Intravascular macrophages in pulmonary capillaries of humans.

Pulmonary intravascular macrophages reside in the pulmonary capillaries and phagocytize bacteria and particulates. These cells are prominent in several animals species, but they have not been described in humans. Samples of lung tissue from patients undergoing thoracotomies for excision of noninfectious diseases were examined with transmission electron microscopy to determine if pulmonary intravascular macrophages are present in humans. The macrophages, with cytoplasm closely adjacent to the capillary and with an irregular contour, were seen in specimens from all patients. The morphologic features of human pulmonary intravascular macrophages resemble the appearance of these cells in animals. The potential significance of pulmonary intravascular macrophages is discussed with regard to sepsis-induced acute respiratory failure.

Complement depletion in a porcine model of septic acute respiratory disease.

In a porcine model of severe septic acute respiratory failure produced by continuous infusion of live Pseudomonas aeruginosa, the role of the complement system was studied by pretreating animals with cobra venom factor (CVF) to deplete C3. Three groups of spontaneously breathing animals were monitored with Swan-Ganz and arterial thermodilution catheters. Group I was pretreated with 80 U/kg of CVF iv 16-18 hours before testing. Group II received Ps. aeruginosa iv (2 X 10(8)/20 kg/minute). Group III was pretreated with CVF and later given the Pseudomonas infusion. The CH50 as a measure of complement activity was less than 7% of normal level in Groups I and III. No changes in respiratory variables occurred in Group I. In Group II, the mean pulmonary artery pressure doubled, intrapulmonary shunt fraction (Qs/Qt) increased, PaO2 decreased, and extravascular lung water doubled in 4 hours. In Group III, the pulmonary hypertension, hypoxemia, increase in Qs/Qt, and increase in EVLW were all significantly less than in Group II. Neutropenia occurred with the Pseudomonas infusion in Groups II and III.

Bacteremia: host-specific lung clearance and pulmonary failure.

Pulmonary effects, lung clearance, and tissue retention of blood-borne Pseudomonas aeruginosa were compared in dogs (n = 5) and pigs (n = 5) during continuous 6-hour intravenous infusion of 1.2(10(9)) bacteria/min/20 kg. Control pigs received an equal volume of sterile saline. In contrast to controls, experimental pigs developed pulmonary artery (PA) hypertension (mean, 30 +/- SE 3; baseline, 17 mm Hg) and pulmonary failure manifested by hypoxemia (mean PaO2, 49 +/- 4; baseline, 78 +/- 2 mm Hg; p less than 0.001), increased intrapulmonary shunting (40 to 50%), noncardiogenic pulmonary edema, and congestive atelectasis, a pattern of pulmonary failure very similar to sepsis-induced ARDS in humans. In dogs, PA pressures wee unchanged from baseline, no edema was detected, and comparable hyperventilation was associated with an increase in PaO2 from 77 +/- 4 (baseline) to 87 +/- 2 mm Hg (p less than 0.001). Tissue retention of viable blood-borne organisms in pigs was greatest in the lungs. In dogs, lung retention was minimal and greatest tissue retention occurred in the liver and spleen. We conclude that both lung clearance of blood-borne organisms and bacteremia-induced pulmonary failure are quite host dependent.

Pulmonary clearance of blood-borne bacteria.

Clearance of blood-borne bacteria has been attributed primarily to a fixed macrophages in the liver and spleen. Although many important nonrespiratory functions of the lung have been reported, a major role for this organ in the clearance of circulating bacteria has not been described. To investigate mechanisms of sepsis induced lung dysfunction and pneumonia, we measured lung clearance, tissue accumulation and morphologic effect of blood-borne. Pseudomonas aeruginosa in pigs. Single pass pulmonary clearance of 60 to 80 per cent occurred over a wide range of infusion concentrations. Tissue concentrations of viable, hematogenously delivered bacteria were greatest in the lungs and exceeded inflowing blood concentrations in the lungs, liver and spleen but were less than inflowing blood concentrations in the heart, kidney and skeletal muscle. Electron microscopy showed phagocytosis of bacteria predominantly by mononuclear cells located within small pulmonary vessels. Viable test organisms were recovered from the upper airways of pigs receiving high dose bacterial infusions but not from pigs in the control group. In this experimental model, an important nonrespiratory function of the lungs is clearance of blood-borne bacteria. If lungs in humans have a similar capacity, retention of circulating organisms may be one mechanism of sepsis induced pulmonary failure.

Comparison of live bacteria infusions in a porcine model of acute respiratory failure.

Acute respiratory failure (ARF) related to sepsis continues to have a high mortality and uncertain pathogenesis. With a reproducible live Pseudomonas aeruginosa infusion pig model, the gas exchange, hemodynamics, and pulmonary clearance of this organism were compared with live Staphylococcus aureus and Escherichia coli. Lightly anesthetized, male, mixed-breed pigs, 15-30 kg, were intubated, allowed to breathe spontaneously, and had femoral artery, central venous, and Swan-Ganz catheterization through cutdowns. After baseline data were collected, approximately 1 X 10(9) organisms/20 kg/min were infused into a central vein for 4 hr with frequent monitoring of the variables. Immediate autopsies were done for related quantitative tissue culture studies. S. aureus pigs maintained a high rate of lung bacterial clearance with pulmonary hypertension, a nonsignificant decrease in PaO2, and relatively normal lungs at autopsy. Ps. aeruginosa and E. coli animals developed systemic hypotension, pulmonary hypertension, increased pulmonary vascular resistance, hypoxemia, and decreased pulmonary clearance. Their lungs had gross congestion and edema. These studies confirm the suitability of E. coli and Ps. aeruginosa infusion into pigs as a model of sepsis-induced ARF in man. The findings also indicate that neither pulmonary hypertension nor bacterial clearance by the lungs is sufficient to cause ARF.