Magnetic resonance imaging quantification of regional cerebral blood flow and cerebrovascular reactivity to carbon dioxide in normotensive and hypertensive rats

Abstract

Hypertension afflicts 25% of the general population and over 50% of the elderly. In the present work, arterial spin labeling MRI was used to non-invasively quantify regional cerebral blood flow (CBF), cerebrovascular resistance and CO(2) reactivity in spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY), at two different ages (3 months and 10 months) and under the effects of two anesthetics, α-chloralose and 2% isoflurane (1.5 MAC). Repeated CBF measurements were highly consistent, differing by less than 10% and 18% within and across animals, respectively. Under α-chloralose, whole brain CBF at normocapnia did not differ between groups (young WKY: 61 ± 3ml/100g/min; adult WKY: 62 ± 4ml/100g/min; young SHR: 70 ± 9ml/100g/min; adult SHR: 69 ± 8ml/100g/min), indicating normal cerebral autoregulation in SHR. At hypercapnia, CBF values increased significantly, and a linear relationship between CBF and PaCO(2) levels was observed. In contrast, 2% isoflurane impaired cerebral autoregulation. Whole brain CBF in SHR was significantly higher than in WKY rats at normocapnia (young SHR: 139 ± 25ml/100g/min; adult SHR: 104 ± 23ml/100g/min; young WKY: 55± 9ml/100g/min; adult WKY: 71 ± 19ml/100g/min). CBF values increased significantly with increasing CO(2); however, there was a clear saturation of CBF at PaCO(2) levels greater than 70mmHg in both young and adult rats, regardless of absolute CBF values, suggesting that isoflurane interferes with the vasodilatory mechanisms of CO(2). This behavior was observed for both cortical and subcortical structures. Under either anesthetic, CO(2) reactivity values in adult SHR were decreased, confirming that hypertension, when combined with age, increases cerebrovascular resistance and reduces cerebrovascular compliance.

Figure 1

(a) Coronal EPI images of a spontaneously hypertensive rat under isoflurane. Five adjacent 2 mm thick slices are shown from posterior (left) to anterior (right). Overlaid on the EPI images are three regions of interest: cortex (blue), caudate putamen (red), and thalamus (green). (b) Corresponding cerebral blood flow (CBF) images acquired under normocapnia show equal sensitivity to perfusion on both cerebral hemispheres, good gray versus white matter contrast, and heterogeneous distribution of CBF across the brain. Grayscale bar expresses the CBF values in ml/100g/min.

Figure 2

Relationship between whole brain cerebral blood flow (CBF) and PaCO₂ measured in normotensive (Wistar Kyoto – WKY) and spontaneously hypertensive (SHR) rats under (a) α-chloralose and (b) isoflurane. While a linear increase in CBF with PaCO₂ levels is obtained under α-chloralose, there is a clear CBF saturation at PaCO₂ levels greater than 70mmHg under isoflurane (polynomial fit).

Figure 3

Mean CBF (a–b) and CVR (c–d) for normotensive (WKY) and hypertensive (SHR) rats at normocapnia, under α-chloralose and isoflurane. (^* compared to young WKY; ^ŧ compared to adult WKY; P < 0.05).

Figure 4

Mean CO₂ reactivity for normotensive (WKY) and hypertensive (SHR) rats, under (a) α-chloralose and (b) isoflurane. (^* compared to young WKY; ^ŧ compared to adult WKY; ^† compared to young SHR; ^§ compared to cortex region of the same rat group; P < 0.05).