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M M Todd

Publications and source records attributed to M M Todd.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cerebral blood flow during hypoxemia and hemodilution in rabbits: different roles for nitric oxide?

Hypoxemia and anemia are associated with increased CBF, but the mechanisms that link the changes in PaO2 or arterial O2 content (CaO2) with CBF are unclear. These experiments were intended to examine the contribution of nitric oxide. CaO2 in pentobarbital-anesthetized rabbits was reduced to approximately 6.5 mL O2/dL by hypoxemia (PaO2 approximately 24 to 26 mm Hg) or hemodilution with hetastarch (hematocrit approximately 14% to 15%). Animals with normal CaO2 (approximately 17.5 to 18 mL O2/dL) served as controls. In part I, each animal was given 3, 10, and 30 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) intravenously (total 43 mg/kg) to inhibit production of nitric oxide. Forebrain CBF was measured with radioactive microspheres approximately 15 to 20 minutes after each dose. Baseline CBF was greater in hypoxemic rabbits (111 +/- 31 mL x 100 g-1 x min-1, mean +/- SD) than in hemodiluted (70 +/- 22 mL x 100 g-1 min-1) or control animals (39 +/- 12 mL x 100 g-1 min-1). L-NAME (which reduced brain tissue nitric oxide synthase activity by approximately 65%) reduced CBF in hypoxemic animals to 80 +/- 23 mL x 100 g-1 x min-1 (P < 0.0001), but had no significant effect on CBF in either anemic or control animals. In four additional rabbits, further hemodilution to a CaO2 of approximately 3.5 mL O2/dL increased baseline CBF to 126 +/- 21 mL x 100 g-1 min-1, but again there was no effect of L-NAME. In part II, animals were anesthetized as above, and a close cranial window was prepared. The cyclic GMP (cGMP) content of the artificial CSF superfusate was measured under baseline conditions, and then after the reduction of CaO2 to approximately 6.5 mL O2/dL by either hypoxemia or hemodilution. Concentrations of cGMP did not change during either control conditions or after hemodilution. However, cGMP increased significantly with the induction of hypoxemia. The cGMP increase in hypoxemic animals could be blocked with L-NAME. These results suggest that nitric oxide plays some role in hypoxemic vasodilation, but not during hemodilution.

Animals↗
PubMed1996

Intracranial pressure and hemodynamic effects of remifentanil versus alfentanil in patients undergoing supratentorial craniotomy.

Remifentanil hydrochloride is an ultra-short-acting esterase metabolized mu-opioid receptor agonist. The purpose of this study was to provide preliminary information regarding the effects of this drug on intracranial pressure (ICP) and mean arterial pressure (MAP) in patients scheduled for craniotomy. Twenty-six patients undergoing excision of supratentorial space-occupying lesions were anesthetized with 0.3-0.8 vol% isoflurane in a 2:1 mixture of nitrous oxide:oxygen. Ventilation was adjusted to provide a Paco2 of < 30 mm Hg. After the first burr hole was drilled, patients (n = 5-6 per group) were administered an intravenous infusion of study drug (placebo, remifentanil 0.5 micrograms/kg or 1.0 micrograms/kg, or alfentanil 10 micrograms/kg or 20 micrograms/kg) over 1 min. Epidural ICP and MAP values were recorded at baseline, at completion of infusion, and every minute for the next 10 min. Blood study drug concentrations were measured immediately after completion of infusion. Neither opioid caused a significant increase in ICP. Both drugs were associated with a dose-dependent decrease in MAP. Remifentanil was 31 times more potent than alfentanil for effects on MAP. We conclude that remifentanil produces similar cerebral perfusion pressure effects as does alfentanil.

Adult↗
PubMed1996

Cervical spine motion with direct laryngoscopy and orotracheal intubation. An in vivo cinefluoroscopic study of subjects without cervical abnormality.

BACKGROUND: Cervical spine kinetics during airway manipulation are poorly understood. This study was undertaken to quantify the extent and distribution of segmental cervical motion produced by direct laryngoscopy and orotracheal intubation in human subjects without cervical abnormality. METHODS: Ten patients without clinical or radiographic evidence of cervical spine abnormality underwent laryngoscopy using a #3 Macintosh blade while under general anesthesia and neuromuscular blockade. Cervical motion was recorded with continuous lateral fluoroscopy. The intubation sequence was divided into distinct stages and the corresponding fluoroscopic images were digitized. Segmental motion, occiput through C5, was calculated for each stage using the digitized data. RESULTS: During exposure and laryngoscope blade insertion, minimal displacement of the skull base and rostral cervical vertebral bodies was observed. Visualization of the larynx created superior rotation of the occiput and C1 in the sagittal plane, and mild inferior rotation of C3-C5. C2 maintained nearneutral posture. This pattern of displacement resulted in extension at each motion segment, with the most significant motion produced at the occipitoatlantal and atlantoaxial joints (mean = 6.8 degrees and 4.7 degrees, respectively). Intubation created slight additional superior rotation at the occiput and C1, without substantial alteration in the posture of C2-C5. After laryngoscope removal, position trended toward baseline at all levels, although exact neutral posture was not regained. CONCLUSIONS: This investigation quantifies the behavior of the normal cervical spine during direct laryngoscopy with a Macintosh blade. With this maneuver, the vast majority of cervical motion is produced at the occipitoatlantal and atlantoaxial joints. The subaxial cervical segments (C2-C5) are displaced only minimally. This study establishes a highly reliable and reproducible method for analyzing cervical motion in real time.

Adult↗
PubMed1996

Effects of hypothermia, pentobarbital, and isoflurane on postdepolarization amino acid release during complete global cerebral ischemia.

BACKGROUND: Hypothermia and anesthetics may protect the brain during ischemia by blocking the release of excitatory amino acids. The effects of hypothermia (28 degrees C), pentobarbital, and isoflurane on postischemic excitatory amino acid concentrations were compared. METHODS: Rats were anesthetized with 0.8% halothane/50% N2O, vascular catheters were placed, and a glass microelectrode and microdialysis cannula were inserted into the cerebral cortex. Experimental groups were: (1) control, pericranial, t = 38 degrees C; (2) hypothermia, t = 28 degrees C; (3) pentobarbital, t = 38 degrees C; and (4) isoflurane, t = 38 degrees C. Halothane/N2O was continued in groups 1 and 2, whereas a deep burst-suppression or isoelectric electroencephalogram was achieved with the test drugs in groups 3 and 4. Cerebral metabolic rates were similar in groups 2, 3, and 4. After a baseline dialysis sample was collected, animals were killed with potassium chloride. The time to terminal depolarization was recorded, after which three consecutive 10-min dialysate samples were collected. Glutamate, aspartate, gamma-aminobutyric acid, and glycine concentrations were measured using high-performance liquid chromatography. RESULTS: Times to terminal depolarization were shorter in both pentobarbital and isoflurane groups than with hypothermia (103 +/- 15 and 127 +/- 10 vs. 195 +/- 20 s respectively, mean +/- SD). However, times to terminal depolarization in all three groups were longer than in control subjects (control = 70 +/- 9s). Postdepolarization concentrations of all compounds were lower in hypothermic animals (vs. normothermic control animals), but no reductions in glutamate, aspartate, or glycine concentrations were noted in pentobarbital or isoflurane groups. gamma-Aminobutyric acid concentrations were reduced by both anesthetics, but not to the same degree as with hypothermia. CONCLUSIONS: Pentobarbital and isoflurane prolonged the time to terminal depolarization, but did not influence the rate at which the extracellular concentrations of glutamate, aspartate, or glycine increased. By contrast, hypothermia reduced the release of all excitatory amino acids. These differences may explain the greater protective efficacy of hypothermia in the face of cerebral ischemia.

Anesthetics, Inhalation↗
PubMed1996

Comparative effects of propofol, pentobarbital, and isoflurane on cerebral blood flow and blood volume.

While intravenous and volatile anesthetics have widely differing effects on cerebral blood flow (CBF), clinical studies suggest that the relative differences in their effects on intracranial pressure (ICP) may be smaller. Because acute changes in ICP are determined primarily by changes in cerebral blood volume (CBV), we compared the impact of propofol, pentobarbital, and isoflurane on CBF and CBV in rats. Equipotent doses of the three agents were determined by tail-clamp studies. Animals were then anesthetized with propofol (20 mg/kg load, 38 mg.kg-1.h-1 infusion), pentobarbital (30 mg/kg load, 20 mg.kg-1.h-1 infusion), or isoflurane 1.6-1.8%. Two hours later, CBF and CBV were measured using 3H-nicotine as a CBF tracer, and 14C-dextran and 99mTc-labeled red cells as markers for cerebral plasma and red blood cell volumes (CPV and CRBCV), respectively. Total CBV was the sum of CPV and CRBCV. CBF was 2.0-2.6 times greater with isoflurane than with propofol or pentobarbital (137 vs. 67 and 52 ml.100 g-1.min-1, respectively). By contrast, while CBV was greater in the isoflurane group than in either the propofol or pentobarbital groups, the magnitude of the intergroup differences were much smaller (propofol = 2.49 +/- 0.28 ml/100 g; pentobarbital = 2.27 +/- 0.15 ml/100 g; isoflurane = 2.77 +/- 0.24 ml/100 g, mean +/- SD). These results suggest that the simple measurement of CBF may not adequately describe the cerebrovascular effects of an anesthetic, at least with respect to predicting the magnitude of the agents likely effects on ICP.

Adjuvants, Anesthesia↗
PubMed1996

Somatosensory evoked potentials correlate with neurological outcome in rabbits undergoing cerebral air embolism.

BACKGROUND AND PURPOSE: Somatosensory evoked potentials (SSEPs) have been used as an outcome measure in models of cerebral air embolism despite the lack of studies correlating SSEPs with other measures of neurological injury. We examined the relationship between SSEPs and neurological impairment in the setting of cerebral air embolism. METHODS: Anesthetized New Zealand White rabbits received either 0, 50, 100, or 150 microL/kg of air into the internal carotid artery. SSEPs were recorded at intervals for the subsequent 2 hours. After the final recording the anesthetic was discontinued, and the animals recovered. Animals were neurologically evaluated at 3 and 24 hours after cerebral air embolism on a scale of zero (normal) to 97 (coma) points. RESULTS: There was a clear relationship between the dose of air and 2-hour SSEP amplitude (P = .00003). SSEP amplitudes at 2 hours were inversely correlated with neurological impairment scores at 3 hours (r = -0.71, P < .0001). SSEP amplitudes at 2 hours were less in animals that died (11 +/- 16%; n = 9) than in those that survived to 24 hours (53 +/- 20%; n = 9) (P = .0008). CONCLUSIONS: These results support SSEPs as an index of neurological impairment in this model of cerebral air embolism.

Animals↗
PubMed1996

Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization.

BACKGROUND AND PURPOSE: Hypothermia slows the increase in extracellular excitatory amino acid (EAA) concentrations during temporary cerebral ischemia. However, it is unclear whether hypothermia slows the rate of EAA release or just delays the time until the first sharp increase (which occurs coincident with terminal depolarization). METHODS: Pericranial temperatures were adjusted to 38 degrees C, 34 degrees C, 31 degrees C, or 25 degrees C in halothane-anesthetized rats. The cortical DC voltage was recorded from a glass microelectrode while the cortical concentrations of glutamate, aspartate, glycine, and gamma-aminobutyric acid (GABA) were measured by microdialysis. A cardiac arrest was induced with intravenous KCl, and the times until electroencephalograph isoelectricity and terminal depolarization were recorded. Dialysate concentrations of the four compounds were measured at 10, 20, and 30 minutes after depolarization. RESULTS: The times to isoelectricity and depolarization varied inversely with temperature; depolarization time increased from 70 +/- 9 seconds at 38 degrees C (mean +/- SD) to 294 +/- 34 seconds at 25 degrees C. The dialysate concentrations of all four compounds increased during ischemia, and the rate of increase was inhibited by cooling. After 30 minutes of ischemia, glutamate concentration in 38 degrees C animals was 58.4 +/- 31.8 mumol/L; this decreased to 15.9 +/- 8.4 mumol/L at 25 degrees C. The magnitude of the effects of temperature on amino acid release differed with the compound measured. For glutamate, the calculated Q10 was 3.63. Corresponding values for aspartate and glycine were 3.68 and 1.95, respectively. By contrast, Q10 for GABA release was 6.31, indicating greater sensitivity to cooling. CONCLUSIONS: These results suggest that effects of hypothermia on EAA concentrations during cerebral ischemia may be the result of both a delay until initial EAA release as well as a direct effect of temperature on the rate of amino acid release. The observed temperature effects are more consistent with carrier-mediated processes controlling EAA release.

Analysis of Variance↗
PubMed1995

The efficacy of routine central venous monitoring in major head and neck surgery: a retrospective review.

STUDY OBJECTIVE: To further define the efficacy of routine central venous catheter placement for major head and neck surgery from the standpoint of fluid and blood administration, and various other parameters of perioperative management. DESIGN: Randomized, retrospective chart review. SETTING: University-affiliated medical center. PATIENTS: 104 patients who had undergone major head and neck surgery (defined as surgery lasting longer than 4 hours with a predicted blood loss of 500 ml or greater) at the University of Iowa Hospitals and Clinics between 1985 and 1992. MEASUREMENTS AND MAIN RESULTS: Central venous monitoring was used in 51 of the 104 (49%) procedures. Patients with and without central monitors did not differ in age, weight, preoperative laboratory values [i.e., hemoglobin (Hb), blood urea nitrogen (BUN), creatinine), incidence of significant cardiac or renal disease, or a smoking history exceeding 30 pack years. In addition, these patients did not differ with respect to the following intraoperative characteristics: general type of anesthetic; duration of surgery; estimate of blood loss; Hb values; lowest urine output per hour; development of oliguria; total urine output; amount of replacement of blood, colloid, or crystalloid; development of systolic blood pressure less than 70 mmHg; or use of a myocutaneous flap. Patients also did not differ with respect to the following postoperative characteristics: duration of stay in the surgical intensive care unit or hospital, BUN or creatinine values on days 1 and 2, total urine output or the development of oliguria on days 1 through 3, incidence of reintubation, fever on days 1 through 5, wound dehiscence, death, myocardial infarction, or the development of pneumonia, pulmonary edema, or sepsis. Patients with central monitors had a greater incidence of having a tracheostomy performed and a slightly lower Hb level on the first postoperative day than those without central monitors. CONCLUSIONS: The study raises doubt about the efficacy of routine central venous catheter placement as a necessary guide for fluid and blood administration for these procedures, or as a necessary adjunct for several other parameters of perioperative management. It suggests the need for a randomized, prospective evaluation.

Blood Urea Nitrogen↗
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

A comparison of the effects of hypothermia, pentobarbital, and isoflurane on cerebral energy stores at the time of ischemic depolarization.

BACKGROUND: In an accompanying article, we report that hypothermia (27-28 degrees C) delayed postischemic cortical depolarization longer than did large-dose pentobarbital or isoflurane anesthesia, even though preischemic cerebral metabolic rates for glucose were similar in the three groups. To examine the mechanism that may underlie these differences, we measured the cerebral concentrations of high-energy phosphates (including adenosine triphosphate [ATP] and adenosine diphosphate) in normal conditions and at the moment of depolarization. METHODS: Rats were anesthetized with 0.8% halothane/50% N2O and prepared for measurement of the cortical direct-current potential by glass microelectrodes. Animals were assigned to one of four groups: (1) halothane/nitrous oxide anesthesia, pericranial temperature approximately 38 degrees C; (2) halothane/nitrous oxide, approximately 28 degrees C; (3) halothane/nitrous oxide anesthesia with pentobarbital added to achieve electroencephalographic isoelectricity, approximately 38 degrees C; or (4) 2.4% isoflurane/50% N2O anesthesia (with electroencephalographic isoelectricity), approximately 38 degrees C. The latter three groups were chosen on the basis of earlier work showing similar cerebral metabolic rates for glucose. In a subgroup of each, circulatory arrest was induced with KCl and the brain was frozen in situ (with liquid nitrogen) at the moment of cortical depolarization. In remaining animals, the brain was frozen without any ischemia. Tissue ATP, adenosine diphosphate, adenosine monophosphate, and phosphocreatine concentrations were measured by high-performance liquid chromatography. RESULTS: High-energy phosphate concentrations in nonischemic brain tissue were similar in all groups (e.g., ATP concentration 2.47-2.79 mumol/g brain). With ischemia, depolarization occurred when ATP concentrations had decreased to 13-18% of normal. There were no significant differences in the concentration of any compound or in the energy charge among the groups, even though the time until depolarization was much longer in hypothermic animals (242 s) than in animals receiving large doses of anesthesia (119 and 132 s) or in normothermic halothane/nitrous oxide animals (73 s). CONCLUSIONS: The ATP/energy charge threshold for cortical depolarization was similar in all groups despite differing temperature or anesthetic conditions. Because hypothermia increased the time until depolarization, the rate of decrease in ATP concentration must have been slower in these animals than in the two groups receiving large-dose anesthetics, despite similar preischemic cerebral metabolic rates for glucose. This finding is similar to that of earlier studies and indicates that factors other than preischemic metabolic rate are responsible for controlling energy utilization after ischemia.

Adenosine Triphosphate↗
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

Angiotensin II contributes to cerebral vasodilatation during hypoxia in the rabbit.

BACKGROUND: and Purpose Hypoxia increases cerebral blood flow (CBF). Hypoxia also exerts a major influence on the renin-angiotensin system. In addition to the circulating renin-angiotensin system, a local renin-angiotensin system appears to be present in the brain, and angiotensin II receptors have been identified in cerebral blood vessels. In this study we tested the hypothesis that endogenous angiotensin II attenuates dilatation of the cerebral vessels during hypoxia. METHODS: Pentobarbital-anesthetized rabbits were prepared for measurement of blood flow (microspheres) and assigned to one of two groups: in group 1 (n = 11), rabbits were subjected to 30 minutes of stable hypoxia (PaO2 = 34 +/- 1 mm Hg, mean +/- SD) followed by 15 minutes of reoxygenation (PaO2 = 177 to 200 mm Hg). Blood flow was measured four times: under control conditions, after 15 and 30 minutes of hypoxia, and after 15 minutes of reoxygenation. This was a control group to characterize changes in CBF during hypoxia. In group 2 (n = 11), blood flow was measured as in the previous group except that an infusion of the angiotensin II receptor antagonist saralasin (1 microgram.kg-1.min-1 IV) was started with the onset of hypoxia and continued through reoxygenation to the end of the experiment. The goal of this group was to examine whether endogenous activation of receptors for angiotensin II influences increases in CBF during hypoxia. In a separate series of experiments we examined the influence of the angiotensin-converting enzyme (ACE) inhibitor captopril on the hypoxic response. Thus, in one group of rabbits we measured CBF in the same manner as in group 1 (n = 13). In another group of rabbits we also measured blood flow as in group 1 except that rabbits received 10 mg/kg of the ACE inhibitor captopril before the control measurement (n = 11). We tested for significant differences between groups using two-way ANOVA. RESULTS: Under control conditions, CBF was similar in all groups and averaged 53 +/- 15 mL.min-1.100 g-1. During hypoxia, CBF increased to a greater extent in the absence versus the presence of saralasin (95 +/- 31 and 104 +/- 30 mL.min-1.100 g-1 versus 72 +/- 24 and 71 +/- 25 mL.min-1.100 g-1, respectively; P = .003). Increase in CBF during hypoxia was also significantly greater in the animals that did not receive captopril versus those that were treated with captopril (100 +/- 24 and 89 +/- 16 mL.min-1.100 g-1 versus 72 +/- 16 and 73 +/- 17 mL.min-1.100 g-1). To rule out the possibility that saralasin produced non-specific attenuation of cerebral vasodilatation, we tested the influence of hypercapnia on CBF in the absence and presence of saralasin. During normocapnia, CBF values were not significantly different in the absence and presence of saralasin (57 +/- 17 and 64 +/- 6 mL.min-1.100 g-1, respectively; P > .05). Hypercapnia increased CBF similarly in the absence and presence of saralasin (81 +/- 22 and 91 +/- 19 mL.min-1.100 g-1; PaCO2 = 61 +/- 2 and 60 +/- 2 mm Hg, respectively; P > .05). CONCLUSIONS: Because the ACE inhibitor captopril and the angiotensin II receptor blocker saralasin attenuated increased in CBF during hypoxia, the findings suggest that endogenous release of angiotensin II contributes to the increase in CBF during hypoxia.

Angiotensin II↗
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↗