RESUMO
BACKGROUND: Our team has previously reported physiologic support by the EXTra-uterine Environment for Neonatal Development (EXTEND) of 105 to 117 days gestational age (GA) lambs for up to 28 days with normal organ maturation. However, the fetal lamb brain matures more rapidly, requiring the study of 90-105 day GA fetal lambs to assess more neurodevelopmentally equivalent lambs to the 23-25 week GA extreme premature infant. METHODS: Extremely preterm lambs (90-95 days of GA) were delivered by C-section and supported by EXTEND. Estimated circuit flows were maintained at around 325 ml/kg/min. After support on EXTEND, MRI and histopathologic analysis were performed and compared to 105-112 days GA control lambs. RESULTS: The extremely preterm group includes 10 animals with a mean GA of 91.6 days, a mean weight at cannulation of 0.98 kg and a mean length of stay on EXTEND of 13.5 days (10-21 days). Hemodynamics and oxygenation showed stable parameters. Animals showed growth and physiologic cardiac function. MRI volumetric and diffusion analysis was comparable to controls. Histologic brain analysis revealed no difference between study groups. CONCLUSION: EXTEND appears to support brain and cardiac development in an earlier gestation, less mature, lamb model. IMPACT: Prolonged (up to 21 days) physiological support of extremely preterm lambs of closer neurodevelopmental equivalence to the 24-28 gestational week human was achieved using the EXTEND system. EXTEND treatment supported brain growth and development in extremely preterm fetal lambs and was not associated with intraventricular hemorrhage or white matter injury. Daily echocardiography demonstrated physiologic heart function, absence of cardiac afterload, and normal developmental increase in cardiac chamber dimensions. This study demonstrates hemodynamic and metabolic support by the EXTEND system in the extremely preterm ovine model.
RESUMO
Drag-reducing polymers (DRPs) are nontoxic water-soluble blood additives that have been shown to beneficially alter hemodynamics when delivered intravenously in nanomolar concentrations. This study examines the ability of DRPs to alter the traffic of mixtures of normal and less-deformable red blood cells (RBCs) through branched microchannels and is intended to support and expand upon previous experiments within straight capillary tubes to promote DRPs for future clinical use. Branched polydimethylsiloxane microchannels were perfused with a mixture of normal bovine RBCs also containing heat-treated less-deformable RBCs at a hematocrit of 30% with 10 ppm of the DRP poly(ethylene oxide) (MW 4M Da). Suspensions were driven by syringe pump, collected at outlets, and RBC dimensions measured while subject to shear stress to determine the proportion of healthy RBCs in each sample. DRPs eliminated evidence of the plasma skimming phenomena and significantly increased the pressure drop across microchannels. Further, DRPs were found to cause an increase in the proportion of healthy RBCs exiting the branch outlet from -8.5 ± 2.5% (control groups) to +12.1 ± 5.4% (n = 6, p = 0.02). These results suggest DRP additives may be used to improve the perfusion of less-deformable RBCs in vivo and indicates their potential for future clinical use.
