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

Abstract

Commonly, acute respiratory failure (ARF) in laboratory animals is induced through the intravenous infusion of oleic acid (OA). The methods by which OA is infused, and the methods by which droplets are generated, differ greatly among investigators. The resulting ARF, and the distribution of the underlying pulmonary pathology, are not highly reproducible. A method was developed that generated a reproducible, known spectrum of OA microdroplets. This method was applied to infuse a known volume of OA into the vena cava superior (VCS) in sheep, to induce ARF. In vitro studies were conducted in an observation chamber filled with saline or plasma. The distal end was cut off a 7F Swan Ganz catheter. The catheter was immersed in an observation chamber. Through one of the channels OA was infused at a low flow rate while saline was infused at variable high flow rates through a second channel. The size and the distribution spectrum of the so generated OA droplets were determined from flash photographic studies. The distribution and the size of the microdroplets depended on the media in the observation chamber, and on the 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 microdroplets 125 +/- 32 microm SD in size. OA microdroplets were generated in situ in the VCS and where then embolized into small pulmonary vessels. A total dose of 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 deterioration in arterial blood gases, and a uniform opacification of all lung fields on chest X-ray films. At autopsy the lungs were diffusely consolidated. A method was developed to standardize the infusion of OA in laboratory animals that resulted in diffuse involvement of the all lungs, with a predictable and reproducible severe acute respiratory failure.