Dataset Information

Impact of Mesenchymal Stromal Cell Delivery Through Cardiopulmonary Bypass on Postnatal Neurogenesis.

ABSTRACT:

Background

Neurodevelopmental impairment is an important challenge for survivors after neonatal surgery with cardiopulmonary bypass (CPB). The subventricular zone, where most neural stem/progenitors originate, plays a critical role in cortical maturation of the frontal lobe. Promoting neurogenesis in the subventricular zone is therefore a potential therapeutic target for preserving cortical growth. Mesenchymal stromal cells (MSCs) promote endogenous regeneration in the rodent brain. We investigated the impact of MSC delivery through CPB on neural stem/progenitor cells and neuroblasts (ie, young neurons) in the piglet subventricular zone.

Methods

Two-week-old piglets (n = 12) were randomly assigned to one of three groups: (1) control, (2) deep hypothermic circulatory arrest, and (3) circulatory arrest, followed by MSC administration. MSCs (10 × 10⁶ per kg) were delivered through CPB during the rewarming period. Neural stem/progenitors, proliferating cells, and neuroblasts were identified with immunohistochemistry at 3 hours after CPB.

Results

CPB-induced insults caused an increased proliferation of neural stem/progenitors (P < .05). MSC delivery reduced the acute proliferation. MSC treatment increased the number of neuroblasts in the outer region of the subventricular zone (P < .05) where they form migrating chains toward the frontal lobe. Conversely, the thickness of the neuroblast-dense band along the lateral ventricle was reduced after treatment (P < .05). These findings suggest that MSC treatment changes neuroblast distribution within the subventricular zone.

Conclusions

MSC delivery through CPB has the potential to mitigate effects of CPB on neural stem/progenitor cells and to promote migration of neuroblasts. Further investigation is necessary to determine the long-term effect of MSC treatment during CPB on postnatal neurogenesis.

SUBMITTER: Maeda T

PROVIDER: S-EPMC7093227 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveMetabolism management plays an essential role during cardiopulmonary bypass (CPB). There are different metabolic management devices integrated to heart-lung machines; the most commonly used and accepted metabolic target is indexed oxygen delivery (DO2i) (280 mL/min/m2) and cardiac index (CI) (2.4 L/min/m2), which can be managed independently or according to other metabolic parameters. Our objective was to compare lactate production during CPB procedures using different metabolic management: DO2i in relation to indexed oxygen extraction ratio (O2ERi) and CI in relation to mixed venous oxygen saturation (SvO2).MethodsData on 500 CPB procedures were retrospectively collected in a specialized regional tertiary cardiac surgery center in Italy between September and 2012 and November 2019. In group A, the DO2i with 280 mL/min/m2 target in relation to O2ERi 25% was used; in group B, CI with 2.4 L/min/m2 target in relation to SvO2 75% was used. During CPB, serial arterial blood gas analyses with blood lactate and glucose determinations were obtained. Hyperlactatemia (HL) was defined as a peak arterial blood lactate concentration >3 mmol/L. The postoperative outcome of patients with or without HL was compared.ResultsEight pre- and intraoperative factors were found to be significantly associated with peak blood lactate level during CPB at univariate analysis. HL (>3 mmol/L) was detected in 15 (6%) patients of group A and in 42 (16.8%) patients of group B (P = .022); hyperglycemia (>160 mg/dL) was found in 23 (9.2%) patients of group A and in 53 (21.2%) patients of group B (P = .038). Patients with HL during CPB had a significant increase in serum creatinine value, higher rate of prolonged mechanical ventilation time and intensive care unit stay. A cutoff of DO2i <270 mL/min/m2 in relation to O2ERi >35% in group A and a cutoff of CI <2.4 L/min/m2 in relation to SvO2 <65% in group B were found to have a positive predictive value of 80% and 75% for HL, respectively. A cutoff of DO2i >290 mL/min/m2 in relation to O2ERi 24% in group A and a cutoff of CI >2.4 L/min/m2 in relation to SvO2 >75% in group B were found to have a negative predictive value of 78% and 62% for HL, respectively.ConclusionsThis retrospective observational analysis showed that management of DO2i in relation to O2ERi was 16% more specific in terms of negative predictive value for HL during CPB compared with the use of CI in relation to SvO2. Group A reported a significant reduction in the incidence of intraoperative lactate peak, correlated with postoperative reduction of serum creatinine value, mechanical ventilation time, and intensive care unit stay, compared with group B.

Project description:Objective: Lactate is often used as a surrogate marker of inappropriate oxygen delivery. It has been shown that hyperlactatemia is associated with worse clinical outcome in children after cardiac surgery. The purpose of this study is to evaluate the association of hyperlactatemia, low systemic oxygen delivery, and hyperglycemia, in children admitted to the pediatric critical care unit after cardiopulmonary bypass. Design: Secondary analysis of an observational cohort study. Setting: Tertiary pediatric critical care unit (PICU). Patients: Ninety-three patients, aged 6 months to 16 years, undergoing cardiac surgery with cardiopulmonary bypass. Interventions: None. Measurements and Main Results: Metabolic tests (blood glucose, lactate, lactate/pyruvate ratio, and ketones) and oxygen extraction (SaO2-SvO2) were performed before anesthesia, at the end of cardiopulmonary bypass, at PICU admission, and at 4 and 12 h after PICU admission. Four hours after PICU admission, 62% of the patients had hyperlactatemia (>2 mmol/L), of whom 55% had normal oxygen extraction (SaO2-SvO2 < 30%). There was no correlation between lactate and oxygen extraction (R = -0.09, p = 0.41) but there was a moderate correlation between lactate and blood glucose (R = 0.55, p < 0.001). Using a logistic regression model, hyperlactatemia at 4 h after PICU admission was independently associated with hyperglycemia (p = 0.007) and lactate/pyruvate ratio (p = 0.007) at the same timepoint, as well as with lactate at PICU admission (p = 0.002), but not with weight (p = 0.45), severity of the cardiac lesion (p = 0.85), duration of bypass (p = 0.16), or oxygen extraction, as evaluated by SaO2-SvO2 (p = 0.54). At 12 h after PICU admission, there was a very week correlation between lactate and blood glucose (R = 0.27, p = 0.007), but none between lactate and oxygen extraction (R = 0.13, p = 0.20). Conclusion: In children after cardiopulmonary bypass, lactates are not correlated with higher oxygen extraction, but are correlated with hyperglycemia, at both 4 and 12 h after PICU admission. Future research is warranted to better define this relationship.