Effects of induced hypertension on cerebral blood flow, energy metabolism and specific gravity during and after transient forebrain ischemia in gerbils

Abstract

After an insult of cerebral ischemia, acute increases in arterial blood pressure (ABP) may cause increases in blood-brain barrier permeability and formation of cerebral edema. However, it has been reported that a short duration of induced hypertension can increase cerebral blood flow (CBF) and decrease the formation of cerebral edema. We evaluated the effects of phenylephrine-inducod hypertension for 15 min and 60 min, respectively, on the CBF, brain energy metabolism and specific gravity (SG) of the brain parenchyma, following after transient forebraln ischemia in gerbils. Materials and Methods: Fifty-two adult male Mongolian gerbils weighing 60-90 g were anesthetized with intraperitoneal injections of pentobarbital (40 mg/kg). Bilateral common carotid arteries were temporarily occluded by aneurysm clips for 60 rain. After occlusions of bilateral common carotid artery (CCAO), gerbils were assigned randomly for one of the following treatment groups which was implemented for 60 rain, 30 min after reperfusion: 15/HT group (n=14), ABP was manipulated during fast 15 rain; increased by 25 mm Hg with phenylephfine infusion (10 I,tg/kg/min), followed by 45 min duration of normotension with saline infusion; 60/HT group (n=14), ABP was increased by 25 mm Hg for 60 min with phenylephrine infusion; N group (n=14), ABP was not manipulated after reperfusion, kept to be normotensive with saline infusion; C group (n=10), ABP was not manipulated after reperfusion without infusions of either phenylephrine or saline. We measured sequential changes in phosphoereatine (PCr)/inorganic phosphate (Pi) ratio, ~-ATP/Pi ratio, and intracellular pH (pHi) after reperfusion by 31p-NMR spectroscopy (6.34Tesla JEOL GSX-270 spectrometer). Measurements were done before CCAO, and 30-, 120-, 150-, 180-, 240-min after reperfusion. CBF was measured continuously at the dorsal cortex by a laser-Doppler flowmcter (Periflux Pf2, Perimed) prior to CCAO, during ischemia, and for 120 rain after reperfusion. Brain parenchymal SG was determined by a microgravimetry 120 min after reperfusion. Samples were taken from the lateral and dorsal cortex in the ischemic territory. Results and Summary: CBF increased significantly (p<0.05) in the 15/HTand 60/HT-groups accompanied with elevations of ABP (p<0.05) as compared with N group. While, in the 60/I-IT group, CBF began to decrease from 30 min during induced hypertension. The ratios of PCr/Pi and ~-ATP/Pi recovered significantly in the 15/HT group as compared with N group 180and 240-min after reperfusion (p<0.01). On the other hand, the 60AIT group did not show good recovery of the brain energy metabolism as compared with N group. In the 60/HT group, pHi decteasod significantly 120 min after reperfusion as compared with those in the 15/HTand N-groups (p<0.05 and p<0.01, respectively). The SG was not different between the 15/HTand N-groups. In the 60/HT group, the SG was less than that in N group (p<0.05). In summary, we evaluated the effects of phenylephrinc-induced hypertension for 15 min and 60 min, respectively, on the CBE brain energy metabolism and SG of the brain parenchyma, following after transient forebraln ischcmia. The results suggest that a short duration of induced hyper~nsion (15 rain) might be beneficial for the recovery of the brain energy metabolism accompanying with increases in CBE without increases of the formation of brain edema. A longer duration of induced hypertension (60 min), on the other hand, might not be beneficial for the recovery of the brain energy metabolism accompanying with increases of the formation of brain edema.