Comparison of hypercapnia‐ and acetazolamide‐induced cerebrovascular responses in piglets

Abstract

Acetazolamide (AZD) produces cerebral vasodilation. The underlying mechanism is unclear, but it is assumed to be largely due to CO2 retention and acidosis. We tested if cerebrovascular effects of AZD were similar to hypercapnia in the newborn pig. We simultaneously used the closed cranial window/intravital microscopy technique to determine pial arteriolar diameters and laser-Doppler flowmetry (LDF). Anesthetized (Na-thiopenthal+α-chloralose), ventilated, 1-day old instrumented piglets (n=26) were divided into 4 experimental groups: time control (n=8), indomethacin or ibuprofen treatments (1 or 30 mg/kg, iv, n=6-6, respectively), and global ischemia/reperfusion (I/R, 10 min induced by elevated intracranial pressure, n=6). Responses to 5–10 % inhaled CO2 were recorded before and after the treatments, and then to AZD (10–20 mg/kg, iv). Consistent with previous studies, hypercapnia produced dose-dependent pial arteriolar vasodilation and similar changes in LDF data that was abolished by indomethacin, unaltered by ibuprofen and significantly attenuated after I/R. AZD elicited similar pial vasodilation (33±7%, change from baseline, 10 mg/kg) and increase in the LDF signal (31±9%). AZD-induced vasodilation was also sensitive to indomethacin and I/R but was unaltered by ibuprofen. Thus, the mechanism of AZD-induced vasodilation appears to be similar to hypercapnia, and pial arteriolar diameter changes reflect changes in cortical perfusion. Supported by OTKA F 043101.