| Summary: | Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect and infants with TOF incur significant right ventricular(RV) dysfunction due to perioperative injury. Insulin has been shown to reduce perioperative myocardial injury and significantly improve postoperative cardiac function. However, studies are limited
to the adult population and the effects in a pediatric heart with a CHD are unknown.
To the best of our knowledge, this is the first randomized, double blind, placebo-controlled clinical study designed to investigate insulin’s potential cardioprotective effects postoperatively and mechanisms of action during pediatric cardiac surgery. Thirty infants with TOF were equally randomly allocated to receive either standard cardioplegia (SC) or 10UI insulin-enhanced (IC). Expression profiles of surgery were generated from biopsies extracted from the right ventricular outflow tract (end ischemia and five minutes of reperfusion) and hybridized to Affymetrix HG-U133A GeneChips. Gene expression profiles were generated using two softwares, ArrayAssist V2.6 (paired t-test) and affylmGUI (ANOVA). Survival rate was 100%. Compared to patients in the SC group, patients in the IC group demonstrated a trend toward a 1.8 fold decrease (p = .06) in reperfusion duration (61.93 ± 61.12 vs. 35.20 ± 23.16 hrs., respectively), a significant 2-fold decrease in the length of ICU stay (p = .04) (4.2 ± 3.9 vs. 2.3 ± 1.1 days, respectively) and a trend toward a 2.5 fold decrease in intubation duration (p= .06) (2.5± 12.2 vs. 55.0 ± 67 hrs., respectively). Patients in the IC group also demonstrated significantly lower inotropic scores, calculated at 12-hour intervals across a 48-hour ICU period, (ANOVA p = .01) and significantly greater urine volume, by 71%, (p = .02). IC evoked a cardioprotective gene expression profile aimed at mitigating perioperative myocardial injury, specifically; apoptosis, inflammation, cardiac hypertrophy, arrythmias and fibrosis. The improved postoperative outcome and cardioprotective gene expression signature with IC suggests that, administration of insulin during cardiac surgery in infants with TOF may prevent cardiac dysfunction as a result of
mitigating perioperative myocardial injury. Overall, this exploratory study demonstrated insulin-enhanced cardioplegia to be a potential cardioprotective agent during pediatric heart surgery.
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