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Biomedical subjects

M M Todd

Publications and source records attributed to M M Todd.

At least 55 records · Page 3Linked to original sources
PubMed1994

The dose-related effects of nitric oxide synthase inhibition on cerebral blood flow during isoflurane and pentobarbital anesthesia.

BACKGROUND: Recent work in animals suggests that nitric oxide may play a role in the cerebral blood flow (CBF) changes produced by anesthetics, particularly the vasodilation seen with volatile anesthetics. It is not clear, however, whether nitric oxide causes the flow increase or simply plays some constitutive role. To distinguish between these possibilities, we studied the dose-related effects of nitric oxide synthase inhibition in rabbits with varying baseline CBFs, produced by anesthesia with isoflurane, low-dose pentobarbital, or high-dose pentobarbital. METHODS: New Zealand White rabbits were anesthetized with 1 MAC isoflurane, low-dose pentobarbital (50-mg/kg load, 7.5-mg.kg-1.h-1 infusion), or high-dose pentobarbital (50-mg/kg load, 20-mg.kg-1.h-1, deep burst-suppression on the electroencephalogram), and prepared for the measurement of CBF using radioactive microspheres. The confluence of sinuses was also exposed to permit sampling of cerebral venous blood and the determination of cerebral metabolic rate for O2 (CMRO2). Normocapnia and normothermia were maintained throughout. After baseline measurements, animals were sequentially given a cumulative total of 3, 13, and 43 mg/kg intravenous N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. CBF and CMRO2 were recorded approximately 10 min after each dose. RESULTS: L-NAME produced a dose-related reduction in CBF in all three anesthetic groups. Statistical examination indicated that the dose response curves were parallel. For example, in isoflurane-anesthetized rabbits, CBF decreased from 77 +/- 19 to 47 +/- 11 ml.100 g-1.min-1 after the 43 mg/kg L-NAME, whereas in high-dose pentobarbital animals, CBF decreased from 42 +/- 15 to 26 +/- 8 ml.100 g-1.min-1 (all values mean +/- SD). Decreases in CMRO2 did not quite achieve significance (P = 0.08), and the CBF/CMRO2 ratio decreased in all animals, suggesting that the CBF reductions were due primarily to direct vasoconstriction. There were no electroencephalographic changes. In separate groups of isoflurane-anesthetized rabbits given 3 mg/kg L-NAME, treatment with 300 mg/kg L-arginine partially reversed the decreases in CBF. By contrast, the effects of 43 mg/kg L-NAME were not reversible with 430 mg/kg L-arginine. CONCLUSIONS: Although L-NAME reduced CBF in all three anesthetic conditions, it did not alter the relative differences among them: CBF in the presence of isoflurane remained much higher than that seen with the barbiturates. This suggests that nitric oxide may not the primary mediator of anesthetic CBF effects, but rather acts to influence background vascular tone in these anesthetized animals.

Amino Acid Oxidoreductases↗
PubMed1994

Ischemic depolarization during halothane-nitrous oxide and isoflurane-nitrous oxide anesthesia. An examination of cerebral blood flow threshold and times to depolarization.

BACKGROUND: Isoflurane-N2O anesthesia (as compared with halothane-N2O) reduces the cerebral blood flow (CBF) at which electroencephalographic changes occur in humans subjected to carotid occlusion. In contrast, no differences were seen in rats when cortical depolarization (instead of the electroencephalogram) was used as the ischemic marker during equi-MAC isoflurane-N2O and halothane-N2O anesthesia. To extend these findings, we used laser-Doppler flowmetry to continuously examine CBF (CBFLDF) and attempted to better define the relation between CBF and the time to depolarization (as a measure of the rate of energy depletion after ischemia). METHODS: Cortical CBFLDF was measured in normothermic, normocarbic rats, and the cortical direct-current potential was recorded using glass microelectrodes. Animals were anesthetized with 0.75 MAC halothane or 0.75 MAC isoflurane, both in 60% N2O. After baseline recordings, both carotid arteries were occluded. Five minutes later mean arterial pressure was rapidly reduced to and held at target values of 50, 45, 40, 30 or 0 mmHg. This mean arterial pressure was maintained (and CBFLDF was continually monitored) until depolarization occurred, or for a maximum of 20 min. RESULTS: CBFLDF values before and after carotid occlusion (but before hypotension) were similar in the two groups. As intended, CBFLDF decreased as postocclusion mean arterial pressure was reduced and the incidence of cortical depolarization increased. The delay until depolarization, defined as the interval between the moment CBFLDF reached 25% of the preocclusion baseline until depolarization occurred, decreased as CBFLDF was reduced. However, there were no intergroup differences except after a circulatory arrest (CBF = 0), where cortical depolarization was seen approximately 30 s later in isoflurane-N2O-anesthetized rats. CONCLUSIONS: The CBF threshold for cortical depolarization as measured by laser-Doppler flowmetry did not differ significantly between halothane-N2O- and isoflurane-N2O-anesthetized rats. There were also no important differences in the times until depolarization, other than a small difference when flow = 0. If the time to depolarization is reflects the potential ischemic injury, the it is unlikely that isoflurane-N2O conveys any protective advantage relative to halothane-N2O.

Anesthesia, Inhalation↗
PubMed1994

Cerebral blood flow and oxygen delivery during hypoxemia and hemodilution: role of arterial oxygen content.

To determine the role of arterial O2 content (CaO2) in the cerebral blood flow (CBF) responses to hypoxemia and hemodilution, CaO2 was progressively reduced from approximately 18 to approximately 6 ml O2/dl in normocapnic, normothermic, pentobarbital-anesthetized rabbits. This was done either by reducing PaO2 (hypoxemia, minimum PaO2 approximately 26 mmHg) or arterial hematocrit (isovolemic hemodilution with hetastarch, minimum hematocrit approximately 14%) while CBF was measured with radioactive microspheres. As CaO2 decreased, CBF increased in both groups but was greater in hypoxemic animals at CaO2 values < or = 9 ml O2/dl. For example, at a CaO2 approximately 6 ml O2/dl, CBF in hypoxemic animals was 110 +/- 38 ml.100 g-1.min-1 (means +/- SD) compared with 82 +/- 22 ml.100 g-1.min-1 in hemodiluted animals (means +/- SD). While calculated cerebral O2 delivery (cerebral DO2) was well maintained in hypoxemic animals, it decreased significantly during hemodilution (from 7.95 +/- 2.92 baseline to 5.08 +/- 1.10 ml O2/dl.100 g-1.min-1 at the lowest CaO2 value). This decrease in cerebral DO2 was offset by an increase in oxygen extraction ratio during hemodilution. By contrast, the small increase in oxygen extraction ratio seen with hypoxemia did not achieve significance. These results suggest that there are different adaptive responses to acute hypoxemia or hemodilution . They also imply that at similar CBF and CaO2 values, tissue O2 availability may be greater during hemodilution than during hypoxemia.

Analysis of Variance↗
PubMed1994

Glutamatergic antagonism: effects on lidocaine-induced seizures in the rat.

We tested the hypothesis that glutamate receptor antagonists increase the dose of lidocaine required to induce seizure activity. Sprague-Dawley rats were anesthetized with halothane in 40% O2/balance N2 and mechanically ventilated. After surgical preparation, halothane was discontinued. Normocapnia, normoxia, and normothermia were maintained. The electroencephalogram (EEG) and arterial blood pressure were monitored continuously. Rats were then randomized to one of six groups (control, one of three intravenous [i.v.] bolus doses of the competitive glutamate N-methyl-D-aspartate [NMDA] receptor antagonist CGS 19755, or one of two i.v. bolus and continuous infusion regimens of the competitive glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)quinoxalline [NBQX]). Thirty minutes after onset of CGS 19755 or NBQX administration (end-tidal halothane < 0.2%), rats received a continuous i.v. infusion of 1.5% lidocaine until EEG seizures occurred. The duration of the infusion (min) and total lidocaine dose (mg/kg) administered were recorded. CGS 19755 increased the lidocaine seizure threshold in a log-linear dose-dependent fashion (P < 10(-6)). The largest dose of CGS 19755 (112.5 mg/kg) increased the time to initial EEG seizure activity more than twofold (e.g., control = 12.6 +/- 2.6 min; CGS 19755 = 28.6 +/- 6.9 min). The effect of AMPA receptor antagonism was less obvious because treatment resulted in an EEG morphology dissimilar to that observed in the CGS 19755 or control groups. Our findings indicate that competitive NMDA receptor antagonists (e.g., CGS 19755) increase the dose of lidocaine required for seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Plasma osmolality and brain water content in a rat glioma model.

Little is known about how intravenous fluids influence peritumoral edema formation. This experiment was designed to determine, in a rat glioma model, whether changes in plasma osmolality alter water content, as assessed by specific gravity (SpGr), in normal and neoplastic cerebral tissue. Cells cultured from an ethylnitrosourea-induced rat glioma were stereotactically implanted into the right striatum of Fischer 344 rats. A tumor growth interval of 21 days was allowed. In a second experiment, rats underwent a 60-second cortical freeze injury followed by 24 hours' recovery. In both experiments, rats were assigned to one of three groups: hypotonic (100 ml/kg of 0.2 mol/L NaCl in H2O, intraperitoneally; resultant plasma osmolality approximately 268 mOsm/kg); isotonic (no treatment; plasma osmolality approximately 298 mOsm/kg); or hypertonic (10 ml/kg of 1.0 mol/L NaCl in H2O, intraperitoneally; plasma osmolality approximately 342 mOsm/kg). Thirty minutes after fluid injection, regional SpGr was determined using a kerosene-bromobenzene gradient. In subsets of rats, the tissue morphology and blood-brain barrier permeability of Evans blue dye were assessed. Tissue within the freeze lesion was stained by Evans blue dye with sharp demarcation. Evans blue dye did not stain gliomatous tissue, and central necrosis was not histologically evident. In isotonic rats, glioma SpGr was reduced (1.0411 +/- 0.0012 g/ml) relative to the contralateral striatum (1.0437 +/- 0.0008 g/ml; P < 0.001). Despite this, a strong linear relation was observed for SpGr and plasma osmolality in both neoplastic and normal tissue. Within the freeze lesion in isotonic rats, SpGr was severely reduced (1.0335 +/- 0.0008 g/ml; P < 0.0001) compared with contralateral frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Microwave fixation for the determination of cerebral blood volume in rats.

The cerebral blood volume (CBV) is sensitive to changing hydrostatic pressures. Thus, measurement methods that rely on removing tissue from unfixed brain may lead to underestimates of the CBV due to the loss of blood from the tissue. In situ fixation of tissue before removal may offer improved accuracy. We employed a triple-label method to measure simultaneously whole brain CBF and CBV in halothane-anesthetized Sprague-Dawley rats, which were then killed either by focused microwave irradiation (approximately 8 kW of incident power x 770 ms) or by decapitation. CBF was measured with [3H]nicotine while the CBV was determined as the sum of the cerebral red cell volume (CRCV--measured with 99mTc-labeled red cells) and the cerebral plasma volume (CPV--measured with [14C]dextran). Animals were studied during hypocarbic (PaCO2 approximately 25 mm Hg), normocarbic, or hypercarbic (PaCO2 approximately 70 mm Hg) conditions. Added studies were performed to verify that the microwave irradiation scheme used was capable of fixing previously administered tracers in place, and also halting the entry of tracer given after irradiation. Results indicate that the method of killing had no effects on CBF measurements, as assessed either by absolute values during normocarbia or responsiveness to changing PaCO2. However, all three volume measurements made using nondiffusible tracers (CRCV, CPV, and CBV) were significantly lower in animals killed by decapitation. Furthermore, CO2 responsiveness for all three variables (as assessed by the slope of the PaCO2/volume) was not evident in decapitated animals. We conclude that in situ fixation offers significant advantages when examining the cerebral distribution space of nondiffusible tracers.

Animals↗
PubMed1993

Halothane decreases the rate of production of cerebrospinal fluid. Possible role of vasopressin V1 receptors.

BACKGROUND: Circulating vasoactive hormones (e.g., vasopressin) play an important role in the regulation of blood flow to the choroid plexus and the rate of cerebrospinal fluid (CSF) production. We tested the hypothesis that halothane decreases CSF production through a vasopressin-related mechanism and examined the related changes in blood flow to the choroid plexus. METHODS: Using ventriculocisternal perfusion, CSF production was measured in chloralose anesthetized, normothermic rabbits whose lungs were mechanically ventilated. Rabbits received either 0.5 minimum alveolar concentration (MAC; end-tidal) of halothane (added to a preestablished chloralose anesthetic), 0.5 MAC of halothane in the presence of a vasopressin V1 antagonist (iv), or the V1 antagonist alone. In addition, we examined animals in which no intervention was made (time control) and animals subjected to a 25% decrease in mean blood pressure produced by hemorrhage, with and without the V1-antagonist. In a separate series of rabbits, regional and total blood flows to the brain and the choroid plexus were measured using radioactive microspheres. These studies were carried out under similar conditions, except that the effects of end-tidal 0.25, 0.5, and 1 MAC of halothane were examined in each rabbit (each added to a preestablished chloralose anesthetic). RESULTS: Under control conditions, blood flow to the choroid plexus averaged 351 +/- 198 ml.min-1.100 g-1 (mean +/- SD) and CSF production averaged 10.1 +/- 1.9 microliters.min.-1. Halothane (0.25, 0.5, and 1 MAC) did not alter choroid plexus blood flow but decreased CSF production by 28 +/- 6% at 0.5 MAC (P < .05). In contrast, 1 MAC of halothane increased total blood flow to the brain by 20 +/- 25% (P < .05). The V1 antagonist, which did not affect production of CSF when given alone, prevented the decrease in CSF production in response to halothane. Hemorrhage decreased blood flow to the choroid plexus but not to the brain, and the V1 antagonist attenuated the decrease in the rate of CSF production by hemorrhage (34 +/- 11% vs. 48 +/- 18%, P < .05). CONCLUSIONS: Halothane decreases CSF production with no net change in the blood flow to the choroid plexus. Decrease in CSF production appears to be mediated through a vasopressin-related mechanism and not to the blood pressure decrease seen during halothane anesthesia.

Animals↗
PubMed1993

The influence of intravascular volume expansion on cerebral blood flow and blood volume in normal rats.

BACKGROUND: Intravascular volume expansion can increase cerebral blood flow (CBF) in patients with cerebral ischemia. However, the changes in CBF produced by volume expansion in the normal brain remain the subject of debate, and the changes on cerebral blood volume (CBV; one determinant of intracranial pressure) have not been described. The effects of acute nondilutional volume expansion on cardiac output (CO), CBF, and CBV in normal rats were examined. METHODS: Normocarbic, normothermic halothane/N2O-anesthetized rats were given 0, 6, 12, 24, or 36 ml of a blood-hetastarch mixture (n = 6 for each group). When volume loading was completed, 3H-nicotine was used to measure CBF, while 99mTc-labeled red cells and 14C-dextran were used to measure cerebral red cell and plasma volumes. Animals were killed by microwave irradiation (8KW x 770 msec). In different animals, cardiac output (CO) was measured by thermodilution during the infusion of 36 ml of blood-hetastarch. RESULTS: Central venous pressure (CVP) increased from 3.9 +/- 0.7 mmHg (mean +/- SD) in control animals to 13.0 +/- 2.0 mmHg in rats given 36 ml of blood. Cardiac output increased to 138 +/- 11% of control. There were no changes in arterial Hct or mean arterial pressure. There were no significant changes in CBF (which varied from 127 +/- 22 ml.100 g-1.min-1 in controls to 102 +/- 14 after the infusion of 36 ml). However, CBV increased in a linear fashion with increasing CVP, from 2.96 +/- 0.57 ml/100 g in control conditions to 4.47 +/- 0.83 ml/100 g after the infusion of 36 ml of blood/hetastarch. CONCLUSIONS: In normal brain, CBF does not change during volume expansion, in spite of an increase in CO. This contradicts earlier studies, the results of which indicate an independent role for cardiac output in CBF control. Cerebral blood volume increased in proportion to CVP, suggesting simple passive venous distention. Whether this could increase ICP and compromise cerebral perfusion remains unclear.

Animals↗
PubMed1993

A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy. Propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide.

BACKGROUND: Different anesthetic agents have different effects on cerebrovascular physiology. However, the importance of these differences in neuroanesthetic practice are unclear. In an effort to determine whether important clinical differences are present, the authors compared three anesthetic techniques in 121 adults undergoing elective surgical removal of a supratentorial, intracranial mass lesion. METHODS: Patients were assigned randomly to one of three groups. In group 1 (n = 40), anesthesia was induced with propofol and maintained with fentanyl (approximately 10 micrograms/kg load, 2-3 micrograms.kg-1.h-1 infusion) and propofol (50-300 micrograms.kg-1.min-1). In group 2 (n = 40), anesthesia was induced with thiopental and maintained with isoflurane and nitrous oxide. Up to 2 micrograms/kg fentanyl was given after replacement of the bone flap. In group 3 (n = 41), anesthesia was induced with thiopental and maintained with fentanyl (approximately 10 micrograms/kg load, 2-3 micrograms.kg-1.h-1 infusion), nitrous oxide, and low-dose isoflurane, if required. Blood pressure, heart rate, expired gas concentrations, and ventilatory parameters were recorded automatically in all patients. Epidural intracranial pressure (ICP) was measured via the first burr hole, brain swelling was rated at the time of dural opening, and emergence was monitored closely. Preoperative computed tomography or magnetic resonance imaging scans were evaluated, and pre- and postoperative neurologic exams were performed by a neurosurgeon unaware of group assignments. Total hospital stay (days) and total hospital cost (exclusive of physician charges) also were reviewed. RESULTS: During induction, higher heart rates were seen in isoflurane/nitrous oxide patients, whereas mean arterial pressure was approximately 10 mmHg less during the maintenance phase (compared with both other groups). Otherwise, there were few intergroup hemodynamic differences. While there were no clinically important intergroup differences in mean ICP (+/- SD)-group 1, ICP = 12 +/- 7 mmHg; group 2, 15 +/- 12 mmHg; group 3, ICP = 11 +/- 8 mmHg-more isoflurane/nitrous oxide patients (nine, group 2) had an ICP > or = 24 mmHg than in the other groups (two each). Emergence was, overall, more rapid with fentanyl/nitrous oxide. For example, the median time until the patient could be awakened by quiet verbal command, e.g., "Open your eye," was 5 min, versus 10 min in the other groups. There were no relationships between ICP and any measurement of emergence (e.g., time to response to commands). Seven of 41 (17%) fentanyl/nitrous oxide patients vomited in the early postoperative period, compared with only 1 of 40 (2.5%) of those given propofol/fentanyl and 2 of 40 (5%) receiving isoflurane/nitrous oxide (P = 0.03). There were no differences in the incidence of new postoperative deficits, total hospital stay, or cost. CONCLUSIONS: Although there are modest differences among the three tested anesthetics, short-term outcome was not affected. These results indicate that, despite their respective cerebrovascular effects, all of the anesthetic regimens used were acceptable in these patients undergoing elective surgery.

Adult↗
PubMed1993

A focal cryogenic brain lesion does not reduce the minimum alveolar concentration for halothane in rats.

BACKGROUND: A focal cortical cryogenic brain injury has been reported to reduce the brain pentobarbital concentrations needed to prevent movement in response to pain in rats. This occurred despite any apparent behavioral changes in the awake animals. To determine whether this was true with other anesthetics, the authors determined the minimum alveolar concentration (MAC) for halothane in normothermic, normocarbic ventilated Sprague-Dawley rats previously subjected to a freezing injury of the parietal cortex. METHODS: Injury was produced in halothane-anesthetized rats by applying a cold (-70 degrees C), 4-mm-diameter brass rod to the exposed dura for 5 or 15 s. Animals then were studied 3 days after injury, a time when cerebral metabolism in the ipsilateral hemisphere reaches a minimum. Minimum alveolar concentration was determined using a tail-clamp stimulus, combined with end-tidal anesthetic sampling. In addition, exploratory activity was measured by the open field test just before MAC determination, and spontaneous nocturnal motility was monitored by an electronic motion sensor during the night before testing. RESULTS: In normal animals subjected only to preparatory surgery, MAC was 1.10 +/- 0.07% (mean +/- SD). Almost identical values were found in rats subjected to 5- and 15-s cryogenic injuries (1.11 +/- 0.07% and 1.08 +/- 0.06%, respectively). There were no intergroup differences in open field test results or in spontaneous nocturnal activity. CONCLUSIONS: These results indicate that a focal cortical brain injury that has no obvious neurologic or behavioral effects in the awake rat does not alter halothane requirements.

Animals↗
PubMed1993

Sevoflurane and halothane reduce focal ischemic brain damage in the rat. Possible influence on thermoregulation.

BACKGROUND: There has been little systematic examination concerning the comparative effects of the anesthetized versus the awake state on outcome from cerebral ischemia. This experiment evaluated infarct volume and neurologic function in rats subjected to temporary focal ischemia while anesthetized with either sevoflurane or halothane. Outcome in these animals was compared to that observed in rats maintained unanesthetized during a similar ischemic insult. METHODS: All rats were anesthetized with halothane and surgically prepared for filament occlusion of the middle cerebral artery. After preparation, one group (Halothane) remained anesthetized with approximately 1.4 MAC halothane. In another group (Sevoflurane), halothane was discontinued and substituted with sevoflurane, which was administered until electroencephalographic burst suppression was evident (approximately 1.4 MAC). The final group (Awake) was allowed to awaken immediately after the onset of ischemia. Middle cerebral artery occlusion persisted for 90 min in all groups. The middle cerebral artery filament then was removed, and a 96-h survival interval was allowed. Neurologic function and infarct volume were determined. Recent evidence indicates that transient mild hyperthermia occurs in awake rats undergoing filament occlusion of the middle cerebral artery. To examine the potential role of mild hyperthermia in this experiment, a second experiment was performed in which rats anesthetized with halothane underwent 90-min focal ischemia, with pericranial temperatures held at either 38.0 degrees C or 39.2 degrees C. RESULTS: Intraischemic mean arterial pressure was 20-25 mmHg lower in the two anesthetized groups compared with awake animals. Despite this finding, cortical infarct volumes (mean +/- SD; Halothane, 17 +/- 32 mm3; Sevoflurane, 36 +/- 57 mm3; Awake, 115 +/- 104 mm3; Sevoflurane, 36 +/- 57 mm3; Awake, 115 +/- 104 mm3) and subcortical infarct volumes (mean +/- SD; Halothane, 39 +/- 57 mm3; Sevoflurane, 50 +/- 29 mm3; Awake, 88 +/- 46 mm3) were reduced in both groups of anesthetized rats. This reduction correlated with improved neurologic function. The rats in whom the pericranial temperature was maintained at 39.2 degrees C had a larger total infarct volume (218 +/- 81 mm3) and increased neurologic deficits when compared to those in whom the pericranial temperature was maintained at 38.0 degrees C (total infarct volume, 75 +/- 77 mm3). CONCLUSIONS: Both halothane and sevoflurane substantially reduced damage in this focal ischemia model when compared to outcome resulting from the same insult induced in awake rats. The reduction in intraischemic mean arterial pressure caused by the anesthetics did not seem contributory to outcome. Brain temperature differences among the groups were not defined. Because small differences in pericranial temperature were shown to have major effects on outcome, further work is required to determine if differences in brain temperature explain the observed protective effects of these anesthetics.

Anesthesia, Inhalation↗
PubMed1993

Cerebral blood flow in a rat glioma model during halothane anesthesia.

Little is known about the influence of infiltrating gliomas on the responsivity of the cerebral circulation to anesthetic agents. Therefore we designed a study to address this issue. Male Fischer 344 rats were assigned to two tumor groups and one sham group. In the two tumor groups, glioma cells were stereotactically injected into the right striatum; animals in the sham group were injected with sterile culture medium only. Either 12 or 16 days after injection, the rats were anesthetized with 1 MAC halothane in 40% O2/balance N2. Local and remote regional cerebral blood flow was then determined using 14C-iodoantipyrine autoradiography. Physiologic values (PaCO2, PaO2, pHa, mean arterial pressure, and rectal temperature) were similar for both tumor and sham groups. Tumor volume was relatively small (cross-sectional diameter = 2-3 mm), and there was no evidence of midline shift in coronal tissue sections. Blood flow within the tumor was substantially reduced relative to adjacent structures (e.g., tumor = 88 +/- 10 ml/100 g/min; adjacent caudate = 161 +/- 23 ml/100 g/min). There were no significant differences between the tumor and sham groups for regional blood flow values in histologically normal tissue in either the injected or contralateral hemispheres. We conclude that this model of brain neoplasia shows no evidence of either local or remote changes in the cerebrovascular responsibility of normal tissue to volatile anesthesia.

Anesthesia, Inhalation↗
PubMed1993

Cerebral autoregulation during moderate hypothermia in rats.

BACKGROUND AND PURPOSE: Little is known about the effects of hypothermia on cerebral autoregulation. The present study was designed to examine cerebral blood flow responses to controlled hemorrhagic hypotension in normothermic and hypothermic rats. METHODS: Cortical blood flow was measured with a laser-Doppler flowmeter in halothane-anesthetized rats assigned to one of three groups: normothermic group 1 (n = 8) with a pericranial temperature of approximately 36.5 degrees C or hypothermic group 2 (n = 8) or group 3 (n = 8) with a pericranial temperature of approximately 30.5 degrees C. In group 2, a PaCO2 of approximately 40 mm Hg was maintained without correction for body temperature. To evaluate the role of PaCO2, in group 3 animals PaCO2 was kept at approximately 40 mm Hg as corrected for body temperature. In all animals, the mean arterial blood pressure was reduced by hemorrhage in increments of 10 mm Hg every 2 minutes. RESULTS: In group 1 animals, a typical autoregulatory curve was observed with cerebral blood flow first falling at or below 75% of baseline at a mean arterial pressure of 57 +/- 15 mm Hg (mean +/- SD). Absolute normotensive cerebral blood flow in group 2 fell to < or = 75% of baseline at a mean arterial pressure of 73 +/- 21 mm Hg. In group 3, no evidence of autoregulation was seen. Cerebral blood flow reached values < or = 75% of baseline at a mean arterial pressure of 82 +/- 14 mm Hg, whereas calculated cerebrovascular resistance failed to show any compensatory vasodilation as the mean arterial pressure decreased. CONCLUSIONS: Different PaCO2 management schemes used during hypothermia may have profound effects on cerebral blood flow and on autoregulation. If PaCO2 is maintained at 40 mm Hg after correction for temperature, autoregulation is abolished. If uncorrected PaCO2 is maintained at approximately 40 mm Hg, some degree of autoregulation is preserved, albeit with a right-shifted "knee."

Animals↗
PubMed1992

Effects of intra-ischemic blood pressure on outcome from 2-vessel occlusion forebrain ischemia in the rat.

Halothane anesthetized Sprague-Dawley rats underwent 10 min of bilateral carotid artery occlusion with mean arterial pressure (MAP) held at 30, 50 or 60 mmHg. Sham rats did not undergo ischemia. A 7-day recovery interval was allowed. Intra-ischemic electroencephalographic (EEG) changes, behavioral function (Days 5-7), and histologic injury (Day 7) were evaluated. Under similar conditions, cerebral blood flow was determined after 10 min ischemia by the [3H]nicotine indicator fractionation technique. EEG isoelectricity was observed in 11 of 11, 5 of 10, and 2 of 11 rats in the 30 mmHg, 50 mmHg, and 60 mmHg groups respectively. Neither passive avoidance cross-over latencies nor general motor scores were affected by intra-ischemic MAP and no differences from sham performance were observed. The per cent of CA1 neurons counted as dead (left and right hemispheres combined) was significantly affected by intra-ischemic MAP (72, 46 and 28% in the 30 mmHg, 50 mmHg, and 60 mmHg groups, respectively; P less than 0.001). A greater than 50% CA1 neuronal mortality rate was present only in those rats exhibiting EEG isoelectricity. However, the number of rats demonstrating greater than a 25% interhemispheric difference in CA1 neuronal loss was greatest in the 50 mmHg group (P less than 0.02). Hippocampal blood flow decreased in association with severity of hypotension (8 +/- 1, 35 +/- 8, and 48 +/- 2 ml/100 g/min (mean +/- S.E.M.) for 30, 50, and 60 mmHg, respectively; P less than 0.01). Again, however, the greatest variability in blood flow was observed at MAP = 50 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The influence of different concentrations of volatile anesthetics on the threshold for cortical spreading depression in rats.

We studied the influence of halothane and isoflurane on the electrical threshold for triggering spreading depression (SD) in rats. While the N-methyl-D-aspartate (NMDA) antagonist ketamine dramatically increased the triggering threshold (and blocked propagation), neither volatile agent had any dose-related effect. High doses of both agents slightly slowed SD propagation rate. These results indicate that volatile agents in typical anesthetic doses can be used in studies of SD in rats, and also suggest that these agents have little effect on NMDA receptor-mediated neurotransmission.

Animals↗
PubMed1992

Multimodality treatment of deep periventricular cerebral arteriovenous malformations.

The surgical treatment of arteriovenous malformations (AVMs) located in deep periventricular regions such as the basal ganglia is associated with marked morbidity and mortality. Approaches through critical brain regions afford limited exposure of the lesions, while surgical dissection is sometimes complicated by acute severe brain swelling and/or hemorrhage in the surrounding tissues. In our approach to deep AVMs, our regimen has evolved from direct staged microsurgical excision under routine fentanyl-N2O-relaxant anesthesia (first four patients) to the use of elective high-dose barbiturate anesthesia (subsequent 12 patients). In the first group of four patients, 11 operations were performed. Two patients improved, one of whom returned to normal neurologically. There were three episodes of acute brain swelling and/or hemorrhage. One patient died as a result, and another deteriorated. In the second group of 12 patients, all but two lesions were completely excised. Among the 10 patients in whom the AVM was completely excised, seven improved, six of whom achieved a good to excellent outcome, with two regaining full neurologic function. Three patients worsened (one as the result of acute brain swelling and/or hemorrhage). There was no death in this group. Only one incidence of acute brain swelling and/or hemorrhage occurred in 26 operations. Even though the number of patients is too small in the first group for meaningful statistical comparison, our intraoperative observations and postoperative results suggest that our evolved multimodality regimen, such as staged excision and the use of elective high-dose barbiturates, was likely to have contributed to the improved treatment results of these formidable lesions.

Adolescent↗
PubMed1992

The role of electrode size on the incidence of spreading depression and on cortical cerebral blood flow as measured by H2 clearance.

Cerebral blood flow was measured by the H2 clearance method 30 and 60 min after the implantation of 300, 250, 125, or 50 microns diameter platinum-iridium electrodes 2 mm deep into the right parietal cortex of normothermic, normocarbic halothane-anesthetized rats. Another group of animals had 50 microns electrodes inserted 1 mm. In all animals, the presence or absence of a wave of spreading depression (SD) was noted at the time of implantation, with recordings made with glass micropipettes. H2 flow values were compared with those measured in gray matter from the same anatomical region (but from different rats), using [3H]nicotine. The incidence of SD ranged from 60% following insertion of 300 microns electrodes to 0% with 50 microns electrodes. H2 clearance flows also varied with electrode size, from 77 +/- 21 ml 100 g-1 min-1 (mean +/- standard deviation) with 300 microns electrodes to 110 +/- 31 and 111 +/- 16 ml 100 g-1 min-1 with 125 and 50 microns electrodes, respectively (insertion depth of 2 mm). A CBF value of 155 +/- 60 ml 100 g-1 min-1 was obtained with 50 micron electrodes inserted only 1 mm. Cortical gray matter blood flow measured with [3H]nicotine was 154 +/- 35 ml 100 g-1 min-1. When the role of SD in subsequent flow measurements was examined, there was a gradual increase in CBF between 30 and 60 min after electrode insertion in those animals with SD, while no such change was seen in rats without SD.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗