H. M. Loick

Effects of anesthesia, surgery, fluid resuscitation, and endotoxin administration on postburn bacterial translocation

The aim of the study reported here was to assess the effects of some clinically relevant factors on the incidence and outcome of postburn bacterial translocation. Miniature pigs in 8 groups (n = 6 in each) underwent: (1) general anesthesia (GA); (2) operation (insertion of Swan-Ganz, arterial, and portal catheters) under GA; (3) burn (40% total body surface area, third degree, under GA); (4) burn and operation; (5) burn, operation, and resuscitation (Parkland); (6) burn, operation, and resuscitation plus endotoxin (100 micrograms/kg IV bolus, 2nd day). Groups 1-6 were killed at 48 hours and tissue samples were harvested for bacteriologic culture. Groups 7 and 8 were the same as 2 and 5, respectively, but were killed at 96 hours. Resuscitation and endotoxin increased postburn bacterial translocation but only endotoxin promoted systemic sepsis. In the absence of additional trauma, translocated bacteria were cleared by 96 hours postburn.

Smoke inhalation causes a delayed increase in airway blood flow to primarily uninjured lung areas

ObjectiveSingle lung inhalation injury causes tissue damage to the contralateral lung. We therefore examined airway blood flow after smoke inhalation in chronic instrumented sheep to get further information about the underlying pathophysiology.Design/patientsThe right lung and lower trachea of 5 animals were smoke-exposed, while their left lung was air-insufflated using a split ventilation technique. Three animals, where both lungs were only air-insufflated, served as controls. Blood flow to the airway was measured using a labeled microsphere technique. All animals were studied for 24 h following smoke inhalation. Then they were sacrificed and their tissues harvested.ResultsThe airway blood flow to the smoke-exposed lung was elevated 11-fold immediately after inhalation injury. The bronchial blood flow to the air insufflated lung became significantly elevated 24 h post-smoke, although to a lesser extent. The control animals did not show any changes of bronchial blood flow during the observation time.ConclusionsDamage to one lung can lead to pathophysiologic changes in the contralateral lung. This response appears to be mediated by hematogenous factors.

Halof hane markedly reduces mesenteric blood flow but does not impair gut mucosal oxygenation in pigs

We investigated the effect of halothane on in mesenteric blood flow and gut mucosal oxygenation. Pittman-Moore mini-pigs (n = 6) were chronically instrumented with aortic, pulmonary arterial (Swan-Ganz), and mesenteric venous catheters and an intestinal tonometer. Blood flow in the superior mesenteric artery was measured with an ultrasonic flow probe. On the day of the experiment, data were obtained before and during halothane administration (1.5% end-tidal). Halothane caused a marked decrease in mesenteric blood flow, associated with an increase in mesenteric vascular resistance. Likewise mesenteric oxygen delivery and consumption were significantly decreased under halothane, while the oxygen extraction rate of the intestine was not significantly changed. There was no significant change in intramucosal gut pH after halothane administration, which indicates that an adequate mucosal tissue oxygenation was maintained. We conclude that the marked halothane-induced reduction in mesenteric blood flow did not seem to impair the oxygenation of the gut mucosa in our experimental model.

Thromboxane receptor blockade with BM 13,177 following toxic airway damage by smoke inhalation in sheep

Thromboxane may play an important role in the pathogenesis of smoked mediated injury. We studied this possibility in 13 chronically instrumented sheep, which had the left lung exposed to smoke. BM 13,177, a thromboxane receptor antagonist, was given intravenously to six animals prior to smoke inhalation and during the experimental period. Seven animals received the vehicle. All animals were studied for 24 h under ventilatory support, then killed prior to harvesting lung tissue. Airway peak and plateau pressures in the vehicle-treated animals were elevated by 27% and 25% from baseline at 24 h post smoke inhalation. Concomitantly, the left pulmonary vascular resistance index rose continuously throughout the study period (baseline = 822 +/- 58; 24 h = 1819 +/- 84 dyn.s.cm-5.m2).BM 13,177 treatment completely prevented the rise in airway pressure, while the left pulmonary vascular resistance index was significantly attenuated (baseline = 726 +/- 79; 24 h = 1470 +/- 158 dyn.s.cm-5.m2) resulting in a significantly higher percentage of cardiac output being delivered to the smoked lung, compared to vehicle-treated animals. Thromboxane receptor blockade did not prevent smoke induced pulmonary edema formation. There was likewise no effect of BM 13,177 on the systemic hemodynamic changes seen following smoke inhalation. There was a decrease in cardiac index and an increase in systemic vascular resistance index in both groups. We conclude that smoke induced changes in airway and pulmonary vascular resistances may be mediated by thromboxanes. However, thromboxanes appear to play no role in the development of pulmonary edema and elevation of systemic vascular resistance following smoke inhalation injury.

The effect of dopamine on pulmonary hemodynamics and tissue damage after inhalation injury in an ovine model.

Hypoxic pulmonary vasoconstriction and reduced blood flow occur as a result of smoke inhalation. The aim of this study was to investigate how the amelioration of blood flow reduction by the vasodilator dopamine affects histopathologic outcome. We exposed the left lungs of chronically instrumented sheep (n = 12) to smoke, awakened them, and studied them for 24 hours. Six hours after inhalation injury, the sheep received randomized infusions of dopamine (9 micrograms/kg/min) or equal volumes of 0.9% saline solution. Pulmonary resistance in the left lungs of animals in the group that received saline solution rose continuously throughout the study period (624 +/- 48 dyne.sec.cm-5/m2 to 1747 +/- 140 dyne.sec.cm-5/m2, baseline to 24 hours after injury). Dopamine treatment caused a significantly lower vascular resistance in the injured lung than did saline solution between 8 and 24 hours after injury. The histologic evaluation of the injured lungs showed epithelial necrosis and cast formation in both groups in addition to an increased wet/dry ratio. No difference in lung injury between the groups could be distinguished. We conclude that the amelioration of blood flow reduction by treatment with dopamine in the lungs that were exposed to smoke did not affect pulmonary damage after inhalation injury.

Plasma copper and iron changes in sheep after left lung inhalation injury: effect of the thromboxane antagonist BM 13.177 (Solutroban).

A significant decline in plasma concentrations of copper and iron were observed in sheep exposed to preferential smoke inhalation of the left lung. The decline was evident 30 minutes after smoke inhalation, and the levels of both trace metals persisted at quite low levels for up to the 18-hour time interval after injury. From that time a gradual recover for copper but not for iron levels was observed so that by 24 hours the levels of copper were in the same range of those at baseline. Copper and iron levels showed an inverse correlation to airway peak and plateau pressures and left lung vascular resistance index and a direct correlation to left lung blood flow. Administration of BM 13.177 (Solutroban), a thromboxane antagonist, before exposure to smoke inhalation protected the sheep from the decline of copper and iron levels in plasma. In these animals airway peak and plateau pressure, left lung vascular resistance, and blood flow were also unmodified. Lipid peroxidation of the lung tissue by oxygen free radicals were lower than in those animals that did not receive BM 13.177. There was likewise a tendency of a decreased wet-to-dry weight ratios in the animals treated with BM 13.177. BM 13.177 treatment in an inhalation injury model might partly protect lung damage and parallels unchanged plasma copper and iron levels. The plasma copper and iron may therefore be an indicator of acute lung damage.

Carbon monoxide and pulmonary circulation in an ovine model

The direct pulmonary vasoconstrictive effects of inhaled carbon monoxide were evaluated in chronically instrumented and anesthetized sheep (1.7% halothane in air) (n = 8). The response to carbon monoxide (2%), which was applied for 8 minutes through a double-lumen tube alternately to the left or right lung of each animal, was compared with baseline values. The induced carboxyhemoglobin level (65%) led to increases in cardiac output, pulmonary arterial pressure, stroke volume index, and heart rate. Systemic vascular resistance decreased, and pulmonary vascular resistance and mean arterial pressure were unchanged. The changes in pressure and flow were equivalent no matter which lung was exposed to carbon monoxide. No diversion of blood from one lung to the other was observed during the test period. We conclude that carbon monoxide does not have a direct pulmonary vasoconstrictive effect. The increase in pulmonary arterial pressure is a result of the decrease in mixed venous oxygen content (stimulus for hypoxic pulmonary vasoconstriction) and the increase in cardiac output.

Endoscopic laser flowmetry: a valid method for detection and quantitative analysis of inhalation injury.

Hyperemia of the tracheobronchial area is a major sign of inhalation injury. However, this is usually a qualitative symptom, without quantitative measurement. We have developed a technique to diagnose inhalation injury and to analyze damaged areas quantitatively with laser-doppler flowmetry. In chronically instrumented sheep (N = 10), the tissue blood flow in the wall of second generation bronchi was determined with an endoscopic flowmeter probe. After baseline data had been obtained, the right lung was exposed to smoke in seven animals. Three sham-smoked animals underwent the same procedure, but without actual smoke. The bronchial blood flow was measured again 30 minutes after insufflation in both groups. Inhalation injury caused a significant increase in flow, from 35.1 +/- 2.6 to 51.7 +/- 2.1 ml/min.100 gm tissue in the airway of the smoked lungs but not in the control lungs. This increase correlated with an increase in the carboxyhemoglobin level (r = 0.87). The sham-smoked animals showed no change in bronchial blood flow. A valid technique for diagnosing inhalation injury in the early phase and a quantitative analysis of injured areas has been demonstrated.