A standardized method of oleic acid infusion in experimental acute respiratory failure

Commonly, acute respiratory failure (ARF) in laboratory animals is induced through the intravenous infusion of oleic acid (OA). The methods by which O A is infused, and the methods by which droplets are generated, differ great ly among investigators. The resulting ARF, and the distribution of the unde rlying pulmonary pathology, are not highly reproducible. A method was devel oped that generated a reproducible, known spectrum of OA microdroplets. Thi s method was applied to infuse a known volume of OA into the vena cava supe rior (VCS) in sheep, to induce ARF. In vitro studies were conducted in an o bservation chamber filled with saline or plasma. The distal end was cut off a 7F Swan Ganz catheter. The catheter was immersed in an observation chamb er. Through one of the channels OA was infused at a low flow rate while sal ine was infused at variable high flow rates through a second channel. The s ize and the distribution spectrum of the so generated OA droplets were dete rmined from flash photographic studies. The distribution and the size of th e microdroplets depended on the media in the observation chamber, and on th e saline infusion rate. In vivo studies were conducted in six anesthetized and ventilated sheep. We chose in our in vivo studies a saline flow rate of 126 mL/min and at an OA flow rate of 3 mL/min, that generated OA microdrop lets 125+/-32 mum SD in size. OA microdroplets were generated in situ in th e VCS and where then embolized into small pulmonary vessels. A total dose o f 0.06 mL/kg of OA was administered in three separate doses of 0.02 mL/kg, each 10 min apart. The evolving ARF was manifested by a progressive deterio ration in arterial blood gases, and a uniform opacification of all lung fie lds on chest X-ray films. At autopsy the lungs were diffusely consolidated. Conclusion: A method was developed to standardize the infusion of OA in la boratory animals that resulted in diffuse involvement of the all lungs, wit h a predictable and reproducible severe acute respiratory failure.