Chronic Fetal Anemia Research Articles

Role of endogenous atrial natriuretic peptide in chronic anemia in the ovine fetus: effects of a non-peptide antagonist for atrial natriuretic peptide receptor.

Chronic fetal anemia causes polyhydramnios and fetal hydrops and is associated with increased fetal diuresis and natriuresis. To determine the role of atrial natriuretic peptide (ANP) in the renal adaptation to chronic fetal anemia we studied the effects of HS-142-1 (HS), a specific inhibitor of the guanylate cyclase-linked ANP receptor (ANP-GC), in two groups of chronically instrumented unanesthetized sheep fetuses. Seven fetuses were made anemic by serial isovolemic hemorrhage over 1 wk, and five fetuses served as nonanemic controls. Over the 7 d of hemorrhage ANP concentrations increased (45 +/- 7 to 234 +/- 15 fmol/mL). Hematocrit and arterial blood oxygen content were significantly lower in the anemic compared with the nonanemic fetuses (13.8 +/- 0.7 versus 34.6 +/- 2.3% and 0.7 +/- 0.1 versus 2.6 +/- 0.2 mmol/L). Before HS urine flow rate, urinary sodium excretion, fractional excretion of sodium, and renal blood flow were increased in the anemic fetuses, and the extracellular fluid volume (inulin space) was increased (674 +/- 94 versus 497 +/- 71 mL/kg). However, GFR was not different between the groups. HS caused a significant increase in the central venous pressure of the anemic fetuses (0.49 +/- 0.03 to 0.70 +/- 0.05 kPa). Urinary excretion of cGMP was considered to be a marker of endogenous ANP renal effect and was measured before and after a single bolus of HS (5.2 +/- 0.30 mg/kg). HS decreased urinary cGMP excretion to 50 and 37% of baseline levels in anemic and nonanemic fetuses, respectively. Urine flow decreased in both nonanemic and anemic fetuses (0.48 +/- 0.13 to 0.25 +/- 0.06 and 1.30 +/- 0.66 +/- 0.06 mL/min). Sodium excretion decreased in both groups after HS (19 +/- 5 to 9 +/- 2 and 83 +/- 16 to 39 +/- 5 mumol/min). GFR decreased after HS (3.0 +/- 0.8 to 2.4 +/- 0.5 and 3.6 +/- 0.3 to 2.6 +/- 0.2 mL/min. Fraction excretion of sodium also decreased in both groups after HS (4.6 +/- 2.7 to 2.7 +/- 0.5 and 16.1 +/- 2.4 to 11 +/- 1.6). Percent decreases in urine flow, sodium excretion, GFR, and fractional excretion of sodium observed in the anemic fetuses were not statistically different from the nonanemic fetuses. Urine flow and sodium excretion did not decrease to control levels after HS, suggesting that factors in addition to ANP contribute to the natriuresis seen with chronic anemia. After HS a transient increase in renal blood flow was observed in the nonanemic fetuses. An immediate and sustained further increase in renal blood flow was observed in the anemic fetuses (336 +/- 37 to 436 +/- 58 mL/min/100 g of kidney). Decreasing GFR and increasing renal blood flow suggests HS may alter the renal microcirculation by reversing ANP-induced constriction of the glomerular efferent arteriole. We conclude that sustained increases of the central venous pressure suggest that ANP inhibition results in decreased fluid movement into perivascular tissue. Endogenous ANP may help to maintain basal renal function in the normal fetal kidney and participates in the renal adaptation to chronic fetal anemia. ANP may promote urine flow and sodium excretion by its effects on both the renal microcirculation and the sodium reabsorptive capacity of the nephron.

Myocardial blood flow and coronary reserve during chronic fetal anemia

Myocardial blood flow and coronary reserve during chronic fetal anemia

Hemodynamics and organ blood flow in fetal sheep subjected to chronic anemia

To investigate cardiovascular adaptation to chronic anemia we studied eight ovine fetuses made anemic by serial isovolemic hemorrhage and seven nonanemic controls. After 1 wk carotid arterial oxygen content was reduced to 1.6 +/- 0.2 ml/dl and hematocrit to 13.3 +/- 1.6% in anemic fetuses compared with 6.9 +/- 1.2 ml/dl and 32.4 +/- 3.9% in controls. Cardiac output was higher in the anemic group (753 +/- 102 vs. 490 +/- 66 ml.min-1.kg fetus-1) as stroke volume and heart rate both increased. Blood flow to the carcass, skin, kidneys, intestines, brain, and heart was increased. Vascular resistance fell in all tissues except the placenta. Central venous pressure, arterial pH, plasma total protein, and blood volume were not different although extravascular fluid accumulated in six of the anemic fetuses. The estimated capillary hydrostatic pressure was greater in anemic (7.6 +/- 1.8 mmHg) than control fetuses (5.0 +/- 1.5 mmHg) and the ratio of precapillary to postcapillary resistance was less. We conclude that reduction in the ratio of precapillary to postcapillary resistance in chronic fetal anemia increases blood flow, oxygen delivery, and capillary hydrostatic pressure.