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Biomedical subjects

D S Warner

Publications and source records attributed to D S Warner.

At least 91 records · Page 5Linked to original sources
PubMed1995

The relation between cerebral metabolic rate and ischemic depolarization. A comparison of the effects of hypothermia, pentobarbital, and isoflurane.

BACKGROUND: Reductions in cerebral metabolic rate may increase the brain's tolerance of ischemia. However, outcome studies suggest that reductions in cerebral metabolic rate produced by anesthetics and by hypothermia may not be equally efficacious. To examine this question, we measured the effects of hypothermia, pentobarbital, and isoflurane on the cerebral metabolic rate for glucose (CMRG) and on the time to the loss of normal membrane ion gradients (terminal ischemic depolarization) of the cortex during complete global ischemia. METHODS: As pericranial temperature was varied between 39 and 25 degrees C in normocapnic halothane-anesthetized rats, CMRG (using 14C-deoxyglucose) or the time to depolarization (using a glass microelectrode in the cortex) after a K(+)-induced cardiac arrest was measured. In other studies, CMRG and depolarization times were measured in normothermic animals (37.7 +/- 0.2 degrees C) anesthetized with high-dose pentobarbital or isoflurane (both producing burst suppression on the electroencephalogram) or in halothane-anesthetized animals whose temperatures were reduced to 27.4 +/- 0.3 degrees C. These three states were designed to produce equivalent CMRG values. RESULTS: As temperature was reduced from 39 to 25 degrees C, CMRG decreased from 66 to 21 microM.100 g-1.min-1 (Q10 = 2.30), and depolarization times increased from 76 to 326 s. In similarly anesthetized animals at approximately 27 degrees C, CMRG was 32 +/- 4 microM.100 g-1.min-1 (mean +/- SD), whereas in normothermic pentobarbital- and isoflurane-anesthetized rats, CMRG values were 33 +/- 3 and 37 +/- 4 microM.100 g-1.min-1, respectively (P = 0.072 by one-way analysis of variance). Despite these similar metabolic rates, the times to depolarization were markedly different: for hypothermia it was 253 +/- 29 s, for pentobarbital 109 +/- 24 s, and for isoflurane 130 +/- 28 s (P < 0.0001). CONCLUSIONS: The time to terminal depolarization is believed to be a measure of the rate at which energy stores are depleted. In this study there was a strong correlation between hypothermic reductions in CMRG and increases in the time to depolarization. This finding supports the belief that metabolic suppression may offer some cerebral protection. However, equivalent reductions in CMRG produced by hypothermia and by anesthesia were not equivalent in their effects on membrane failure. Whether hypothermia slows energy depletion by some unique mechanism or directly retards depolarization is unknown.

Animals↗
PubMed1995

Halothane reduces focal ischemic injury in the rat when brain temperature is controlled.

BACKGROUND: Previous work has demonstrated that rats anesthetized with halothane during focal cerebral ischemia have better histologic and neurologic outcome than do rats undergoing the same insult when awake. The purpose of this experiment was to determine whether this difference persists when brain temperature is held similar in halothane-anesthetized and awake experimental groups. METHODS: Two ischemia experiments were performed. In both, the middle cerebral artery was occluded for 90 min. Temperature was monitored from a radiotelemetered thermistor implanted in the cerebral cortex. Four days after ischemia, infarct volume and neurologic function were assessed. In experiment 1, brain temperature was not controlled in awake rats. Temperature in rats anesthetized with halothane, approximately 1 minimum alveolar concentration, was regulated by servomechanism by surface heating or cooling to replicate the temperature profiles generated by awake animals. To address methodologic issues regarding infarct volume analysis, a subset of nine rats was examined for the effect of the histologic staining technique and the mathematical modeling algorithms used for computation of infarct volume values. In experiment 2, the brain temperature of awake and halothane-anesthetized rats was maintained normothermic (38.0 degrees C) throughout ischemia and early recirculation. RESULTS: In experiment 1 no difference between groups was observed for cortical (halothane 146 +/- 95 mm3 and awake 126 +/- 108 mm3; P = 0.64) or subcortical (halothane 110 +/- 48 mm3 and awake 100 +/- 66 mm3; P = 0.66) infarct volume. Neurologic function was also similar between groups. Total infarct volume was approximately 11% greater when histologic sections were stained with hematoxylin and eosin than when they were stained with nitro blue tetrazolium, although volumes correlated closely between the two techniques (r2 = 0.996). Analysis by orthogonal or frustum projection from two-dimensional planimetric areas to three-dimensional volumes resulted in nearly identical values (r2 = 0.999). In experiment 2, halothane-anesthetized rats experienced a 46% reduction in cortical infarct volume (halothane 106 +/- 97 mm3 and awake 197 +/- 103 mm3; P = 0.03). The incidence of hemiparesis was reduced in the anesthetized group (P = 0.03). CONCLUSIONS: When brain temperature was maintained normothermic throughout the focal ischemic insult, a neurologic and histologic protective effect for halothane anesthesia was observed. This effect of halothane was not sufficient to persist when large variations in brain temperature were allowed. Regulation of brain temperature is a critical factor in the determination of the effects of anesthetics on focal ischemic brain damage.

Animals↗
PubMed1995

A comparison of anesthetic techniques for awake intubation in neurosurgical patients.

Two different methods of achieving upper airway anesthesia for awake fiberoptic intubation were prospectively compared in patients undergoing surgery for cervical spine instability. Forty patients were randomized to either topical anesthesia or nerve block groups. Topical anesthesia patients were administered nebulized 4% lidocaine (approximately 20 ml) via the oropharynx plus a transtracheal injection of 4% lidocaine (3 ml). Nerve block patients underwent bilateral glossopharyngeal and superior laryngeal nerve blocks with 2% lidocaine (0.5-2 ml per injection site) plus a transtracheal injection of 4% lidocaine (3 ml). The quality of anesthesia for intubation was graded by observers blinded to group assignment. Mean arterial pressure, heart rate, Pao2, Paco2, pHa, SpO2, and plasma lidocaine concentrations were measured during the intubation sequence. Patient recall of intubation and discomfort were assessed during the postoperative period with visual analog scales. Time required for successful intubation and quality of intubation were not different between groups. Physiologic values for the two groups were similar. The mean total dose of lidocaine in the topical anesthesia group was approximately 2 times greater than that in the nerve block group (815 versus 349 mg; p < 0.0001). In contrast, mean plasma lidocaine concentration at initiation of intubation in the topical anesthesia group was half that of nerve block group (2.16 versus 4.23 micrograms/ml; p < 0.0001). Ten minutes later there was no difference for plasma lidocaine concentration between groups. No patients had evidence of seizures or neurologic change during the procedure. There was no difference in patient perception of discomfort during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Temporal thresholds for hyperglycemia-augmented ischemic brain damage in rats.

BACKGROUND AND PURPOSE: Although acute hyperglycemia is known to increase global ischemic brain damage, the duration of ischemia necessary to elicit such an effect is unknown. Accordingly, an experiment was performed to determine the duration of forebrain ischemia at which hyperglycemia becomes a factor in histological and behavioral outcome in rats. METHODS: Fasted rats were anesthetized and prepared for forebrain ischemia. Before ischemia, rats received either intravenous saline (plasma glucose, 112 +/- 18 mg/dL) or glucose (plasma glucose, 343 +/- 50 mg/dL). After 4, 8, 12, or 15 minutes of ischemia (n = 12), recovery was allowed. Rats surviving 7 days underwent evaluation of motor function and then histological analysis of damage in the caudate putamen, hippocampal CA1, and substantia nigra pars reticulata. RESULTS: After 4 minutes of ischemia, damage was present in all structures. Only in the caudate putamen was hyperglycemia associated with worsened damage, but this did not result in seizures or death. After 8 minutes of ischemia, seizures occurred in 33% of hyperglycemic rats, and a hyperglycemic effect on damage in the CA1 and substantia nigra pars reticulata was observed. No seizures or mortality occurred in normoglycemic rats regardless of duration of ischemia. Longer durations of ischemia resulted in an increased incidence of seizures and mortality in hyperglycemic rats only. Among surviving rats, motor function was worsened in hyperglycemic rats after 12 minutes of ischemia. CONCLUSIONS: Hyperglycemia-augmented brain damage is evident after global ischemic insults as brief as 4 minutes and becomes critical to survival after 8 minutes of ischemia.

Animals↗
PubMed1994

Effects of glycine receptor antagonism on spreading depression in the rat.

Spreading depression (SD) in the rat brain is inhibited by N-methyl-D-aspartate (NMDA) receptor antagonists. Because the NMDA receptor glycine recognition site must be occupied for activation of the NMDA ionophore, we hypothesized that antagonism of the glycine receptor would also affect SD. In halothane anesthetized rats, SD was initiated by electrocortical stimulation. Both the initiation threshold and propagation rate of SD were recorded. Rats were then administered the glycine receptor antagonist ACEA-1021 (or vehicle only) or ketamine and the stimulus was repeated. Rats were then killed and terminal depolarization was observed for. Ketamine completely inhibited initiation of SD. In contrast, all rats treated with ACEA-1021 exhibited SD. While ACEA-1021 caused no difference in the stimulation threshold for SD, propagation rate was decreased in a dose-dependent fashion. Terminal depolarization occurred in all rats. Antagonism of glycine at the NMDA receptor recognition site did not inhibit initiation of SD but played a modulatory role in the mechanism of its propagation.

Animals↗
PubMed1994

The hemispheric cerebrovascular response to hemodilution is attenuated by a focal cryogenic brain injury.

Experimental brain injury attenuates the normal increase in cerebral blood flow (CBF) that accompanies a fall in PaO2, and this may contribute to the well-known detrimental effects of hypoxia following closed head injury. Anemia is also known to adversely affect posttraumatic survival, and it is reasonable to hypothesize that this too may be related to an altered cerebrovascular response. Therefore, to examine this possibility, pentobarbital-anesthetized rabbits were subjected to a left posterior parietal cryogenic cortical injury, followed 90 min later by isovolemic hemodilution with hetastarch. Unlesioned control animals underwent an identical degree of hemodilution. CBF was measured using radioactive microspheres. In control animals, hemodilution was accompanied by a marked increase in CBF in all brain regions. For example, in the left posterior cortex, CBF increased from 30 +/- 14 mL/100 g/min (baseline Hct = 42 +/- 2%, mean +/- SD) to 100 +/- 20 mL/100 g/min at Hct = 12 +/- 1%. By contrast, there was a markedly attenuated response throughout the left (ipsilateral) hemisphere of injured animals, even in cortical regions distant from the injury. For example, in the left posterior cortex, CBF changed from a baseline of 32 +/- 21 mL/100 g/min (baseline) to 40 +/- 14 mL/100 g/min at the lowest Hct. CBF responses to hemodilution were unaltered in the contralateral hemisphere and in the hindbrain. These data indicate that a localized brain lesion can produce widespread ipsilateral alterations in the CBF response to hemodilution, with resultant compromise in cerebral O2 delivery. These data support the argument that the CBF increase produced by hemodilution is an active vasodilatory process rather than a passive response to changing blood viscosity.

Animals↗
PubMed1994

The incidence of pneumocephalus after supratentorial craniotomy. Observations on the disappearance of intracranial air.

BACKGROUND: Pneumocephalus occurs in a variety of clinical settings and has important anesthetic implications, particularly if N2O is used. One common cause of pneumocephalus is a craniotomy or craniectomy, and therefore, patients undergoing these neurosurgical procedures may be at increased risk for the development of tension pneumocephalus if N2O is used during a subsequent anesthetic. However, because the rate at which a postoperative pneumocephalus resolves has not been well defined, the duration of this risk period is unknown. METHODS: Department of Anesthesia billing codes were used to identify all patients undergoing supratentorial craniotomy between 1986 and 1990. This list was cross-indexed with Department of Radiology data to generate a list of patients who had had a computed tomographic scan of the head performed on or after the day of their surgery. From this list, 240 scans were examined for the presence of intracranial air. The magnitude of pneumocephalus, if present, was ranked as large, moderate, small, or trace. RESULTS: Air was seen in all scans obtained in the first 2 post-operative days. Sixty-six percent of these pneumocephali were judged to be moderate or large. The incidence of pneumocephalus decreased to 75% by postoperative day 7. During the 2nd and 3rd postoperative weeks, the incidence of pneumocephalus decreased to 59.6 and 26.3%, respectively. The size of the pneumocephali also decreased. Still, 11.8% of the scans obtained during the 2nd postoperative week had pneumocephali that were judged to be moderate or large. CONCLUSIONS: These data indicate that all patients have pneumocephalus immediately after a supratentorial craniotomy. Although the incidence and size of pneumocephali decrease over time, a significant number of patients have an intracranial air collection large enough to put them at risk for complication if N2O is used during a second anesthetic in the first 3 weeks after the first procedure. This information should be considered in the evaluation of the patient and in the selection of anesthetic agents.

Anesthesia, General↗
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

Minimum alveolar concentration for halothane in the rat is resistant to effects of forebrain ischemia and reperfusion.

BACKGROUND: Because glutamate antagonists can substantially alter the minimum alveolar concentration (MAC) of volatile anesthetics, glutamate has been implicated as an important neurotransmitter in processes contributing to the anesthetic state. Cerebral ischemia profoundly alters glutamatergic neurotransmission and thus may also alter halothane MAC. METHODS: Fasted rats were surgically prepared for forebrain ischemia. One half of the animals served as operative shams (n = 24). Remaining rats underwent 10 min of bilateral carotid occlusion combined with systemic hypotension (n = 24). In animals in both groups brain circulation was restored for 1 h, 24 h, or 7 days (n = 8). At each of these intervals, MAC for halothane was determined by the tail-clamp method. Histologic damage in the hippocampus, cortex, caudoputamen, and thalamus was measured in animals allowed to survive 7 days. RESULTS: Blood pressure, arterial blood gas tensions and pH, pericranial temperature, and plasma glucose values measured immediately before ischemia were similar among groups. Neither ischemia nor duration of reperfusion significantly altered halothane MAC as compared with operative shams (sham 1 h = 0.9 +/- 0.1 vol%, 24 h = 1.0 +/- 0.1 vol%, 7 days = 1.0 +/- 0.2 vol%; ischemia 1 h = 0.9 +/- 0.1 vol%, 24 h = 0.9 +/- 0.1 vol%, 7 days = 1.0 +/- 0.2 vol%). Histologic damage in the hippocampus and caudoputamen was severe in the ischemic group of animals. Mild injury was observed in the motor and cingulate cortex as well as the thalamus. There was no evidence of histologic injury in sham-operated animals. CONCLUSIONS: The absence of effect of ischemic forebrain injury on halothane MAC is consistent with findings made in other models of supratentorial cerebral injury. These results support the contention that anatomic foci for motor responses elicited during MAC determination are localized at levels caudal to the forebrain.

Animals↗
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

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.

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