Cortical bone microperfusion: response to ischemia and changes in major arterial blood flow.

In order to investigate the effects of short-term ischemia on cortical bone microperfusion, an isolated porcine tibia diaphyseal preparation based on intact nutrient vessels was developed. Laser Doppler flowmetry (LDF) was utilized to assess continuously the cortical microcirculation and the response to short-term ischemia. The femoral artery was isolated and clamped to develop the condition of bone ischemia. On release of the clamp, reactive hyperemia was documented in all animals. Using a roller pump connected to a segment of femoral artery, the same preparation was utilized to investigate the effect of a changing femoral artery flow on the cortical microcirculation. A positive correlation between LDF output and change in arterial inflow (r = 0.64) was defined. This model has the potential for studying the effect of ischemia on bone cell viability.     

Cerebral blood flow autoregulation in experimental subarachnoid haemorrhage in rat

Summary Haemodynamic instability is of great importance in clinical management of patients with subarachnoid haemorrhage (SAH). The significance of angiographically demonstrable vasospasm for disturbances of cerebral blood flow (CBF) and cerebral autoregulation has not yet been clarified.The present study was designed to describe disturbances of cerebral autoregulation during the timecourse of experimental SAH (eSAH) in rats. A second aim of the study was to relate the results to a reported timecourse of angiographic vasospasm in the same animal model. Previous studies have shown that the timecourse of angiographically visible vasospasm in eSAH is biphasic with maximal spasm at 10 min and 2 days after induction of eSAH. At 5 days, the vasospasms have resolved.CBF was measured using a¹³³-Xenon intracarotid injection method which allowed serial measurements of mean hemispheric CBF during controlled manipulations of arterial blood pressure. In this way, an autoregulation curve could be constructed.The present study shows that autoregulation is severely disturbed or even totally absent at 2 and 5 days after eSAH. Thus there seems to be no direct correlation between presence of angiographic vasospasm and impairment of autoregulation, or that the impairment of autoregulation is more protracted than the presence of cerebral vasospasm, presuming a correlation exist.     

Hyperoxia and the cerebral hemodynamic responses to moderate hyperventilation

BACKGROUND: A reduction in the arterial partial pressure of CO2 (PaCO2) leads to a rapid reduction in cerebral blood flow (CBF). However, despite continuing hypocapnia there is secondary recovery of CBF over time as a result of increases in lactic acid production. Hyperoxia is thought to modulate the production of lactic acid. This study examined the kinetics of middle cerebral artery flow velocity (MCA FV) reduction during hyperventilation, and its modulation by hyperoxia. METHODS: Cerebral blood flow was assessed using transcranial Doppler ultrasound in nine healthy, awake human volunteers. Subjects were ventilated, via a mouthpiece, to achieve a stable end-tidal CO2 (PETCO2). After a 20-min baseline period the minute volume on the ventilator was passively increased by approximately 20% to reduce PETCO2 by 0.75-1 kPa. After a 10-min stabilization period the new PETCO2 level was maintained at a constant level for 20 min, and MCA FV recovery was measured during this 20-min period. Subjects undertook the protocol breathing air and breathing 100% oxygen. RESULTS: The PETCO2 level was (mean +/- SD) 4.9 +/- 0.4 kPa (normoxia baseline), 4.0 +/- 0.3 kPa (normoxia hyperventilation), 4.6 +/- 0.4 kPa (hyperoxia baseline) and 3.9 +/- 0.4 kPa (hyperoxia hyperventilation). CO2 reactivity was significantly lower with normoxia than hyperoxia (16.5 +/- 3.8 vs. 21.2 +/- 4.6 % kPa-1; P< 0.05). Middle cerebral artery FV recovery was significantly more rapid with normoxia than hyperoxia (0.23 +/- 0.17 vs. 0.08 +/- 0.1 % baseline min-1; P< 0.01). CONCLUSIONS: Our results suggest that cerebral hemodynamic responses to moderate hyperventilation are different in normoxic and hyperoxic conditions. Clinical assessment of CO2 reactivity and CBF recovery during hyperventilation should take the degree of arterial oxygenation into account.     

The acute effect of nimodipine on cerebral blood flow,its CO2 reactivity,and cerebral oxygen metabolism in human volunteers

Summary The present study was undertaken in 8 healthy volunteers to examine the effect of a clinically relevant dose of nimodipine (NIM) (15 and 30 microgram/kg/h) on CBF, its CO₂ reactivity, and CMRO₂. Mean arterial blood pressure (MABP) was measured intra-arterially. Regional CBF was measured by SPECT of inhaled Xenon-133. During the CO₂ reactivity tests changes in CBF were estimated by the arterio-venous-oxygen-difference method. Median CBF was 52 ml/ 100 g/min (48–53) with a normal regional distribution, and median baseline MABP was 96 mmHg (92–99). MABP was slightly reduced, by 8 mmHg (7–9), and 9 mmHg (4–11) after infusion of NIM for 2 and 4 hours, respectively. CBF, however, remained constant, although correction for changes in PaCO₂, revealed a slight increase after 4 hours (p=0.08). CMRO2 was 3.5 ml/100 g/min (3.2–3.5) and was not changed by the infusion of NIM. At arterial CO₂ tensions ranging from 4.0 to 6.5 Kpa the CO₂ reactivity was 3.0% CBF/ 0.1 kPa (2.6–3.7) and decreased significantly to 2.6% CBF/0.1 kPa (1.8–3.2) after the infusion of NIM for 3 hours (p=0.02). The median slope of the LnCBFsat/PaCO₂ relationship was 1.5 at baseline compared to 1.3 after NIM (p<0.01). No side effects were observed.The present study shows a decreased CO₂ of the cerebral vessels and a maintained coupling of CBF and CMRO₂ during the infusion of nimodipine.     

The influence of changes in blood flow on the accuracy of pulse oximetry in humans

Oxygen saturation (SpO2) was measured with a pulse oximeter in ten healthy, young men breathing air. A pulse oximeter probe was attached to the second toe and a laser Doppler probe to the first toe of the same foot for measurement of changes in peripheral blood flow. The pulse oximeter and laser Doppler readings were simultaneously compared when the foot was positioned 40 cm (position 1) above heart level, elevated 10 cm (position 2) above heart level and horizontally at heart level (position 3). Using this experimental human model, we achieved various blood flows. The AC and DC optical signals used for determination of oxygen saturation were recorded from the pulse oximeter and analysed. There was a significant increase (P less than 0.05) between position 1 and 3 in blood flow as measured by the laser Doppler flow meter. The corresponding pulse oximeter readings of haemoglobin saturation also increased significantly (P less than 0.05) comparing these two leg positions. Analysing the AC- and DC optical signals, the AC value of infrared light increased considerably, while the AC value of the red light decreased slightly. The DC values of red and infrared light did not change significantly. In summary, when blood flow was decreased, the ratio of red to infrared transmitted light was changed, resulting in a low SpO2 reading.     

Effects of stellate ganglion block on cerebral haemodynamics as assessed by transcranial Doppler ultrasonography

Background. Stellate ganglion block (SGB) causes vasodilatationin the skin of the head and neck because of regional sympatheticblock. Its effects on cerebral haemodynamics, in health or indisease, are not clear. We evaluated the effects of SGB on ipsilateralmiddle cerebral artery flow velocity (MCAFV), estimated cerebralperfusion pressure (eCPP), zero flow pressure (ZFP), carbondioxide reactivity (CO₂R) and cerebral autoregulation usingtranscranial Doppler ultrasonography (TCD). Methods. Twenty male patients, with pre-existing brachial plexusinjury, and undergoing SGB for the treatment of complex regionalpain syndrome of the upper limb, were studied. For SGB, 10 mlof plain lidocaine 2% was used and the onset of block was confirmedby presence of ipsilateral Horner's syndrome. The MCAFV, eCPP,ZFP, CO₂R, and cerebral autoregulation were assessed beforeand after SGB using established TCD methods. The changes inthese variables were analysed using Wilcoxon's signed rank test. Results. The block caused a significant decrease in MCAFV frommedian (inter-quartile range) value of 61 (53, 67) to 55 (46,60) cm s^–1, a significant increase in eCPP from 59 (51,67) to 70 (60, 78) mm Hg, and a significant decrease in ZFPfrom 32 (26, 39) to 25 (16, 30) mm Hg. There were no significantchanges in CO₂R or cerebral autoregulation. Conclusion. The increase in eCPP, decrease in ZFP, and no changesin CO₂R or cerebral autoregulation suggest that the SGB decreasescerebral vascular tone without affecting the capacity of thevessels to autoregulate. These effects may be of therapeuticadvantage in relieving cerebral vasospasm in certain clinicalsettings.     

Effects of sevoflurane on intracranial pressure, cerebral blood flow and cerebral metabolism: A dose-response study in patients subjected to craniotomy for cerebral tumours

Background: Studies concerning the cerebrovascular effects of sevoflurane in patients with space-occupying lesions are few. This study was carried out as a dose-response study comparing the effects of increasing sevoflurane concentration (1.5% (0.7 MAC) to 2.5% (1.3 MAC)) on cerebral blood flow (CBF), intracranial pressure (ICP), cerebrovascular resistance (CVR), metabolic rate of oxygen (CMRO₂) and CO₂-reactivity in patients subjected to craniotomy for supratentorial brain tumours.
Methods: Anaesthesia was induced with propofol/fentanyl/atracurium and maintained with 1.5% sevoflurane in air/oxygen at normocapnia. Blood pressure was maintained constant by ephedrine. In group 1 (n=10), the patients received continuously 1.5% sevoflurane. Subdural ICP, CBF and CMRO₂ were measured twice at 30-min intervals. In group 2 (n=10), sevoflurane concentration was increased from 1.5% to 2.5% after CBF₁. CBF₂ was measured after 20 min during 2.5% sevoflurane. Finally, CO₂-reactivity was studied in both groups.
Results: In group 1, no time-dependent alterations in CBF, CVR, ICP and CMRO₂ were found. In group 2, an increase in sevoflurane from 1.5% to 2.5% resulted in an increase in CBF from 29 ± 10 to 34±12 ml 100g⁻¹ min⁻¹ and a decrease in CVR from 2.7±0.9 to 2.3±1.2 mmHg ml⁻¹ min 100g ( P <0.05), while ICP and CMRO₂ were unchanged. CO₂-reactivity was maintained at 1.5% and 2.5% sevoflurane.
Conclusion: Sevoflurane is a cerebral vasodilator in patients with cerebral tumours. Sevoflurane increases CBF and decreases CVR in a dose-dependent manner. CO₂-reactivity is preserved during 1.5% and 2.5% sevoflurane.     

The use of laser Doppler flowmetry to evaluate anterior cruciate blood flow

The purpose of this study was to quantitate the blood flow of the anterior cruciate ligament in vivo. Functional flow was evaluated using laser Doppler flowmetry (LDF), for which the output signal, blood cell flux (BCF), is expressed in terms of volts. Ten patients undergoing routine arthroscopic surgery with clinically intact anterior cruciate ligaments were selected at random for participation in the study. Under arthroscopic visualization, a 2.2-mm probe was placed through a trocar sleeve into the anterior cruciate ligament after the arthroscopic procedure. Pulsatile flow within the ligament was observed in all patients. The mean maximum BCF value ranged from 101 to 274 mV; SD range was +/- 3-9 mV. The mean minimum BCF ranged from 75 to 197 mV; SD range was +/- 0 to 9 mV. Laser Doppler flowmetry offers significant promise as a method for measurement of in vivo anterior cruciate and cruciate substitution blood flow.     

Comparison of two laser Doppler flowmetry systems for bone blood flow analysis

Summary The development of laser Doppler flowmetry (LDF) has provided a real-time, reliable method for monitoring capillary perfusion in multiple tissues. LDF has potential for the experimental and clinical assessment of bone blood flow. To compare the accuracy and ease of use of two commercially available laser Doppler flowmeters with different mechanisms for processing the Doppler-shifted component of light, estimates of bone blood flow were obtained in a sheep model using the two systems, and the values derived then compared with estimates of bone blood flow also obtained in a sheep using the technique of injection of labeled microspheres. The single-channel laser Doppler flowmeter, the LD 5000, processes the reference and Doppler-shifted beams on the surface of a single photodetector using optical heterodyning for measurement. The dual-channel flowmeter, the Periflux 2, uses two optical fibers to transmit reference and Doppler-shifted light to two separate photodetectors. The differential amplification and detection system improves the signal-to-noise ratio. Measurement of both metaphyseal (cancellous) and diaphyseal (cortical) blood flow using both LDF systems was compared with values obtained with an injection of⁸⁵Sr-labeled microspheres in three sheep. The LDF measurements were repeated after occlusion of the left femoral artery, and a⁴⁶Sc microsphere injection was performed prior to animal sacrifice. Two of the animals developed vasomotor instability, resulting in poor correlation between the measurements obtained with the Periflux 2, which is motion sensitive, and the values obtained with the microsphere method. High correlation was apparent in two of the three animals for the LD 5000 and the microsphere values. Four additional sheep were evaluated using only the Periflux 2, and the data collected yielded R values of 0.6–0.98. Both the single- and dual-channel LDF systems offer accurate assessment of local cortical and cancellous bone blood flow.     

The effect of ketanserin on cerebral blood flow and cerebrovascular CO2 reactivity in healthy volunteers

Summary The effect of the anti-hypertensive agent ketanserin on the cerebral blood flow (CBF) and the cerebrovascular CO₂ reactivity was examined in 10 healthy volunteers. Ketanserin was administered as an intravenous bolus of 10 mg followed by an infusion of 6mg/h. Before administration CBF was measured by single photon emission computerized tomography (SPECT) of inhaled¹³³ Xenon. Then arterial CO₂ tension was subsequently decreased by voluntary hyperventilation and increased by breathing an air/CO₂ mixture. The relative changes in CBF induced by the changes in arterial CO₂ tension were estimated by the cerebral arterio-venous oxygen content difference method. One hour following the start of ketanserin infusion the SPECT measurement and CO₂ manipulations were repeated.The CO₂ reactivity (expressed as the slope of the regression line of the linear relation between CBF and PaCO₂), was unchanged, i.e. 3.2%/0.1 kPa before ketanserin and 4. 1%/0.1 kPa during ketanserin, respectively. Using regression lines from a semi-logarithmic plot the CO₂ reactivity was also unchanged 3.4%/0.1 kPa and 3.5%/0.1 kPa, respectively. Ketanserin did not change CBF. The cerebral oxygen metabolism (CMRO₂) was decreased 19% one hour after the start of infusion of ketanserin.In conclusion administration of ketanserin in a clinically relevant dose to healthy volunteers does not change the regional CBF not the cerebrovascular CO₂ reactivity, but a decrease in CMRO₂ was observed. However further studies are needed to clarify whether ketanserin in fact has a depressing effect on CMRO₂ or whether the different results are caused by methodological errors or stocastic variation.     

Applied cerebral physiology

This article reviews cerebral metabolism and blood flow, and the pressure dynamics within the cranial cavity. The brain functions within the confines of the cranial cavity and it is important to understand the dynamics of the parenchyma, cerebrospinal fluid and blood in relation to intracranial pressure (ICP) and metabolic needs. It requires an uninterrupted supply of oxygen and glucose to maintain its basal energy requirements and these are increased during periods of enhanced activity. Cerebral blood flow (CBF) is therefore critical for normal cerebral function. Its control is dictated by local intrinsic metabolic needs as well as extraneous factors such as arterial blood pressure, arterial carbon dioxide and oxygen tension, temperature and neural factors; all of which can be measured to guide therapy.     

Effects of desflurane on cerebral autoregulation

The aim of this study was to determine the effects of desflurane,at 1 and 1.5 MAC, on cerebral autoregulation. Data were analysedfrom eight patients undergoing non-neurosurgical procedure.The blood flow velocity in the middle cerebral artery was measuredby transcranial Doppler ultrasound and cerebral autoregulationwas assessed by the transient hyperaemic response test. Partialpressure of the end-tidal carbon dioxide (PE'_CO2) and mean arterialpressure were measured throughout the study. Anaesthesia wasinduced with propofol and was maintained with desflurane atend-tidal concentrations of 7.4% (1 MAC) or 10.8% (1.5 MAC).The order of administration of the desflurane concentrationswas determined randomly and a period of 15 min was allowed forequilibration at each concentration. The transient hyperaemicresponse tests were performed before induction of anaesthesiaand after equilibration with each concentration of desflurane.An infusion of phenylephrine was used to maintain pre-inductionmean arterial pressure and ventilation was adjusted to maintainthe pre-induction value of PE'_CO2 throughout the study. Twoindices derived from the transient hyperaemic response test(the transient hyperaemic response ratio and the strength ofautoregulation) were used to assess cerebral autoregulation.Desflurane resulted in a marked and significant impairment incerebral autoregulation; at concentrations of 1.5 MAC, autoregulationwas almost abolished. Br J Anaesth 2001; 87: 193–7     

CO2 cerebrovascular reactivity as a function of perfusion pressure — a modelling study

Summary A mathematical model is described that demonstrated the properties of cerebral vascular resistance and compliance expressed as a function of cerebral perfusion pressure (CPP) and arterial CO₂ partial pressure (PaCO₂). The hypercapnic induced shift of the lower limit of autoregulation to a higher range of CPP, as shown by this model, is a useful characteristic that facilitates the differentiation between normal and impaired autoregulation described previously in experimental studies. Dynamic properties of cerebrovascular circulation derived from the relationship between pulse wave of CBF waveform and CPP have been analysed at different levels of PaCO₂-phenomenon, being often described as dependence of blood flow velocity pulsatility index on the autoregulatory reserve. The model was also used to interpret interhemispheric asymmetry of CBF reactivity to changes in arterial concentration of CO₂ in patients with carotid artery stenosis.     

Renal vascular response to left atrial injection. An experimental study in the pig

It has previously been shown that a rapid, transient and pronounced reduction in superficial renal cortical blood flow can be elicited by injection of 1 ml of plasma into the left atrium of the anaesthetized pig. This renal vascular response might constitute an important error in measurements of renal blood flow by means of the microsphere technique. In the present study we have investigated total renal (ultrasonic Doppler) and superficial renal cortical (laser Doppler flowmetry) blood flow after left atrial injections of saline and autologous blood. The average reductions in total renal blood flow were 4.7 ± 2.4% (mean ± s.d.) and 18.4 ± 12.5% (mean ± s.d.) for the blood and saline injections, respectively. The flow reduction was more pronounced in the superficial renal cortex with average reductions of 17.4 ± 26.0% (mean ± s.d.) and 59.4 ± 38.5% (mean ± s.d.) for blood and saline, respectively (laser Doppler flowmetry). Furthermore, two consecutive injections of microspheres were performed. The results from the second injection were compared with those from the first injection. In the superficial renal cortex the second injection indicated a significant reduction in blood flow and an significantly increased heterogeneity in the blood flow in two different tissue volumes. No corresponding differences were found in the juxtamedullary cortex. These results indicate that the renal vascular response to a left atrial injection is detectable as a reduction in total renal blood flow and is most pronounced in the superficial renal cortex. All these results taken together constitute an important error in measurements of superficial renal cortical blood flow by the microsphere technique.     

Assessment of the relationship between standard probe and implantable fiber measurements of cortical bone blood flow: A canine study

Laser Doppler flowmetry (LDF) has been used to assess cortical bone blood flow in various clinical situations, such as osteomyelitis and osteonecrosis. Standard metal-sheathed probes containing optical fibers, applied to cortical bone for perfusion measurements, require direct exposure of the bone surface for each measurement, making nonanesthetized assessments over time impractical. Implantable optical fibers offer a noninvasive method for evaluating cortical bone perfusion without repeated surgical exposure of the bone after initial surgical implantation of the fibers.In vitro studies have shown the reliability of laser Doppler (LD) fibers compared with those of the standard probe. This investigation studied the relationship between measurements of cortical bone perfusion obtained by implanted optical (LD) fibers and standard (LDF) probesin vivo. Midshaft tibial fractures were created in the right hindlimb of 11 adult, large (>25 kg) dogs and stabilized by low contact-dynamic compression plate fixation. Cortical bone blood flow was measured by LDF using standard probes and implantable fibers at five sites along the tibia prefracture, postfracture, immediately postplate application, and at 10 weeks postplating, immediately prior to euthanasia. The implantable fibers were secured onto the cortical bone via the plate and led through a percutaneous exit site. Histological examination of the inguinal and popliteal lymph nodes and soft tissue surrounding the fibers revealed mild inflammation. No significant correlation of blood flow assessed by the implantable fibers and standard probe occurred immediately postfracture (r < 0.13,P > 0.62). However, a statistically significant correlation was seen postplate application at one of the measurement sites in the distal fracture fragment (r = 0.78,P < 0.003). The fibers remained intact and functional until an average of 3 weeks at which time they either fractured or were removed by the animals. This is the firstin vivo study assessing the reliability of implantable fibers for the measurement of cortical bone blood flow. Further modification of the fibers will be necessary to improve their longevity and durability for assessment of cortical bone blood flow.     

Cervical spinal cord stimulation increases cerebral cortical blood flow in an experimental cerebral vasospasm model

Summary Background. Cerebral microcirculatory changes during cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH) are still controversial and uncertain. The aim of our study is to demonstrate that spinal cord stimulation (SCS) augments cerebral cortical microcirculatory blood flow in an experimental cerebral vasospasm model by using Laser Doppler Flowmetry (LDF).Method. The experiments were carried out on 24 New Zealand rabbits. Three experimental groups were designed. In group 1, Cerebral cortical blood flow (CCoBF) was evaluated by LDF in 8 rabbits. In group 2, Intracisternal saline injection and cervical epidural electrode placement without SCS were performed in 8 animals before LDF. In group 3, LDF was performed before and after SCS on the 4^th day of SAH in 8 rabbits. CCoBF parameters obtained from LDF data were compared.Findings. The occurrence of vasospasm after SAH was demonstrated with significant changes in LDF values. In all SAH animals, SCS resulted in significant increase (30%) in CCoBF. This increase was observed to continue even after the cessation of the stimulation.Conclusions. These results indicate that SCS improves cortical ischemia due to vasospasm after induced SAH. The cervical SCS may constitute a new therapeutic modality in treating disturbed CCoBF due to vasospasm.     

Grading and outcome prediction of cases of aneurysmal subarachnoid haemorrhage by bedside xenon cerebral blood flowmetry

Summary Ninety-six patients with aneurysmal subarachnoid haemorrhage underwent serial measurement of regional cerebral blood flow throughout the period of their treatment over the period of 5 years (1983 to 1988). A portable bedside xenon cerebral blood flow machine was used in this study and the initial slope index (ISI) values showed a clear relationship between reduction of cerebral blood flow and deteriorating clinical grade. Furthermore, serial measurements showed a statistically significant relationship between drop of cerebral blood flow, at anytime during the course of the disease, and fatal or less than satisfactory outcome.     

Effects of haemorrhagic hypotension on the subcapsular artery and microvasculature of the rat testis

Developing germ cells may be sensitive to even moderate reductions in blood flow. Surprisingly, however, experimental evidence suggests that the rat testis may be unable to maintain its blood flow during a decrease in systemic blood pressure. This study was therefore performed in order to answer the following questions: Is the testis able to maintain its blood flow during moderate to major reductions in blood pressure and, if so, at which level of the testicular vasculature (main artery or microcirculation) does this compensatory response take place? Moderate (-20%) and major (-40%) reductions in blood pressure were induced in anaesthetized rats by haemorrhage and the effects on testicular microvascular blood flow and subcapsular testicular artery diameter were examined by using laser Doppler flowmetry and in vivo video-microscopy respectively. Haemorrhagic hypotension led to decreased local testicular blood flow, but the relative reductions in flow were generally only half as large as the reductions in blood pressure. Hypotension also decreased the diameter of the main subcapsular testicular artery. During large reductions in blood pressure the subcapsular testicular artery constricts and testicular blood flow decreases. However, blood flow is reduced proportionally less than the mean arterial pressure, suggesting that local regulatory mechanisms are present in the testicular microvasculature, which may prevent blood flow from falling below a critical level.     

Effect of adenosine-induced hypotension on the cerebral autoregulation in the anesthetized pig

The influence on cerebral blood flow (CBF) and autoregulation of systemic adenosine infusion, at doses that produced a 29 +/- 4% (0.28 +/- 0.06 mg/kg/min) or a 55 +/- 2% (0.49 +/- 0.07 mg/kg/min) reduction of mean arterial blood pressure (MABP), was evaluated in 12 normoventilated fentanyl/N2) anesthetized pigs. CBF was determined as sagittal sinus outflow and recorded continuously by an electromagnetic technique. Autoregulation was evaluated by two formal tests: infusion of angiotensin for elevation of MABP, and reduction of myocardial filling pressure by caval block for graded MABP decrease before, during and after adenosine infusion. CBF as well as cerebral metabolic rate of oxygen were unaffected during both levels of hypotension and were not significantly altered after the hypotension. Signs of impaired autoregulation were found during the angiotensin test as well as during the caval block at light hypotension (92 +/- 3 mmHg, 12.3 +/- 0.4 kPa), while autoregulation was completely abolished at moderate hypotension (59 +/- 2 mmHg, 7.9 +/- 0.3 kPa). After termination of adenosine-induced hypotension, autoregulation was restored in all animals within 60 min. It is concluded that systemically administered adenosine preserves CBF, even at low MABP levels, by a direct cerebral vasodilatory effect. However, the cerebral autoregulatory mechanisms are impaired or abolished in a dose-dependent and reversible manner.