Regional variability in the CBF response to mild hypotension correlates with heterogeneous CBF after focal cerebral ischemia

Abstract

Regional variability in cerebral blood flow (CBF) during mild hypotension has been demonstrated (Kharlamov et al, Neurosci Lett 368: 151–156, 2004). We hypothesize that regional changes in CBF in response to hypotension can predict the CBF changes in the same brain after focal ischemia. Male Sprague/Dawley rats (n=4) were intubated and mechanically ventilated (0.5–1.5% isoflurane, 70% N2O balance O2). An 8-mm diameter closed cranial window was placed between bregma and lambda. Focal ischemia was produced by transection of the left MCA and bilateral common carotid artery occlusion (MCAT). Laser speckle flowmetry (LSF) allowed simultaneous measurement of CBF in different cortical regions. CBF was measured in at least 70 separate regions of interest (ROI, 310 microns diameter): a) before blood withdrawal at a mean arterial pressure (MAP) of 100 mmHg, CBF1; b) during hemorrhagic hypotension, MAP 70 mmHg, CBF2; c) after blood re-infusion and before MCAT at MAP 100 mmHg, CBF3; d) after MCAT at MAP 100 mmHg, CBF4. In each ROI, the response to hypotension and MCAT were expressed as %CBF70 [100*(CBF2/CBF1)] and %CBFMCAT [100*(CBF4/CBF3)], respectively. Using these percentages, ROIs were divided into three types (LF, NF, and HF) with the boundaries of 85% and 120%, and 45% and 120%, respectively. For each ROI, we analyzed changes in the CBF response from hypotension to MCAT between the categories LF, NF, and HF as presented in the Table. Analysis of CBF in individual animals demonstrated that in rats 1 and 2 (see Table 1) the total % of ROIs with the same level of response were 55 and 57%, respectively. In most of those ROIs the flow after ischemia remained in the NF category (53%). In another two rats the hypotension LF ROIs remained as LF after MCAT (61% and 42%). At 2 h after MCAT 5915% (n=4, mean STD) of ROIs remained in the same category as during mild hypotension, and 2515% (n=4, mean STD) reduced from NF ROIs during hypotension to LF after MCAT. ROIs with HF during hypotension either stayed in the same category or reduced to NF after MCAT, but never became LF. Therefore, regional changes of CBF during mild hypotension were predictive of the flow changes in the ischemic brain. Table 1