The effect of indomethacin on systemic and renal hemodynamics in neonatal piglets during experimental endotoxemia

Abstract

Systemic and renal hemodynamics are affected by prostaglandin production during endotoxemia. To study indomethacin effects on endotoxinemia in a neonatal piglet model, sixteen 7-10 day old piglets were anesthetized, ventilated, and catheterized. Mean arterial pressure (MAP), heart rate (HR), and urine output were continuously monitored. Endotoxin (0.06 mcg/kg) was injected after baseline measurements. We studied two groups with either endotoxinemia alone (n = 7) or an additional indomethacin infusion (0.2 mg/kg per h, n = 9). HR, MAP, renal blood flow (RBF), systemic and renal vascular resistance (SVR, RVR), cardiac index (CI), and glomerular filtration rate (GFR), were obtained at baseline, at 1, 2 and 3 h. We observed a drop in CI and an increase in SVR and HR within 3 h of endotoxinemia, while MAP remained unchanged. These effects were prevented by indomethacin. RVR was not altered significantly. Endotoxinemia triggered a drop of RBF in both control (P < 0.01) and intervention group (P < 0.05). In the intervention group, drop of GFR, urine volume, and paraaminohippuric acid clearance were apparent signs of nephrotoxicity (P < 0.01, <0.05, and <0.01). In conclusion, indomethacin maintains hemodynamic parameters during endotoxinemia at the expense of nephrotoxicity. We speculate that indomethacin counteracts the renoprotective effect of prostaglandins. © 2008 Springer-Verlag.