Intravenous crocetinate prolongs survival in a rat model of lethal hypoxemia

OBJECTIVETo examine whether a carotenoid, trans-sodium crocetinate, has beneficial effects on hemodynamic status and short-term outcome in a rat model of lethal hypoxemia. DESIGNRandomized, placebo-controlled study. SETTINGMedical school laboratory. SUBJECTSEighteen spontaneously breathing, anesthetized Sprague-Dawley rats (six per group). INTERVENTIONSRats underwent instrumentation to measure blood pressure, aortic and renal blood flow, arterial blood gases, bladder epithelial oxygen tension (by an intraluminal Clark electrode), and hepatic microvascular oxygen tension (measured by porphyrin phosphorescence). After stabilization, the rats were subjected to breathing 10% inspired oxygen concentration. After 10 mins, they were administered 1.25 mL/kg intravenous boluses of either isotonic saline (control), normal strength crocetinate (40 μg/mL), or a concentrated crocetinate solution (60 μg/mL). These boluses were repeated at 30-min intervals until either death or 3 hrs had elapsed. MEASUREMENTS AND MAIN RESULTSWith the onset of hypoxemia, we observed a rapid reduction in blood pressure and renal blood flow, maintenance of aortic blood flow, an increase in arterial base deficit, and falls in oxygen tensions in arterial blood, bladder epithelium, and hepatic microvasculature. A progressive deterioration in the control rats was noted, with only two of the six animals surviving for 3 hrs. However, all 12 rats in the two crocetinate groups survived for 3 hrs, with hemodynamic stability until 150 mins and a slow decline thereafter. CONCLUSIONSTrans-sodium crocetinate improved hemodynamic status and prolonged survival in this model of severe acute hypoxic hypoxia. To our knowledge, this is the first demonstration of an intravenous agent having such an effect.