Background: We performed experiments to test whether isoflurane pretreatment produces vascular effects, especially at the levels of arterioles and capillaries affecting regional cerebral blood flow (rCBF), O2 supply and consumption, or capillary permeability in focal cerebral ischemia. Because inducible nitric oxide synthase (iNOS) was implicated as one of the mechanisms of isoflurane preconditioning, the effect of iNOS inhibition on rCBF was also studied. Methods: Twenty-four hours before middle cerebral artery (MCA) occlusion, rats were pretreated with 2% isoflurane for 30 minutes using an endotracheal tube and mechanical ventilation for the isoflurane preconditioned (IsoPC) group. For the group of iNOS inhibition, aminoguanidine 200 mg/kg was injected IP 30 minutes before isoflurane pretreatment. One hour after MCA occlusion, rCBF was measured using 14C-iodoantipyrine autoradiography. Alternate slices of the tissue were used to determine arteriolar and venular O2 saturation using cryo microspectrophotometry. Capillary permeability was determined by measuring the transfer coefficient (Ki) of 14C-α-aminoisobutyric acid. Additional measurements of rCBF were performed at 3 hours after MCA occlusion. Results: MCA occlusion decreased rCBF and O2 consumption and increased Ki in both the control and the IsoPC groups at 1 hour after MCA occlusion. In the ischemic cortex (IC), the rCBF and O2 consumption were significantly greater in the IsoPC group than in the control group (+40% and +41%, respectively), but they were similar in the contralateral cortex between the 2 groups. There was no difference in Ki between the groups in the IC or in the contralateral cortex. The increase of rCBF in the IC (+50%) was sustained in the IsoPC group at 3 hours after MCA occlusion. With iNOS inhibition, the increase of rCBF in the IC with isoflurane pretreatment became insignificant. Conclusions: Our data demonstrate that isoflurane pretreatment improved rCBF and increased the regional O2 supply and consumption in the focal ischemic area but did not affect capillary permeability during the early stage of focal cerebral ischemia. The isoflurane-induced increase in rCBF in the ischemic area became insignificant with inhibition of iNOS.
All Science Journal Classification (ASJC) codes
- Anesthesiology and Pain Medicine