Effects of Xenon on Cerebral Blood Flow and Cerebral Glucose Utilization in Rats

Background: The effects of xenon inhalation on mean and local cerebral blood flow (CBF) and mean and local cerebral glucose utilization (CGU) were investigated using iodo-[14C]antipyrine and [14C]deoxyglucose autoradiography.

Methods: Rats were randomly assigned to the following groups: conscious controls (n = 12); 30% (n = 12) or 70% xenon (n = 12) for 45 min for the measurement of local CBF and CGU; or 70% xenon for 2 min (n = 6) or 5 min (n = 6) for the measurement of local CBF only.

Results: Compared with conscious controls, steady state inhalation of 30 or 70% xenon did not result in changes of either local or mean CBF. However, mean CBF increased by 48 and 37% after 2 and 5 min of 70% xenon short inhalation, which was entirely caused by an increased local CBF in cortical brain regions. Mean CGU determined during steady state 30 or 70% xenon inhalation remained unchanged, although local CGU decreased in 7 (30% xenon) and 18 (70% xenon) of the 40 examined brain regions. The correlation between CBF and CGU in 40 local brain structures was maintained during steady state inhalation of both 30 and 70% xenon inhalation, although at an increased slope at 70% xenon.     

Bone Blood Flow in Conscious Dogs at Rest and During Exercise

Using the microsphere technique bone blood flow was measured in different anatomical and functional regions in long bones in conscious dogs. The measurements were performed during physical exercise upon a treadmill, and the bone blood flow values were obtained as prework resting values after 1 and 2 hours of exercise and after I hour of rest.

The perfusion rates increased 50 per cent from 1.6 to 2.5 ml 100 g tissue^-1 min^-1 in the femoral and tibial cortical bones during work. In the cancellous bone of the femoral head an increase from 12.6 to 20.6 ml 100 g tissue^-1 min^-1 was found. Equal flow responses were determined in the fat-filled tibia-condylar and femoral supracondylar bone. The increase took place after 2 hours' exercise, but nonstatisti-cally verified increased perfusion was found after 1 hour's work. The alternation in bone blood flow suggests that bone has a capability of physical vasodilatation during muscular work but the flow response is slow and therefore the vasodilatation seems mediated by a metabolically induced stimulus.     

Variability in the Magnitude of the Cerebral Blood Flow Response and the Shape of the Cerebral Blood Flow: Pressure Autoregulation Curve during Hypotension in Normal Rats

Background: The maintenance of constant cerebral blood flow (CBF) as mean cerebral perfusion pressure (CPP) varies is commonly referred to as CBF-pressure autoregulation. The lower limit of autoregulation is the CPP at which the vasodilatory capacity is exhausted and flow falls with pressure. We evaluated variability in the magnitude of percent change in CBF during the hypotensive portion of the autoregulatory curve. We hypothesize that this variability, in normal animals, obeys a Gaussian distribution and characterizes a vasodilatory mechanism that is inherently different from that described by the lower limit.

Methods: Sixty-five male Sprague-Dawley rats were anesthetized with 0.5-1% halothane and 70% nitrous oxide in oxygen. Body temperature was maintained at 37[degrees]C. Using a closed, superfused cranial window, CBF (as % of control) was determined using laser Doppler flowmetry (LDF) through the window with the intracranial pressure set at 10 mmHg. Animals with low vascular reactivity to inhaled carbon dioxide and superfused adenosine diphosphate (ADP) or acetylcholine were excluded. MABP was sequentially lowered by exsanguination to 100, 85, 70, 55, and 40 mmHg. Using the %CBF versus CPP plots for each curve (1) the lower limit of autoregulation was identified; (2) the pattern of autoregulation was classified as "peak" (a rise in LDF flow of at least 15% as arterial pressure was dropped), "classic" (plateau with a fall), or "none" (a fall in LDF flow of greater than 15%); (3) the area under the autoregulatory curve between CPPs of 30 and 90 mmHg was calculated; and (4) the magnitude of the %CBF response to hypotension was assessed by determining the %CBF at a CPP of 60 mmHg (%CBFCPP60).

Results: Of the 65 curves, 21 had the peak pattern, 33 the classic pattern, and 11 the none pattern. The %CBFCPP60 and autoregulatory area displayed Gaussian distributions, consistent with normal variability. Although %CBFCPP60, autoregulatory area, and pattern were significantly correlated (r or [rho] > 0.84, P < 0.001), the lower limit correlated weakly with autoregulatory area (r = 0.34, P = 0.012), and not at all with autoregulatory pattern or %CBFCPP60.     

Relationship between Local Cerebral Blood Flow and Metabolism during Mild and Moderate Hypothermia in Rats

Background: Hypothermia may interfere with the relationship between cerebral blood flow (CBF) and metabolism. Because this conclusion was based on the analysis of global values, the question remains whether hypothermic CBF/metabolism uncoupling exists on a local cerebral level. This study investigated the effects of hypothermic anesthesia on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU).

Methods: Thirty-six rats were anesthetized with isoflurane (1 minimum alveolar concentration) and artificially ventilated to maintain normal arterial carbon dioxide partial pressure (p H-stat). Pericranial temperature was maintained as normothermic (37.5[degrees]C, n = 12) or was reduced to 35[degrees]C (n = 12) or 32[degrees]C (n = 12). Pericranial temperature was maintained constant for 60 min until LCBF or LCGU were measured by autoradiography. Twelve conscious rats served as normothermic controls.

Results: Compared with conscious animals, mean CBF remained unchanged during normothermic anesthesia. Mean CBF significantly increased during mild hypothermia but was unchanged during moderate hypothermia. During normothermic anesthesia, mean CGU was 45% lower than in conscious controls (P < 0.05). No further CGU reduction was found during mild hypothermia, whereas CGU further decreased during moderate hypothermia (48%;P < 0.05). Local analysis showed a linear LCBF/LCGU relationship in conscious (r = 0.94) and anesthetized (r = 0.94) normothermic animals, as well as in both hypothermic groups (35[degrees]C: r = 0.92; 32[degrees]C: r = 0.95;P < 0.05). The LCBF-to-LCGU ratio increased from 1.4 (conscious controls) to 2.4 (normothermic isoflurane) and 3.6 ml/[mu]mol (mild and moderate hypothermia, P < 0.05).     

Local Cerebral Blood Flow, Local Cerebral Glucose Utilization, and Flow-Metabolism Coupling during Sevoflurane versus Isoflurane Anesthesia in Rats

Background: Compared to isoflurane, knowledge of local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) during sevoflurane anesthesia is limited.

Methods: LCGU, LCBF, and their overall means were measured in Sprague-Dawley rats (8 groups, n = 6 each) during sevoflurane and isoflurane anesthesia, 1 and 2 MAC, and in conscious control animals (2 groups, n = 6 each) using the autoradiographic 2-[(14) C]deoxy-D-glucose and 4-iodo-N-methyl-[(14) C]antipyrine methods.

Results: During anesthesia, mean cerebral glucose utilization was decreased: control, 56 +/- 5 [micro sign]mol [middle dot] 100 g-1 [middle dot]-1; 1 MAC isoflurane, 32 +/- 4 [micro sign]mol [middle dot] 100 g-1 [middle dot] min-1 (-43%); 1 MAC sevoflurane, 37 +/- 5 [micro sign]mol [middle dot] 100 g-1 [middle dot] min-1 (-34%); 2 MAC isoflurane, 23 +/- 3 [micro sign]mol [middle dot] 100 g-1 [middle dot] min-1 (-58%); 2 MAC sevoflurane, 23 +/- 5 [micro sign]mol [middle dot] 100 g-1 [middle dot] min-1 (-59%). Local analysis showed a reduction in LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased as follows: control, 93 +/- 8 ml [middle dot] 100 g-1 [middle dot] min-1; 1 MAC isoflurane, 119 +/- 19 ml [middle dot] 100 g-1 [middle dot] min-1 (+28%); 1 MAC sevoflurane, 104 +/- 15 ml [middle dot] 100 g-1 [middle dot] min-1 (+12%); 2 MAC isoflurane, 149 +/- 17 ml [middle dot] 100 g-1 [middle dot] min-1 (+60%); 2 MAC sevoflurane, 118 +/- 21 ml [middle dot] 100 g-1 [middle dot] min-1 (+27%). LCBF was increased in most brain structures investigated. Correlation coefficients obtained for the relationship between LCGU and LCBF were as follows: control, 0.93; 1 MAC isoflurane, 0.89; 2 MAC isoflurane, 0.71; 1 MAC sevoflurane, 0.83; 2 MAC sevoflurane, 0.59).     

Early Effects of Acid-Base Management during Hypothermia on Cerebral Infarct Volume, Edema, and Cerebral Blood Flow in Acute Focal Cerebral Ischemia in Rats

Background: Although the frequency for the use of moderate hypothermia in acute ischemic stroke is increasing, the optimal acid-base management during hypothermia remains unclear. This study investigates the effect of pH- and [alpha]-stat acid-base management on cerebral blood flow (CBF), infarct volume, and cerebral edema in a model of transient focal cerebral ischemia in rats.

Methods: Twenty Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h during normothermic conditions followed by 5 h of reperfusion during hypothermia (33[degrees]C). Animals were artificially ventilated with either [alpha]- (n = 10) or pH-stat management (n = 10). CBF was analyzed 7 h after induction of MCAO by iodo[14C]antipyrine autoradiography. Cerebral infarct volume and cerebral edema were measured by high-contrast silver infarct staining (SIS).

Results: Compared with the [alpha]-stat regimen, pH-stat management reduced cerebral infarct volume (98.3 +/- 33.2 mm3vs. 53.6 +/- 21.6 mm3;P >= 0.05 mean +/- SD) and cerebral edema (10.6 +/- 4.0%vs. 3.1 +/- 2.4%;P >= 0.05). Global CBF during pH-stat management exceeded that of [alpha]-stat animals (69.5 +/- 12.3 ml [middle dot] 100 g-1 [middle dot] min-1vs. 54.7 +/- 13.3 ml [middle dot] 100 g-1 [middle dot] min-1;P >= 0.05). The regional CBF of the ischemic hemisphere was 62.1 +/- 11.2 ml [middle dot] 100 g-1 [middle dot] min-1 in the pH-stat group versus 48.2 +/- 7.2 ml [middle dot] 100 g-1 [middle dot] min-1 in the [alpha]-stat group (P >= 0.05).     

Influence of Enflurane on Cerebral Blood Flow in Man

Cerebral blood flow was measured by means of a 10-channel cerebrograph in anesthe-tised patients before and during 2% enfluranc. This investigation was carried out after carotid angiography; 2 3 mCi Xe¹³³ was injected into the internal carotid artery. The clearance curves of Xe^l33 were captured by 10 scintillation counters. In addition to regional cerebral blood flow (rCBF), arterial blood pressure, heart rate, stroke volume, cardiac output and arterial blood gases were measured in seven adult patients.
During 2% enflurane, a small, and in two regions a significant decrease in rCBF was observed. Mean arterial pressure and heart rate decreased significantly, but cardiac output did not. The decrease in PaCo2 was not significant.     

Nitroprusside-Hypotension: Cerebral Blood Flow and Cerebral Oxygen Consumption in Neurosurgical Patients

The effects of nitroprusside-induced hypotension on cerebral blood flow and cerebral oxygen consumption were investigated in nine patients scheduled for cerebral arterial aneurysm surgery. Anesthesia was maintained with nitrous oxide/oxygen and fentanyl; muscle relaxation was achieved with pancuronium; Paco₂ was maintained at 4.79-5.32 kPa. Mean arterial pressure was reduced to 50 mm Hg by nitroprusside infusion after opening of the dura. Measurements were recorded and blood samples were taken 15 min before induction of hypotension, during stable hypotension and 15 min after termination of nitroprusside infusion. Measurements included: cerebral blood flow, using the argon-washin technique, cardiac output (thermodilution), mean arterial pressure and heart rate. Cerebral blood flow averaged 56 ± 6 ml/min. 100 g before hypotension. Nitroprusside produced hypotension but did not significantly alter cerebral blood flow (61 ± 7 ml/min · 100 g). Cerebral blood flow remained virtually at preinfusion values upon cessation of infusion (53 ± 6 ml/min · 100 g). Cerebral oxygen uptake averaged 3 ± 0.2 ml/min · 100 g before hypotension and did not change significantly during hypotension (3.3 ± 0.3 ml/min · 100 g) and after termination of hypotension (2.7 ± 0.3 ml/min · 100 g). In two patients nitroprusside produced a 17 and 20% increase, respectively, in cerebral blood flow with no change in cerebral oxygen consumption, together with a marked increase in cardiac output and heart rate.     

Regional Blood Flow in Experimental Myositis Ossificans: A Microsphere Study in Conscious Rabbits

In a recent model for heterotopic bone formation (Michelsson et al. 1980), muscular oedema, swelling and necrosis is seen in the quadriceps muscle of rabbit hind limbs immobilized for at least 2 weeks when, from the second week, the immobilized limb is subjected to daily forcible mobilization lasting about 5 min. According to this model, heterotopic calcification develops gradually from the second week of forcible mobilization and is located in the vastus intermedins region. Between the fourth and fifth week of immobilization and forcible mobilization, heterotopic bone formation is seen in virtually all cases. The histological findings are similar to those in human ectopic bone formation.

In the present investigation the labelled microsphere technique was used to study the regional blood flow effects in the early development of myositis ossificans with this model. The results are quite different from those reported by other investigators on immobilization alone and point to a causal relation between regional blood flow and forcible mobilization of the immobilized rabbit hind limb. Prostaglandins as mediators between the traumatic inflammation, a part of the circulatory effects observed and the induction of new bone is suggested.     

Role of Angiotensin II in Renal Vasoconstriction with Acute Hypoxemia and Hypercapnic Acidosis in Conscious Dogs

To evaluate the role ofrenin-angiotensin in the renal vasoconstriction with combined acute hypoxemia and hypercapnic acidosis preceded by acute hypoxemia, we studied eight conscious mongrel uninephrectomized dogs with chronic renal catheters and controlled sodium intake (80 mEq/24 h ± 4 days). The animals were studied during combined acute hypoxemia and hypercapnic acidosis (Pa_O2 34 ± 1 mm Hg, Pa_CO2 57 ± 1 mm Hg, pH 7.20 ± 0.01) preceded by 80 min of acute hypoxemia (Pa_O234 ± 1 mm Hg) during: (a) intrarenal infusion of vehicle (n = 8); or (b) intrarenal administration of the angiotensin II antagonist [Sar¹, Ala⁸]-AII, 70 ng kg^?1 min^?1 (n = 8). The combination of acute hypoxemia and hypercapnic acidosis resulted in diminished effective renal plasma flow and increased renal vascular resistance during intrarenal vehicle infusion. Intrarenal [Sar¹, Ala⁸]-AII did not abolish the renal vasoconstriction in the initial 20 min of this combined blood gas derangement but resulted in a more prompt return of the renal vascular variables toward control levels with continuation of the blood gas derangement for an additional 20 min, suggesting a role for angiotensin in renal vasoconstriction. These observations suggest that while rennin—angiotensin may not mediate the initial renal vasoconstriction in the first 20 min of combined acute hypoxemia and hypercapnic acidosis, in uninephrectomized conscious dogs, it attenuates the spontaneous recovery of renal hemodynamic variables to baseline as the blood gas derangement continues.     

Cerebral Blood Flow in the Acute Phase after Head Injury

In 40 comatose patients with severe head injury, cerebral blood flow (CBF) studies were performed with the 133Xenon washout technique over the most severely injured hemisphere. All patients were mildly sedated with diazepam, chlorpromazine and meperidine and subjected to respiratory support. Simultaneously with the CBF study, intraventricular pressure (IVP), systemic arterial pressure (SAP) and ventricular fluid (VF) lactate, pyruvate and pH were measured. The results indicate a positive correlation between CBF and lactate in patients with a good recovery, irrespective of the time after the trauma, and a positive correlation irrespective of outcome, if the measurements were performed more than 3 days after the trauma. In patients with mainly supratentorial lesions without signs of brain-stem lesions, CBF and CPP were positively correlated, while CBF and ICP were negatively correlated (lost autoregulation). In contradistinction, CBF was positively correlated to ICP and PaCO2 in patients with diffuse brain injury. In some cases of repeated dynamic studies, the clinical course seemed to be related to changes in the measured parameters.     

Controlled Hypotension with Sodium Nitroprusside: Effects on Cerebral Blood Flow and Cerebral Venous Blood Gases in Patients Operated for Cerebral Aneurysms

The effect on cerebral haemodynamics of arterial hypotension induced by sodium nitroprusside infusion was studied in nine patients at the end of operations for intracranial aneurysms under N2O-O2-halothane anaesthesia. Cerebral blood flow (CBF), using the intraarterial 133Xe injection method, and cerebral jugular venous blood gases were monitored before, during and after the induced hypotension. CBF and jugular venous oxygen tension (PvO2) remained constant during the hypotensive period. Following its termination, a 13% increase in CBF occurred (P less than 0.05) and PvO2 showed the same trend, a 5% increase (P less than 0.30). Regional CBF recordings (rCBF) in 16 small areas within the cerebral hemisphere were obtained at each measurement. In four of the patients, rCBF abnormalities were present in the form of hyperaemic regions, probably induced by the operation or the disease itself. The focal abnormalities were not accentuated during hypotension nor were ischaemic regions disclosed. It is concluded that sodium nitroprusside has only a minor influence on cerebral haemodynamics in the anaesthetized state.     

Effects of Fentanyl on Local Cerebral Blood Flow in the Rat

Fentanyl reduces the cortical cerebral blood flow and metabolic rate for oxygen in rats, though seizure activity occurs in some animals at high doses. However, the effects of fentanyl on blood flow and metabolism in subcortical structures have not been clearly delineated. The present study examines the effects of intravenous fentanyl (100 or 400 μg·kg^-1) on local cerebral blood flow (1-CBF) in paralyzed, mechanically ventilated rats. Rats ventilated with 70% N₂O in 30% O₂ served as controls. Local CBF was measured using ¹⁴C-iodoantipyrine and autoradiography. Blood pressure, Pao₂, Paco₂, pH, and temperature were comparable in all groups. The EEG showed slow wave activity in most animals given 100 μg·kg^-1 fentanyl while seizure activity occurred in all animals given 400 μg·kg^-1 fentanyl. With 100 μg·kg^-1 fentanyl, CBF tended to be depressed in all cortical and subcortical areas, except the peri-aqueductal gray; and with 400 μg·kg^-1 fentanyl, 1-CBF tended to be elevated (compared to 100 μg·kg^-1 fentanyl) in most areas of the brain. The limbic system structures, however, were most affected by 400 μg·kg^-1 fentanyl with statistically significant increases (compared to the 100 μg · kg^-1 group) in 1-CBF of 86% and 67% respectively in the amygdala and septal nucleus. These results confirm that moderately high doses of fentanyl which cause slow wave activity on the EEG also depress 1-CBF in rats; moreover, doses of fentanyl that produce seizure activity produce increases in 1-CBF in most cerebral structures with greatest effects on limbic system 1-CBF.     

Propofol and Thiopental Do Not Interfere with Regional Cerebral Blood Flow Response at Sedative Concentrations

Background: Anesthetics may affect the regional cerebral blood flow (rCBF) response associated with increased brain activity in humans. rCBF was measured as auditory stimulus rate was increased during propofol and thiopental administration.

Methods: After informed consent, 10 right-handed male volunteer participants (aged 33.5 +/- 10.4 yr, weighing 74.5 +/- 8.4 kg) received thiopental (n = 4) or propofol (n = 6) intravenously at stepwise target concentrations of propofol 1.2 and 2.5-3, or thiopental 4 and 7-9 [mu]g/ml, representing sedative and hypnotic drug concentrations. The latter made volunteers unresponsive to voice or mild stimulation. Quantitative positron emission tomographic brain images were obtained at 0, 20, and 40 auditory words per minute at each drug concentration. Using SPM99 analysis, 10-mm spherical regions of interest were identified by peak covariation of word rate with rCBF across all conditions and drug concentrations. Individual mean rCBF responses in these and primary auditory cortex (Heschl's gyri) were obtained.

Results: Significant increases in rCBF with auditory word rate occurred in temporal lobes bilaterally at baseline (significance, T = 4.95). There was no change in this response during sedation (T = 5.60). During unresponsiveness seven of 10 participants had a diminished response in the left temporal lobe (T = 3.18). Global CBF, corrected for changes in Pco2 (3% [middle dot]mmHg Pco2-1), was reduced 15% by sedation and 27% during unresponsiveness.