Effects of Prostaglandins and Indomethacin on Cerebral Blood Flow and Cerebral Oxygen Consumption of Conscious Newborn Piglets

Abstract

The effects of the prostaglandins (PG) PGE(1), PGE(2), PGF(2α) and PGI(2), and of indomethacin on cerebral blood flow (CBF) and cerebral metabolic rate for O(2) (CMRO(2)) were studied in 60 1-to 3-day-old conscious piglets. Effects of PGs in indomethacin-treated animals were also measured. CBF was measured by radiolabelled microspheres prior to and 45 s after intracarotid bolus injections of 0.1 -10 μg/kg PGE(1) and 0.01-1 μg/kg PGE(2), PGF(2α) and PGI(2). PGE(1) decreased CBF by 30% at the dose of 0.1 μg/kg and increased it by 39.5% (n = 6) at the higher dose of 10 μg/kg. PGE(2) (n = 6) increased CBF at all doses administered. PGF(2α) (0.01 μg/kg, n = 8), which is a potent cerebral vasoconstrictor in adults, and PGI(2) (0.1 μg/kg, n = 6) significantly increased CBF in newborn piglets (p < 0.05). CMRO(2) correlated with CBF in all groups of animals, except for those injected with PGI(2). Indomethacin (3 mg/kg i.v.) decreased CBF by 39% (p < 0.01, n = 6). This effect was partially reversed by PGI(2), but not by PGE(1) and PGF(2α). Sagittal venous blood and arterial-sagittal venous blood differences in concentrations of PGF(2α), but not of PGE and 6-keto-PGF(1α), correlated weakly but positively (r = 0.4, p < 0.05) with CBF in indomethacin-treated piglets. These data indicate that PGs exert significant effects on cerebral circulation in the newborn. Primary PGs are principally cerebral vasodilators and are devoid of vasoconstrictive effects in the newborn, except for PGE(1) which produces vasoconstriction at low dose (0.1 μg/kg). Thus, we speculate that a relative deficiency in cerebral vasoconstrictor effect of PGs may contribute to the reduced upper limit of the CBF autoregulatory range of the newborn.

A meta-analysis of ibuprofen versus indomethacin for closure of patent ductus arteriosus

“…INDO significantly decreases CBF and mitochondrial oxidative function in animals and human newborns [5,16] and inferentially perturbs neuronal function. In contrast, IBU exerts no effect on cerebral and mesenteric blood flow [5,6,20,23,24] and probably has little effect on cerebral perfusion. Whether IBU will prove to have a positive impact on later neurological outcome remains to be seen.…”

“…However, It is noteworthy that despite a substantial reduction in IVH and a significant increase in PDA closure by INDO [10,17,26] there is minimal or no evidence of improved neurosensory or pulmonary outcomes at 18 to 21 months follow-up and even up to school age [18,19,27,33]. INDO significantly decreases CBF and mitochondrial oxidative function in animals and human newborns [5,16] and inferentially perturbs neuronal function. In contrast, IBU exerts no effect on cerebral and mesenteric blood flow [5,6,20,23,24] and probably has little effect on cerebral perfusion.…”

Patent Ductus Arteriosus: Are Current Neonatal Treatment Options Better or Worse Than No Treatment at All?

“…It appears to be as effective as indomethacin in producing PDA closure in very low birthweight infants (at least in infants with a mean gestational age of 28 weeks) (71). In contrast with indomethacin, ibuprofen does not appear to affect mesenteric blood flow (46, 59, 61) and has less of an effect on renal perfusion, oliguria (46, 59, 61), and cerebral blood flow (54, 61, 72, 73). Animal studies suggest that ibuprofen may have some cytoprotective effects in the intestinal tract (74).…”

The Renal Hemodynamic Effects of Ibuprofen in the Newborn Rabbit

“…For a thorough discussion on this subject, the reader is referred to the literature (5,(31)(32)(33)(34)(35)(36). To complicate matters, it is now well known that chloride plays a role in the various responses to COX inhibition in the kidney of the isolated, adult rat (37).…”