/- 35 mg min m(-3)) while spontaneously breathing, whereas control animals (Group 2 n = 5) were exposed to air. At 30 min post-exposure, anaesthesia was deepened in order to allow the initiation of intermittent positive pressure ventilation and the animals were monitored for up to 24 h. Cardiovascular and respiratory parameters were monitored every 30 min and blood samples were taken for arterial and mixed venous blood gas analysis and clinical chemistry. A detailed post-mortem and histopathology was carried out on all animals following death or euthanasia at the end of the 24-h monitoring period. Control animals (Group 2) all survived until the end of the 24-h monitoring period with normal pathophysiological parameters. Histopathology showed only minimal passive congestion of the lung. Following exposure to phosgene (Group 1) there was one survivor to 24 h, with the remainder dying between 16.5 and 23 h (mean = 20 h). Histopathology from these animals showed areas of widespread pulmonary oedema, petechial haemorrhage and bronchial epithelial necrosis. There was also a significant increase in lung wet weight/body weight ratio (P < 0.001). During and immediately following exposure, a transient decrease in oxygen saturation and stroke volume index was observed. From 6 h there were significant decreases in arterial pH (P < 0.01), P(a)O(2) (P < 0.01) and lung compliance (P < 0.01), whereas oxygen delivery and consumption was reduced from 15 h onwards in phosgene-exposed animals. Mean pulmonary artery pressure of phosgene-exposed animals was increased from 15 h post-exposure, with periods of increased pulmonary vascular resistance index being recorded from 9 h onwards. We have developed a reproducible model of phosgene-induced lung injury in the anaesthetized pig. We have followed changes in cardiovascular and pulmonary dynamics for up to 24 h after exposure in order to demonstrate evidence of primary acute lung injury from 16 h post-exposure. Histopathology showed evidence of widespread damage to the lung and there was also a significant increase in lung wet weight/body weight ratio (P < 0.001).

Effect of Chromium Picolinate Supplementation on Growth Performance and Meat Characteristics of Swine

“…The aim was to elucidate the effect of CrPic supplementation on the growth performance and meat characteristics of swine for the entire period, in order to provide guidance to those engaged in animal husbandry on the levels of CrPic, which can usefully be added to feeds. In addition, the digestive and respiratory systems [19] of humans and swine are similar, and because of this, pigs are often used as animal models for the study of potential metabolic mechanisms of action of drugs and additives. Our study also provides data regarding the effect of Cr supplementation on growth that can be applied to children.…”

Effect of PEEP on phosgene-induced lung edema: Pilot study on dogs using protective ventilation strategies

“…Unsurprisingly, anti-inflammatory mitigation principles (dexamethasone and salicylate alone and in combination; Liu et al, 2013;Luo et al, 2014) were inefficacious. Supportive evidence of a cardiogenic etiopathology seems to be that non-invasive, early protective mechanical ventilation proved to be beneficial in this explorative dog model as well as in pigs using a longer postexposure ventilation period as used as in this study (Brown et al, 2002;Parkhouse et al, 2007). Further research is warranted to investigate the outcome over an extended post-phosgene exposure time-period up to 24 h. With increased post-exposure period any increasing circulatory instability may require a well-balanced, ideally conservative, fluid resuscitation.…”

Intravenous Administration of Hyperoxygenated Solution Attenuates Pulmonary Edema Formation in Phosgene-Induced Acute Lung Injury in Rabbits

“…Under normal conditions, there are a little fliud which attend the exchange of body fliud to maintain physiological functions. Exposure to phosgene results in the infiltration of protein and erythrocyte into lung tissue space and pulmonary alveoli, which causes exchange and running disorder of fluid leading to fluid accumulation in lung, which contributes to the formation of lung edema [5][6][7]. In addition, inhalation of phosgene also leads to cell aggregation in lung tissue, especially a great quantity of neutrophilic granulocyte.…”

“…Inhalation of phosgene will lead to lesion of pulmonary alveolus-capillary membrane with the increasing permeability to liquid and solute, which makes liquid aggregate in pulmonary alveolus and interstitial space that result in permeable lung edema with the chief pathological and physiological changes of severe hypoxemia [3,4]. Meanwhile, plenty of phagocytic cells, such as heterophil granulocytes, aggregate and release toxic products including oxyradical [5,6]. Toxic products, such as oxyradical released by necrotic tissue and PMN, can cause bronchoconstriction and aggravate oxygen deficiency [7,8].…”