Autoregulation of cerebral blood flow in patients with orthostatic hypotension after spinal cord injury

Two groups of patients who developed orthostatic hypotension (OH) after spinal cord injury (SCI) were studied. In the first group all patients (4 females and 6 males) were asymptomatic, whereas in the second group (1 female and 9 males) all had clinical manifestations of hypotension. All but 3 patients were tetraplegic, and these patients were paraplegic above the T6 level. For this study blood pressure (BP), heart rate and cerebral blood flow (CBF) velocity were measured simultaneously on a tilt table at 0, 30, 60, and 80 degrees. Cerebral blood flow in the middle cerebral artery was measured bilaterally utilising the transcranial Doppler technique. In asymptomatic patients the mean baseline (0 degrees) BP (110 +/- 16/70 +/- 77 mm Hg systolic/diastolic) was not significantly different from the BP (106 +/- 16/68 +/- 11 mm Hg) of symptomatic patients. The mean maximal change in BP during tilting in the asymptomatic group (-23 +/- 10/10 +/- 7 mm Hg) was also not significantly different when compared to the symptomatic group (-29 +/- 13/11 +/- 6 mm Hg). CBF in the symptomatic group during the hypotensive reaction at 80 degrees was 32.5 +/- 5 cm/sec, while at the same body position in the asymptomatic group it was 40.9 +/- 8 cm/sec (significant at the p less than 0.02). In addition, CBF decreased in the symptomatic group at 80 degrees to 55.5 +/- 9.6% of baseline, while in the asymptomatic group the fall was 69.3 +/- 7.2% (p less than 0.001). Our data suggest that autoregulation of CBF rather than systemic BP plays a dominant role in the adaptation to OH in patients with SCI.     

Effects of graded hyperventilation on cerebral blood flow autoregulation in experimental subarachnoid hemorrhage.

An impaired CBF autoregulation can be restored by hyperventilation at a PaCO2 level of about 2.9 to 4.1 kPa (22 to 31 mm Hg). However, it is uncertain whether the restoring effect can take place at lesser degrees of hypocapnia. In the current study, CBF autoregulation was studied at four PaCO2 levels: 5.33 kPa (40 mm Hg, normoventilation), 4.67 kPa (35 mm Hg, slight hyperventilation), 4.00 kPa (30 mm Hg, moderate hyperventilation), and 3.33 kPa (25 mm Hg, profound hyperventilation). At each PaCO2 level, eight rats 2 days after experimental subarachnoid hemorrhage (SAH) and eight sham-operated controls were studied. The CBF was measured by the intracarotid 133Xe method. The CBF autoregulation was found to be intact in all controls but completely disturbed in the normoventilated SAH rats. However, by slight hyperventilation, CBF autoregulation was restored in seven of eight SAH rats with a decline in CBF of 10%. The CBF autoregulation was found intact in all of the moderately or profoundly hyperventilated SAH rats, whereas the decline in CBF was 21% and 28%, respectively. In conclusion, hyperventilation to a PaCO2 level between 4.00 and 4.67 kPa (30 to 35 mm Hg) appears to be sufficient for reestablishing an impaired autoregulation after SAH.     

Multimodality monitoring during passive tilt and Valsalva maneuver under hypercapnia.

In occlusive cerebrovascular disease cerebral blood flow (CBF) autoregulation can be impaired and constant CBF during fluctuations in blood pressure (BP) cannot be guaranteed. Therefore, an assessment of cerebral autoregulation should consider not only responsiveness to CO2 or Diamox. Passive tilting (PT) and Valsalva maneuver (VM) are established tests for cardiovascular autoregulatory function by provoking BP changes. To develop a comprehensive test for vasomotor reactivity with a potential increase of sensitivity and specificity, the authors combined these maneuvers. Blood pressure, corrected to represent arterial pressure at the level of the circle of Willis, middle cerebral artery Doppler frequencies (DF), heart rate (HR) and endtidal partial pressure of CO2 (PtCO2) were measured continuously and noninvasively in 81 healthy subjects (19-74 years). Passive tilt and Valsalva maneuver were performed under normocapnia (mean, 39 + 4 mmHg CO2) and under hypercapnia (mean, 51 + 5 mm Hg CO2). Resting BP, HR, and DF increased significantly under hypercapnia. Under normocapnia and hypercapnia, PT induced only minor, nonsignificant changes in mean BP at the level of the circle of Willis compared to baseline (normocapnia: + 2 + 15 mm Hg; hypercapnia: -3 +/- 13 mm Hg). This corresponded with a nonsignificant decrease of the mean of DF (normocapnia: -4 +/- 11%; hypercapnia -6 +/- 12%). Orthostasis reduced pulsatility of BP by a predominantly diastolic increase of BP without significant changes in pulsatility of DF. Valsalva maneuver, with its characteristic rapid changes of BP due to elevated intrathoracic pressure, showed no significant BP differences in changes to baseline between normocapnic and hypercapnic conditions. Under both conditions the decrease in BP in phase II was accompanied by significantly increased pulsatility index ratio (PIDF/PIBP). Valsalva maneuver and PT as established tests in autonomic control of circulation provoked not only changes in time-mean of BP but also in pulsatility of BP. The significant increase in pulsatility ratio and decrease of the DF/BP ratio during normocapnia and hypercapnia indicated preserved CBF autoregulation within a wide range of CO2 partial pressures. Hypercapnia did not significantly influence the autoregulatory indices during VM and PT. Physiologically submaximally dilated cerebral arterioles can guarantee unchanged dynamics of cerebral autoregulation. Combined BP and MCA-DF assessment under hypercapnia enables investigating the effect of rapid changes of blood pressure on CO2-induced predilated cerebral arterioles. Assuming no interference of hypercapnia-induced vasodilation, VM, with its rapid, distinct changes in BP, seems especially to be adequate provocation for CBF autoregulation. This combined vasomotor reactivity might provide a more sensitive diagnostic tool to detect impaired cerebral autoregulation very early.     

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.     

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)     

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.     

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.     

Brain luxury perfusion during cardiopulmonary bypass in humans. A study of the cerebral blood flow response to changes in CO2, O2, and blood pressure

CBF and related parameters were studied in 68 patients before, during, and following cardiopulmonary bypass. CBF was measured using the intraarterial 133Xe injection method. The extracorporeal circuit was nonpulsatile with a bubble oxygenator administering 3-5% CO2 in the main group of hypercapnic patients (n = 59) and no CO2 in a second group of hypocapnic patients. In the hypercapnic patients, marked changes in CBF occurred during bypass. Evidence was found of a brain luxury perfusion that could not be related to the effect of CO2 per se. Mean CBF was 29 ml/100 g/min just before bypass, 49 ml/100 g/min at steady-state hypothermia (27 degrees C), reached a maximum of 73 ml/100 g/min during the rewarming phase (32 degrees C), fell to 56 ml/100 g/min at steady-state normothermic bypass (37 degrees C), and was 48 ml/100 g/min shortly after bypass was stopped. Addition of CO2 evoked systemic vasodilation with low blood pressure and a rebound hyperemia. The hypocapnic group responded more physiologically to the induced changes in hematocrit (Htc) and temperature, CBF being 25, 23, 25, 34, and 35 ml/100 g/min, respectively, during the five corresponding periods. Carbon dioxide was an important regulator of CBF during all phases of cardiac surgery, the responsiveness of CBF being approximately 4% for each 1-mm Hg change of PaCO2. The level of MABP was important for the CO2 response. At low blood pressure states, the CBF responsiveness to changes in PaCO2 was almost abolished. An optimal level of PaCO2 during hypothermic bypass of approximately 25 mm Hg (at actual temperature) is recommended. A normal autoregulatory response of CBF to changes in blood pressure was found during and following bypass. The lower limit of autoregulation was at pressure levels of approximately 50-60 mm Hg. CBF autoregulation was almost abolished at PaCO2 levels of greater than 50 mm Hg. The degree of hemodilution neither affected the CO2 response nor impaired CBF autoregulation, although, as would be expected, it influenced CBF: In 33 women CBF was 55 ml/100 g/min at an Htc of 24%, as compared with 42 ml/100 g/min in 35 men (Htc = 28%). High PaO2 was a vasoconstrictor, the autoregulatory plateau being narrowed. The lower limit of autoregulation was shifted to a higher pressure when PaO2 was low.     

Interplay of cerebral autoregulation and neurovascular coupling evaluated by functional TCD in different orthostatic conditions

BACKGROUND: Adequate cerebral blood flow (CBF) is mainly governed by neurovascular coupling (NC) which adapts local CBF to underlying cortical activity,and cerebral autoregulation (CA)that tends to maintain constant CBF despite changes in arterial blood pressure (BP). Since it was suggested that resistance vessels play an important role in both mechanisms, we investigated the irregulative interplay by performing a functional transcranial Doppler(f-TCD) test under different orthostatic conditions. METHODS: Fifteen healthy volunteers performed a visual reading test stimulation task after stabilized in sitting, supine and upright position on a tilt table. Simultaneously, BP and heart rate (HR) were recorded by a photoplethysmographic method and CBF velocity was measured with TCD in left posterior cerebral artery, and, as a reference, also in right middle cerebral artery. Evoked flow velocity (FV) responses were evaluated by a control system approach for systolic and diastolic data. Parameters studied were baseline FV with eyes closed, stable FV under stimulation (gain), oscillatory feature (natural frequency) and damping (attenuation) of the control system model, rate time, and also systolic and diastolic BP and HR. ANOVA test was used for comparing the values of variables in different postural settings, inferring statistical significance at a p < 0,05 level. RESULTS: Although there was a significant variation on the different orthostatic conditions in systolic (p = 0,027) and diastolic (p = 0,001) BP and HR (p = 0,0001), there was no significant change in the basal or evoked CBF velocities. CONCLUSIONS: An intact CA compensates the different orthostatic conditions completely thus allowing an independent regulation of NC according to the metabolic needs of cortical stimulation.     

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.     

Regional cerebral hemodynamics among hypertensive patients with lacunar infarctions during blood pressure control in subacute and chronic phases.

In hypertensive acute stroke patients, the use of antihypertensive treatment is often delayed because autoregulation of cerebral blood flow (CBF) is often impaired during the first 4 weeks after large brain infarctions. However, little is known as to whether such delay is necessary in cases of small to moderate size brain infarction. We compared changes of regional CBF during antihypertensive treatment in subacute and chronic phases of lacunar infarction. Blood pressure was controlled with an angiotensin-converting enzyme inhibitor (n=6) or dihydropyridine calcium antagonist (n=8), administered orally for 2 weeks during the subacute (n=7) and chronic phases after (n=7) lacunar infarction. CBF was measured by the stable xenon-computed tomography (CT) method. Blood pressure decreased significantly from 132+/-20 mm Hg (mean+/-standard deviation) to 118+/-14 mm Hg (P<.05, paired t-test) in subacute patients and from 135+/-17 mm Hg to 113+/-12 mm Hg (P<.001, paired t-test) in chronic patients. There was no significant reduction either in mean hemispheric blood flow or in deep white matter blood flow during each phase. We condlude that mild control of blood pressure among hypertensive patients with lacunar infarctions does not produce clinically significant decreases in regional CBF during subacute phases of infarction.     

Acute sympathetic denervation does not eliminate the effect of angiotensin converting enzyme inhibition on CBF autoregulation in spontaneously hypertensive rats

The effect of angiotensin converting enzyme inhibition with captopril (10 mg/kg i.v.) on CBF autoregulation was studied in 16 spontaneously hypertensive rats (8 control and 8 treated with captopril) subjected to acute cervical sympathectomy. CBF was measured repetitively by the intra-arterial 133Xe injection method, during the manipulation of MABP by norepinephrine or hemorrhagic hypotension. Prior to the administration of drugs, baseline MABP was 112 +/- 10 mm Hg in the control group and 119 +/- 11 mm Hg in the captopril group. Baseline CBF was 99 +/- 19 ml/100 g/min, with no difference in the two groups. In agreement with previous findings in rats with intact sympathetic nerves, the lower limit of CBF autoregulation was reduced from the MABP interval of 70-89 to 50-69 mm Hg by captopril.     

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.     

Rapid autoregulation of cerebral blood flow: a laser-Doppler flowmetry study.

The mechanisms underlying autoregulation of CBF were studied in 19 rabbits using laser-Doppler flowmetry. A cranial plexiglas window was chronically inserted in the skull with dental cement under general anesthesia. The animals then were reanesthetized 5-7 days later and subjected to aortic bleeding while CBF was measured with the probe placed on the window. In the first set of experiments, MABP was decreased (from 90 to 30 mm Hg) and was maintained constant for 1 min. During the first seconds, CBF followed the steep decrease of MABP. Then, CBF increased and reached a plateau within 3-13 s, depending on the severity of hypotension. Hyperemia occurred when blood was restored, and the CBF recovered from this posthypotensive hyperemia with a rapid phase (within 2 s) and a slow phase (total recovery within 1 min). The lower limit of autoregulation was found to be 40 mm Hg. An increase in CBF due to papaverine showed that vasodilation was not maximal below this limit. In the second set of experiments, the rabbits were subjected to four episodes of hypotension at 40 mm Hg each but of different durations (from 2-3 to 60 s). The posthypotensive hyperemia was not influenced by the duration of hypotension, but the time of the total recovery phase increased with the duration of hypotension. We conclude that there exist rapid adaptive mechanisms leading to autoregulation and that the vasodilation is not dependent upon the duration of hypotension.     

Regional differences in vascular autoregulation in the rat brain in severe insulin-induced hypoglycemia

The present experiments were undertaken to determine if loss of vascular autoregulation during severe hypoglycemia shows regional differences that could help to explain the localization of hypoglycemic cell damage. Artificially ventilated rats (70% N2O) were subjected to a 30-min insulin-induced hypoglycemic coma (with cessation of EEG activity), with mean arterial blood pressure being maintained at 140, 120, 100, and 80 mm Hg. After 30 min of hypoglycemia, local cerebral blood flow (CBF) in 25 brain structures was measured autoradiographically with a [14C]iodoantipyrine technique. Since local CBF values did not differ between the 120 and the 100 mm Hg groups, the animals of these groups were pooled (110 mm Hg group). The results showed that at a blood pressure of 140 mm Hg, CBF was increased in 22 of 25 structures analyzed, the maximal values approximating 300% of control. At 110 mm Hg, cerebral cortical structures had CBF values that were either decreased, normal, or slightly increased; however, many subcortical structures (and cerebellum) showed markedly increased flow rates. Although a lowering of blood pressure to 80 mm Hg usually further reduced flow rates, some of these latter structures also had well-maintained CBF values at that pressure. Thus, there were large interstructural variations of local CBF at any of the pressures examined. Analysis of the pressure-flow relationship showed loss of autoregulation in some structures, whereas others had remarkably well-preserved CBF values at low pressures. The results indicate that during severe hypoglycemia, even relatively moderate arterial hypotension may add a circulatory insult to the primary one, and they strongly suggest that any such insult affects some brain structures more than others.     

Cerebral blood flow is regulated by changes in blood pressure and in blood viscosity alike

There is still considerable controversy regarding the influence of blood viscosity upon CBF. We have measured CBF with microspheres in 23 cats. Autoregulation was disturbed in the left caudate nucleus by microsurgical occlusion of the left middle cerebral artery. Induced hypertension or hypotension was used and i.v. mannitol (1 g/kg) administered. In all cats blood viscosity decreased an average of 16% at 15 minutes and, in 16 cats, increased 10% at 75 minutes post-mannitol. CBF in the right caudate was 79 +/- 6 ml/100g/min, in the left 38 +/- 6 (p less than 0.001). Only minor changes of CBF occurred in areas with presumed normal autoregulation, including the right caudate, in conjunction with pressure or viscosity changes. In the left caudate CBF decreased 21% with hypotension and 18% with higher viscosity, more than on the right (p less than 0.01 and p less than 0.2, respectively). CBF increased in the left caudate 56% with hypertension and 47% with lower viscosity, again much more than on the right (p less than 0.001 and p less than 0.01, respectively). In the other area which is (nearly) exclusively supplied by the middle cerebral artery of the cat, i.e., the ectosylvian cortex, results were similar to those in the caudate nucleus. These results show that viscosity changes must result in compensatory readjustments of vessel diameter, but that these adjustments do not occur where autoregulation to pressure changes is known to be defective. The adjustments to viscosity changes might be called blood viscosity autoregulation of CBF. We hypothesize that pressure autoregulation and blood viscosity autoregulation share the same mechanism.     

Nitric oxide synthase inhibition depresses the height of the cerebral blood flow-pressure autoregulation curve during moderate hypotension.

Variations in the height of the CBF response to hypotension have been described recently in normal animals. The authors evaluated the effects of nitric oxide synthase (NOS) inhibition on these variations in height using laser Doppler flowmetry in 42 anesthetized (halothane and N2O) male Sprague-Dawley rats prepared with a superfused closed cranial window. In four groups (time control, enantiomer control, NOS inhibition, and reinfusion control) exsanguination to MABPs from 100 to 40 mm Hg was used to produce autoregulatory curves. For each curve the lower limit of autoregulation (the MABP at the first decrease in CBF) was identified; the pattern of autoregulation was classified as "peak" (15% increase in %CBF), "classic" (plateau with a decrease at the lower limit of autoregulation), or "none" (15% decrease in %CBF); and the autoregulatory height as the %CBF at 70 mm Hg (%CBF(70)) was determined. NOS inhibition decreased %CBF(70) in the NOS inhibition group (P = 0.014), in the control (combined time and enantiomer control) group (P = 0.015), and in the reinfusion control group (P = 0.025). NOS inhibition via superfusion depressed the autoregulatory pattern (P = 0.02, McNemar test on changes in autoregulatory pattern) compared with control (P = 0.375). Analysis of covariance showed that changes induced by NOS inhibition in the parameters of autoregulatory height are not related to changes in the lower limit, but are strongly (P < 0.001) related to each other. NOS inhibition depressed the autoregulatory pattern, decreasing the seemingly paradoxical increase in CBF as blood pressure decreases. These results suggest that nitric oxide increases CBF near the lower limit and augments the hypotensive portion of the autoregulatory curve.     

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.     

Cerebrovascular and metabolic changes during the delayed vasospasm following experimental subarachnoid hemorrhage in baboons, and treatment with a calcium antagonist

A model has been designed in baboons for simulating the clinical situation during the late phase of vasospasm in patients with subarachnoid hemorrhage (SAH). A total amount of 14-33 ml autologous blood was injected into the cisternal system on 3 occasions in the course of 4 days. Neurological symptoms were seen, and the mortality rate was 29%. Angiography 3 days after the last injection showed arterial vasoconstriction amounting to 23% in the vertebro-basilar system, and 11% (right) and 18% (left) in the carotid system. Cerebral blood flow (CBF) measured by the intra-arterial 133Xe technique and the cerebral metabolic rate of oxygen (CMRO2) were reduced by 18% and 11%, respectively. The hypercapnic CBF response was significantly impaired, from a mean of 3.90 ml/100 g/min to 1.72 ml/100 g/min of flow increase for each mm Hg elevation of paCO2. Autoregulation, tested by administration of angiotensin II, was also significantly affected as evidenced by a pressure-dependent increment of CBF during hypertension in 5 out of 7 animals tested. The impaired autoregulation was reflected in the autoregulatory index, which in the whole group increased from 0.06 ml/100 g/min for each mm Hg increase in MABP in the pre-SAH animals to 0.29 ml/100 g/min per mm Hg post-SAH. Treatment with the calcium antagonist, nimodipine (0.5 microgram/kg/min i.v. during 45 min), enhanced CBF significantly by 17% before experimental SAH, whereas after SAH the effect was slight and did not reach statistical significance; CMRO2 was not significantly affected in either group. Intravenous nimodipine combined with hypertension resulted in a marked increase in the autoregulatory index to 1.58 ml/100 g/min per mm Hg in pre-SAH animals and a less pronounced increment to 0.58 ml/100 g/min per mm Hg following experimental SAH. The beneficial effect of nimodipine reported in SAH patients is therefore, in view of our findings, more likely due primarily to a protective mechanism at the cellular level than to an influence on the vascular bed.     

Evaluation of cerebral autoregulation following diffuse brain injury in rats

Abstract

The normal cerebral circulation has the ability to maintain a stable cerebral blood flow over a wide range of cerebral perfusion p(essures and this is known as cerebral autoregulation. This autoregulation may be impaired in the injured brain. Closed head injury was induced in 28 Sprague-Dawley rats weighing 400-450 g. Four groups were studied: control group, head injured rat from meter height using 350 g, 400 g and 450 g respectively. CBF, volume velocity was monitored using laser-Doppler flowmetry together with monitoring of ICP and arterial blood pressure. Correlation to assess the relationship between CBF and CPP was done in each animal every hour. If correlation coefficient was> 0.85 and CPP was within normal range, loss of autoregulation was hypothesized. Chi square test, ANOVA test and unpaired Studen(s t-test were done and significant level of p < 0.05 was established. Mean CBF in injured rats was significantly lower than controls (p = 0.028) at the fifth hour. CBV was lower in the group of 450 g 1 m impact than in controls at 3 h (p = 0.04). Velocity in the group ofall injured rats, was significantly lower than in controls at 3 h (p = 0.032) and at 4 h (p = 0.027). Loss ofautoregulation was seen during first four hours after trauma in all groups of rats who sustained injury. Statistical significant difference (p = 0.041) in loss of autoregulation between injured and control animals was seen. No loss of autoregulation was observed in the control group. In conclusion CBF and CPP provide information about loss of autoregulation in diffuse brain injury. Decrease in CBF and increase of ICP is observed as a result ofloss of cerebral autoregulation. Knowledge of loss of autoregulation could give important information and help in the management of head injured patients. [Neural Res 1997; 19: 393-402]