Brain Blood Flow Responses to Indomethacin during Hemorrhagic Hypotension in Newborn Piglets

Abstract

Indomethacin has been shown to reduce cerebral blood flow and cerebral blood flow velocities in newborn infants and animals of various species. To answer the question of whether there may be a compromise of cerebral perfusion in hypotensive infants who have been treated with indomethacin, cerebral blood flow and cerebral vascular resistance were determined in 10 control and 16 indomethacin-treated 1-day-old piglets during (1) steady state conditions; (2) 10 min after the administration of saline or a 0.2-mg/kg dose of indomethacin; (3) 1 h after saline or indomethacin administration, and (4) 10 min after induction of moderate hemorrhagic hypotension. Mean arterial blood pressures increased immediately after the infusion of indomethacin in the experimental group. Cerebral blood flows did not change throughout the study despite hemorrhagic hypotension in controls; cerebral blood flows were significantly decreased 10 min after indomethacin infusion in the experimental animals. However, total and regional cerebral blood flows were not further decreased in the presence of moderate hypotension. Cerebral vascular resistance increased 10 min after indomethacin infusion but returned to steady state 1 h following the indomethacin dose. These results suggest that indomethacin lowers baseline cerebral blood flow, but does not impair cerebrovascular regulatory responses during acute, moderate hemorrhagic hypotension in the newborn piglet.

Age-dependent cerebral hemodynamic effects of indomethacin in the newborn piglet

“…Furthermore, among piglets treated with indomethacin, those Ͼ13 h of age displayed a significant decrease in CBF immediately postinfusion, whereas initial decreases in CBF in piglets Ͻ13 h of age did not reach statistical significance. Although this initial reduction in CBF with indomethacin administration has been previously observed and documented in both newborn humans and animals (10,19,34,36,37), the subsequent period of elevated CBF and CBV in piglets Ͻ13 h of age has not been reported. This is due in part to the use of older piglets and in part to a lack of data at similarly extended time periods in previous indomethacin studies.…”

“…Indomethacin is known to inhibit the production of prostanoids through blockage of both constitutive and inducible isoforms of the cyclooxygenase (COX) enzyme, COX-1 and COX-2, respectively, in the arachidonic acid cascade (13, 28,29). Because of their importance in the maintenance and control of cerebral hemodynamics, it has previously been suggested that indomethacin may exert its cerebral hemodynamic effects through inhibition of prostanoid production (14,19). Postnatal cerebral hemodynamic adaptation is mediated by changes in prostanoid production (1,11,12,17).…”

Correlation of Near Infrared Spectroscopy Cerebral Blood Flow Estimations and Microsphere Quantitations in Newborn Piglets

“…As reported for previous studies from our laboratory [14][15][16][17], during each MS blood flow quantitations, 300,000 to 500,000 MSs labelled with one of four radionuclides ( 141 Ce, 51 Cr, 85 Sr, or 105 Nb) were infused into the left cardiac ventricle via the cardiac catheter over 10 s. Commencing just before the MS infusion, and continuing for 1 min and 10 s, a reference sample was withdrawn from the abdominal aortic catheter. This blood was replaced with lightly heparinized sibling donor blood to maintain a stable hematocrit.…”

Primer consenso clínico de SIBEN: enfoque diagnóstico y terapéutico del ductus arterioso permeable en recién nacidos pretérmino

“…Son muchos los estudios realizados en animales [273][274][275][276][277][278][279] , pero su análisis escapa al objetivo de este artículo. En resumen, el ibuprofeno reduce el tamaño del infarto de forma comparable a como lo haría la hipotermia, el efecto de la indometacina sobre la hemodinámica no estaría relacionado con el sistema de los prostanoides, es independiente del sistema parasimpático y parece mediado por la vasopresina y los opiodes.…”