Cerebral blood flow autoregulation in the rat.

Summary:We investigated the effect of angiotensin AT! and AT2 receptor blockade on the upper limit of CBF autoregulation in pentobarbital-anesthetized rats. CBF was measured by laser-Doppler flowmetry from the pari etal cortex and MABP was increased by intravenous phenylephrine infusion. Neither the AT! antagonist 10-sartan nor the AT2 ligand PD 123319 nor angiotensin II (ANG II) in the presence of losartan affected baseline CBF. When the blood pressure was increased in the con trol group, CBF remained fairly constant up to 145 mm Hg and increased steeply after 150 mm Hg. Both PD 123319 (7-10 mglkg) and losartan (1-10 mglkg) shifted the upper limit of CBF autoregulation toward higher presAngiotensin II (ANG II) is a key regulator of car diovascular function. On the basis of displacement with selective ligands, ANG II receptors have been classified in AT) and AT2 subtypes (Chiu et aI., 1989; Whitebread et aI., 1989 298sures. Intravenous infusion of PD 123319 was more ef fective than bolus injection. The losartan effect was dose dependent. Selective stimulation of AT 2 receptors with an intravenous ANG II infusion (0.54 J.Lg/min) in the pres ence of losartan did not reverse the effect of losartan on CBF autoregulation, but, on the contrary, appeared to further shift the upper limit of autoregulation toward higher pressures. The results implicate a role for both AT I and AT 2 angiotensin receptors in the regulation of CBF.

Section: Discussionsupporting

confidence: 89%

Nonpeptide Angiotensin AT₁ and AT₂ Receptor Ligands Modulate the Upper Limit of Cerebral Blood Flow Autoregulation in Rats

Strömberg

Näveri

Saavedra

1993

“…Hernandez et al (1978) demonstrated a total increase in CBF of 4.9 mll00 g-I min-I mm Hg Peo2 -\ over a range of 25-62 mm Hg.…”

Section: Discussionmentioning

confidence: 91%

Total Cerebral Ischemia: Effect of Alterations in Arterial PCO₂ on Cerebral Microcirculation

Koch

Jackson

Schmiedl

et al. 1984

Radiolabeled 15-μm microspheres were used to examine alterations in regional CBF and cerebrovascular resistance in response to changes in arterial PCO2. Flow measurements were obtained before and 1–3 and 24 h after 12 min of total cerebral ischemia. Striking sensitivity of blood flow in all areas of the central nervous system was shown to changes in arterial PCO2 between 24 and 50 mm Hg during the control nonischemic period. Following 12 min of total cerebral ischemia, cerebrovascular resistance increased, producing a decrease in regional blood flow when the important controlling variables for CBF were held constant. One to 3 h after total cerebral ischemia, the effect of variations in arterial PCO2 on cerebral blood flow was almost completely abolished. Within 24 h after total cerebral ischemia, the sensitivity of CBF to changes in PCO2 was almost completely restored, whereas the secondary severe neurologic deficit remained. Therapeutic interventions following global cerebral ischemia, designed to ameliorate the “no-reflow” phenomenon and minimize residual ischemic neurologic damage, must take into account this marked early postischemic reduction in sensitivity to normally potent cerebrovasodilatory influences.

“…The pressure flow relationships for the cerebral circulation have been weII defined, and the cerebral perfusion pres sure is 80 mm Hg in humans under normal condi tions. However, autoregulation keeps CBF rela tively constant when the BP is within the range of 60 to 150 mm Hg in the rat (Hernandez et al, 1978), similar to that of other species, including primates and humans (Harper, 1966). The hypotension to 40 mm Hg in our study is absolutely out of the range of autoregulation, and it is not surprising that infarc tion was 25 ± 14% and 40 ± 12% at MCAO dura tions of 60 and 120 min, respectively, compared to 5 ± 3% and 19 ± 15% with the same MCAO dura tion when the BP was 80 mm Hg, Although MCAO at BP >80 mm Hg was not feasible in this series of experiments, 60 min of MCAO produced only mild scattered ischemic cell change in a similar model using Wi star rats at normal BP (Nagasawa and Kogure, 1989).…”

Section: Discussionmentioning

confidence: 99%

Graded Hypotension and MCA Occlusion Duration: Effect in Transient Focal Ischemia

Zhu

Auer

1995

The first 2 h of middle cerebral artery occlu sion (MCAO) are likely critical in determining the final outcome in ischemic stroke. To study this early postisch emic period, male Wistar rats (n = 161) were subjected to right MCAO with closely spaced step variations in both duration of MCAO and blood pressure (BP), using the intraluminal suture technique. Quantitative neuropathol ogy was performed at 25 coronal planes of the brain after I-week survival. Atrophy was measured as the difference between the two hemispheres and was added to cortical and striatal necrosis to obtain total tissue loss. Damage consistently increased monotonically with increasing du ration of occlusion only when infarct size was expressed as percentage of the contralateral hemisphere, but not when expressed as mm 3 , because of variable tissue size. The results showed that already at 1 week, the quantity of tissue loss due to resorption and trans synaptic effects ap proached the quantity of geographically traceable necro sis in cortex and striatum. Minimum brain damage (5%) occurred after 60 min at a BP of 80 mm Hg, with almost no cortical necrosis. Damage was extremely sensitive to hypotension and MCAO duration. At a BP of 40 mm Hg, 60 min of MCAO produced 25% damage, accelerating every 20 min during the 2-h period studied. At BP 80 mm Hg, 120 min of MCAO produced the same damage as onlyThe histologic outcome of middle cerebral artery occlusion (MCAO) is critical in determining the fi nal neurologic deficit in acute ischemic stroke. With the advent of thrombolytic therapy and early treat ment within the first 2 h after stroke (Brott et al. , Received October 18, 1994; final revision received February 9, 1995; accepted March 3, 1995. Address correspondence and reprint requests to Dr. Roland N. Auer, Health Science Center, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4Nl.Abbreviations used: BP, blood pressure; CCA, common ca rotid artery; ECA, external carotid artery; rCA, internal carotid artery; MCAO, middle cerebral artery occlusion; rCBF, regional CBF; SHR, spontaneously hypertensive rats. 98080 min of MCAO at BP 60 mm Hg. At 60-, 80-, 100-, and l20-min duration of MCAO, infarct size was significantly reduced with increasing BP. Analysis of the independent contribution of BP and MCAO duration revealed that BP played a greater role in determining infarct size than did MCAO duration. Ipsilateral hippocampal damage was seen in CAl and, in some animals, CA3. Necrotic neu rons in hippocampus wer;e found in 21 animals, including four with bilateral hippocampal damage, largely but not exclusively distributed in the hypotensive groups. Con tralateral necrotizing damage was seen in cortex and hip pocampus as selective neuronal necrosis and as cortical infarction in two animals. Ipsilateral and contralateral hippocampal damage reproduced the pattern of selective vulnerability seen in global ischemia. The histologic pen umbra (rim of selective neuronal necrosis surrounding the infarct) increased over time at BP 8...