Tezosentan + Iloprost in Acute Lung Injury
Meconium aspiration
First-pass pooled human meconium, suspended in physiological sodium chloride at a concentration of 20%, was filtered and stored in 20 mL syringes at -20°C. The meconium was thawed in hot water immediately before use. Animals received fractionated deep intratracheal instillation of the meconium solution at incremental steps of initially 0.50 ml/kg, followed by 0.25 ml/kg thereafter until mean pulmonary artery pressure had doubled frome baseline. In pilot tests we have shown, that meconium titration to pulmonary artery pressure more than twice the baseline led to death of these animals before end of the observation period due to right heart failure. After each instillation of meconium ventilation rate was increased to 30 breaths/minute and a FIO2 of 1.0 was given for 3 minutes and than reset (FIO2 0.4, 20 breaths/minute) in order to counteract severe pulmonary vasoconstriction and subsequent acute right heart failure.In order to strictly define pharmocological effects no further respiratory adjustments were done for the remaining experimental observation.
Multiple Inert Gas Elimination Technique
Ventilation-perfusion distributions were determined using the multiple inert gas elimination technique (MIGET) (1, 2). A mixture of six inert gases including sulphur hexafluoride, ethane, cyclopropane, halothane, ether, and acetone dissolved in saline was infused via an auricular vein and arterial and mixed venous blood samples were collected in duplicate into heparinized matched-barrel glass syringes. Mixed expired gas samples were collected from a heated mixing chamber into gas-tight glass syringes. With blood gas partition coefficients known, retentions (R, equal to the ratio of arterial to mixed venous partial pressure), and excretions (E, equal to the ratio of mixed expired to mixed venous partial pressure) for the inert gases were determined using gas chromatography (HP-5890, Series II; Hewlett-Packard, Wilmington, DE), and ventilation-perfusion distributions were obtained from the inert gas data (2). The following descriptions of ventilation/perfusion mismatch were used: 1) Modality of the distributions of ventilation and perfusion (uni- or bi-modality); 2) First moment of the perfusion distribution (Mean of Q); 3) Second moment (homogeneity) of the perfusion distribution (log SDQ); 4) Blood flow to unventilated lung units, (shunt flow, VA/Q = 0); 5) Blood flow to poorly ventilated lung units, (low VA/Q, VA/Q > 0.005 through 0.1); 6) Blood flow to normally ventilated lung units, (normal VA/Q, VA/Q > 0.1 through 10); 7) Blood flow to poorly perfused lung units, (high VA/Q, VA/Q > 10 through 100); 8) Ventilation of unperfused lung units, (alveolar dead space , VA/Q > 100).
References to the electronic supplementary material
1.Wagner PD, Naumann PF, Laravuso RB (1974) Simultaneous measurement of eight foreign gases in blood using gas chromatography. J Appl Physiol 36:600-605
2. Wagner PD, Saltzman JA, West JB (1974) Measurement of continuous distributions
of ventilation–perfusion ratios: theory. J Appl Physiol 36:588–599