Cerebral Blood Flow in Rats with Renal and Spontaneous Hypertension: Resetting of the Lower Limit of Autoregulation

Barry, David I.; Strandgaard, Svend; Graham, David I.; Brændstrup, Otto; Svendsen, U. G.; Vorstrup, Sissel; Hemmingsen, Ralf; Bolwig, Tom G.

doi:10.1038/jcbfm.1982.35

Cited by 108 publications

(47 citation statements)

References 19 publications

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“…to those described in SHR (Barry et al, 1982). Nonetheless, and as discussed above, the intrinsic susceptibility of SHR to stroke independently from arterial hypertension may explain the exaggerated hypoperfusion seen at 240 minutes after occlusion in SHR relative to RH-WKY.…”

Section: Discussionmentioning

confidence: 82%

Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Letourneur

Roussel

Toutain

et al. 2010

J Cereb Blood Flow Metab

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Although chronic arterial hypertension (CAH) increases the risk of stroke and the severity of the resultant lesion, it is rarely integrated in preclinical studies. Here, we analyzed the impact of CAH on the acute spatiotemporal evolution of the ischemic penumbra as defined by the perfusion-weighted imaging/diffusion-weighted imaging mismatch. Sequential 7T-MRI examinations were performed from 30 minutes up to 4 hours after permanent cerebral ischemia in genetically hypertensive rats (spontaneously hypertensive rats, SHR), renovascular-hypertensive rats (RH-WKY), and their normotensive controls (Wistar-Kyoto rats, WKY). The apparent diffusion coefficient (ADC)-defined lesion was larger in hypertensive rats than in normotensive animals as early as 30 minutes after the ischemia. The ischemic penumbra was smaller in both genetically and renovascular-hypertensive rats (at 30 minutes; SHR = 66 ± 25 mm 3 , RH-WKY = 55 ± 17 mm 3 versus WKY = 117 ± 14 mm 3 ; P < 0.008) and there was no significant difference between the perfusion deficit and ADC lesion (mismatch definition of penumbra) as early as 90 minutes after the occlusion. Genetic hypertension and induced renovascular hypertension resulted in larger lesion and smaller penumbra that vanished rapidly. These data support the need to integrate CAH in preclinical studies relative to the treatment of stroke, as failure to do so may lead to preclinical results nonpredictive of clinical trials, which include hypertensive patients.

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Section: Discussionmentioning

confidence: 82%

Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Letourneur

Roussel

Toutain

et al. 2010

J Cereb Blood Flow Metab

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“…Once blood pressure stabilizes, the vessels may undergo morphological and/or functional changes corresponding to a new set point of cerebral blood flow autoregulation. 21,22 This allows them to function normally in the phase of chronic stable hypertension. The fact that strokes were less common during stable hypertension suggests that the modified vasculature provides at least partial protection from catastrophic infarcts and hemorrhages.…”

Section: Discussionmentioning

confidence: 99%

Serial Magnetic Resonance Imaging of Rat Brain After Induction of Renal Hypertension

Bigio

Yan²,

Kozłowski³

et al. 1999

Stroke

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Background and Purpose-Hypertension is a major risk factor for ischemic and hemorrhagic stroke and may also cause more chronic and subtle brain injury. Progressive brain changes in a rat model of renal hypertension have been assessed to better understand the pathogenesis of hypertensive brain damage. Methods-Young adult rats were made hypertensive by partial occlusion of both renal arteries. MR images of brain were obtained weekly, and histopathological outcome was assessed. A separate group of rats was used to measure brain specific gravity and Evans blue dye content as an indicator of extravasation. Results-Rats developed maximal mean systolic blood pressures of 173 to Ͼ300 mm Hg, reaching a plateau in 6 to 8 weeks. Rats whose mean systolic pressure never exceeded 210 mm Hg never had brain lesions, while rats whose mean systolic pressure exceeded 276 mm Hg consistently developed brain lesions. Brain T2 values increased with increasing blood pressure. Lesions seen on MRI corresponded to those seen histologically. MRI also demonstrated transient brain expansion, probably due to diffusely increased water content, and rarely demonstrated focal cortical edema, which had no histological correlate. These transient phenomena, as well as hemorrhagic and ischemic infarcts, occurred mainly during the phase of climbing blood pressure and early stages of stable hypertension. Conclusions-Serial MRI reveals aspects of hypertensive brain disease that cannot be studied by histological examination alone.The observed phenomena are likely related to loss of autoregulation and/or blood-brain barrier integrity. Breach of blood vessel integrity is less likely once the vessels become accustomed to high pressures. (Stroke. 1999;30:2440-2447.)

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“…In chronic hypertension, the limits of autoregulation to SAP changes are shifted to higher SAP levels in humans (Strandgaard et al, 1973) and in animals (Barry et al, 1982). For the SHR, the lower limit was reported to lie between 70 and 95 mm Hg (Fu jishima and Omae, 1976;Barry et al, 1981;Fuji shima et al, 1983), whereas the upper limit is -180 mm Hg (Waldemar et al, 1987).…”

Section: Sap/rcbf Relationships In Normal Cortical Brain Tissuementioning

confidence: 99%

Autoregulation of Cerebral Blood Flow in Experimental Focal Brain Ischemia

Dirnagl

Pulsinelli

1990

J Cereb Blood Flow Metab

166

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Summary:The relationship between systemic arterial pressure (SAP) and neocortical microcirculatory blood flow (CBF) in areas of focal cerebral ischemia was stud ied in 15 spontaneously hypertensive rats (SHRs) anes thetized with halothane (0.5%). Ischemia was induced by ipsilateral middle cerebral artery/common carotid artery occlusion and CBF was monitored continuously in the ischemic territory using laser-Doppler flow me try during manipulation of SAP with I-norepinephrine (hyperten sion) or nitroprusside (hypotension). In eight SHRs not subjected to focal ischemia, we demonstrated that 0.5% halothane and the surgical manipUlations did not impair autoregulation. Autoregulation was partly preserved in ischemic brain tissue with a CBF of > 30% of preocclu sion values. In areas where ischemic CBF was <30% of It is controversial whether increasing systemic arterial pressure (SAP) can improve the neurologi cal outcome after acute stroke (Olsen, 1982;Yatsu, 1982;Grotta, 1987; Meyer et aI., 1987). Studies in experimental animals have shown that raising SAP to hypertensive levels after induction of cerebral ischemia can lessen brain damage (Safar et aI., 1976; Hayashi et aI., 1984; Aspey et aI., 1987; Drummond et aI., 1988). Clinical data showing im proved neurological outcome associated with hy pertension after stroke are anecdotal (Farhat and Schneider, 1967 327 preocclusion values, autoregulation was completely lost. Changes in SAP had a greater influence on CBF in tissue areas where CBF ranged from 15 to 30% of baseline (9% change in CBF with each 10% change in SAP) than in areas where CBF was <15% of baseline (6% change in CBF with each 10% change in SAP). These findings dem onstrate that the relationship between CBF and SAP in areas of focal ischemia is highly dependent on the sever ity of ischemia. Autoregulation is lost in a gradual manner until CBF falls below 30% of normal. In areas without autoregulation, the slope of the CBF/SAP relationship is inversely related to the degree of ischemia. Key Words: Arterial blood pressure-Cerebral blood flow autoregula tion-Experimental focal cerebral ischemia. Van Dellen and Buchanan, 1977). PomerantzOn the other hand, there is experimental (Fenske et aI., 1975; Spatz et aI., 1976;Michenfelder and Milde, 1977; Bleyaert et aI., 1980; Kogure et aI., 1981) and clinical (Gottstein and Seel, 1977) evi dence for a worsening of outcome from increasing SAP above normal levels after cerebral ischemia. The enhanced formation of cerebral edema, intra cranial hypertension, cerebral hemorrhage, pulmo nary edema, and cardiac failure by arterial hyper tension might all contribute to this worsening. The potential benefit of increasing SAP during cerebral ischemia is based on the assumption that this measure will increase CBF in tissue where au toregulation has been lost (Meyer et aI., 1973a, b). Though it is generally accepted that autoregulation is lost in ischemic brain, little is known about the quantitative relationships among SAP, CBF auto regulation, and level of ischemia. Th...

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Cerebral Blood Flow in Rats with Renal and Spontaneous Hypertension: Resetting of the Lower Limit of Autoregulation

Cited by 108 publications

References 19 publications

Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Impact of Genetic and Renovascular Chronic Arterial Hypertension on the Acute Spatiotemporal Evolution of the Ischemic Penumbra: A Sequential Study with MRI in the Rat

Serial Magnetic Resonance Imaging of Rat Brain After Induction of Renal Hypertension

Autoregulation of Cerebral Blood Flow in Experimental Focal Brain Ischemia

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