Distribution of cerebral blood flow during halothane versus isoflurane anesthesia in rats

The effects of halothane versus isoflurane on distribution of cerebral blood flow (CBF) were compared using 14C-iodoantipyrine autoradiography. Sprague-Dawley rats were exposed to 1 MAC of either halothane (n = 8) or isoflurane (n = 7) in 33% O2/balance nitrogen for 55 min prior to determination of CBF. Normoxia, normothermia, and normocapnia were maintained throughout the experiment and arterial pressures (MAP) were held within the range of 90-100 mmHg by infusion of blood. Coronal autoradiographic brain images were then digitized and optical density values converted to CBF with the use of 14C autoradiographic standards and arterial radioactivity data. Hemispheric, neocortical, subcortical, and selected local anatomical regions were defined on a cathode ray screen display by cursor outline. Mean CBF for each region was determined at each of eight standardized coronal brain sections, and area weighted average values for the whole brain were also calculated. Hemispheric CBF was identical in the two anesthetic groups: halothane = 150 +/- 16 ml.100 gm-1.min-1; isoflurane = 147 +/- 19 ml.100 gm-1.min-1. However, neocortical CBF was greater in halothane anesthetized animals (halothane = 185 +/- 16 ml.100 gm-1.min-1; isoflurane = 154 +/- 19 ml.100 gm-1.min-1, P = .004). The authors conclude that halothane and isoflurane exert regionally selective effects on CBF with halothane appearing to have a more pronounced effect on the neocortex. Previously reported discrepancies concerning the relative effects of these two agents on CBF may be due to inherent differences in the tissue regions measured by the different techniques.     

The effect of hypervolemic hemodilution with and without hypertension on cerebral blood flow following middle cerebral artery occlusion in rats anesthetized with isoflurane

The effect of hypervolemic hemodilution or hypervolemic hemodilution with dopamine-induced hypertension on cerebral blood flow (CBF) was investigated during 1.2 MAC isoflurane anesthesia in rats (n = 24) subjected to middle cerebral artery occlusion (MCAO). Prior to MCAO each animal was randomized to one of the following groups: 1) control, mean arterial pressure (89 +/- 10 mmHg [mean +/- SD]), blood volume, and hematocrit (46 +/- 1) were not manipulated; 2) hypervolemic hemodilution (HH), 30 min before MCAO, 5% albumin was administered to reduce the hematocrit to 29-32%; or 3) hypervolemic hemodilution/dopamine hypertension (HH/Dop), hemodilution was accomplished and dopamine (10 micrograms.kg-1.min-1) was infused during the ischemic period to achieve a mean arterial pressure of 111 +/- 10 mmHg (mean +/- SD). Ten minutes after occlusion of the left middle cerebral artery, CBF was determined using 14C-iodoantipyrine. Five coronal brain sections were analyzed to determine the area within each brain section with CBF ranges of 0-15 ml.100 g-1.min-1 and 15-23 ml.100 g-1.min-1. The area of 0-15 ml.100 g-1.min-1 CBF was less in both the HH and HH/Dop groups compared with control (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of mannitol on cerebral blood flow and microcirculation during experimental middle cerebral artery occlusion

Regional cerebral blood flow (rCBF) was measured during and after a 2-3 hour occlusion period of the middle cerebral artery (MCA) in cats with the hydrogen clearance technique. The effects of mannitol upon rCBF were studied. Transient hypotension during occlusion dropped the blood flow to near zero on the occluded side, leading to postischemic hypoperfusion. Mannitol failed to modify blood flow during the occlusion period, but was effective in preventing any further decrease of blood flow during hypotension. Animals receiving mannitol had an improved postischemic recovery of blood flow. The correlation of ischemic severity and postischemic brain damage and the effects of mannitol on these parameters are discussed.     

Changes in cerebral blood flow over time during isoflurane anesthesia in dogs

The present study assessed the impact of time (6 h) on cerebral blood flow (CBF) during isoflurane anesthesia with and without vasopressor administration. All animals were prepared for measurement of CBF by the radiolabeled microsphere method under 1.4% end-tidal (1.0 MAC) isoflurane anesthesia. Surgery required 45 min and was followed by a 15 min stabilization period. In group 1 (n = 6), isoflurane 1.4% was administered for 6 h. CBF after 1 h of isoflurane was 92 +/- 9 ml/min/100 g (mean +/- SEM) and declined to 61 +/- 5 ml/min/100 g at 2 h and further declined to 37 +/- 5 ml/min/100 g at 6 hr. In group 2 (n = 6), isoflurane 1.4% was administered during the first hour. Thereafter, isoflurane 1.4% was continued, angiotensin II (0.3 mug/kg/min) was administered intravenously, and blood was withdrawn to maintain CPP constant for an additional 5 h, with hourly CBF determination. In this group, control CBF was 95 +/- 16 ml/min/100 g and flow was maintained at the control level through 4 h and then declined to 50 +/- 5 ml/min/100 g at 5 and 6 h. In group 3 (n = 6), 1.4% isoflurane was administered and phenylephrine (2.0 mug/kg/min) infusion was combined with hemorrhage to maintain control CPP in an identical sequence to group 2. In group 3, control CBF was 88 +/- 14 ml/min/100 g. As in group 1, CBF decreased significantly at 2 h (p < 0.05) to 68 +/- 13 ml/min/100 g and further declined to 49 +/- 7 ml/min/100 g at 6 h. In all three groups, CMRO2 remained at control levels and there were no changes in arterial carbon dioxide or CPP for the duration of the study. These data demonstrate that the hyperemia caused by isoflurane resolves over time during stable 1 MAC isoflurane anesthesia. The unanticipated interaction of angiotensin II and isoflurane producing a sustained cerebral hyperemia suggests that previous studies that used angiotensin II to support MABP during isoflurane may have reported the effects of angiotensin II in addition to or rather than the effects of isoflurane.     

Influence of aortic blood flow velocity on changes of middle cerebral artery blood flow velocity during isoflurane and sevoflurane anaesthesia

BACKGROUND AND OBJECTIVE: We studied the influence of systemic (aortic) blood flow velocity on changes of cerebral blood flow velocity under isoflurane or sevoflurane anaesthesia. METHODS: Forty patients (age: isoflurane 24-62 years; sevoflurane 24-61 years; ASA I-III) requiring general anaesthesia undergoing routine spinal surgery were randomly assigned to either group. Cerebral blood flow velocity was measured in the middle cerebral artery by transcranial Doppler sonography (depth: 50-60 mm). Systemic blood flow velocity was determined by transthoracic Doppler sonography at the aortic valve. Heart rate, arterial pressure, arterial oxygen saturation and body temperature were monitored. After standardized anaesthesia induction (propofol, remifentanil, vecuronium) sevoflurane or isoflurane were used as single agent anaesthetics. Cerebral blood flow velocity and systemic blood flow velocity were measured in the awake patient (baseline) and repeated 5 min after reaching a steady state of inspiratory and end-expiratory concentrations of 0.75, 1.00, and 1.25 mean alveolar concentrations of either anaesthetic. To calculate the influence of systemic blood flow velocity on cerebral blood flow velocity, we defined the cerebral-systemic blood flow velocity index (CSvI). CSvI of 100% indicates a 1:1 relationship of changes of cerebral blood flow velocity and systemic blood flow velocity. RESULTS: Isoflurane and sevoflurane reduced both cerebral blood flow velocity and systemic blood flow velocity. The CSvI decreased significantly at all three concentrations vs. 100% (isoflurane/sevoflurane: 0.75 MAC: 85 +/- 25%/81 +/- 23%, 1.0 MAC: 79 +/- 19%/74 +/- 16%, 1.25 MAC: 71 +/- 16%/79 +/- 21%; [mean +/- SD] P = 0.0001). CONCLUSIONS: The reduction of the CSvI vs. 100% indicates a direct reduction of cerebral blood flow velocity caused by isoflurane/sevoflurane, independently of systemic blood flow velocity.     

Treatment of intraoperative middle cerebral artery occlusion with pentobarbital and extracranial-intracranial bypass. Case report.

A patient with a meningioma of the medial sphenoid wing underwent inadvertent intraoperative occlusion of the middle cerebral artery. Neurological deficit and infarction were presumably prevented by immediate administration of pentobarbital followed by extracranial-intracranial bypass.     

Local coupling of cerebral blood flow to cerebral glucose metabolism during inhalational anesthesia in rats: desflurane versus isoflurane

BACKGROUND: It is not known whether the effects of desflurane on local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) are different from those of other volatile anesthetics. METHODS: Using the autoradiographic iodoantipyrine and deoxyglucose methods, LCGU, LCBF, and their overall means were measured in 60 Sprague-Dawley rats (10 groups, n = 6 each) during desflurane and isoflurane anesthesia and in conscious controls. RESULTS: During anesthesia, mean cerebral glucose utilization was decreased compared with conscious controls: 1 minimum alveolar concentration (MAC) desflurane: -52%; 1 MAC isoflurane: -44%; 2 MAC desflurane: -62%; and 2 MAC isoflurane: -60%. Local analysis showed a reduction of LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased: 1 MAC desflurane: +40%; 1 MAC isoflurane: +43%; 2 MAC desflurane and 2 MAC isoflurane: +70%. LCBF was increased in all brain structures investigated except in the auditory cortex. No significant differences (P < 0.05) could be observed between both anesthetics for mean values of cerebral glucose use and blood flow. Correlation coefficients obtained for the relation between LCGU and LCBF were as follows: controls: 0.95; 1 MAC desflurane: 0.89; 2 MAC desflurane: 0.60; 1 MAC isoflurane: 0.87; and 2 MAC isoflurane: 0.68. CONCLUSION: Differences in the physicochemical properties of desflurane compared with isoflurane are not associated with major differences in the effects of both volatile anesthetics on cerebral glucose utilization, blood flow, and the coupling between LCBF and LCGU.     

Indomethacin-mediated improvement following middle cerebral artery occlusion in cats. Effects of anesthesia

Focal cerebral ischemia initiates multiple detrimental effects in the brain. Chief among these are the regional development of ischemic edema, decreased local perfusion, altered neuronal function, and eventual infarction. To determine if pretreatment with the cyclo-oxygenase inhibitor, indomethacin, would result in improvement in these parameters, adult cats were given indomethacin or control solvent (4 mg/kg intraperitoneally twice daily) and were studied for periods up to 24 hours after right middle cerebral artery occlusion. The interaction of anesthetic agents with indomethacin was also examined in separate groups of experimental animals using pentobarbital and ketamine. In cats allowed to recover from pentobarbital anesthesia, indomethacin reduced gray and white matter edema at 6 and 24 hours after occlusion (p less than 0.05). This was noted in densely areas (indomethacin = 84.3%, control = 87.5%), "penumbra" regions (indomethacin = 82.5%, control = 85.3%), and in nonischemic zones (indomethacin = 81.5%, control = 82.3%) at 24 hours. Somatosensory evoked potential amplitude and central latency were also improved in the indomethacin group (p less than 0.05), as was cerebral perfusion (p less than 0.05). In animals anesthetized with continuous ketamine administration, cerebral edema and perfusion as well as evoked potentials were not significantly improved in any region by indomethacin. Regional cerebral blood flow in the group was increased by indomethacin in the nonischemic opposite hemisphere (indomethacin = 64.7 cc/100 gm/min, control = 48.5 cc/100 gm/min, p less than 0.05), but not in the penumbra region of the ischemic hemisphere (indomethacin = 15.0 cc/100 gm/min, control = 18.6 cc/100 gm/min, p less than 0.05), when measured 4 hours after occlusion. This suggested a steal phenomenon. Beneficial effects of indomethacin were evident in the presence of pentobarbital, but not after ketamine anesthesia. This suggests a synergism dependent on decreased arachidonic acid production from pentobarbital-stabilized membranes coupled with diminished production of cyclic endoperoxides from available arachidonate due to inhibition of cyclo-oxygenase with indomethacin.     

Changes in local cerebral blood flow,local EEG,and flow in the distal stump of the middle cerebral artery in cats with occlusion of the middle cerebral artery

Summary The local EEG, the local cerebral blood flow (1CBF), and the flow in the distal stump of the occluded middle cerebral artery were simultaneously recorded in 28 acute experiments in cats. Nembutal anaesthesia was used eleven times, and Halothane anaesthesia 17 times.The recordings were made via platinum electrodes: 12 in the ischaemic hemisphere, and 2–3 in the opposite non-ischaemic hemisphere. The flow in the occluded middle cerebral artery was recorded via a platinum electrode introduced into this artery via the transorbital approach. The changes in 1EEG, 1CBF, and middle cerebral artery flow were studied during normotension, hypertension, and hypotension. A beneficial effect of hypertension was noted in the acute phase of brain ischaemia. Hypertension counteracted also the diaschisis in the non-ischaemic part of the ischaemic hemisphere and in the opposite non-ischaemic hemisphere. A correlation between 1EEG changes and 1CBF changes was noted. In addition an interesting discrepancy was observed between the rapid H₂ clearance in the middle cerebral artery stump and the much slower H₂ clearance in the ischaemic brain area.Significant differences between experiments under Halothane and experiments under Nembutal anaesthesia were noted. In the acute phase those changes are probably the result of the different levels of blood pressure in those two groups.     

Hemodilution during cardiopulmonary bypass increases cerebral infarct volume after middle cerebral artery occlusion in rats

Although the optimal hematocrit during cardiopulmonary bypass (CPB) is not defined, excessive hemodilution may lead to organ ischemia via a reduction in oxygen-carrying capacity uncompensated by autoregulatory and/or rheologic increases in organ blood flow. As a result, the consequences of hemodilution in patients at risk for cerebral ischemia are not clearly understood. We designed this study to evaluate the effects of hemodilution in the setting of focal cerebral ischemia during CPB. Wistar rats surgically prepared for CPB were randomized to either hemodilution (hemoglobin (Hb), 6 g/dL; n = 9) or control (Hb, 11 g/dL; n = 8) groups and subsequently exposed to focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Immediately after the onset of MCAO (maintained for 90 min), 65 min of hypothermic (28 degrees C) CPB was initiated. Twenty-four hours later, functional neurological outcome and cerebral infarct volume were determined. Compared with controls, the hemodilution group had worse neurological performance (new score = 8 [2], hemodilution; versus 10 [2], control; P = 0.030) and larger total cerebral infarct volumes (182 +/- 84 mm(3), hemodilution; versus 103 +/- 58 mm(3), control; P = 0.043). In this experimental model of CPB with reversible MCAO-induced focal cerebral ischemia, hemodilution worsened neurological function and increased cerebral infarct volume.     

Response to CO2 and autoregulation of cortical cerebral blood flow during isoflurane anesthesia

Response to CO2 and autoregulation of cortical cerebral blood flow (CBF) during isoflurane anesthesia were studied in 10 patients undergoing neurosurgery. The patients were anesthetized with 0.5 to 1.2% end-tidal isoflurane and 66% nitrous oxide in oxygen. The CBF was measured by thermal diffusion using a flow probe with a Peltier stack. PaCO2 was controlled to produce hypocarbia, normocarbia and hypercarbia by changing tidal volume and respiratory rate. Arterial blood pressure was altered. Hypotension was achieved by intravenous infusion of trimetaphan and hypertension was induced by intravenous administration of metaraminol. During isoflurane anesthesia the response to CO2 of CBF was kept at PaCO2 between 27.8 and 53.9 mmHg. The following relationship was obtained. CBF = 2.54 x PaCO2-53.0, r = 0.59, n = 131 The autoregulation of CBF was evaluated in 7 patients, and in 2 patients, the autoregulation of CBF was abolished.     

High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats

OBJECT: Ibuprofen is an antiinflammatory drug that disrupts leukocyte-endothelial cell interactions by limiting expression of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), also known as CD54. The authors hypothesized that ibuprofen could reduce the size of the infarct associated with transient focal ischemia by inhibition of ICAM-1 expression, and they evaluated its effects in rats treated with middle cerebral artery (MCA) occlusion. Ibuprofen treatment was compared with mild systemic hypothermia, which is known to be neuroprotective and is commonly used during neurosurgical procedures. METHODS: The maximum ibuprofen dose (240 mg/kg/day) that could be tolerated with no systemic toxicity was established in the initial experiments. In the efficacy experiment, rats were pretreated with vehicle, ibuprofen, or hypothermia (33 degrees C) prior to 2 hours of MCA occlusion; then their brains were harvested at 24 hours of reperfusion for histological studies. End-ischemic cerebral blood flow (CBF) was evaluated using [14C]iodoantipyrine autoradiography in additional cohorts. Expression of ICAM-1 within ischemic compared with nonischemic caudate nucleus and putamen (striatum) or cortex was evaluated using immunohistochemical studies. Compared with vehicle treatment, ibuprofen produced a 46.2% reduction (p = 0.01) in striatal infarcts, which was comparable to hypothermia (48.7% reduction, p = 0.02). Ibuprofen did not alter end-ischemic CBF in any region studied, and the ibuprofen treatment group had the lowest proportion of animals with marked ICAM-1 staining. CONCLUSIONS: Ibuprofen given in maximum tolerated doses reduces the striatal infarct size after focal cerebral ischemia. The neuroprotective mechanism does not work through preservation of intraischemic CBF and is consistent with inhibition of ICAM-1 expression; however, at the doses used in this study, other effects of ibuprofen on platelet and endothelial function are possible.     

Losartan increases renal blood flow during isoflurane anesthesia in sheep

BACKGROUND: Inhaled anesthetics cause a transient reversible depression of renal function by direct renal effects or indirectly by changes in neurohumoral systems or cardiovascular performance. When the sympathetic nervous activity is decreased during anesthesia, other vasoactive systems like vasopressin (AVP) and particularly the renin angiotensin system (RAS) are of importance for blood pressure maintenance. Little is known about how the renal circulation is affected by angiotensin receptor blockade during isoflurane anesthesia. METHODS: The study was performed on isoflurane anesthetized sheep equipped with flow probes (placed around a femoral and a renal artery) and a pulmonary artery catheter. During stable conditions the sheep were given one or more of the following substances: isotonic saline (NaCl); losartan (LOS) 10 mg x kg(-1); prazosin (PRAZ) 0.2 mg x kg(-1) and a vasopressin V1-receptor antagonist (AVP-a) 10 microg x kg(-1). RESULTS: LOS and AVP-a did not affect mean arterial pressure (MAP), whereas PRAZ lowered MAP significantly (from 98+/-12 to 65+/-7 mmHg). Renal blood flow (RBF) increased after LOS treatment (148+/-34 to 222+/-33 ml x min(-1)). The other substances were without effect on RBF. Femoral blood flow remained unchanged after all treatments. CONCLUSION: We conclude that the sympathoadrenal system is still the major determinant for blood pressure maintenance during isoflurane anesthesia in sheep. The apparently increased activity of the renin angiotensin system in this situation causes a reduction in renal blood flow, which is counteracted by angiotensin II AT1-receptor blockade.     

异氟醚预处理对大脑中动脉闭塞大鼠胶质细胞中Toll样受体4表达的影响

目的观察异氟醚预处理对大脑中动脉闭塞(MCAO)模型大鼠胶质细胞中Toll样受体4(TLR4)表达的影响。方法雄性SD大鼠48只,体重250～300g,随机均分为三组:假手术组(S组)、MCAO模型组(M组)、异氟醚预处理组(I组)。2h后进行再灌注,再灌注24h后进行神经功能评分,检测脑梗死容积,分别测定每个视野内TLR4与星形胶质细胞标记物(GFAP)共存阳性细胞数和TLR4与小胶质细胞标记物(OX42)共存阳性细胞数。结果与M组相比,I组神经功能评分降低,脑梗死容积减少,GFAP和OX42阳性细胞数均减少(P<0.05)。结论异氟醚预处理具有脑保护作用,抑制TLR4的表达及胶质细胞的活化可能是其作用机制之一。     

Local cerebral blood flow after middle cerebral artery occlusion in rabbits following transposition of omentum to the brain

Transposition of pedicled omental grafts to the brain has been shown to minimize the effects of cerebral infarction in dogs and monkeys. An experimental study in which pedicled omental grafts and free non-revascularized omental grafts were placed on the brains of rabbits is reported. With the use of a modified inhaled hydrogen clearance technique to measure blood flow in the brain tissue, it was determined that the pedicled omental graft minimized the effects of middle cerebral artery occlusion by maintaining a collateral blood supply and limiting the decline of local cerebral flow. Superposition of free omental grafts on the brain had no effect on the threshold for infarction.     

异氟醚和异氟醚/N2O麻醉时的脑血流CO2反应性

目的 比较颅脑手术中相同ＭＡＣ（１．３ＭＡＣ）的异氟醚和异氟醚／Ｎ２Ｏ麻醉时的脑血流ＣＯ２反应性。方法 选择ＡＳＡⅠ￣Ⅱ级颅内肿瘤病人行择期开颅手术２０例,随机分为两组：异氟醚组（Ⅰ）：吸入１．５％异氟醚、空气、氧气;异氟醚／Ｎ２Ｏ组（Ｎ）：吸入０．８％异氟醚、（６０￣６５）％Ｎ２Ｏ、氧气,每组１０例。在ＰａＣＯ２为５．３ｋＰａ、３．７ｋＰａ时分别抽取动脉、颈内静脉球部血行血气分析。根据Ｆｉｃｋ公     

No evidence for blood flow redistribution with isoflurane or halothane during acute coronary artery occlusion in fentanyl-anesthetized dogs

The present study examines the postulate that isoflurane, in contrast to halothane, causes redistribution of blood flow away from an ischemic myocardial region through vasodilation of adjacent normally perfused myocardium. The study was performed in open-chest dogs anesthetized with fentanyl; ischemia was induced by occlusion of the left anterior descending coronary artery. At 0.6% alveolar concentration, isoflurane increased transmural blood flow to 125% of control values (P less than 0.05) in the normal region without concomitant changes in blood flow to the ischemic region or in the endocardial/epicardial flow ratio in the ischemic region. The evidence excludes either transmural steal or regional redistribution phenomena. Myocardial blood flow variables returned to control values at 1.8% isoflurane, and no blood flow redistribution effects were evident. In contrast, whereas halothane 0.4% caused no significant effect on myocardial blood flows, an alveolar concentration of 1.2% decreased transmural blood flow to normally perfused left ventricle to 70% of control (P less than 0.05). Regional myocardial oxygen consumption in the normal and ischemic areas decreased at higher alveolar concentrations and was unchanged at the lower concentrations for both agents. Myocardial lactate production from the ischemic region was unchanged with either agent, suggesting that, in terms of metabolic changes, neither agent worsened ischemia during sustained occlusion of the left anterior descending coronary artery. The present data show no evidence for worsening of myocardial ischemia with either isoflurane or halothane. Isoflurane causes a relatively greater increase in perfusion compared to myocardial oxygen consumption of normally perfused myocardium; nevertheless, sufficient coronary vascular reserve remains in the native collateral circulation so that myocardial metabolic supply-and-demand relationships during ischemia are not further compromised.