Abstract

Introduction: Alkaline phosphatase (AP) may be protective after CV surgery through dephosphorylation of endotoxin and extracellular adenine nucleotides. AP activity falls after infant CV surgery and low activity is associated with increased support requirements. However, the kinetics of AP loss and recovery, the isoenzymes involved, and the temporal relation of low AP activity to increased support are unknown. We hypothesized loss of all isoenzymes during surgery leads to decreased AP activity and that early low AP activity is associated with increased cardiovascular support at 6-48hr. Methods: Prospective study of 93 infants <120 d/o undergoing CV surgery with bypass. Total/isoenzyme specific AP activity and vasoactive inotropic score (VIS) were obtained pre-operation, pre-separation and at 6, 24, 48 and 72hr after ICU admission. AP activities were determined by commercial assay and concentration by multiplex immunoassay. Low AP activity was defined as ≤80 U/L. Results: Median AP activity decreased through 6hr due to decreased bone and liver 2 isoenzyme activities (fig 1). Liver 1 isoenzyme increased post-bypass then decreased through 72hr. Activity was highly correlated with concentration at all time points (r=0.83-0.89; p<0.0001). Nadir AP activity coincided with peak VIS. Infants with low AP activity at 6hr had significantly higher VIS through 48hr (6hr 12.1 vs 8.1, p<0.0005; 24hr 11.2 vs 5.3, p<0.0001; 48hr 6.9 vs 3.0, p<0.0005). Similar findings occurred with low pre-separation and 24hr AP activity. On multivariate analysis, low AP activity at 6hr was independently associated with higher VIS at 6, 24 and 48hr. Conclusions: Loss of bone and liver 2 isoenzymes leads to decreased AP activity after infant CV surgery. Low early AP activity is associated with increased cardiovascular support requirements 6-48hr later. AP activity may serve as an early biomarker of post-operative hemodynamic instability and a potential therapeutic target in this population.

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