Impact of cardiopulmonary bypass on cerebrovascular autoregulation assessed by ultrafast ultrasound imaging.

Newborns with congenital heart disease undergoing cardiac surgery are at risk of neurodevelopmental impairment with limited understanding of the impact of intra-operative cardiopulmonary bypass (CPB), deep hypothermia and selective cerebral perfusion on the brain. We hypothesized that a novel ultrasound technique, ultrafast power Doppler (UPD), can assess variations of cerebral blood volume (CBV) in neonates undergoing cardiac surgery requiring CPB. UPD was performed before, during and after surgery in newborns with hypoplastic left heart syndrome undergoing a Norwood operation. We found that global CBV was not significantly different between patients and controls (P = 0.98) and between pre- and post-surgery (P = 0.62). UPD was able to monitor changes in CBV throughout surgery, revealing regional differences in CBV during hypothermia during which CBV correlated with CPB flow rate (R2  = 0.52, P = 0.021). Brain injury on post-operative magnetic resonance imaging was observed in patients with higher maximum variation in CBV. Our findings suggest that UPD can quantify global and regional brain perfusion variation during neonatal cardiac surgery with this first intra-operative application demonstrating an association between CBV and CPB flow rate, suggesting loss of autoregulation. Therefore, the measurement of CBV by UPD could enable optimization of cerebral perfusion during cardiac surgery in neonates. KEY POINTS: The impact of cardiopulmonary bypass (CPB) on the neonatal brain undergoing cardiac surgery is poorly understood. Ultrafast power Doppler (UPD) quantifies cerebral blood volume (CBV), a surrogate of brain perfusion. CBV varies throughout CPB surgery and is associated with variation of the bypass pump flow rate during deep hypothermia. Association between CBV and bypass pump flow rate suggests loss of cerebrovascular autoregulatory processes. Quantitative monitoring of cerebral perfusion by UPD could provide a direct parameter to optimize CPB flow rate.

Use of Serratus Plane Block for Repair of Coarctation of Aorta: A Report of 3 Cases.

OBJECTIVES: The practice of regional anesthesia techniques (thoracic, epidural, paravertebral) in pediatric cardiac surgery enhances perioperative outcomes such as improved perioperative analgesia, decreased stress response, early extubation, and shortened hospital stay. However, these blocks can be technically challenging and can be associated with unacceptable failure rate and complications in infants. For these reasons, regional anesthesia is sometimes avoided in pediatric cardiac surgery. We describe the simple and effective serratus plane block for thoracotomy analgesia in 2 neonates and a child. CASE REPORT: We present 3 pediatric patients, each of whom was having coarctation repair and received an ultrasound-guided serratus plane block for thoracotomy analgesia. The patients were 3 days, 14 days, and 4 years old, weighing from 1.9 to 16 kg. The serratus plane block was performed prior to surgical incision. The block was technically simple compared with thoracic epidural or paravertebral block. All patients were extubated immediately after completion of surgery. Apart from the induction dose of fentanyl (2 µg/kg), no further opioids were required intraoperatively. Postoperative opioid requirements as well as duration of intensive care and hospital stay were lower than recent averages (for the same demographic and procedure) in our hospital. CONCLUSIONS: We propose that the serratus plane block is a simple procedure that provides good perioperative analgesia for infant thoracotomy, potentially facilitating early extubation and a shorter hospital stay.

Clathrin-mediated endocytosis and recycling of the neuron-specific Na+/H+ exchanger NHE5 isoform. Regulation by phosphatidylinositol 3'-kinase and the actin cytoskeleton.

Mammalian Na+/H+ exchangers (NHEs) are a family of integral membrane proteins that play central roles in sodium, acid-base, and cell volume homeostasis. The recently cloned NHE5 isoform is expressed predominantly in brain, but its functional and cellular properties are poorly understood. To facilitate its characterization, an epitope-tagged construct of NHE5 was ectopically expressed in nonneuronal and neuronal cells. In NHE-deficient Chinese hamster ovary AP-1 cells, NHE5 localized at the plasmalemma, but a significant fraction accumulated intracellularly in vesicles that concentrated in a juxtanuclear region. Similarly, in nerve growth factor-differentiated neuroendocrine PC12 cells and primary hippocampal neurons, immunolabeling of NHE5 was detected in endomembrane vesicles in the perinuclear region of the cell body but also along the processes. More detailed characterization in AP-1 cells using organelle-specific markers showed that NHE5 co-localized with internalized transferrin, a marker of recycling endosomes. Transient transfection of a dominant negative mutant of dynamin-1, which inhibits clathrin-mediated endocytosis, blocked uptake of transferrin as well as internalization of NHE5. Likewise, wortmannin inhibition of phosphatidylinositol 3'-kinase, a lipid kinase implicated in endosomal traffic, induced coalescence of vesicles containing NHE5 and caused a pronounced inhibition of plasmalemmal Na+/H+ exchange. By contrast, disruption of the F-actin cytoskeleton with cytochalasin D increased cell surface NHE5 activity and abundance. These observations demonstrate that NHE5 is localized to the recycling endosomal pathway and is dynamically regulated by phosphatidylinositol 3'-kinase and by the state of F-actin assembly.