Total and regional cerebral blood flow during hypotension, hypertension, and hypocapnia. Effect of sympathetic denervation in dogs.

Mueller, Shirley M.; Heistad, Donald D.; Marcus, Melvin L.

doi:10.1161/01.res.41.3.350

Cited by 108 publications

(50 citation statements)

References 31 publications

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“…In 1977, a group studying the CBF response to hypotension in dogs unexpectedly observed a selective reduction of blood flow in their single white matter region of interest located in the centrum semiovale. 47 Five years later, a similar study revealed selective reduction of blood flow in 3 of 5 white matter regions assessed: a periventricular region, a deep white matter region, and a visual radiation region. 48 There is one study 26 that provides evidence of a steal phenomenon in the white matter of normal human subjects.…”

Section: Discussionmentioning

confidence: 85%

Selective Reduction of Blood Flow to White Matter During Hypercapnia Corresponds With Leukoaraiosis

Mandell

Han²,

Poublanc³

et al. 2008

Stroke

109

122

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Background and Purpose-Age-related white matter disease (leukoaraiosis) clusters in bands in the centrum semiovale, about the occipital and frontal horns of the lateral ventricles, in the corpus callosum, and internal capsule. Cerebrovascular anatomy suggests that some of these locations represent border zones between arterial supply territories. We hypothesized that there are zones of reduced cerebrovascular reserve (susceptible to selective reductions in blood flow, ie, steal phenomenon) in the white matter of young, healthy subjects, the physiological correlate of these anatomically defined border zones. Furthermore, we hypothesized that these zones spatially correspond with the regions where the elderly develop leukoaraiosis. Methods-Twenty-eight healthy volunteers underwent functional MR mapping of the cerebrovascular response to hypercapnia. We studied 18 subjects by blood oxygen level-dependent MRI and 10 subjects by arterial spin labeling MRI. We controlled both end-tidal pCO 2 and pO 2 . All functional data was registered in Montreal Neurological Institute space and generated composite blood oxygen level-dependent MR and arterial spin labeling MR maps of cerebrovascular reserve. We compared these maps with frequency maps of leukoaraiosis published previously. Results-Composite maps demonstrated significant (90% CI excluding the value zero) steal phenomenon in the white matter. This steal was induced by relatively small changes in end-tidal pCO 2 . It occurred precisely in those locations where elderly patients develop leukoaraiosis. Key Words: cerebrovascular accident Ⅲ cerebrovascular disorders Ⅲ magnetic resonance imaging S ince the advent of CT, physicians and researchers have noted the prevalence of abnormality in the white matter of elderly human brain. Characterized by patchy or diffuse low density on CT images, and corresponding hyperintensity on T2-weighted MRIs, this abnormality histopathologically represents rarefaction of myelin, loss of axons and oligodendrocytes, dilatation of perivascular spaces, and mild gliosis. 1 It is simply called white matter disease, or leukoaraiosis, 2 literally meaning diminution of white matter density. Leukoaraiosis clusters in several locations: cigar-shaped bands in the deep white matter of the centrum semiovale, 3,4 in the white matter about the occipital and frontal horns of the lateral ventricles, [3][4][5] in the genu and splenium of the corpus callosum, 3,5 and in the posterior limb of the internal capsule. 4 Prevalence increases with age with some degree of leukoaraiosis in more than half of those older than 60 years of age. 6 It was initially considered a benign age-related change, but more recent studies suggest it may be associated with cognitive dysfunction 7 and the development of dementia. 8 Despite growing appreciation of its clinical significance, the pathogenesis of leukoaraiosis is poorly understood. 9 Evidence suggests an ischemic process, 10 but what causes the ischemia? Conclusions-ThisOne theory is based on a concept of "internal border zon...

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Section: Discussionmentioning

confidence: 85%

Selective Reduction of Blood Flow to White Matter During Hypercapnia Corresponds With Leukoaraiosis

Mandell

Han²,

Poublanc³

et al. 2008

Stroke

109

122

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“…In previous studies we have demonstrated regional differences in the response to decreases in cerebral perfusion pressure in normotensive dogs 10 and rabbits. 11 We found that hypotension redistributes CBF, so that blood flow to brainstem is maintained better than flow to cerebrum or cerebellum.…”

mentioning

confidence: 83%

Regional cerebral blood flow during hypotension in normotensive and stroke-prone spontaneously hypertensive rats: effect of sympathetic denervation.

Sadoshima¹,

Heistad²

1983

Stroke

Self Cite

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SUMMARY This study was performed to determine whether, in hypertensive and normotensive rats, chronic sympathetic denervation impairs cerebral vasodilator responses during hypotension, and to determine whether there are regional differences in the autoregulatory response of brain vessels during hypotension. The superior cervical ganglion was removed on one side in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive (WKY) rats. Cerebral blood flow (CBF) was measured with microspheres when the rats were 5-6 months old. Chronic sympathetic denervation had little or no effect on cerebral vasodilator responses during acute hypotension in SHRSP and WKY. We suggest that the increase in incidence of ischemic infarction that we have observed previously after chronic sympathetic denervation in SHRSP probably is not the result of ischemia during episodes of hypotension. We also observed major regional differences in the response of cerebral vessels during acute hypotension in SHRSP: blood flow to brainstem was preserved better than flow to cerebrum and cerebellum. Thus the "lower limit" of the autoregulatory plateau differs in various regions of the brain in SHRSP.Stroke Vol 14, No 4, 1983 SYMPATHETIC DENERVATION in young strokeprone spontaneously hypertensive rats (SHRSP) impairs development of cerebral vascular hypertrophy 1,2 and increases the incidence of cerebral hemorrhage and ischemic infarction.2 Chronic sympathetic denervation also impairs the cerebral vasoconstrictor response to increases in arterial pressure.3 It seems likely that impairment of the cerebral vasoconstrictor response during increases in pressure may be an important mechanism by which sympathetic denervation results in cerebral hemorrhage in SHRSP.Hemodynamic mechanisms by which sympathetic denervation leads to ischemic infarction in SHRSP are not clear. One possibility is that sympathetic denervation impairs autoregulatory cerebral vasodilatation during hypotension and thereby leads to ischemia. In the rabbit ear artery, vessels are less distensible after chronic sympathetic denervation. 4 In SHRSP, cerebral vasodilator responses to seizures are not increased after sympathetic denervation 3 despite a reduction in wall/lumen ratio. This finding suggests that sympathetic denervation may decrease the compliance of cerebral vessels and impair dilator responses. Thus, the first goal of this study was to determine whether chronic sympathetic denervation impairs cerebral vasodilator responses during hypotension, and thus might be a mechanism by which sympathetic denervation leads to ischemic infarction in SHRSP.The pressure-flow relationship of cerebral vessels is shifted to the right in chronic hypertension. Received October 1, 1982; revision accepted January 17, 1983.the "lower limit" of autoregulation is increased in chronic hypertension, so that reduction in pressure to levels that do not decrease cerebral blood flow (CBF) in normotensive patients results in decreases in CBF in hypertensives. Because total CBF was measured in pre...

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“…At present, the myogenic vasomotor mechanism is used primarily to explain the presence of autoregulation of CBF, which aims to protect the brain from high volume and pressure (Faraci et al, 1989;Harper et al, 1984;Mellander, 1989;Mueller et al, 1977). Much less is known regarding the role of flowdependent regulation of CBF, although in vivo during changes in pressure, flow changes, as well.…”

Section: Flow-induced Constriction Of Isolated Cerebral Arteries and mentioning

confidence: 99%

Isolated Human and Rat Cerebral Arteries Constrict to Increases in Flow: Role of 20-HETE and TP Receptors

Tóth

Rozsa

Springó

et al. 2011

J Cereb Blood Flow Metab

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Elevation of intraluminal pressure increases vasomotor tone, which thought to have a substantial role in regulation of cerebral blood flow (CBF). Interestingly, responses of cerebral vessels to increases in flow varied and have not been studied in human cerebral arteries. We hypothesized that increases in flow elicit constrictions of isolated human and rat cerebral arteries and aimed to elucidate the underlying mechanisms. Human cerebral arteries and rat middle cerebral arteries constricted to increases in flow (P < 0.05). Simultaneous increase in intraluminal flow + pressure further reduced the diameter compared with pressure-induced changes (P < 0.05), leading to constant estimated CBF. Flow-induced constrictions were abolished by HET0016 (inhibitor of synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) or inhibition of COXs or blocking TP (thromboxane A 2 /prostaglandin H 2 , receptors and attenuated by scavenging reactive oxygen species (ROS). Flow-enhanced ROS formation was significantly reduced by HET0016. In conclusion, in human and rat cerebral arteries (1) increases in flow elicit constrictions, (2) signaling mechanism of flow-induced constriction of cerebral arteries involves enhanced production of ROS, COX activity, and mediated by 20-HETE via TP receptors, and (3) we propose that simultaneous operation of pressure-and flow-induced constrictions is necessary to provide an effective autoregulation of CBF.

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Total and regional cerebral blood flow during hypotension, hypertension, and hypocapnia. Effect of sympathetic denervation in dogs.

Cited by 108 publications

References 31 publications

Selective Reduction of Blood Flow to White Matter During Hypercapnia Corresponds With Leukoaraiosis

Selective Reduction of Blood Flow to White Matter During Hypercapnia Corresponds With Leukoaraiosis

Regional cerebral blood flow during hypotension in normotensive and stroke-prone spontaneously hypertensive rats: effect of sympathetic denervation.

Isolated Human and Rat Cerebral Arteries Constrict to Increases in Flow: Role of 20-HETE and TP Receptors

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