Quantitative cerebral blood flow and metabolism determination in the first 48 hours after severe head injury with a new dynamic SPECT device

OBJECTIVE: To determine cerebral blood flow (CBF) and metabolism in the acute phase after severe head injury by a new dynamic SPECT device using 133Xenon and to evaluate a possible role of CBF and metabolism in the determination of prognosis. DESIGN: Prospective study. SETTING: General intensive care unit in a universitary teaching hospital. SUBJECTS: 23 severely head injured patients having CT scan and CBF determination, intracranial pressure (ICP) and jugular bulb oxygen saturation monitoring in the first 48 hours. MEASUREMENTS AND MAIN RESULTS: CBF varied from 18.0 to 60.0 ml/100 g/min. No correlation was found between early CBF and severity of trauma evaluated with the Glasgow Coma Score (GCS) (F = 2.151, p = 0.142) and between CBF and prognosis at 6 months evaluated with Glasgow outcome score (GOS) (F = 0.491, p = 0.622: rs = 0.251, p = 0.246). CMRO2 was depressed in relation to the severity of injury, specifically ranging from 0.9 +/- 0.5 ml/100 g/min in patients with GCS 3 to 1.7 +/- 0.8 ml/100 g/min in patients with GCS 6-7. In no patient with CMRO2 less than 0.8 ml/100 g/min was a good outcome observed. A significant correlation was found between GCS and GOS (rs = 0.699, p = 0.0002), between CMRO2 and GOS (F = 4.303, p = 0.031; rs = 0.525, p = 0.013) and between AJDO2 and GOS (F = 3.602, p = 0.046; rs = 0.491, p = 0.017). Fronto-occipital ratio (F/O) of CBF distribution was significantly lower than normal values (chi 2 = 18.658, p = 0.001) but did not correlate either with prognosis (chi 2 = 1.626, p = 0.443) or with severity (chi 2 = 1.913, p = 0.384). CONCLUSIONS: CBF in the first 48 hours after trauma varies within a large range of values and is not correlated with severity and prognosis. Clinical evaluation with GCS and CMRO2 are much more reliable indicators of severity of head trauma and have a significant role in the determination of prognosis. F/O ration is significantly altered from normal values confirming "post-traumatic hypofrontalism" but does not correlate with severity and prognosis.     

Pulsatile versus nonpulsatile cardiopulmonary bypass. No difference in brain blood flow or metabolism at 27 degrees C

BACKGROUND: It is unclear whether nonpulsatile perfusion adversely affects the brain. This study compared cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) betwen pulsatile and nonpulsatile cardiopulmonary bypass (CPB) in rabbits at 27 degrees C. METHODS: In experiment A, 24 anesthetized New Zealand white rabbits underwent pulsatile CPB at 27 degrees C, using alpha-stat acid-base management. Animals were randomized to three groups based upon the duration of the period of systolic ejection (100, 120, 140 ms) and were perfused for 20 min at each of three pulse rates (150, 200, 250 pulse/min), generating nine arterial pressure waveforms. Arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (radiolabeled microspheres), and CMRO2 (Fick) were measured at the end of each 20-min period. In experiment B, 16 anesthetized rabbits were randomized to pulsatile (120-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 27 degrees C. AFter 1 h, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF and CMRO2 were measured. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all nine waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile bypass, 30 +/- 4 versus 32 +/- 5 ml.100 g-1.min-1, respectively. CMRO2 did not differ between pulsatile and nonpulsatile bypass, 1.7 +/- 0.2 versus 1.6 +/- 0.2 ml.100 g-1.min-1, respectively. CONCLUSIONS: During CPB in rabbits at 27 degrees C, neither CBF nor CMRO2 is affected by flow character.     

Vasopressin combined with epinephrine decreases cerebral perfusion compared with vasopressin alone during cardiopulmonary resuscitation in pigs

BACKGROUND AND PURPOSE: It is unknown whether a combination of vasopressin and epinephrine may be superior to vasopressin alone by targeting both nonadrenergic and adrenergic receptors. METHODS: After 15 minutes of cardiac arrest (13 minutes of ventricular fibrillation and 2 minutes of pulseless electrical activity) and 3 minutes of chest compressions, 16 animals were randomly treated with either 0.8 U/kg vasopressin (n = 8) or 0.8 U/kg vasopressin combined with 200 microg/kg epinephrine (n = 8). RESULTS: Comparison of vasopressin with vasopressin and epinephrine at 90 seconds and 5 minutes after drug administration resulted in comparable mean (+/-SEM) coronary perfusion pressure (54+/-3 versus 57+/-5 and 36+/-4 versus 35+/-4 mm Hg, respectively), cerebral perfusion pressure (59+/-6 versus 65+/-8 and 40+/-6 versus 39+/-6 mm Hg, respectively), and median (25th to 75th percentiles) left ventricular myocardial blood flow [116 (81 to 143) versus 108 (97 to 125) and 44 (35 to 81) versus 62 (42 to 74) mL x min(-1) x 100 g(-1), respectively], but significantly increased (P<0.05) total cerebral blood flow [81 (77 to 95) versus 39 (34 to 58) and 50 (43 to 52) versus 28 (16 to 35) mL x min(-1) x 100 g(-1), respectively]. Return of spontaneous circulation rates in both groups were comparable (vasopressin, 7 of 8; vasopressin and epinephrine, 6 of 8). CONCLUSIONS: Comparison of vasopressin with vasopressin and epinephrine resulted in comparable left ventricular myocardial blood flow but significantly increased cerebral perfusion.     

Heparin inhibits leukocyte rolling in pial vessels and attenuates inflammatory changes in a rat model of experimental bacterial meningitis

Heparin is a natural proteoglycan that was first described in 1916. In addition to its well characterized effect on blood coagulation, it is becoming clear that heparin also modulates inflammatory processes on several levels, including the interference with leukocyte-endothelium interaction. Anecdotal observations suggest a better clinical outcome of heparin-treated patients with bacterial meningitis. The authors demonstrate that heparin, a glycosaminoglycan, inhibits significantly in the early phase of experimental pneumococcal meningitis the increase of 1) regional cerebral blood flow (125 +/- 18 versus 247 +/- 42%), 2) intracranial pressure (4.5 +/- 2.0 versus 12.1 +/- 2.2 mm Hg), 3) brain edema (brain water content: 78.23 +/- 0.33 versus 79.49 +/- 0.46%), and 4) influx of leukocytes (571 +/- 397 versus 2400 +/- 875 cells/microL) to the cerebrospinal fluid compared with untreated rats. To elucidate the possible mechanism of this observation, the authors investigated for the first time leukocyte rolling in an inflammatory model in brain venules by confocal laser scanning microscopy in vivo. Heparin significantly attenuates leukocyte rolling at 2, 3, and 4 hours (2.8 +/- 1.3 versus 7.9 +/- 3.2/100 microm/min), as well as leukocyte sticking at 4 hours (2.1 +/- 0.4 versus 3.5 +/- 1.0/100 microm/min) after meningitis induction compared with untreated animals. The authors conclude that heparin can modulate acute central nervous system inflammation and, in particular, leukocyte-endothelium interaction, a key process in the cascade of injury in bacterial meningitis. They propose to evaluate further the potential of heparin in central nervous system inflammation in basic and clinical studies.     

Effects of cisatracurium on cerebral and cardiovascular hemodynamics in patients with severe brain injury

BACKGROUND: For neuroanesthesia and neurocritical care the use of drugs that do not increase or preferentially decrease intracranial pressure (ICP) or change cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) are preferred. The current study investigates the effects of a single rapid bolus dose of cisatracurium on cerebral blood flow velocity, ICP, CPP, mean arterial pressure (MAP) and heart rate (HR) in 24 mechanically ventilated patients with intracranial hypertension after severe brain trauma (Glasgow coma scale <6) under continuous sedation with sufentanil and midazolam. METHODS: Patients were randomly assigned to receive either 2xED95 (n=12) or 4xED95 (n=12) of cisatracurium as a rapid i.v. bolus injection. Before and after bolus administration mean cerebral blood flow velocity (BFV, cm/s) was measured in the middle cerebral artery using a 2-MHz transcranial Doppler sonography system, ICP (mm Hg) was measured using an extradural probe, and MAP (mm Hg) and HR (b/min) were measured during a study period of 20 min. Cerebral perfusion pressure (CPP=MAP-ICP) was also calculated. RESULTS: Our data show that a single bolus dose of up to 4xED95 cisatracurium caused no significant (P<0.05) changes in BFV, ICP, CPP, MAP and HR. Possible histamine-related events were not observed during the study. CONCLUSIONS: The results from this study suggest that cisatracurium is a safe neuromuscular blocking agent for use in adult severe brain-injured patients with increased ICP under mild hyperventilation and continuous sedation.     

Effect of the no-flow interval and hypothermia on cerebral blood flow and metabolism during cardiopulmonary resuscitation in dogs

BACKGROUND and PURPOSE: We sought (1) to determine the effect of brief periods of no flow on the subsequent forebrain blood flow during cardiopulmonary resuscitation (CPR) and (2) to test the hypothesis that hypothermia prevents the impact of the no-flow duration on cerebral blood flow (CBF) during CPR. METHODS: No-flow intervals of 1.5, 3, and 6 minutes before CPR at brain temperatures of 28 degreesC and 38 degreesC were compared in 6 groups of anesthetized dogs. Microsphere-determined CBF and metabolism were measured before and during vest CPR adjusted to maintain cerebral perfusion pressure at 25 mm Hg. RESULTS: Increasing the no-flow interval from 1.5 to 6 minutes at 38 degreesC decreased the CBF (18. 6+/-3.6 to 6.1+/-1.7 mL/100 g per minute) and the cerebral metabolic rate (2.1+/-0.3 to 0.7+/-0.2 mL/100 g per minute) during CPR. Cooling to 28 degreesC before and during the arrest eliminated the detrimental effects of increasing the no-flow interval on CBF (16. 8+/-1.0 to 14.8+/-1.9 mL/100 g per minute) and cerebral metabolic rate (1.1+/-0.1 to 1.3+/-0.1 mL/100 g per minute). Unlike the forebrain, 6 minutes of preceding cardiac arrest did not affect brain stem blood flow during CPR. CONCLUSIONS: Increasing the no-flow interval to 6 minutes in normothermic animals decreases the supratentorial blood flow and cerebral metabolic rate during CPR at a cerebral perfusion pressure of 25 mm Hg. Cooling to 28 degreesC eliminates the detrimental impact of the 6-minute no-flow interval on the reflow produced during CPR. The brain-protective effects of hypothermia include improving reflow during CPR after cardiac arrest. The effect of hypothermia and the impact of short durations of no flow on reperfusion indicate that increasing viscosity and reflex vasoconstriction are unlikely causes of the "no-reflow" phenomenon.     

Short-term lack of cerebral perfusion with good outcome. Advantages of early intracranial pressure monitoring

A 21-year-old man was injured by a tailboard of a truck. He suffered a severe head injury with bilateral depressed skull fractures necessitating surgical decompression. On admission to the hospital the patient showed bending to pain stimuli (Glasgow Coma Score 5). Anisocoria was noticed from the beginning. Initial intracranial pressure (ICP), measured 3 hours after injury, was 30 mm Hg, and the cerebral perfusion pressure (CPP) was 70 mm Hg. During surgical elevation of the skull fracture on the right side an un-explainable rise of ICP to values of 100 mm Hg occurred, which corresponded to the mean arterial blood pressure (MAP). At the same time both pupils were dilated and fixed indicating a lack of cerebral perfusion. Due to immediate trephination of the opposite side, the ICP was lowered to values below 20 mm Hg, and sufficient cerebral perfusion (above 50 mm Hg) was regained. The patient showed a good recovery and was transferred to a rehabilitation center 5 weeks after injury. This case report emphasizes the importance of early and continuous intracranial pressure monitoring for adequate therapy in neurosurgical emergencies.     

Pulsatile versus nonpulsatile flow. No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits

BACKGROUND: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees C. METHODS: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees C for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees C. At 30 and 60 min of CPB, physiologic measurements were made as before. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 +/- 6 vs. 77 +/- 9 ml.100 g-1.min-1, respectively (median +/- quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 +/- 0.5 vs. 4.1 +/- 0.6 ml O2.100 g-1.min-1, respectively) and decreased slightly (0.4 +/- 0.4 ml O2.100 g-1.min-1) between measurements. CONCLUSIONS: During CPB in rabbits at 37 degrees C, neither CBF nor CMRO2 is affected by arterial pulsation. The absence of pulsation per se is not responsible for the small decreases in CMRO2 observed during CPB.     

Determination of optimum retrograde cerebral perfusion conditions

Retrograde cerebral perfusion through a superior vena caval cannula is a new technique used to protect the brain during operations on the aortic arch. We measured cerebral tissue blood flow, oxygen consumption, and cerebrospinal fluid pressure under various perfusion conditions in hypothermic (20 degrees C) mongrel dogs (n = 18, 12.8 +/- 0.6 kg) to determine the optimum conditions for retrograde cerebral perfusion. Retrograde cerebral perfusion was performed by infusion via the superior vena caval cannula and drainage via the ascending aortic cannula while the inferior vena cava and azygos vein were clamped. Retrograde cerebral perfusion was performed as the external jugular venous pressure was changed from 15 to 35 mm Hg in increments of 5 mm Hg. Cerebral tissue blood flow was measured by the hydrogen clearance method. Hypothermic retrograde cerebral perfusion with an external jugular venous pressure of 25 mm Hg provided about half the cerebral tissue blood flow of hypothermic (20 degrees C) cardiopulmonary bypass with a flow rate of 1000 ml/min (13.7 +/- 7.9 versus 32.7 +/- 8.5 ml/min per 100 gm). It decreased significantly as the external jugular venous pressure was decreased from 25 to 15 mm Hg but did not increase significantly as the external jugular venous pressure was increased from 25 to 35 mm Hg. Whole-body oxygen consumption during hypothermic retrograde cerebral perfusion with an external jugular venous pressure of 25 mm Hg was one quarter of that during hypothermic cardiopulmonary bypass (3.4 +/- 0.7 versus 12.7 +/- 5.6 ml/min) and varied in proportion to external jugular venous pressure. The cerebrospinal fluid pressure was a little lower than the external jugular venous pressure (19.2 +/- 4.5 mm Hg versus 24.8 +/- 2.4 mm Hg) but also varied with the external jugular venous pressure. The cerebrospinal fluid pressure remained lower than 25 mm Hg so long as the external jugular venous pressure remained lower than 25 mm Hg. High external jugular venous pressure was associated with high intracranial pressure, which restricts cerebral tissue blood flow and may cause brain edema. We believe that a venous pressure of 25 mm Hg is the optimum condition for retrograde cerebral perfusion.     

Effect of modified ultrafiltration in high-risk patients undergoing operations for congenital heart disease

BACKGROUND: Modified ultrafiltration (MUF) after cardiopulmonary bypass (CPB) in children decreases body water, removes inflammatory mediators, improves hemodynamics, and decreases transfusion requirements. The optimal target population for MUF needs to be defined. This prospective, randomized study attempted to identify the best candidates for MUF during operations for congenital heart disease. METHODS: Informed consent was obtained from 100 consecutive patients with complex congenital heart disease undergoing operations with CPB. They were randomized into a control group (n = 50) of conventional ultrafiltration during bypass and an experimental group using dilutional ultrafiltration during bypass and venovenous modified ultrafiltration after bypass (MUF group, n = 50). Postoperative arterial oxygenation, duration of ventilatory support, transfusion requirements, hematocrit, chest tube output, and time to chest tube removal were compared between the groups stratified by age and weight, CPB technique, existence of preoperative pulmonary hypertension, and diagnosis. RESULTS: There were no MUF-related complications. In patients with preoperative pulmonary hypertension, MUF significantly improved postoperative oxygenation (445 +/- 129 mm Hg versus control: 307 +/- 113 mm Hg, p = 0.002), shortened ventilatory support (42.9 +/- 29.5 hours versus control: 162.4 +/- 131.2 hours, p = 0.0005), decreased blood transfusion (red blood cells: 16.2 +/- 18.2 mL/kg versus control: 41.4 +/- 27.8 mL/kg, p = 0.01; coagulation factors: 5.3. +/- 6.9 mL/kg versus control: 32.3 +/- 15.5 mL/kg, p = 0.01), and led to earlier chest tube removal. In neonates (< or =30 days), MUF significantly reduced transfusion of coagulation factors (5.4 +/- 5.0 mL/kg versus control: 39.9 +/- 25.8 mL/kg, p = 0.007), and duration of ventilatory support (59.3 +/- 36.2 hours versus 242.1 +/- 143.1 hours, p = 0.0009). In patients with prolonged CPB (>120 minutes), MUF significantly reduced the duration of ventilatory support (44.7 +/- 37.0 hours versus 128.7 +/- 133.4 hours, p = 0.002). No significant differences were observed between MUF and control patients for any parameter in the presence of ventricular septal defect without pulmonary hypertension, tetralogy of Fallot, or aortic stenosis. CONCLUSIONS: Modified ultrafiltration after CPB is safe and decreases the need for homologous blood transfusion, the duration of ventilatory support, and chest tube placement in selected patients with complex congenital heart disease. The optimal use of MUF includes patients with preoperative pulmonary hypertension, neonates, and patients who require prolonged CPB.     

Changes in maternal middle cerebral artery blood flow velocity associated with general anesthesia in severe preeclampsia

In women with severe preeclampsia, significant increases in mean arterial pressures (MAP) are common after rapid induction of general anesthesia (GA) and tracheal intubation. The objectives of this prospective study were to assess the effects of the rapid induction-intubation technique on middle cerebral artery (MCA) flow velocity in severe preeclampsia and to examine the correlation between mean MCA flow velocity (Vm) and MAP. Eight women with severe preeclampsia (study group) and six normotensive women at term (control group) scheduled to undergo cesarean section under GA were studied. Before induction, patients in the study group received i.v. labetalol in divided doses to lower diastolic pressures to <100 mm Hg. Anesthesia was induced with pentothal 4-5 mg/kg, followed by succinylcholine 1.5 mg/kg to facilitate tracheal intubation. A transcranial Doppler was used to measure Vm. Both Vm and MAP were recorded before induction and every minute for 6 min after intubation. In the study group, after the administration of labetalol, MAP decreased from 129 +/- 9 to 113 +/- 9 mm Hg (P < 0.05), and Vm decreased from 59 +/- 11 to 54 +/- 10 cm/s (P < 0.05). After intubation, MAP increased from 113 +/- 9 to 134 +/- 5 mm Hg (P < 0.001), and Vm increased from 54 +/- 10 to 70 +/- 10 cm/s (P < 0.001). In the control group, while MAP increased significantly from 89 +/- 6 to 96 +/- 4 mm Hg (P < 0.05) after intubation, the concurrent increase in Vm from 49 +/- 5 to 54 +/- 7 cm/s was not significant. There was a significant positive pooled correlation between Vm and MAP (r = 0.5, P < 0.0006) in the study group but not in the control group (r = 0.24). After induction and intubation, both Vm and MAP values were significantly increased in the study group patients at all observation points compared with the control group patients. The findings indicate that Vm increases significantly after rapid-sequence induction of GA and tracheal intubation in women with severe preeclampsia, and there seems to be a direct relationship between MAP and Vm. Implications: In women with severe preeclampsia, rapid-sequence induction of general anesthesia and tracheal intubation can cause severe hypertension. Our results indicate that the increase in blood pressure is associated with a significant increase in maternal cerebral blood flow velocity and that there is a significant correlation between these two variables.     

Effects of mild (33 degrees C) and moderate (29 degrees C) hypothermia on cerebral blood flow and metabolism, lactate, and extracellular glutamate in experimental head injury

The effects of mild (33 degrees C) and moderate (29 degrees C) hypothermia were investigated to determine which temperature was more effective against compression-induced cerebral ischemia. Eighteen cats were anesthetized. The animals were divided into three groups according to deep-brain temperature (control, 37 degrees C; mild hypothermia, 33 degrees C; and moderate hypothermia, 29 degrees C). Intracranial pressure (ICP) and cerebral blood flow (CBF) were monitored, the latter by hydrogen clearance. Arteriovenous oxygen difference (AVDO2) and cerebral venous oxygen saturation (ScvO2) were measured in blood samples from the superior sagittal sinus. The cerebral metabolic rate of oxygen (CMRO2) and the cerebral metabolic rate of lactate (CMR lactate) were calculated. Extracellular glutamate was measured by microdialysis. ICP was increased by inflation of an epidural balloon until CBF became zero, and this ischemia was maintained for 5 min, after which the balloon was quickly deflated. All parameters were recorded over 6 h. Evans blue was injected to examine vascular permeability changes. CBF was decreased by 56% by mild hypothermia and by 77% by moderate hypothermia. Mild hypothermia had a coupled metabolic suppression whereas moderate hypothermia significantly increased AVDO2 and decreased ScvO2, producing a low CBF/CMRO2 (relative ischemia). After balloon deflation, all three groups showed reactive hyperemia, which was significantly reduced by mild and moderate hypothermia. CBF then decreased to 50% of pre-inflation values and ScvO2 decreased (post-ischemic hypoperfusion). CBF/CMRO2, ScvO2, and AVDO2 did not differ significantly between the three groups. After balloon deflation, all three groups showed increased CMR lactate, which was significantly reduced by mild and moderate hypothermia. Extracellular glutamate increased in control animals (3.8 +/- 1.72 microM), an effect most effectively suppressed in the mild hypothermia group (1.0 +/- 0.46 microM). Damaged tissue volumes as indicated by Evans blue dye extravasation were 729 +/- 89 mm3 in control, 247 +/- 56 mm3 in mild hypothermia, and 267 +/- 35 mm3 in moderate hypothermia animals. These data suggest that mild hypothermia (33 degrees C) might be the optimal brain temperature to treat compression-related cerebral ischemia.     

Effect of N-methyl-D-aspartate receptor blockade on the control of cerebral O2 supply/consumption balance during hypoxia in newborn pigs

Using dizocilpine (MK-801), we tested the hypothesis that N-methyl-D-aspartate (NMDA) receptors are important controllers of cerebral O2 supply/consumption balance in newborn piglets both during normoxia and hypoxia. Twenty-five 2 to 7-day-old piglets were anesthetized and divided into four groups: (1) Normoxia (n = 6), (2) Normoxia + MK-801 (n = 6), (3) Hypoxia (n = 6), and (4) Hypoxia + MK-801 (n = 7). Regional cerebral blood flow (rCBF) in ml/min/100 g was measured using 14C-iodoantipyrine, and we determined arterial and venous O2 saturations by microspectrophotometry, calculating cerebral O2 consumption (VO2) in ml O2/min/100 g in the cortex, hypothalamus and pons. MK-801 did not significantly affect regional VO2 or rCBF in normoxic piglets. Hypoxia resulted in an increase in local rCBF compared to controls: from 41 +/- 6 to 103 +/- 18 in the cortex; 34 +/- 7 to 101 +/- 20 in the hypothalamus; and 45 +/- 10 to 95 +/- 11 in the pons. Pretreatment with MK-801 abolished this hypoxic flow effect in the cortex (51 +/- 2) and hypothalamus (49 +/- 5), but not in the pons (91 +/- 17). Similar results were observed for VO2 with control values of 1.9 +/- 0.3, 1.6 +/- 0.2 and 2.1 +/- 0.3 for the cortex, hypothalamus and pons respectively. Hypoxia resulted in an increase in the VO2 to 3.9 +/- 0.4 (cortex), 3.8 +/- 0.6 (hypothalamus) and 3.9 +/- 0.8 (pons). Pretreatment with MK-801 prior to hypoxia abolished these effects in the cortex (2.1 +/- 0.2) and hypothalamus (2.1 +/- 0.2), but not in the pons (2.9 +/- 0.2). These findings suggest that NMDA receptors may play a role in the control of cerebral metabolism during hypoxia in this immature porcine model.     

Maintenance of baseline angiotensin II potentiates insulin hypertension in rats

Chronic insulin infusion in rats increases mean arterial pressure (MAP) by a mechanism dependent on angiotensin II (Ang II). However, the fact that plasma renin activity (PRA) decreases with insulin infusion suggests that Ang II sensitivity is increased and that the parallel reduction in Ang II may partly counteract any hypertensive action of insulin. This study tested that hypothesis by clamping Ang II at baseline levels during chronic insulin infusion. Sprague-Dawley rats were instrumented with artery and vein catheters, and MAP was measured 24 hours per day. In seven angiotensin clamped rats (AC rats), renin-angiotensin II system activity was clamped at normal levels throughout the study by continuous intravenous infusion of the angiotensin-converting enzyme inhibitor benazepril at 5 mg/kg per day (which decreased MAP by 18+/-2 mm Hg) together with intravenous Ang II at 5 ng/kg per minute. Control MAP in AC rats after clamping averaged 99+/-1 mm Hg, which was not different from the 101+/-2 mm Hg measured before clamping Ang II levels. Control MAP in the 8 vehicle-infused rats averaged 105+/-2 mm Hg. A 7-day infusion of insulin (1.5 mU/kg per minute IV) plus glucose (20 mg/kg per minute IV) increased MAP in both groups of rats; however, the increase in MAP was significantly greater in AC rats (12+/-1 versus 5+/-1 mm Hg). This enhanced hypertensive response to insulin in AC rats was associated with a greater increase in renal vascular resistance (153+/-10% versus 119+/-6% of control) and a significant increase in renal formation of thromboxane (149+/-11% of control). Thus, decreased Ang II during insulin infusion limits the renal vasoconstrictor and hypertensive actions of insulin, and this may be caused, at least in part, by attenuation of renal thromboxane production.     

Differential regional hemodynamic effects of corticotropin in conscious sheep

The regional hemodynamic effects of 5 days of intravenous infusion of corticotropin (ACTH) (5 micrograms/kg per day) were examined in conscious sheep (n = 8). Mean arterial pressure increased from 81 +/- 2 to 93 +/- 3 mm Hg (P < .001) on day 2 of ACTH and remained at this level during the infusion. Cardiac output increased from 5.13 +/- 0.19 to 6.06 +/- 0.33 L/min (P < .01) because of an increase in stroke volume from 65 +/- 4 to 79 +/- 8 mL per beat (P < .01); heart rate remained unchanged. ACTH did not alter total peripheral conductance but had differential effects on regional conductances. Mesenteric conductance fell from 5.8 +/- 0.2 to a minimum of 4.9 +/- 0.3 (mL/min)/mm Hg (P < .05), and renal conductance increased from 3.5 +/- 0.3 to 4.6 +/- 0.3 (mL/min)/mm Hg (P < .001). There was a small increase in iliac conductance (P < .05) and no change in coronary conductance. Mesenteric and iliac conductances fell progressively over 24 to 48 hours, whereas renal conductance increased rapidly after 3 hours of ACTH, reaching a maximum after 6 hours. Renal blood flow was increased during ACTH infusion from 278 +/- 18 to 403 +/- 23 mL/min (P < .001); mesenteric blood flow was unchanged; there was a small increase in iliac blood flow (P < .01); and coronary blood flow increased (P < .05), paralleling the change in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of cerebral blood flow and CO2 reactivity after controlled cortical impact by perfusion magnetic resonance imaging using arterial spin-labeling in rats

We measured CBF and CO2 reactivity after traumatic brain injury (TBI) produced by controlled cortical impact (CCI) using magnetic resonance imaging (MRI) and spin-labeled carotid artery water protons as an endogenous tracer. Fourteen Sprague-Dawley rats divided into TBI (CCI; 4.02 +/- 0.14 m/s velocity; 2.5 mm deformation), sham, and control groups were studied 24 hours after TBI or surgery. Perfusion maps were generated during normocarbia (Paco2 30 to 40 mm Hg) and hypocarbia (PaCO2 15 to 25 mm Hg). During normocarbia, CBF was reduced within a cortical region of interest (ROI, injured versus contralateral) after TBI (200 +/- 82 versus 296 +/- 65 mL.100 g-1.min-1, P < 0.05). Within a contusion-enriched ROI, CBF was reduced after TBI (142 +/- 73 versus 280 +/- 64 mL.100 g-1.min-1, P < 0.05). Cerebral blood flow in the sham group was modestly reduced (212 +/- 112 versus 262 +/- 118 mL.100 g-1.min-1, P < 0.05). Also, TBI widened the distribution of CBF in injured and contralateral cortex. Hypocarbia reduced cortical CBF in control (48%), sham (45%), and TBI rats (48%) versus normocarbia, P < 0.05. In the contusion-enriched ROI, only controls showed a significant reduction in CBF, suggesting blunted CO2 reactivity in the sham and TBI group. CO2 reactivity was reduced in the sham (13%) and TBI (30%) groups within the cortical ROI (versus contralateral cortex). These values were increased twofold within the contusion-enriched ROI but were not statistically significant. After TBI, hypocarbia narrowed the CBF distribution in the injured cortex. We conclude that perfusion MRI using arterial spin-labeling is feasible for the serial, noninvasive measurement of CBF and CO2 reactivity in rats.     

Cerebral blood flow and oxidative brain metabolism during and after moderate and profound arterial hypoxaemia

In anaesthetized artificially ventilated dogs, the effect of graded arterial hypoxaemia on cerebral blood flow (CBF) and on the oxidative carbohydrate metabolism of the brain was tested. It is shown that the hypoxic vasodilatory influence on cerebral vessels is present even at moderate systemic hypoxaemia, provide that PaCO2 is kept within normal limits. At PaO2 of about 50 Torr, CBF increased from 56.6 to 89.7 ml/100g/min. With increasing cerebral hyperamia (CBF increased to 110.9 ml/100g/min, at PaO2 of 30 Torr), CMRO2 (4.2 ml/100g/min) was not significantly raised above its normal level (4.7 ml/100g/min) even with profound arterial hypoxaemia. This shows that CMRO2 levels are poor indices of hypoxic hypoxia. A disproportionately high increase in cerebral glucose uptake (CMR glucose levels rose from 4.4 to 10.4 mg/100g/min) and enhanced cerebral glycolysis (CMR lactate changed from 0.2 to 1.6 mg/100g/min) at moderately reduced PaO2 (50 Torr) indicated early metabolic changes which became more marked with further falls in arterial oxygen tension. However, 60 minutes after restoration of a normal PaO2 level, CBF and brain metabolism were found to have completely recovered. It is concluded that a short period of profound systemic hypoxaemia does not produce long lasting metabolic and circulatory disorders of the brain provided the cerebral perfusion pressure does not vary, and is kept at normal levels.     

Intracranial pressure and cerebral perfusion pressure in clinically normal equine neonates

Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were determined in 8 clinically normal neonatal foals. After the foals oriented themselves and nursed the mares, they were sedated as necessary, and local anesthesia was provided for making the skin incisions. Using a technique similar to that used in human beings, an indwelling subdural catheter was placed to measure ICP. Carotid artery catheterization was used to measure arterial blood pressure. Cerebral perfusion pressure was calculated as the difference between mean arterial blood pressure and ICP. Intracranial pressure and CPP readings were taken twice during each 24-hour period, starting at 6 hours of age and continuing through 72 hours of age. Mean (+/- SD) ICP were 5.83 +/- 1.82, 8.81 +/- 2.06, and 9.55 +/- 1.55 mm of Hg (range, 2 to 15 mm of Hg), and mean CPP were 80.19 +/- 10.34, 75.30 +/- 10.86, and 76.80 +/- 12.59 mm of Hg (range, 50 to 109 mm of Hg) for each of the first three 24-hour periods after birth, respectively. All 8 foals had physical and neurologic examinations, CSF analysis, and computerized axial tomography evaluations. The foals manifested normal behavior during the interval of measurements, and adverse effects of the procedure were not detected during the monitoring period. Establishment of normal values for ICP and CPP are important to clinicians who have the opportunity to apply this technique for monitoring and evaluating neonatal foals with signs of CNS dysfunction.     

Effects of sufentanil on cerebral hemodynamics and intracranial pressure in patients with brain injury

BACKGROUND: The current study investigates the effects of sufentanil on cerebral blood flow velocity and intracranial pressure (ICP) in 30 patients with intracranial hypertension after severe brain trauma (Glasgow coma scale < 6). METHODS: Mechanical ventilation (FIO2 0.25-0.4) was adjusted to maintain arterial carbon dioxide tensions of 28-30 mmHg. Continuous infusion of midazolam (200 micrograms/kg/h intravenous) and fentanyl (2 micrograms/kg/h intravenous) was used for sedation. Mean arterial blood pressure (MAP, mmHg) was adjusted using norepinephrine infusion (1-5 micrograms/min). Mean blood flow velocity (Vmean, cm/s) was measured in the middle cerebral artery using a 2-MHz transcranial Doppler sonography system. ICP (mmHg) was measured using an epidural probe. After baseline measurements, a bolus of 3 micrograms/kg sufentanil was injected, and all parameters were continuously recorded for 30 min. The patients were assigned retrospectively to the following groups according to their blood pressure responses to sufentanil: group 1, MAP decrease of less than 10 mmHg, and group 2, MAP decrease of more than 10 mmHg. RESULTS: Heart rate, arterial blood gases, and esophageal temperature did not change over time in all patients. In 18 patients, MAP did not decrease after sufentanil (group 1). In 12 patients, sufentanil decreased MAP > 10 mmHg from baseline despite norepinephrine infusion (group 2). ICP was constant in patients with maintained MAP (group 1) but was significantly increased in patients with decreased MAP. Vmean did not change with sufentanil injection regardless of changes in MAP. CONCLUSIONS: The current data show that sufentanil (3 micrograms/kg intravenous) has no significant effect on middle cerebral artery blood flow velocity and ICP in patients with brain injury, intracranial hypertension, and controlled MAP. However, transient increases in ICP without changes in middle cerebral artery blood flow velocity may occur concomitant with decreases in MAP. This suggests that increases in ICP seen with sufentanil may be due to autoregulatory decreases in cerebral vascular resistance secondary to systemic hypotension.     

The effect of clonidine on cerebral blood flow velocity, carbon dioxide cerebral vasoreactivity, and response to increased arterial pressure in human volunteers

BACKGROUND: Because patients may be taking clonidine chronically or may be receiving it as a premedication before surgery, the authors investigated its effect on cerebral hemodynamics. METHODS: In nine volunteers, middle cerebral artery mean blood flow velocity (Vm) was measured using transcranial Doppler ultrasonography (TCD). CO2 vasoreactivity was measured before clonidine administration (preclonidine), 90 min after clonidine, 5 microg/kg orally, then following restoration of mean arterial pressure (MAP) to the preclonidine level. In addition, Vm was measured after a phenylephrine-induced 30-mmHg increase in MAP. RESULTS: After clonidine administration, Vm decreased from 62 +/- 9 to 48 +/- 8 cm/s (P < 0.01), and MAP decreased from 86 +/- 10 to 63 +/- 5 mmHg (P < 0.01; mean +/- SD). Clonidine decreased the CO2 vasoreactivity slope from 2.2 +/- 0.4 to 1.2 +/- 0.5 cm x s(-1) x mmHg(-1) (P < 0.05); restoring MAP to the preclonidine level increased the slope to 1.60 +/- 0.5 cm x s(-1) x mmHg(-1), still less than the preclonidine slope (P < 0.05). CO2 vasoreactivity expressed as a percentage change in Vm, decreased after clonidine, 3.5 +/- 0.8 versus 2.4 +/- 0.8 %/mmHg (P < 0.05); this difference disappeared after restoration of MAP, 3.1 +/- 1.2 %/mmHg. With a 30-mmHg increase in MAP, Vm increased by 13% before and after clonidine (P < 0.05). CONCLUSIONS: Clonidine, 5 microg/kg orally, decreases Vm and slightly attenuates cerebral CO2 vasoreactivity, therefore decreased cerebral blood flow and mildly attenuated CO2 vasoreactivity should be anticipated.