B. Urbain

Acute Effects of Endotoxin Inhalation on the Respiratory Tract in Pigs: Interaction with Ammonia

AbstractThe acute respiratory effects of endotoxin inhalation (0–400 μ/kg) have been evaluated in pigs. Endotoxin (LPS from Escherichia coli 0127:B8 and 055:B5) nebulization had no direct effect on the nasal mucosa. An in vitro bronchial hyperreactivity to acetylcholine and histamine, related to the endotoxin dosage, was recorded. In the lung, significant endotoxin dose-dependent increases in the total cell, alveolar macrophage, and neutrophil counts in the BAL fluid were recorded. Following intrabronchial administration of endotoxin, the cellular response was significantly higher than that obtained after nebulization. Neither the dry to wet lung weight ratio (DW/WW) nor the albumin concentration in the BAL fluid was affected. When endotoxins were infused intravenously, the lung cellular response was accompanied by an increase in the albumin concentration in the BAL fluid. In pigs exposed for 6 days to 50 ppm ammonia, endotoxin nebulization induced a significant increase in the albumin concentration and t...

Permeability of the endothelium and partitioning of the pulmonary blood flow resistance in isolated perfused pig lungs: effects of breed and age.

The right and left lungs of 5 healthy Minipigs and of 13 healthy Landrace piglets were isolated, perfused at constant pressure and maintained in an isogravimetric state under zone III conditions (pulmonary venous pressure>alveolar pressure). By applying the double, arterial and venous, occlusion technique, the total blood flow resistance (Rt) was partitioned into four components: arterial (Ra), pre-(Ra′) and post-capillary (Rv′) and venous (Rv). The capillary filtration coefficient (Kf,c) was evaluated by measuring the weight gained by the lungs when the arterial and venous pressures were suddenly increased. In the youngest Landrace piglets (5 weeks old), there was an uncontrolled vasoconstriction which sometimes prevented perfusion of the lungs and induced a large increase inRt. These high values ofRt were decreased by tolazoline administration. The values ofRt recorded in older pigs (12–13 weeks old) were lower in Minipigs (33.66±3.77 cmH2O min L−1 per 100 g of lungs;n=5) than in Landrace piglets (55.20±6.18 cmH2O min L−1 per 100 g;n=5). This breed difference was due to the differences inRa′ andRv′. The mean values ofKf,c were 0.193±0.015 and 0.202±0.029 ml min (cmH2O)−1 per 100 g of the lungs in Minipigs and Landrace piglets respectively. All these parameters were stable for the 3 hours following the equilibrium period. It was concluded that: (1) There is an age-related maturation of the control of the vasomotor tone in porcine lungs. (2) Pulmonary microvascular haemodynamics are influenced by the breed of the pigs. (3) There was no difference in theKf,c values between both the breeds. (4) A comparison of the values reported for dogs and rabbits with our data shows that the pre- and post-capillary resistances and, to a lesser extent, the arterial and venous resistances are relatively high in pigs.

ENDOTOXIN-INDUCED MICROVASCULAR INJURY IN ISOLATED AND PERFUSED PIG LUNGS

The lungs of 13 healthy Landrace piglets were isolated, perfused and maintained in an isogravimetric state under zone III conditions. By applying vascular occlusion methods, the total blood flow resistance (Rt) was partitioned into four components: arterial (Ra), pre- (Ra′) and post-capillary (Rv′), and venous (Rv). The capillary filtration coefficient (Kf,c) was evaluated using a gravimetric technique. A bolus of 55 µg ofEscherichia coli endotoxins (LPS) per 100 g of lung was injected into the arterial reservoir of eight lungs, followed by an infusion of LPS at a rate of 55 µg per 100 g of lung per hour for 180 min. A bolus of theophylline (85 mg per 100 g of lung weight) was injected into the arterial reservoir after the last determination of theKf,c value. All the parameters were evaluated again when the lungs reached a new steady state. Endotoxin induced a significant increase inRt from 54.7 ± 7.0 at zero time to 184.7±44.2 cm H2O min L−1 (100 g)−1 180 minutes later, which can be ascribed to the increase inRa′ andRv′. These haemodynamic modifications were related to the increases in the arterial pressure and in the pressure at the distal end of the arterial segment and to the decreases in the pressure at the proximal end of the venous segment and in the blood flow. The capillary pressure and the lung weight remained unchanged. Endotoxin infusion infusion induced an increase in theKf,c value from 0.208±0.011 (att=0) to 0.391±0.034 ml min−1 (cmH2O)−1 (100 g)−1 (att=180). Administration of theophylline significantly reducedRt,Ra,Ra′ andRv′ towards or under the baseline values and also induced a significant increase in the lung weight and in theKf,c value. It was concluded that the endotoxin-induced increase in the total blood flow resistance can be ascribed to a vasospasm occurring at the level of the pre- and post-capillary small vessels and that changes in the permeability of the endothelium greatly contribute to the development of the pulmonary oedema observed in endotoxaemic pigs.