Impact of red blood cell transfusions on intestinal barrier function in preterm infants.

OBJECTIVE: To determine the relationships of red blood cell (RBC) transfusion and enteral feeding to changes in intestinal permeability (IP) measured by the relative intestinal uptake of lactulose (La) and rhamnose (Rh) in preterm infants <33 wk gestation. DESIGN/METHODS: Infants 240-326wk gestation received La/Rh solution enterally on study days 1, 8 and 15.Urinary La/Rh ratio was measured by HPLC. Hematocrit preceding transfusion, total RBC transfusion volume, volume/kg, and feeding status during each study interval (birth-d1; d1-d8, and d8-d15) were determined. RESULTS: Of the seventeen (40.5%) subjects who received≥1 transfusion during the study period, 12 (70.6%) infants were <28 wk gestation and 5 (29.4%) infants were≥28 wk gestation, p < 0.0001. Lower pre-transfusion hematocrit was observed in intervals preceding high IP (La/Rh > 0.05) than in intervals preceding low IP (La/Rh≤0.05) measurements (33 vs 35.8, p = 0.1051). RBC transfusions occurred more frequently in intervals preceding high IP than in intervals preceding low IP (26.8%; vs 8.3%, p = 0.0275) with 5-fold higher total RBC volume and volume/kg in intervals preceding any time point with high IP. RBC transfusion during an interval was associated with a three-fold increased risk of high IP (aOR 2.7; 95% C.I 0.564-12.814; p = 0.2143). Exclusive breast milk exposure and post-menstrual age reduced the risk for high IP following RBC transfusion. CONCLUSIONS: Both RBC transfusion number and volume was associated with subsequent high IP measurements in preterm infants <33 weeks gestation and potentially may contribute to impairment of the preterm intestinal barrier.

Phosphodiesterase activity in intrapulmonary arteries and veins of perinatal lambs.

The transition from fetal to newborn life is marked by a reduction in pulmonary vascular tone mediated by the intracellular second messengers, cGMP and cAMP. We have compared the rates of phosphodiesterase (PDE)-catalyzed hydrolysis of cGMP and cAMP in intrapulmonary vessels of fetal (146 +/- 2 days gestation) and newborn (3-7-day-old) lambs, each n = 6. Lung vessels of second to sixth generations were dissected and cytosol was prepared by differential centrifugation. PDE activity in cytosol was determined by radiometric assay of the hydrolysis of exogenous nucleotides at 30 degrees C for 10 min. Rates of hydrolysis (pmol/min/mg protein) of cGMP were 225 +/- 38 in fetal arteries and different from 151 +/- 7 in veins. In newborn vessels, the rates were 155 +/- 49 and 63 +/- 13 in arteries and veins, respectively. Rates of cAMP hydrolysis by the fetus were 80 +/- 11 in arteries and 45 +/- 16 veins. In newborn lambs the rates were 69 +/- 10 in arteries and different from 18 +/- 4 in veins. Inhibition of PDE activity by zaprinast, a cGMP-specific PDE inhibitor, and rolipram, a cAMP-specific PDE inhibitor, was more in veins of fetal and newborn lambs. Our data show that rates of hydrolysis of the cyclic nucleotides were faster in fetal vessels than in the newborn. We speculate that this would result in a greater accumulation of the cyclic nucleotides in newborn vessels, particularly the veins, and therefore endow the veins with less vascular tone.

Antenatal glucocorticoid treatment attenuates immediate postnatal prostacyclin and thromboxane levels in plasma of very preterm lambs.

The effect of antenatal glucocorticoid treatment on the production of cyclooxygenase metabolites was studied in very preterm lambs. Seven fetal lambs, 121 days of gestation, received a single dose of betamethasone, 0.5 mg/kg i.m., 48 h prior to delivery. Five age-matched controls received saline intramuscularly. Each fetus was delivered and ventilated for 3 h and sacrificed. Plasma was prepared from blood drawn from the umbilical cord of each fetus, and 60, 120 and 180 min after delivery. Mesenteric (MESA) and femoral (FEMA) arteries were isolated and incubated in Krebs' buffer for 10 min at 37 degrees C. Samples were extracted for prostacyclin (PGI2), and thromboxane (Tx)A2, purified by HPLC and measured by specific radioimmunoassay. Amounts of metabolites measured postnatally from betamethasone-treated preterm lambs were significantly lower (p < 0.05) than the amounts from saline lambs. Prostacyclin production by MESA and FEMA of betamethasone-treated lambs was lower than by vessels of saline-treated lambs. There was no difference in TxA2 production by vessels from the two groups of preterm lambs. Our data show that antenatal betamethasone treatment decreased systemic prostanoid production suggesting a decreased reactivity of the vascular membrane.