The effects of HA1077, a novel protein kinase inhibitor, on reductions of cerebral blood flow and glucose metabolism following acute and/or chronic bilateral carotid artery ligation in Wistar rats.

The effects of HA1077, a novel protein kinase inhibitor on local cerebral blood flow (LCBF) 2.5 h (acute) after permanent bilateral carotid artery ligation (BCAL) and on LCBF and local cerebral glucose utilisation (LCGU) one week (chronic) after BCAL were studied in conscious Wistar rats. Use was made of quantitative autoradiographic 14C-iodoantipyrine and the 14C-2-deoxyglucose techniques and 24 anatomically discrete regions of the brain. HA1077 (1 or 3 mg/kg) or saline was infused i.v. over a 30 min period. HA1077 significantly increased LCBF after acute BCAL in one of the 23 decreased regions in rats given 1 mg/kg, and in 14 of 23 decreased regions in rats given 3 mg/kg, compared to findings in the saline-treated group. Significant increases in LCBF and LCGU after chronic BCAL were noted in seven of the 13 decreased regions and in four of the 11 decreased regions in rats given 3 mg/kg, as compared to observations in the corresponding saline-treated group, respectively. The LCBF and LCGU reductions in forebrain regions with global ischaemia after acute and/or chronic BCAL were overcome by HA1077. These results suggest that HA1077 may be considered for treatment of subjects with acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism.