Jeffrey S. Heinle

The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts

The use of xenografts (Xgs) from distantly related species to relieve the increasing shortage of organs for clinical transplantation is prevented by the occurrence of hyperacute rejection (HAR). This process, in which C activation plays a central role, cannot be inhibited with currently available immunosuppressants. In two clinically relevant xenotransplantation models, this study evaluated the effect of C inhibition using recombinant soluble complement receptor type 1 (sCR1) on HAR. In an ex vivo model in which porcine cardiac Xgs were perfused with human blood, cardiac function ceased within 34 min when the perfusate blood was untreated (n = 3). When the perfusate blood was treated with sCR1 (300 micrograms/ml), cardiac Xg function was maintained for up to 4 hr (n = 3). Immunohistologic examination of these Xgs demonstrated deposition of C3b/iC3b and C3d in Xgs perfused with untreated human blood but only C3d deposition in those Xgs perfused with sCR1-treated human blood. These findings are consistent with the cofactor activity of sCR1 for factor I-mediated degradation of deposited C3b/iC3b to C3d. Treatment with sCR1 also prevented the histopathologic changes of HAR observed when untreated blood was used as the perfusate. In an in vivo pig-to-primate heterotopic cardiac xenotransplantation model, in which porcine Xgs transplanted into untreated cynomolgus monkey recipients underwent HAR in 1 hr or less (n = 3), a single intravenous bolus of sCR1 (15 mg/kg) administered to the recipient immediately before Xg reperfusion markedly inhibited total and alternative pathway serum C activity and prolonged Xg survival to between 48 and 90 hr (n = 5). These studies confirm the important role of C activation in HAR of porcine cardiac Xgs by primates and indicate that sCR1 may be a useful agent for xenotransplantation.

Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring

BACKGROUND New intraparenchymal brain injury on magnetic resonance imaging is observed in 36% to 73% of neonates after cardiac surgery with cardiopulmonary bypass. Brain immaturity in this population is common. We performed brain magnetic resonance imaging before and after neonatal cardiac surgery, using a high-flow cardiopulmonary bypass protocol, hypothesizing that brain injury on magnetic resonance imaging would be associated with brain immaturity. METHODS Cardiopulmonary bypass protocol included 150 mL . kg(-1) . min(-1) flows, pH stat management, hematocrit > 30%, and high-flow antegrade cerebral perfusion. Regional brain oxygen saturation was monitored, with a treatment protocol for regional brain oxygen saturation < 50%. Brain magnetic resonance imaging, consisting of T1-, T2-, and diffusion-weighted imaging, and magnetic resonance spectroscopy were performed preoperatively, 7 days postoperatively, and at age 3 to 6 months. RESULTS Twenty-four of 67 patients (36%) had new postoperative white matter injury, infarction, or hemorrhage, and 16% had new white matter injury. Associations with preoperative brain injury included low brain maturity score (P = .002). Postoperative white matter injury was associated with single-ventricle diagnosis (P = .02), preoperative white matter injury (P < .001), and low brain maturity score (P = .05). Low brain maturity score was also associated with more severe postoperative brain injury (P = .01). Forty-five patients had a third scan, with a 27% incidence of new minor lesions, but 58% of previous lesions had partially or completely resolved. CONCLUSIONS We observed a significant incidence of both pre- and postoperative magnetic resonance imaging abnormality and an association with brain immaturity. Many lesions resolved in the first 6 months after surgery. Timing of delivery and surgery with bypass could affect the risk of brain injury.

Early extubation after cardiac operations in neonates and young infants

OBJECTIVE This study was undertaken to determine the feasibility of early extubation of the neonate and young infant after surgical repair of congenital heart lesions. METHODS The records of all patients less than 90 days of age who had cardiac operations over a 1-year period were reviewed. During this time, all patients were managed as potential candidates for early extubation. Fifty-six patients are included with a mean age of 32 +/- 31 days and a mean weight of 3.7 +/- 0.9 kg. RESULTS Twenty-eight patients (50%) were extubated in the operating room or within 3 hours after arriving in the intensive care unit. This included 38% of patients less than 7 days of age, 50% of patients 8 to 30 days of age, 44% of patients 31 to 60 days of age, and 69% of patients 61 to 90 days of age. Three patients (11%) extubated early required reintubation. No deaths were related to early extubation. Only one patient was negatively affected by early extubation. Patients extubated early had shorter stays in the intensive care unit (3.3 +/- 3.9 vs 6.7 +/- 2.9 days) and shorter postoperative hospital stays (5.9 +/- 3.3 vs 13.5 +/- 9.7 days), as well as lower intensive care unit (

The association between brain injury, perioperative anesthetic exposure, and 12‐month neurodevelopmental outcomes after neonatal cardiac surgery: a retrospective cohort study

5,851 +/-

Current Expectations for Surgical Repair of Isolated Ventricular Septal Defects

7,225 vs

Ex vivo characterization of human anti-porcine hyperacute cardiac rejection.

12,064 +/-

Changing Expectations for Neurological Outcomes After the Neonatal Arterial Switch Operation

4,419) and total hospital (

Repeat Sternotomy in Congenital Heart Surgery: No Longer a Risk Factor

21,108 +/-

Fenestration during Fontan palliation: Now the exception instead of the rule

14,941 vs

Neurodevelopmental Outcomes After Regional Cerebral Perfusion With Neuromonitoring for Neonatal Aortic Arch Reconstruction

31,608 +/-