[Effects of alprostadil and ulinastatin on inflammatory response and lung injury after cardiopulmonary bypass in pediatric patients with congenital heart diseases].

OBJECTIVE

To investigate the therapeutic effects of alprostadil (Lipo-PGE1) and Ulinastatin on inflammatory response and lung injury after cardiopulmonary bypass (CPB) in pediatric patients with congenital heart diseases.

METHODS

58 children with congenital heart diseases, including atrial septal defect, ventricular septal defect, and atrioventricular septal defect, scheduled to undergo CPB, aged 4 - 72 months, were randomly divided into 4 groups: alprostadil Group P (n = 15) receiving alprostadil 10 ng/ml added into the prime solution and continuous pump infusion of alprostadil 10 ngxkg(-1)xmin(-1) via central vein until the end of operation, Group U (n = 15) receiving ulinastatin 20 000 U/kg divided into several doses to be added into the prime solution, Group PU (n = 14) receiving alprostadil and ulinastatin according to the above protocols, and Group C (control group, n = 14) receiving normal saline of the equal volume. Electrocardiogram (ECG), heart rate (HR), pulse oxygen saturation (SpO(2)), and mean arterial pressure (MAP) were continuously monitored during operation. Duration of mechanical ventilation and staying in ICU were also recorded. Plasma neutrophil (PMN), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha and matrix metalloproteinase (MMP-9) levels in the radial arterial blood samples were measured after induction of anesthesia before CPB (T(1)), 30 minutes and (T(2)), 2 hours (T(3)), 6 hours (T(4)), and 24 hours (T(5)) after the declamping of aorta. Inhaled oxygen concentration and arterial blood gas analysis were recorded at T(1), T(2), and T(3) for calculation of oxygenation index (OI).

RESULTS

There were no significant differences in the MAP and HR among these four groups at any time points (all P > 0.05). The umbers of PMN and the levels of IL-6, IL-8, and TNF-alpha at T(2) and T(3) of Groups P, U, and PU were all significantly lower than that of Group C (all P < 0.05), with those of Group PU being the lowest. The IL-10 levels at T(2) and T(3) of Groups U and PU were significantly higher than that of Group C (both P < 0.05), the level of MMP-9 at T(2) and T(3) of Groups U and PU were significantly lower than that of Group C (all P < 0.05), however, there was not significant difference between Group P and Group C (P > 0.05). The OIs at T(2) of Groups P, U, and PU were significantly higher than that of Group C (all P < 0.05). The mechanical ventilation time of Groups P, U, and PU were all significantly shorter than that of Group C, and that of Group PU was significantly shorter than that of group C (P < 0.05).

CONCLUSION

Decreasing the inflammatory response after CPB, alprostadil and ulinastatin used during CPB effectively reduce the pulmonary injury via inhibition of the neutrophil activation and cytokines release.