A perfluorochemical emulsion for prehospital resuscitation of experimental hemorrhagic shock: a prospective, randomized, controlled study.

OBJECTIVE: To evaluate the efficacy of a novel, oxygen-transporting perfluorochemical emulsion as a prehospital therapy, using a canine hemorrhagic shock model based on compromised tissue oxygenation. DESIGN: Prospective, randomized, controlled study. SETTING: HemaGen animal laboratory. SUBJECTS: Sixteen healthy, adult male grade beagles (weight 8 to 14 kg). INTERVENTIONS: Administration of lactated Ringer's solution (n = 8), 15 mL/kg and perfluorochemical emulsion admixed with physiologic salts (n = 8), 15 mL/kg. MEASUREMENTS AND MAIN RESULTS: PaO2 increased significantly (p < .01) in the perfluorochemical-treated animals for 2 hrs after resuscitation. Mixed venous PO2 returned to preshock values in the perfluorochemical-treated dogs for 60 mins after fluid administration (p < .01). Normalization of hemodynamic variables was not observed in either group. Although not statistically significant, survival of the lactated Ringer's solution-treated animals was 63% compared with 100% for the perfluorochemical-treated dogs at 3 hrs after resuscitation. CONCLUSIONS: Resuscitation with a perfluorochemical emulsion augmented oxygen transport and restored global tissue oxygenation after massive hemorrhage, which translated into improved survival when compared with the group receiving an equal volume of lactated Ringer's solution.

Endothelial response to perfluorochemical perfusion.

The purpose of this study was to evaluate, in vivo, the effect of perfluorochemical (PFC) blood substitutes on arterial endothelium following total blood replacement. Conscious-female-Sprague-Dawley rats (150-200 gms) were isovolumically exchange perfused with 3 blood volumes of PFC emulsion in an oxygen chamber. The exchange was performed at 0.5 ml/min via an indwelling-intracardiac-double-lumen catheter. One hour after the exchange, the animal was sacrificed and the circulatory system flushed free of blood and PFC emulsion with Dulbecco's solution, followed by perfusion fixation with glutaraldehyde solution. The heart, lungs and thoracic aorta were excised. The pulmonary arterial endothelial cell response was determined by scanning electron microscopy (SEM) following acute exposure to PFC emulsions under conditions of varied pH, oncotic pressure and emulsion age. These endothelial surfaces exhibited increased microvilli, leukocyte adhesion, fibrin deposition and subendothelium exposure. The magnitude of these abnormal responses varied with the degree of alkalinity and reduced oncotic pressure of the perfusate.

A method for evaluation of blood substitutes in the conscious animal.

Physiological evaluation of new and potential blood replacement agents has not kept pace with the development of such agents. Current procedures involve partial or total blood replacement in the anesthetized animal. This introduces the variable of anesthesia and eliminates the ability to observe behavior changes during blood replacement. Clinically, many patients receive blood or will receive artificial agents while sedated or under anesthesia, whereas others will be conscious. It is essential that evaluative studies be performed on the awake animal using procedures that are nontraumatic and nonrestrictive. A technique for isovolumic exchange perfusion utilizing an indwelling, heparin-coated, double-lumen catheter in the right atrium of a conscious rat is described. This animal model system permits continuous pre- and postperfusion monitoring. Nearly total blood replacement with perfluorochemical blood substitutes causes no discerniable discomfort or adverse reactions in the animal. Such animals thrive and replace missing hematologic components in 1-3 wk. The technique described can, with minimal modification, be used for isovolumic exchange perfusion of larger animals.