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Free radical-induced complement activation
70
Burns (1989)
Ibuprofen and chest-wall bums Sheep were given deep bums covering 30 per cent of the body surface area on either the walls of the chest or on the flanks. When the burn affected the chest wall (and in contrast to the flank bums) there were immediate decreases in cardiac output, central venous pressure, pulmonary wedge pressure and urine output. The temperature of the pulmonary artery blood increased from 38 to 42°C and the plasma prostacyclin levels increased IO-fold. The chest-wall bums increased the initial fluid requirements to restore filling pressures by 50 per cent and decreased static lung compliance by mechanisms other than increased lung oedema. At 6-7 hours postbum chest wall escharotomies halted the progressive decreases in compliance, urine output and stroke output. Postmortem analysis in the chest bum group showed increased amounts of malondialdehyde, the product of oxygen radical-induced !ipid peroxidation. Pretreatment of the chest bum with ibuprofen prevented the initial vasodilator and lung compliance changes and decreased the lung tissue malondialdehyde content. Demling R. H., Zhu D. G. and Lalonde C. (1988) Early pulmonary and hemodynamic effects of a chest wall bum (effect of ibuprofen). Surgery 104, (I), 10-17. Efficacy of resuscitation
Vol. IS/No.
1
Clark W. R., Nieman G. F., Goyette D. et al. (1988) Effects of crystalloid on lung fluid balance after smoke inhalation. Ann. Surg. 208, (I), 56-64. Free radical-induced
complement
activation
Groups of rats with partial skin thickness bums covering 25 per cent of the body surface area were given either oxygen radical scavengers or antioxidant enzymes or xanthine oxidase inhibitors or an iron chelator or rendered complement or neutrophil depleted. Plasma from the area of the bum was examined for total haemolytic complement activity, the content of C5arelated chemotactic peptide and the relationship of oxygen products to the appearance of this peptide. Xanthine oxidase inhibitors, hydroxyl radical scavengers and complement depletion diminished the production of C5a activity at the bum site whereas neutrophil depletion was without effect. These results suggest that C5a activity may be related to oxygen products from xanthine oxidase. The catalase sensitivity and iron dependency of C5a generation suggest that hydroxyl radicals may be related to the appearance of C5a and complement activation. Oldham K. T., Guice K. S., Till G. 0. et al. (1988) Activation of complement by hydroxyl radical in thermal injury. Surgery 104, (2), 272-279.
solutions
Thirty-six sheep with deep bums covering 40 per cent of the body surface area were divided into four groups and nine other sheep acted as controls. All animals received either Ringer’s lactate or hypertonic saline (250 mmol/l Na/l) with or without 12.5 g/l of normal human albumin to determine the effectiveness of resuscitation. While all animals survived the bum and showed reasonable haemodynamic stability during the study, the group receiving Ringer’s lactate with albumin restored their cardiac output to prebum values sooner, showed higher serum albumin and colloid osmotic pressure levels by 24 h postinjury, experienced no electrolyte or acid/base inbalances and maintained serum osmolality within normal limits. In contrast to the other three solutions Ringer’s lactate plus albumin did not induce oedema in unburned tissues and seemed optimal for bum resuscitation. Carvajal H. F. and Parks D. H. (1988) Optimal composition of bum resuscitation fluids. Crit. Cure Med. 26, (7), 695-700.
rIL-2 improves immunocompetence In vitro studies of splenocytes from mice with scalds covering one-quarter of the body surface area indicated that the addition of recombinant interleukin 2 (rIL-2) restored the T-cell mitogen responses to normal. In a controlled study the mice received daily injections of either dextrose solution or rIL-2 for 6 days and then at 10 days postbum were subjected to caecal ligation and puncture. By 14 days postbum all of the dextrose-treated animals had died whereas 45 per cent of the rIL-2 treated animals were still alive. The rIL-2 did not appear to be toxic and had the beneficial effect of restoring immunocompetence. Gough D. B., Moss N. M., Jordan A. et al. (1988) Recombinant interleukin 2(rIL-2) improves immune response and host resistance to septic challenge in thermally injured mice. Surgery 104, (2), 292-300. Leucocyte
Water content of smoke-injured
lungs
The vulnerability of the smoke-injured lung to the iv. infusion of large volumes (IO per cent of body weight) of Ringer’s lactate was assessed in dogs who had inhaled smoke. The three groups of animals received either only fluid or only smoke or smoke and fluid. The increase in wet to dry lung weight ratio was 2 per cent after only fluid, 28 per cent after only smoke and 42 per cent after the mixture. This latter group showed pulmonary oedema. The colloid osmotic pressure decreased to the same levels in both groups given fluid. The rise in the minimum surface tension of lung extracts was similar in both groups exposed to smoke. Changes in the microvascular pressure, epithelial and endothelial damage and inactivation of surfactant seem to combine to cause the increased extravascular lung water content.
depletion limits smoke injury
Cotton smoke inhalation injury was inflicted on normal sheep and those that had previously been made leucocyte deficient with nitrogen mustard. Although both groups of animals had identical smoke exposures (as indexed by carboxyhaemoglobin levels), the smoke plus leucocyte-depleted group showed significantly smaller rises in pulmonary artery pressure, pulmonary vascular resistance and pulmonary lymph flow. The P~o,/~?o, ratio did not fall to the same extent nor was there a fall in PuO,. There was no increase in oxygen radical production or antiprotease consumption in the smoke plus leucocyte-depleted group compared with rises in the smoke-alone group. Basadre J. 0.. Sugi K., Traber D. L. et al. (1988) The effect of leucocyte depletion on smoke inhalation injury in sheep. Surgery 104, (2), 208-215.
Burns (1989)
Ibuprofen and chest-wall bums Sheep were given deep bums covering 30 per cent of the body surface area on either the walls of the chest or on the flanks. When the burn affected the chest wall (and in contrast to the flank bums) there were immediate decreases in cardiac output, central venous pressure, pulmonary wedge pressure and urine output. The temperature of the pulmonary artery blood increased from 38 to 42°C and the plasma prostacyclin levels increased IO-fold. The chest-wall bums increased the initial fluid requirements to restore filling pressures by 50 per cent and decreased static lung compliance by mechanisms other than increased lung oedema. At 6-7 hours postbum chest wall escharotomies halted the progressive decreases in compliance, urine output and stroke output. Postmortem analysis in the chest bum group showed increased amounts of malondialdehyde, the product of oxygen radical-induced !ipid peroxidation. Pretreatment of the chest bum with ibuprofen prevented the initial vasodilator and lung compliance changes and decreased the lung tissue malondialdehyde content. Demling R. H., Zhu D. G. and Lalonde C. (1988) Early pulmonary and hemodynamic effects of a chest wall bum (effect of ibuprofen). Surgery 104, (I), 10-17. Efficacy of resuscitation
Vol. IS/No.
1
Clark W. R., Nieman G. F., Goyette D. et al. (1988) Effects of crystalloid on lung fluid balance after smoke inhalation. Ann. Surg. 208, (I), 56-64. Free radical-induced
complement
activation
Groups of rats with partial skin thickness bums covering 25 per cent of the body surface area were given either oxygen radical scavengers or antioxidant enzymes or xanthine oxidase inhibitors or an iron chelator or rendered complement or neutrophil depleted. Plasma from the area of the bum was examined for total haemolytic complement activity, the content of C5arelated chemotactic peptide and the relationship of oxygen products to the appearance of this peptide. Xanthine oxidase inhibitors, hydroxyl radical scavengers and complement depletion diminished the production of C5a activity at the bum site whereas neutrophil depletion was without effect. These results suggest that C5a activity may be related to oxygen products from xanthine oxidase. The catalase sensitivity and iron dependency of C5a generation suggest that hydroxyl radicals may be related to the appearance of C5a and complement activation. Oldham K. T., Guice K. S., Till G. 0. et al. (1988) Activation of complement by hydroxyl radical in thermal injury. Surgery 104, (2), 272-279.
solutions
Thirty-six sheep with deep bums covering 40 per cent of the body surface area were divided into four groups and nine other sheep acted as controls. All animals received either Ringer’s lactate or hypertonic saline (250 mmol/l Na/l) with or without 12.5 g/l of normal human albumin to determine the effectiveness of resuscitation. While all animals survived the bum and showed reasonable haemodynamic stability during the study, the group receiving Ringer’s lactate with albumin restored their cardiac output to prebum values sooner, showed higher serum albumin and colloid osmotic pressure levels by 24 h postinjury, experienced no electrolyte or acid/base inbalances and maintained serum osmolality within normal limits. In contrast to the other three solutions Ringer’s lactate plus albumin did not induce oedema in unburned tissues and seemed optimal for bum resuscitation. Carvajal H. F. and Parks D. H. (1988) Optimal composition of bum resuscitation fluids. Crit. Cure Med. 26, (7), 695-700.
rIL-2 improves immunocompetence In vitro studies of splenocytes from mice with scalds covering one-quarter of the body surface area indicated that the addition of recombinant interleukin 2 (rIL-2) restored the T-cell mitogen responses to normal. In a controlled study the mice received daily injections of either dextrose solution or rIL-2 for 6 days and then at 10 days postbum were subjected to caecal ligation and puncture. By 14 days postbum all of the dextrose-treated animals had died whereas 45 per cent of the rIL-2 treated animals were still alive. The rIL-2 did not appear to be toxic and had the beneficial effect of restoring immunocompetence. Gough D. B., Moss N. M., Jordan A. et al. (1988) Recombinant interleukin 2(rIL-2) improves immune response and host resistance to septic challenge in thermally injured mice. Surgery 104, (2), 292-300. Leucocyte
Water content of smoke-injured
lungs
The vulnerability of the smoke-injured lung to the iv. infusion of large volumes (IO per cent of body weight) of Ringer’s lactate was assessed in dogs who had inhaled smoke. The three groups of animals received either only fluid or only smoke or smoke and fluid. The increase in wet to dry lung weight ratio was 2 per cent after only fluid, 28 per cent after only smoke and 42 per cent after the mixture. This latter group showed pulmonary oedema. The colloid osmotic pressure decreased to the same levels in both groups given fluid. The rise in the minimum surface tension of lung extracts was similar in both groups exposed to smoke. Changes in the microvascular pressure, epithelial and endothelial damage and inactivation of surfactant seem to combine to cause the increased extravascular lung water content.
depletion limits smoke injury
Cotton smoke inhalation injury was inflicted on normal sheep and those that had previously been made leucocyte deficient with nitrogen mustard. Although both groups of animals had identical smoke exposures (as indexed by carboxyhaemoglobin levels), the smoke plus leucocyte-depleted group showed significantly smaller rises in pulmonary artery pressure, pulmonary vascular resistance and pulmonary lymph flow. The P~o,/~?o, ratio did not fall to the same extent nor was there a fall in PuO,. There was no increase in oxygen radical production or antiprotease consumption in the smoke plus leucocyte-depleted group compared with rises in the smoke-alone group. Basadre J. 0.. Sugi K., Traber D. L. et al. (1988) The effect of leucocyte depletion on smoke inhalation injury in sheep. Surgery 104, (2), 208-215.