Detection of alpha II-spectrin breakdown products in the serum of neonates with congenital heart disease*

Abstract

Objectives: To determine if alpha II-spectrin breakdown products can be detected in the serum of neonates with congenital heart disease in the perioperative period.

Design: Prospective observational cohort study.

Setting: Pediatric cardiac ICU in an urban tertiary care academic center.

Patients: Neonates with congenital heart disease undergoing surgical repair or palliation.

Interventions: Serial blood sampling for measurement of 120 and 150 kDa spectrin breakdown products.

Measurements and main results: Fourteen neonates with congenital heart disease undergoing cardiac surgery were evaluated. Nine infants underwent open-heart surgery and five underwent closed-heart surgery. Serum spectrin breakdown products were measured with sandwich enzyme-linked immunosorbent assay preoperatively and then 6, 24, 48, 72, and 96 hours following surgery. Brain imaging was obtained as part of routine clinical care in 12 patients preoperatively and six patients postoperatively. Six patients had normal preoperative imaging (three closed-heart surgery and three open-heart surgery), whereas six had evidence of neurologic injury prior to surgery (one closed-heart surgery and five open-heart surgery). Only one patient had a postoperative imaging study that lacked injury. All others demonstrated infarction or hemorrhage. Spectrin breakdown product 120 kDa significantly increased 24 hours after open-heart surgery compared to preoperative values and time-matched closed-heart surgery levels. Spectrin breakdown product 150 kDa significantly increased 6 hours after open-heart surgery compared to preoperative values. There was no significant change in spectrin breakdown products following closed-heart surgery. Peak spectrin breakdown products significantly increased following open-heart surgery compared to closed-heart surgery.

Conclusions: Spectrin breakdown products can be detected in the serum of neonates with congenital heart disease in the perioperative period and levels increased to a greater degree in infants following open-heart surgery. These findings suggest that, in future work, serum spectrin breakdown products may potentially be developed as biomarkers for brain necrosis and apoptosis in infants with congenital heart disease.

Figure 1

Postoperative serum alpha II-spectrin breakdown product (AIISBDP) levels over time. Levels of SBDP120 (A) and SBDP150 (B) are depicted. Preoperative values are plotted at the zero hour time point. Open squares with solid trend line represent values from patients in the closed-heart surgery (CHS) cohort (n = 5). Closed squares with dashed trend line represent values from patients in the open-heart surgery (OHS) cohort (n = 9). Values are means ± SE. *p < 0.05 versus OHS zero hour time point; †p < 0.001 versus. OHS zero hour time point and CHS 6, 24, and 48 hr time points.

Figure 2

Peak postoperative serum alpha II-spectrin breakdown product (AIISBDP) levels. Box plots for SBDP120 (A) and SBDP150 (B) peak levels following open-heart surgery (n = 9) and closed-heart surgery (CHS) (n = 5) are depicted. Dashed lines represent mean SBDP values from patients who lacked radiographic evidence of brain injury. *p < 0.04 versus CHS and uninjured values; †p < 0.03 versus CHS and uninjured values. Filled circles represent outliers.