The impact of cyclooxygenase inhibition with ketorolac on regional cerebral perfusion in healthy adults

INTRODUCTION: Non-selective cyclooxygenase (COX) inhibition tests the role of COX on cerebrovascular control. Most studies using COX inhibitors (typically Indomethacin) demonstrate robust decreases in cerebral blood flow (CBF) (20-42%), but have focused primarily on middle cerebral artery (MCA) velocity, which does not quantify CBF or provide insight into regional differences in the influence of COX on basal CBF control. The purpose of this study was to determine global and regional microvascular effects of COX inhibition to gain a better understanding of mechanisms underlying resting CBF control. HYPOTHESIS: We hypothesize that microvascular CBF will be attenuated after ketorolac infusion globally and in discrete regions. METHODS: Young healthy adults (M=4, F=2) were included in the study (age: 24 ± 3, BMI: 22.4 ± 0.7). Participants completed two Arterial Spin Labeling (ASL) scans. ASL scans were completed before and after a 3-minute intravenous infusion of ketorolac (0.495 mg/kg, mean dose 33.9 ±2.8 mg). ASL analysis was completed in SPM12. ASL analysis included smoothing grey matter, co-registering and normalizing raw data, brain masking and region of interest processing. A two-way repeated measures ANOVA with a Tukey's post hoc were computed in SigmaPlot13. RESULTS: Global cerebral blood flow during room air (58±15mL/100g/min) did not change after ketorolac infusion (57±24mL/100g/min)(p=0.83). Regional cerebral blood flow for pre-ketorolac infusion and post-ketorolac infusion were not significantly different((PRE mL/100g/min, POST mL/100g/min(p-value)): Frontal lobes(Left:66±15, 65±23(p=0.87),Right: 68 ±15, 66 ±25(p=0.62)),Temporal lobes(Left: 56±12, 54±22(p=0.82); Right: 56±14, 54±24(p=0.61)),Parietal lobes (Left:56±12, 57±25(p=0.95); Right: 59±16, 59±26(p=0.99)), Occipital lobes(Left: 51±15, 54±30(p=0.58); Right: 50±16, 54±32(p=.44))). DISCUSSION: Our findings suggest ketorolac does not alter microvascular perfusion in healthy adults, suggesting not all COX inhibitors act on cerebral vasculature equally. These data add to previous work by comprehensively interrogating the entire brain rather than flow (or velocity) through single arteries. CONCLUSION: There were no effect of ketorolac on global or regional cerebral blood flow in healthy adult. © FASEB.