Adaptive responses during anemia and its correction in lambs

Abstract

There is limited information available on which to base decisions regarding red blood cell (RBC) transfusion treatment in anemic newborn infants. Using a conscious newborn lamb model of progressive anemia, we sought to identify accessible metabolic and cardiovascular measures of hypoxia that might provide guidance in the management of anemic infants. We hypothesized that severe phlebotomy-induced isovolemic anemia and its reversal after RBC transfusion result in a defined pattern of adaptive responses. Anemia was produced over 2 days by serial phlebotomy (with plasma replacement) to Hb levels of 30-40 g/l. During the ensuing 2 days, Hb was restored to pretransfusion baseline levels by repeated RBC transfusion. Area-under-the-curve methodology was utilized for defining the Hb level at which individual study variables demonstrated significant change. Significant reciprocal changes (P < 0.05) of equivalent magnitude were observed during the phlebotomy and transfusion phases for cardiac output, plasma erythropoietin (Epo) concentration, oxygen extraction ratio, oxygen delivery, venous oxygen saturation, and blood lactate concentration. No significant change was observed in resting oxygen consumption. Cardiac output and plasma Epo concentration increased at Hb levels <75 g/l, oxygen delivery and oxygen extraction ratio decreased at Hb levels <60 g/l, and venous oxygen saturation decreased and blood lactate concentration increased at Hb levels <55 g/l. We speculate that plasma Epo and blood lactate concentrations may be useful measures of clinically significant anemia in infants and may indicate when an infant might benefit from a RBC transfusion.

Haemodynamic effects of erythrocyte transfusion in preterm infants

“…Nelle et al [14] reported no change in non-invasively measured blood pressure. A decrease in HR after red cell transfusion has been more consistently reported in anaemic subjects [8,9,13,14,26], most probably explained by mitigation of tissue hypoxia and concomitant tachycardia [27]. We observed a similar, albeit statistically non-significant ( P =0.062), trend towards decreased HR after the transfusion during the early neonatal period, although the infants in the present study were not anaemic.…”

Red blood transfusion in preterm infants: changes in glucose, electrolytes and acid base balance

“…[17] This was relevant clinically in our study when we observed a statistically significant decrease in the heart rate of our infants after transfusion, suggesting that this decrease in heart rate was most probably explained by the migitation of tissue hypoxia and concomitant tachycardia. [18]…”

Red blood cell (RBC) volume can be independently determined in vivo in the sheep using ovine RBCs labeled at different densities of biotin

“…First, this capability adds to the potential utility of the sheep as a model for preclinical testing 2–6. Second, we speculate that extending the studies of RBCs labeled with multiple distinct biotin densities to humans including sequential measurement of RCV and red cell survival (e.g., 24-hour survival post-transfusion recovery and circulating lifespan) will be successful and will offer the opportunity to perform these studies in human fetuses, infants, children, and pregnant women.…”