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 (Kfc) was evaluated using a gravimetric technique. A bolus of 55 micrograms of Escherichia 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 micrograms 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 the Kfc value. All the parameters were evaluated again when the lungs reached a new steady state. Endotoxin induced a significant increase in Rt from 54.7 +/- 7.0 at zero time to 184.7 +/- 44.2 cmH2O min L-1 (100 g)-1 180 minutes later, which can be ascribed to the increase in Ra' and Rv'. 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 induced an increase in the Kfc value from 0.208 +/- 0.011 (at t = 0) to 0.391 +/- 0.034 ml min-1 (cmH2O)-1 (100 g)-1 (at t = 180). Administration of theophylline significantly reduced Rt,Ra,Ra' and Rv' towards or under the baseline values and also induced a significant increase in the lung weight and in the Kfc 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.