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Ibuprofen enhances retinal and choroidal blood flow autoregulation in newborn piglets
1Montreal Children's Hospital, Developmental Pharmacology and Perinatal Research, Canada.
Insights
Prostanoids regulate newborn retinal and choroidal blood flow autoregulation. Ibuprofen significantly reduced prostanoid levels, impacting blood flow during blood pressure changes.
Area of Science:
- Physiology
- Neonatal Physiology
- Ocular Physiology
Background:
- Prostanoids play a crucial role in regulating blood flow in various tissues.
- Autoregulation of blood flow is vital for maintaining tissue perfusion, especially in developing organs.
- The specific role of prostanoids in the autoregulation of retinal and choroidal blood flow in newborns is not fully understood.
Purpose of the Study:
- To investigate the role of prostanoids in the autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) in newborn piglets.
- To determine how systemic blood pressure fluctuations affect RBF and ChBF in the presence and absence of prostanoid synthesis.
Main Methods:
- Measurements of RBF, ChBF, and prostanoid concentrations (PGE, PGF2 alpha, 6-keto-PGF1 alpha, TXB2) in newborn piglets across a wide range of mean systemic blood pressure (17-117 mm Hg).
- Induction of hypertension and hypotension using balloon-tipped catheters.
- Treatment with ibuprofen (a prostanoid synthesis inhibitor) or its vehicle.
Main Results:
- In vehicle-treated piglets, RBF autoregulation was maintained between 50-90 mm Hg, with deviations outside this range. ChBF increased with blood pressure throughout the studied range.
- Prostanoid concentrations increased during hypotension (<50 mm Hg) and prostaglandin concentrations increased during hypertension (>90 mm Hg).
- Ibuprofen treatment drastically reduced basal prostanoid levels and abolished their changes during induced hypotension and hypertension, altering blood flow dynamics.
Conclusions:
- Prostanoids are integral to the autoregulation of RBF and ChBF in newborns, particularly under conditions of altered blood pressure.
- Inhibition of prostanoid synthesis by ibuprofen significantly impacts the ability of the newborn eye to maintain blood flow homeostasis.
- These findings highlight the critical role of prostanoids in protecting ocular perfusion in the neonatal period.
Abstract:
The role of prostanoids in setting the range of autoregulation of retinal blood flow (RBF) and choroidal blood flow (ChBF) in the newborn was assessed. The RBF, ChBF, and arterial and cerebral sinus concentrations of PGE, PGF2 alpha, 6-keto-PGF1 alpha and TXB2 were measured over a wide range of mean systemic blood pressure (blood pressure (BP): 17-117 mm Hg) in newborn piglets treated with ibuprofen (30 mg/kg iv) or its vehicle (n = 8, in each group). Hypertension and hypotension were induced 80 min apart on each animal, by inflating balloon-tipped catheters placed at the aortic isthmus and root, respectively. Blood flow and prostanoid concentrations were measured 20 min before (basal) and during the induced changes in BP. In vehicle-treated piglets, RBF did not change with BP between 50 and 90 mm Hg (r = 0.33, P = 0.27), but changed as a function of BP beyond this range (tau = 0.52, P less than 0.01); ChBF increased with BP throughout the range studied (17-117 mm Hg; tau = 0.89, P less than 0.001). The relationship between O2 delivery to the retina and choroid and BP (tau greater than 0.43, P less than 0.01) was similar to that seen between RBF and ChBF with BP. The concentration of all prostanoids increased when BP was reduced to less than 50 mm Hg. When BP was raised to more than 90 mm Hg, prostaglandin concentrations increased, and those of TXB2 did not change. Ibuprofen treatment reduced the basal concentrations of all prostanoids to nearly undetectable levels and prevented their changes during hypotension and hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)