Catherine Wong

Early Lung Dysfunction after Major Burns: Role of Edema and Vasoactive Mediators

We determined the effect of a body burn on pulmonary function. Full-thickness burns varying in size from 25 to 70% of total body surface (TBS), were produced in sheep. Resuscitation was performed with lactated Ringers. We noted an increase in lung transvascular fluid flux as measured by lymph flow, Q1, during the resuscitation period, varying from one- to threefold over baseline with the degree of increase directly proportional to the burn size. The increase in QL could be totally explained by the degree of hypoproteinemia which was also proportional to burn size. Transient pulmonary hypertension 20 +/- 4 to 26 +/- 5 mm Hg and a decrease in PaO2 from 90 +/- 5 to 83 +/- 6 torr occurred in the 50 and 70% burns as well as a significant decrease in lung compliance. These alterations were not due to pulmonary edema as there was no increase in measured lung water. Also, the increase in QL could be prevented by using a combination of Dextran and protein for resuscitation but this had no effect on the hypertension or hypoxia. Burn lymph and venous plasma thromboxane levels were increased during this period of lung dysfunction. Ibuprofen 12.5 mg/kg preburn and 12.5 mg/kg every 2 hours postburn decreased the degree of dysfunction suggesting a cause and effect relationship.

Effect of a body burn on the lung response to endotoxin.

Our purpose was, in general, to determine the effect of a body burn on the pulmonary response to endotoxemia and, specifically, to determine whether increased thromboxane (TxA2) production by the burn wound was responsible for the accentuated lung injury. Thirty-two unanesthetized sheep with lung and soft tissue lymph fistulae were studied. Twelve sheep were given a sublethal dose of intravenous E. coli endotoxin (2 micrograms/kg). A characteristic two-phase injury was noted as evidenced by early pulmonary hypertension and hypoxia and later increased lung permeability. TxA2 was significantly increased in lung lymph as well as aortic plasma relative to venous plasma, indicating the lung to be the source. Twelve of 12 sheep survived. Five of 13 sheep died from endotoxemia when given 3-5 days after a 25% total body surface (TBS) burn and five of seven died with endotoxin (2 micrograms/kg) and a 50% burn. Physiologic parameters were at preburn levels before endotoxin. Animals died both during the early phase from hypoxia and the later phase due, in large part, to increasing pulmonary dysfunction. Absolute levels of TxA2 were not increased in the postburn animals, nor was there a clear release of TxA2 from burn tissue to explain the accentuated response. Prostacyclin levels were, however, less elevated in postburn animals in response to endotoxin, thereby altering the TxA2/PGI2 ratio in favor of TxA2. However, a cause and effect relationship between the increased lung injury and TxA2 remains undetermined. Lymph flow or lymph protein content was not altered in burn tissue in response to endotoxin.

Chemotactic activity of plasma and lung lymph in sheep with endotoxemia: Effect of hydroxyl radical scavengers

The formation and release of circulating chemoattractants has been considered to be responsible for the initial pulmonary leukostasis and subsequent pulmonary vascular injury seen with endotoxemia. Oxygen radicals released from granulocytes can produce these factors. Our purpose was (1) to determine whether chemotaxins are released with endotoxemia and whether the lung is the source of these factors and (2) if there is a cause and effect relationship between the release of chemoattractants and the lung injury. Lung lymph flow, QL, lymph protein clearance, and vascular pressures were used to monitor lung vascular integrity. Escherichia coli endotoxin was infused into 12 sheep. Six sheep were pretreated with dimethyl thiourea (DMTU), a scavenger of hydroxide ion radicals. Chemotactic activity (CA) of plasma and lung lymph was determined during baseline, the pulmonary hypertensive phase, and the permeability phase of the lung injury. It was found that endotoxemia was associated with generation of a granulocyte chemotactic factor in plasma but not in lung lymph. The peak increase in plasma CA occurred after the early pulmonary leukostasis. Pretreatment with DMTU eliminated the increased CA but had no effect on the initial leukopenia or the lung injury. It was concluded that (1) the lung is not the major source of increased CA after endotoxin and (2) increased plasma CA occurs but does not appear to be causative of the initial pulmonary leukostasis or the granulocyte-induced lung injury.