Novel techniques to study cardiopulmonary physiology in a preclinical, saline-lavage model of the acute respiratory distress syndrome

The acute respiratory distress syndrome (ARDS) affects 24.4% of all patients requiring mechanical ventilation and has an associated mortality of up to 46%. The complex pathophysiology of the cardiopulmonary system is difficult to study, particularly in the critically ill patient. Pre-clinical models of ARDS afford the possibility to investigate this complex physiology, which allows increased understanding of that physiology and the potential to develop tools which could be translated to clinical practice. This thesis presents experimental studies of two novel techniques to study cardiopulmonary physiology in a mechanically ventilated porcine saline-lavage model of ARDS. Using fluorescence quenching real-time measurement of PaO2 and dynamic computed tomography (CT), the cyclical recruitment/derecruitment of atelectasis (CA) is demonstrated and the previously accepted hypothesis that CA is the main determinant of cyclical oscillations in PaO2 is challenged. Real-time changes in PaO2 over the course of breath-hold manoeuvres are used to estimate the effective lung volume (ELV). PaO2 measured ELV is compared against ELV measured using whole lung CT scans. The PaO2 model follows the expected linear relationship with CT volumes and is able to track changes in lung volume with good concordance. The Inspired Sinewave Technique (IST) is a non-invasive technique which can provide measurements of ELV and cardiac output (Q˙). IST’s measurements of ELV compare well to those made with SF6 washout and CT. IST’s ability to track PEEP-induced changes in ELV shows excellent concordance with both SF6 and CT. Comparing IST’s measurements of Q˙ against those made with intermittent pulmonary artery thermodilution (PATD), IST tracks changes in Q˙ well in the uninjured animal model. Agreement between Q˙ measurements taken with IST and PATD show less agreement in the injured animal model. The presented results support translational research into both real-time PaO2 measurement and IST. Both techniques have the potential to provide bedside monitoring of important physiologcial parameters in mechanically ventilated patients.