Hypotension as a complication of hypoglycemia leads to enhanced energy failure but no increase in neuronal necrosis

The hypothesis that arterial hypotension aggravates hypoglycemic brain damage was tested. Thirty minutes of insulin induced hypoglycemia with a flat EEG ("isoelectricity") was compared in seven series of rats. In three series of animals, the energy state of the cerebral cortex was determined at blood pressures of 140, 100 and 80 mm Hg respectively. Hypotension during hypoglycemia exacerbated cortical energy failure. In the fourth to sixth series, blood pressure was adjusted during isoelectricity to 160, 100 and 60 mm Hg, respectively. A seventh series had induced hypotension to 60 mm Hg only in the recovery period. Quantitation of neuronal death was performed in the fourth to seventh series of rats by direct visual counting of acidophilic neurons in sub-serially sectioned brains after one week survival. Although the first three series demonstrated enhanced deterioration of the cerebral energy state with lower blood pressures during hypoglycemia, the fourth to seventh series showed no augmentation of quantitated hypoglycemic neuronal necrosis. The distinct distribution of hypoglycemic brain damage, suggesting a fluid-borne toxin, was present at normal and reduced blood pressures, with no tendency toward an ischemic pattern of pathology. In spite of previously demonstrated reductions of cerebral blood flow to ischemic levels in regions with pronounced loss of autoregulation, no regional exacerbation of neuronal necrosis was seen in these brain areas. It is concluded that hypoglycemic brain damage is distinct from ischemic brain damage, and that the two insults are not additive. Furthermore, moderate hypotension to 60 mm Hg does not aggravate the damage in spite of an enhanced energy failure.     

Regional cerebral blood flow autoregulation in normotensive and spontaneously hypertensive rats--effects of sympathetic denervation

The present study was designed to investigate the effect of acute sympathetic denervation on the regional cerebral blood flow (CBF) autoregulation during acute elevation of blood pressure in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). CBF to the parietal cortex and thalamus was measured by the hydrogen clearance method and, to test autoregulation, systemic arterial blood pressure was elevated by intravenous infusion of phenylephrine. Superior cervical ganglia were removed on both sides to interrupt sympathetic innervation in the deeper structures of the brain. Acute bilateral sympathetic denervation did not alter the resting blood pressure or CBF in either SHR or WKY. In innervated SHR, resting mean arterial pressure (MAP) was 165 +/- 5 mm Hg (mean +/- SEM) and the upper limit of autoregulation in the cortex was 210 +/- 3 mm Hg, which was significantly lower than that in the thalamus (229 +/- 3 mm Hg, p less than 0.02). In bilaterally denervated SHR, the upper limits were lowered to 193 +/- 4 mm Hg in the cortex (p less than 0.02 vs. innervated SHR) and to 207 +/- 5 mm Hg in the thalamus (p less than 0.02 vs. innervated). In WKY, resting MAP was approximately 55 mm Hg lower than that in SHR. Acute denervation reduced the upper limits from 142 +/- 3 mm Hg to 130 +/- 4 in the cortex (p less than 0.05) and from 158 +/- 4 to 145 +/- 4 in the thalamus (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endorphinergic mechanisms in cerebral blood flow autoregulation

The influence of naturally occurring opioid peptides (Met-enkephalin (Met-Enk), dynorphin (DYN), β-endorphin (β-EP)) as well as morphine and the opiate antagonist naloxone and specific antisera on cerebral blood flow autoregulation was studied in anesthetized, artificially ventillated rats. Local hypothalamic blood flow (CBF, H₂-gas clearance technique) and total cerebral blood volume (CBV, photoelectric method) were simultaneously recorded. Autoregulation was tested by determining CBF and CBV during consecutive stepwise lowering of the systemic mean arterial pressure to 80, 60 and 40 mm Hg, by hemorrhage. Resting CBF decreased following Met-Enk, DYN, β-EP or morphine administration without simultaneous changes in CBV. Naloxone administration, on the contrary, increased CBV without affecting local CBF. Autoregulation of cerebral blood flow was maintained until 80 mm Hg, but not completely at 60 and 40 mm Hg arterial pressure in the control group. General opiate receptor blockade by 1 mg/kg s.c. naloxone abolished autoregulation at all levels, since CBF and CBV passively followed the arterial pressure changes. Intracerebroventricularly injected naloxone (1 μg/kg) as well as a specific antiserum against β-EP, but not against Met-Enk or DYN, resulted in the very same effect as peripherally injected naloxone. The present findings suggest that central, periventricular β-endorphinergic mechanisms might play a major role in CBF autoregulation.     

Auditory nerve-brain stem evoked potentials in cats during manipulation of the cerebral perfusion pressure

In order to study the effects of various degrees of cerebral ischemia on the auditory nerve-brain stem evoked potentials (BAEP), the cerebral perfusion pressure (CPP), defined as the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP), was systemically manipulated in anesthetized, paralyzed and ventilated cats. The CPP was varied by decreasing MAP, either by hemorrhage or by the infusion of a vasodilating drug, and elevating ICP by infusion of mock CSF into the cisterna magna, or by MAP depression and ICP elevation simultaneously. Even though the lower limit of adequate CPP is considered to be 40 mm Hg, the EEG became isoelectric at an average CPP of 24 mm Hg and the BAEP became isoelectric at an average CPP of 7 mm Hg. These extremely low CPP values of 7-24 mm Hg are far below the range of autoregulation of cerebral blood flow (CBF) so that the brain stem auditory pathway is still capable of generating its electrical response (BAEP) at very low CBF. This is paradoxical since these same regions of the brain have been shown to have the highest levels or regional metabolism as shown by their very high local cerebral blood flow and local glucose utilization.     

Chronic antihypertensive treatment in the rat reverses hypertension-induced changes in cerebral blood flow autoregulation

Cerebral blood flow (CBF) autoregulation was studied in renal hypertensive rats receiving chronic antihypertensive treatment. Young Wistar Kyoto rats (WKY) were made hypertensive by the Loomis procedure i.e. partial infarction of one kidney with contralateral nephrectomy. Systolic tail blood pressure was measured at 2-week intervals throughout the study. After two months, by which time the rats had been severely hypertensive for 5-6 weeks, antihypertensive treatment was begun; reserpine, dihydralazine and hydrochlorothiazide were administered in the drinking water. Blood pressure fell rapidly to normotensive levels and remained so. Following two months of antihypertensive treatment, the lower blood pressure limit of CBF autoregulation was studied during controlled bleeding. In age-matched untreated renal hypertensive WKY, the lower limit of autoregulation was in the mean arterial pressure range 90-109 mm Hg, as compared to 50-69 mm Hg in age-matched normotensive WKY. In contradistinction to the untreated rats, the treated rats had a normal lower limit of autoregulation, i.e. 50-69 mm Hg. It was inferred that the reversal of the functional change in CBF autoregulation reflected reversal of hypertension-induced cerebrovascular hypertrophy/hyperplasia.     

Effects of dopamine on cortical blood flow and somatosensory evoked potentials in the acute stages of cerebral ischemia

Effects of intravenous infusion of dopamine on local cortical blood flow (CBF) and somatosensory evoked potentials (SEP) was evaluated using canine cerebral ischemia, which was produced by middle cerebral artery occlusion. CBF was monitored with a H2 clearance method and SEP. P1 to N1 peak to peak amplitude (V1) was recorded by stimulating the sciatic nerve on the contralateral side. CBF and SEP recovered at doses of 5 and 10 gamma, despite almost no increase of systemic arterial pressure. CBF and SEP were restored at doses of dopamine of 20 and 30 gamma, with an increase of mean systemic arterial pressure 5 to 15 mm Hg and similar results were obtained at doses of 25 gamma. Recovery of SEP was slight at extremely high doses of dopamine (65 gamma), despite a definite increase of mean systemic arterial pressure (MSAP) and CBF.     

Laser speckle flowmetry for the study of cerebrovascular physiology in normal and ischemic mouse cortex.

Laser speckle flowmetry (LSF) is useful to assess noninvasively two-dimensional cerebral blood flow (CBF) with high temporal and spatial resolution. The authors show that LSF can image the spatiotemporal dynamics of CBF changes in mice through an intact skull. When measured by LSF, peak CBF increases during whisker stimulation closely correlated with simultaneous laser-Doppler flowmetry (LDF) measurements, and were greater within the branches of the middle cerebral artery supplying barrel cortex than within barrel cortex capillary bed itself. When LSF was used to study the response to inhaled CO2 (5%), the flow increase was similar to the response reported using LDF. For the upper and lower limits of autoregulation, mean arterial pressure values were 110 and 40 mm Hg, respectively. They also show a linear relationship between absolute resting CBF, as determined by [C]iodoamphetamine technique, and 1/tau(c) values obtained using LSF, and used 1/tau(c) values to compare resting CBF between different animals. Finally, the authors studied CBF changes after distal middle cerebral artery ligation, and developed a model to investigate the spatial distribution and hemodynamics of moderate to severely ischemic cortex. In summary, LSF has distinct advantages over LDF for CBF monitoring because of high spatial resolution.     

Cerebrovascular effects of prostaglandin inhibitors in the gerbil

Autoregulation of cerebral blood flow (CBF) to mean arterial blood pressure (MABP) of 40-50 mm Hg has been demonstrated in the spontaneously breathing gerbil anaesthetised with barbiturate (60 mg/kg). CO2 reactivity has also been assessed at 2.8% change CBF/mm Hg change in arterial PCO2. In six animals pretreated with indomethacin (3 mg/kg), autoregulation was preserved although the resting CBF was significantly reduced, but CO2 reactivity was completely abolished. 1-n-Butyl imidazole, a specific thromboxane synthetase inhibitor, was used in six other animals (3 mg/kg), and this abolished CO2 reactivity while preserving autoregulation; the effect of this agent has not been described previously. Both drugs inhibit different pathways of prostaglandin metabolism and may interfere with normal CO2 reactivity in several ways. Two explanations are that prostaglandins constitute the final common pathway in effecting cerebrovascular response to CO2 or, alternatively, that the free radicals and ionic fluxes generated during prostaglandin metabolism are a coincidental source of the hydrogen ion changes required.     

Effect of perindopril on cerebral and renal perfusion on normotensives in mild early ischaemic stroke: a randomized controlled trial

BACKGROUND AND PURPOSE: Blood pressure reduction is central to secondary prevention after stroke, but the optimal time to start therapy is unknown. Cerebral autoregulation is impaired early after ischaemic insult, and any changes in systemic blood pressure may be reflected in cerebral perfusion. However, early initiation in hospital may better assure continued long-term treatment. We have investigated the effect of the angiotensin-converting enzyme inhibitor perindopril on blood pressure, global and focal cerebral blood flow (CBF) and glomerular filtration rate (GFR) in a normotensive acute stroke population. METHODS: Twenty-five patients within 4-8 days of mild ischaemic stroke/transient ischaemic attack and with diastolic blood pressure 70-90 mm Hg were randomized to receive perindopril 2 or 4 mg daily versus placebo according to estimated GFR. Mean arterial blood pressure (MABP), internal carotid artery (ICA) flow and middle cerebral artery velocity (MCAv) were measured prior to dosing, over the following 24 h and at 2 weeks. Brain hexamethyl propylene amino oxide single photon emission computed tomography (SPECT) was performed before dosing and at estimated time of peak drug effect (6-8 h after first dose). GFR measurement using a (51)Cr-ethylene diamine tetraacetic acid technique was undertaken prior to medication and repeated at 2 weeks. RESULTS: MABP was reduced throughout the first 24 h with a mean MABP reduction of 9.3 mm Hg (95% CI 7.4-11.3 mm Hg), maximal placebo corrected fall of 12.5 mm Hg at 10 h post-dose, p = 0.005. No significant change occurred in ICA flow, MCAv or CBF measured by SPECT: change from baseline in symptomatic hemisphere CBF was -0.02 (SD 3.11) ml/100 g/min (treated group) compared with 0 (SD 3.01) (placebo group). Similarly, no significant change was observed in cortical CBF. Mean within-group change in GFR was 2.7 +/- 10.1 in the treated group and -4.3 +/- 6.7 in the placebo group (p = NS). DISCUSSION: Antihypertensive therapy with perindopril may be introduced in the first week after mild ischaemic stroke in normotensive patients without affecting global or regional CBF or affecting GFR.     

Effects of hypotension induced with sodium nitroprusside on the cerebral circulation before, and one week after, the subarachnoid injection of blood.

Cerebral blood flow (CBF) and mean arterial pressure (MAP) were monitored in six normal baboons and six further animals in which an artificial subarachnoid haemorrhage (SAH) had been induced one week previously. MAP was reduced by the infusion of sodium nitroprusside. In the normal animals with administration of sodium nitroprusside, CBF increased initially but started to decrease as MAP was reduced below 65 mm Hg and fell below its baseline value when MAP was less than 50 mm Hg. In the SAH group, there was no initial hyperaemic response and CBF fell below baseline values when MAP was reduced below 50 mm Hg. When, during the infusion of the sodium nitroprusside, MAP was returned to normal using angiotensin, CBF increased above its baseline value. These results suggest that the cerebrovascular effects of sodium nitroprusside are the net result of competition between direct cerebral vasodilatation, falling arterial blood pressure and the degree of impairment of the "autoregulatory" mechanism. Evidence of ischaemic brain damage was found in the arterial boundary zones of both groups of animals.     

Cerebral blood flow during dihydralazine-induced hypotension in hypertensive rats

The cerebrovascular effects of graded, controlled dihydralazine-induced hypotension were studied in rats with renal hypertension (RHR) and spontaneous hypertension (SHR). Repeated measurements of cerebral blood flow (CBF) were made using the intraarterial 133Xenon injection technique in anaesthetised normocapnic animals. Dihydralazine was administered in single increasing i.v. doses (0.1 to 2 mg/kg), and CBF measured after each dose when a stable blood pressure had been reached. From a resting level of 145 +/- 7 mm Hg in RHR and 138 +/- 11 mm Hg in SHR, mean arterial pressure (MAP) fell stepwise to a minimum of around 50 mm Hg. CBF was preserved during dihydralazine induced hypotension, and remained at the resting level of 79 +/- 13 ml/100 g . min in RHR and 88 +/- 16 ml/100 g . min in SHR. Following 2 hours hypotension at the lowest pressure reached, the rats were sacrificed by perfusion fixation and the brains processed for light microscopy. Evidence of regional ischaemic brain damage was found in 4 of 11 animals: in 2 cases the damage appeared to be accentuated in the arterial boundary zones. Although the lower limit of CBF autoregulation in these rats is around 100 mm Hg during haemorrhagic hypotension, dihydralazine brought MAP to around 50 mm Hg without any concomitant fall in CBF. This was interpreted as being due to direct dilatation of cerebral resistance vessels. The combination of low pressure and direct dilatation may have resulted in uneven perfusion, thus accounting for the regional ischaemic lesions.     

Unique microvascular characteristics of the dorsal root ganglion in the rat.

Physiological characteristics of dorsal root ganglia microvessels have not been reported in detail. In this study we examined local blood flow and oxygen tension in the L4 dorsal root ganglion (DRG) of the rat. Under normal physiological conditions, local DRG blood flow measured 36.1 +/- 2.7 ml/100 g/min, over twice that within the endoneurium of the sciatic nerve. DRG blood flow was better maintained during hypotension than endoneurial blood flow suggesting partial autoregulation. Unlike endoneurium, there was relative constancy of flow between mean arterial pressures of 60 and 120 mm Hg. Hypercarbia with acidosis, and hypocarbia with alkalosis did not influence blood flow. The histogram of oxygen tensions within the dorsal root ganglion resembled that in brain but included more values at lower tensions than observed in published endoneurial histograms. Theses findings suggest that the DRG differ from endoneurium in ways that reflect the higher metabolic requirements of neural soma.     

Hypertension with hemodilution prevents multifocal cerebral hypoperfusion after cardiac arrest in dogs.

BACKGROUND: Improved neurological outcome with postarrest hypertensive hemodilution in an earlier study could be the result of more homogeneous cerebral perfusion and improved O2 delivery. We explored global, regional, and local cerebral blood flow by stable xenon-enhanced computed tomography and global cerebral metabolism in our dog cardiac arrest model. METHODS: Ventricular fibrillation cardiac arrest of 12.5 minutes was reversed by brief cardiopulmonary bypass, followed by life support to 4 hours postarrest. We compared control group I (n = 5; mean arterial blood pressure, 100 mm Hg; hematocrit, greater than or equal to 35%) with immediately postarrest reflow-promoted group II (n = 5; mean arterial blood pressure, 140-110 mm Hg; hypervolemic hemodilution with plasma substitute to hematocrit, 20-25%). RESULTS: After initial hyperemia in both groups, during the "delayed hypoperfusion phase" at 1-4 hours postarrest, global cerebral blood flow was 51-60% of baseline in group I versus 85-100% of baseline in group II (p less than 0.01). Percentages of brain tissue voxels with no flow, trickle flow, or low flow were lower (p less than 0.01) and mean regional cerebral blood flow values were higher in group II (p less than 0.01). Global cerebral oxygen uptake recovered to near baseline values at 3-4 hours postarrest in both groups. Postarrest arterial O2 content, however, in hemodiluted group II was 40-50% of that in group I. Thus, the O2 uptake/delivery ratio was increased (worsened) in both groups at 2-4 hours postarrest. CONCLUSIONS: After prolonged cardiac arrest, immediately induced moderate hypertensive hemodilution to hematocrit 20-25% can normalize cerebral blood flow patterns (improve homogeneity of cerebral perfusion), but does not improve cerebral O2 delivery, since the flow benefit is offset by decreased arterial O2 content. Individualized titration of hematocrit or hemodilution with acellular O2 carrying blood substitute (stroma-free hemoglobin or fluorocarbon solution) would be required to improve O2 uptake/delivery ratio.     

Autoregulatory capacity and the effect of isovolemic hemodilution on local cerebral blood flow

The effect of isovolemic hemodilution with dextran 40 on local cerebral blood flow was measured in eight cats by means of the hydrogen clearance technique. Under normotension the decrease of hematocrit from 35% to 25% causes a sudden increase of up to 30% in local cerebral blood flow. After lowering the mean arterial blood pressure from 140 to 80 mm Hg, hemodilution did not alter cerebral blood flow significantly. From this observation it is concluded that the increase of cerebral blood flow following hemodilution is caused by compensatory vasodilatation and not by reduction of blood viscosity. This could imply that hemodilution cannot improve blood flow in areas of impaired autoregulation.     

Effect of short-term hyperventilation on cerebral blood flow autoregulation in patients with acute bacterial meningitis

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) autoregulation is impaired in patients with acute bacterial meningitis: this may be caused by cerebral arteriolar dilatation. We tested the hypothesis that CBF autoregulation is recovered by acute mechanical hyperventilation in 9 adult patients with acute bacterial meningitis. METHODS: Norepinephrine was infused to increase mean arterial pressure (MAP) 30 mm Hg from baseline. Relative changes in CBF were concomitantly recorded by transcranial Doppler ultrasonography of the middle cerebral artery, measuring mean flow velocity (V(mean)), and by measurement of arterial to jugular oxygen content difference (a-v DO(2)). The slope of the regression line between MAP and V(mean) was calculated. Measurements were performed during normoventilation and repeated after 30 minutes of mechanical hyperventilation. RESULTS: At normoventilation (median PaCO(2) 4.4 kPa, range 3.5 to 4.9), MAP was increased from 68 mm Hg (60 to 101) to 109 mm Hg (95 to 126). V(mean) increased with MAP from 48 cm/s (30 to 61) to 65 cm/s(33 to 86) (P<0.01), and a-v DO(2) decreased from 2.2 mmol/L (1.0 to 2.7) to 1.4 mmol/L (0.8 to 1.8) (P<0.05). During hyperventilation (PaCO(2) 3.5 kPa, range 3.3 to 4.1), MAP was increased from 76 mm Hg (58 to 92) to 109 mm Hg (95 to 121). V(mean) increased from 45 cm/s (29 to 55) to 53 cm/s (33 to 78) (P<0.01), and a-v DO(2) decreased from 2.5 mmol/L (1.8 to 3.0) to 1.8 mmol/L (1.2 to 2.4) (P<0.05). Four patients recovered autoregulation completely during hyperventilation. The slope of the autoregulation curve decreased during hyperventilation compared with normoventilation (P<0.05). CONCLUSIONS: CBF autoregulation is partially recovered during short-term mechanical hyperventilation in patients with acute bacterial meningitis, indicating that cerebral arteriolar dilation in part accounts for the regulatory impairment of CBF in these patients.     

Noninvasive monitoring of hypertensive breakthrough of cerebral autoregulation in a patient with acute ischemic stroke

BACKGROUND AND PURPOSE: We describe the first documentation of hypertensive breakthrough of cerebral autoregulation in a patient with acute stroke with transcranial Doppler sonography. CASE DESCRIPTION: A 55-year-old patient with acute left hemispheric stroke was treated with moderate hypothermia. He died of transtentorial herniation 4 days after admission. Static cerebral autoregulation (sCA) of the unaffected hemisphere was evaluated 6 times during this period and always found to be intact. A bolus application of epinephrine resulted in a hypertensive episode (mean arterial pressure (MAP) 135 mm Hg); hypertensive breakthrough of cerebral autoregulation was evident when MAP exceeded approximately 110 mm Hg. Interestingly, no such breakthrough was evident during testing of sCA, even when MAP reached 120 mm Hg. CONCLUSIONS: Our observation suggests that (1) the pace of the MAP increase is crucial for the occurrence of a hypertensive breakthrough of the cerebral autoregulation and (2) the disturbance of cerebral autoregulation is potentially longer as previously assumed.     

Autoregulation of cerebral blood flow surrounding acute (6 to 22 hours) intracerebral hemorrhage.

BACKGROUND: Arterial hypertension is common in the first 24 hours after acute intracerebral hemorrhage (ICH). Although increased blood pressure usually declines to baseline values within several days, the appropriate treatment during the acute period has remained controversial. Arguments against treatment of hypertension in patients with acute ICH are based primarily on the concern that reducing arterial blood pressure will reduce cerebral blood flow (CBF). The authors undertook this study to provide further information on the changes in whole-brain and periclot regional CBF that occur with pharmacologic reductions in mean arterial pressure (MAP) in patients with acute ICH. METHODS: Fourteen patients with acute supratentorial ICH 1 to 45 mL in size were studied 6 to 22 hours after onset. CBF was measured with PET and (15)O-water. After completion of the first CBF measurement, patients were randomized to receive either nicardipine or labetalol to reduce MAP by 15%, and the CBF study was repeated. RESULTS: MAP was lowered by -16.7 +/- 5.4% from 143 +/- 10 to 119 +/- 11 mm Hg. There was no significant change in either global CBF or periclot CBF. Calculation of the 95% CI demonstrated that there is less than a 5% chance that global or periclot CBF fell by more than -2.7 mL x 100 g(-1) x min(-1). CONCLUSION: In patients with small- to medium-sized acute ICH, autoregulation of CBF was preserved with arterial blood pressure reductions in the range studied.     

Bradykinin antagonist counteracts the acute effect of both angiotensin-converting enzyme inhibition and of angiotensin receptor blockade on the lower limit of autoregulation of cerebral blood flow

The lower limit of autoregulation of cerebral blood flow (CBF) can be modulated with both angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). The influence of bradykinin antagonism on ARB-induced changes was the subject of this study. CBF was measured in Sprague–Dawley rats with laser Doppler technique. The blood pressure was lowered by controlled bleeding. Six groups of rats were studied: a control group and five groups given drugs intravenously: an ACE inhibitor (enalaprilat), an ARB (candesartan), a bradykinin-2 receptor antagonist (Hoe 140), a combination of enalaprilat and Hoe 140, and a combination of candesartan and Hoe 140. In the control group, the lower limit of CBF autoregulation was 54±9 mm Hg (mean±s.d.), with enalaprilat it was 46±6, with candesartan 39±8, with Hoe 140 53±6, with enalaprilat/Hoe 140 52±6, and with candesartan/Hoe 140 50±7. Both enalaprilat and candesartan lowered the lower limit of autoregulation of CBF significantly. The bradykinin antagonist abolished not only the effect of the ACE inhibitor but surprisingly also the effect of the ARB on the lower limit of CBF autoregulation, the latter suggesting an effect on intravascular bradykinin.     

The Effect of Valsartan versus Non-RAAS Treatment on Autoregulation of Cerebral Blood Flow

Background: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). Methods: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO(2) pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. Results: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (-0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (-0.23 ± 0.06 vs. -0.08 ± 0.07%, p = 0.07). Conclusions: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.     

Transcranial Doppler sonographic studies of cerebral autoregulation in Shy-Drager syndrome

Summary A study is reported of mean arterial blood pressure and heart rate in four patients suffering from Shy-Drager syndrome. Blood flow velocity in the middle cerebral artery (MCA) was recorded by transcranial Doppler sonography. Concomitant changes in cerebral blood flow and the effect of cerebral autoregulation were thus examined. During tilt (60°, head up) mean arterial blood pressure decreased by 40 mm Hg or 35%, while MCA blood flow velocity dropped by 14 cm/s or 28% (mean values). The lower percentage reduction in flow velocity may indicate a preserved cerebral autoregulation in central autonomic insufficiency.