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M M Todd

Publications and source records attributed to M M Todd.

At least 19 recordsLinked to original sources
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↗
PubMed1992

A comparison of the vasodilating effects of halothane and isoflurane on the isolated rabbit basilar artery with and without intact endothelium.

Although volatile anesthetics result in cerebral arterial dilation, the precise mechanisms underlying this effect are not known. In vitro tension recordings were used to study the vasodilating potencies of halothane and isoflurane in isolated cerebral vessels and to examine the possible role of the endothelium in modulating any effects observed. Cylindrical segments of the rabbit basilar artery and midline ear artery from the same animal were placed in a flow-through bath of 37 degrees C oxygenated (95% O2/5% CO2) physiologic salt solution and stretched to a resting tension of approximately 2,000 dynes. They were then constricted with 3.0 x 10(-2) M K+, 1.0 x 10(-3) M norepinephrine, or 5.0 x 10(-6) M serotonin and exposed to either halothane or isoflurane at concentrations of approximately 0.5, 1.0, 1.5, and 2.0 MAC in varied order for 15 min at each concentration. A 30-min period of perfusion with anesthetic-free, vasoconstrictor-containing perfusate separated successive exposures to an anesthetic. Vessels prepared in this fashion retained their responsiveness to both vasoconstrictors and volatile anesthetics for as long as 4 h. They also relaxed appropriately to acetylcholine, indicating that the endothelium was intact. Concentrations of volatile anesthetic in the tissue perfusate were directly measured using gas chromatography, and the relationship between bath concentrations (expressed as MAC fractions) and the degree of relaxation were determined. The data were analyzed by parallel line regression. Halothane was found to be a significantly more potent vasodilator of the isolated basilar artery than was isoflurane. For example, in K(+)-constricted vessels, the concentration of halothane needed to produce a 50% reduction in tension was 1.32 MAC, compared with 1.66 MAC for isoflurane. Comparable differences were found in the basilar artery in the presence of other constrictors. However, there was no significant difference between the two agents in their effects upon the ear artery. In a separate series of experiments, the endothelium of basilar artery segments was removed by drying. Removal was confirmed by observing a diminished dilator response to acetylcholine. These vessels were subsequently constricted with K+, and relaxation dose-response curves were obtained for both halothane and isoflurane. There were no differences in the dose-response curves for deendothelialized versus intact vessels, with halothane still the more potent relaxant after endothelial removal. These data demonstrate that halothane and isoflurane cause a dose-dependent relaxation of rabbit cerebral vessels, regardless of the vasoconstrictor used. Halothane was a more potent relaxant of the basilar artery when expressed on a MAC-fraction basis.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

A comparison of cerebral ischemic flow thresholds during halothane/N2O and isoflurane/N2O anesthesia in rats.

Isoflurane/N2O anesthesia has been reported to reduce the cerebral blood flow (CBF) threshold at which electroencephalographic changes occur in humans during carotid occlusion (when compared to halothane/N2O). To further evaluate this observation, normocapnic, normothermic rats were anesthetized with 0.75 MAC isoflurane or halothane in combination with 60% N2O. The electrocorticogram (ECoG) and the cortical DC potential were recorded using glass microelectrodes. Both carotid arteries were occluded, and mean arterial pressure (MAP) was reduced over 3-5 min (by phlebotomy) to predetermined values between 30 and 75 mmHg. This MAP was maintained for 10 min, and CBF was then measured in cortical gray matter using [3H]-nicotine. Flows were then correlated with ECoG changes and with the presence or absence of cortical depolarization (which reflects the loss of transmembrane ion homeostasis). In other rats, the cortical cerebral metabolic rate for glucose (CMRglu) was determined autoradiographically using [14C]-deoxyglucose. Finally, the time to depolarization was determined in rats killed with KCl and in rats subjected to hypotension (MAP = 30-35 mmHg) followed by abrupt bilateral carotid occlusion. The distributions of CBF values in the anesthetic groups were essentially identical. The incidence of either major ECoG changes or isoelectricity did not differ between anesthetics. The CBF associated with major ECoG changes (excluding isoelectricity) were 35 +/- 12 and 39 +/- 18 ml.100 g-1.min-1 in the halothane/N2O and isoflurane/N2O groups respectively (mean +/- SD, difference not significant [NS]). Isoelectricity was seen at 7 +/- 4 ml.100 g-1.min-1 (median = 6.5) with halothane/N2O and 17 +/- 19 ml.100 g-1.min-1 (median = 11) with isoflurane/N2O (again, NS). The incidence of sustained depolarization did not differ between anesthetics (9 of 25 for halothane/N2O, 8 of 24 with isoflurane/N2O). CBF associated with sustained depolarization was 13 +/- 12 ml.100 g-1.min-1 (median = 10) with halothane/N2O, compared with 9 +/- 6 ml.100 g-1.min-1 (median = 9) for isoflurane/N2O (NS). In rats subjected to cardiac arrest, the time to depolarization was longer with isoflurane/N2O (102 +/- 19 s vs. 77 +/- 7 s). In rats subjected to carotid occlusion at a MAP = 30-35 mmHg, the time to depolarization was again longer with isoflurane/N2O (210 +/- 78 s vs. 122 +/- 44 s). Cortical CMRglu was lower with isoflurane/N2O (25 +/- 5 mumol.100 g-1.min-1) than with halothane (43 +/- 13 mumol.100 g-1.min-1, P = 0.03). The results indicate that isoflurane/N2O anesthesia delays the onset of ischemic cell depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, Inhalation↗
PubMed1992

Comparative effects of propofol and halothane on outcome from temporary middle cerebral artery occlusion in the rat.

Because propofol has cerebral effects similar to those observed for barbiturates, we postulated that it too might offer protection against a focal cerebral ischemic insult. Spontaneously hypertensive male rats were anesthetized with halothane (in 50% O2/balance N2), and their tracheas were intubated and their lungs mechanically ventilated. A right subtemporal craniectomy was performed and a 10-0 suture placed around the middle cerebral artery. Rats were then randomly assigned to one of two anesthetic groups. In one half of the rats (n = 14), the inspired halothane concentration was reduced to 0.5-0.7%. In the remainder (n = 14), halothane was discontinued, and an intravenous infusion of 1% propofol was given in doses sufficient to produce and maintain electroencephalographic burst suppression. The middle cerebral artery was then reversibly ligated for 2 h while pericranial temperature was maintained at 37.0 +/- 0.1 degrees C (mean +/- SD). After the ligature was removed and reperfusion confirmed, all rats were allowed to recover for 96 h. Neurologic evaluations were performed at both 24 and 96 h postischemia. The rats were then killed and the brains removed, frozen, sectioned, and stained with nitro blue tetrazolium. Infarct volume was determined by computerized planimetry. Physiologic values were similar between anesthetic groups, although plasma glucose was significantly greater during ischemia in the halothane group (125 +/- 25 vs. 83 +/- 8 mg/dl, P less than 0.001). At both 24 and 96 h postischemia, neurologic deficits were mild but without a difference between groups. Neurologic scores at 96 h postischemia correlated with cerebral infarct volume (r = 0.49, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1992

Brain blood flow and metabolism do not decrease at stable brain temperature during cardiopulmonary bypass in rabbits.

Cerebral blood flow (CBF) during human hypothermic cardiopulmonary bypass has been reported to decrease with time, suggesting that progressive cerebral vasoconstriction or embolic obstruction may occur. We tested the hypotheses: 1) that observed CBF reductions were due to continued undetected brain cooling and 2) that CBF during cardiopulmonary bypass would be stable after achievement of constant brain temperature. Anesthetized New Zealand White rabbits underwent cardiopulmonary bypass (membrane oxygenator, centrifugal pump, bifemoral arterial perfusion) and were assigned to one of three bypass management groups based on perfusate temperature and PaCO2 management: group 1 (37 degrees C, n = 8); group 2 (27 degrees C, pH-stat, n = 9); and group 3 (27 degrees C, alpha-stat, n = 8). Systemic hemodynamics, and cerebral cortical, esophageal, and arterial perfusate temperatures were recorded every 10 min for the first hour of bypass and again at 90 min. CBF and masseter blood flow (radiolabeled microspheres) were determined at 30, 60, and 90 min of bypass, while the cerebral metabolic rate for oxygen (CMRO2) was determined at 60 and 90 min. Groups were comparable with respect to mean arterial pressure, central venous pressure, hematocrit, and arterial oxygen content throughout bypass. Cortical temperature was stable in normothermic (group 1) animals, and there was no significant change in CBF between 30 and 90 min of bypass: 68 +/- 18 versus 73 +/- 20 ml.100 g-1.min-1 (mean +/- SD). In the hypothermic groups (2 and 3), cortical temperature equilibration (95% of the total change) required 41 +/- 6 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

AMPA receptor competitive antagonism reduces halothane MAC in rats.

Various subtypes of receptors have been identified for glutamate, an excitatory neurotransmitter. Previous studies have shown that antagonism of glutamate at the NMDA receptors reduces minimum alveolar concentration (MAC) for volatile anesthetics. NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline) is a selective antagonist at the glutamatergic AMPA receptor. The purpose of this experiment was to determine whether AMPA receptor antagonism influences halothane MAC in the rat. Sprague-Dawley rats were anesthetized with halothane in 50% O2/balance N2, tracheally intubated and the lungs were mechanically ventilated. Increasing doses of NBQX were intravenously infused in three groups while the control group was infused with vehicle (D5W). Halothane MAC was then determined by the tail-clamp method. Halothane MAC was log-linearly related to plasma NBQX concentrations (MAC = 0.125 (In plasma concentration NBQX) + 1.035, r2 = 0.77). A maximal 58% reduction of halothane MAC was achieved with an NBQX loading dose of 42 mg/kg followed by a continuous infusion rate of 36 mg x kg-1 x h-1 (control = 1.02 +/- 0.07%; NBQX = 0.43 +/- 0.12%; P < .01). Larger doses of NBQX were not possible because of the poor aqueous solubility of this compound. In a separate experiment, awake rats were randomly assigned to groups based on the dose of NBQX infused. Pa(CO2) and mean arterial pressure were measured at time 0 and at 5 and 30 min after start of NBQX infusion. The infusion was then stopped. Time until recovery of the righting reflex was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1992

Cerebral blood flow, blood volume, and brain tissue hematocrit during isovolemic hemodilution with hetastarch in rats.

The influence of isovolemic hemodilution with 6% hetastarch [hematocrits (Hct) ranging from 43 to 20%] on cerebral blood flow (CBF), cerebral red blood cell and plasma volumes, total cerebral blood volume (CBV), and cerebral Hct was examined in normothermic, normocarbic, halothane-anesthetized Sprague-Dawley rats. CBF was measured via the indicator-fractionation method ([3H]nicotine), red blood cell volume was measured using 99mTc-labeled red blood cells, while plasma volume was measured using [14C]dextran. Brain tissue was fixed in situ by microwave irradiation. All data plots (e.g., CBF vs. Hct) were fitted by linear regression methods. Hemodilution was associated with a progressive increase in forebrain CBF (from a fitted value of 78 ml.100 g-1.min-1 at Hct = 43%, to 171 ml.100 g-1.min-1 at 20%). Cerebral plasma volume also rose, while red blood cell volume decreased. Total CBV (i.e., the sum of red blood cell and plasma volumes) increased in parallel with CBF (from 2.51 ml/100 g at Hct = 43 to 4.94 ml/100 g at Hct = 20%). This increase is larger than can be explained by a simple increase in the diameter of arterial/arteriolar resistance vessels and may be due to either capillary recruitment or to an increase in the volume of postarteriolar structures. Calculated cerebral tissue hematocrit decreased. The magnitude of this decrease was larger than the reduction in arterial Hct; the ratio of cerebral to arterial Hct decreased from 0.780 at an arterial Hct equaling 43% to 0.458 at Hct equaling 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Insulin-induced normoglycemia improves ischemic outcome in hyperglycemic rats.

BACKGROUND AND PURPOSE: Hyperglycemia is known to aggravate ischemic brain damage. This study sought to determine if preischemic insulin-induced normoglycemia would improve outcome in hyperglycemic rats. METHODS: Normal rats and rats with 5-7 days of streptozotocin-induced diabetes were studied. Normal rats served as either fasted normoglycemic controls or dextrose-infused (hyperglycemic) controls. In the acutely diabetic rats either no insulin was given or insulin was given at 30 or 90 minutes before ischemia so as to induce preischemic normoglycemia. All rats underwent 10 minutes of forebrain ischemia. After 5 days of recovery, motor function and histological outcome were assessed. RESULTS: Untreated diabetic rats and dextrose-infused control rats had greater hippocampal CA1 damage than normoglycemic control rats. In contrast, insulin-treated diabetic rats had less hippocampal CA1 damage than either untreated diabetic rats or dextrose-infused control rats. Injury in the two insulin-treated groups was not significantly different from that in the normoglycemic control group (all three groups had plasma glucose values of 120-150 mg/dl immediately prior to ischemia). Despite similar plasma glucose values (300-400 mg/dl), fewer postischemic seizures (0% versus 67%) were observed in the untreated diabetic group than in the dextrose-infused control group (p < 0.001). CONCLUSIONS: Hyperglycemia caused by either dextrose infusion or streptozotocin-induced diabetes resulted in exacerbated ischemic brain damage. Insulin therapy to rapidly induce preischemic normoglycemia improved outcome from forebrain ischemia in the acutely diabetic rats. Glucose-infused hyperglycemic rats frequently exhibited postischemic generalized seizures while acutely diabetic rats did not. The latter results implicate some adaptive/protective mechanism associated with acute streptozotocin-induced diabetes that results in a decreased sensitivity to hyperglycemia-augmented ischemic brain damage.

Animals↗
PubMed1992

Mild hypothermia reduces infarct size resulting from temporary but not permanent focal ischemia in rats.

BACKGROUND AND PURPOSE: Mild hypothermia (32-35 degrees C) has been repeatedly shown in laboratory models to reduce damage resulting from global cerebral ischemic insults. Little information is available, however, regarding the protective potential of mild hypothermia against focal ischemia. We designed the present study to determine whether mild hypothermia influences outcome from either temporary or permanent middle cerebral artery occlusion in the rat. METHODS: In experiment 1 (permanent occlusion), mechanically ventilated, halothane-anesthetized spontaneously hypertensive rats underwent permanent ligation of the middle cerebral artery. Pericranial temperature was maintained at either 37 degrees C (n = 11) or 33 degrees C (n = 11) during the first 2 hours of occlusion. In experiment 2 (temporary occlusion), the vessel was occluded for 1 hour only. Pericranial temperature was controlled at either 37 degrees C (n = 12) or 33 degrees C (n = 14) during ischemia and for 1 hour after reperfusion. In both experiments, the rats were allowed to recover, with neurological function scored at 24 and 96 hours after onset of ischemia. Cerebral infarct volume (as determined by nitro blue tetrazolium staining) was planimetrically evaluated 96 hours after onset of ischemia. RESULTS: No difference in infarct volume was observed between groups undergoing permanent occlusion (177 +/- 53 mm3 for 37 degrees C rats, 167 +/- 71 mm3 for 33 degrees C rats [mean +/- SD]). Although neurologic function correlated with infarct volume at 96 hours (all animals in experiment 1 combined; p less than 0.01), we were unable to demonstrate an intergroup difference in function. In animals undergoing temporary occlusion, mean +/- SD infarct volume was 48% less in the hypothermic group (89 +/- 54 mm3 for 37 degrees C, 46 +/- 31 mm3 for 33 degrees C; p less than 0.03). Neurological function again correlated with infarct size (p less than 0.02), but improvement in function approached significance for the hypothermic group (p less than 0.06) at 24 hours after reperfusion only. CONCLUSIONS: Benefits from mild hypothermia may be obtained under conditions of temporary but not permanent middle cerebral artery occlusion in the rat.

Animals↗
PubMed1992

Pregnancy does not alter the threshold for lidocaine-induced seizures in the rat.

Although altered effects of various anesthetics have been demonstrated during pregnancy, published studies have incompletely defined potential pregnancy-induced changes in the central nervous system toxicity of lidocaine. Accordingly, the seizure threshold for lidocaine was measured in three groups of mechanically ventilated rats breathing 70% N2O-30% O2: male (n = 21), nonpregnant female (n = 19), and pregnant female (n = 23). Lidocaine was administered intravenously at a constant rate of 2.3 mg.kg-1.min-1 while the electroencephalogram was monitored continuously. Total doses of lidocaine and the durations of lidocaine infusion necessary to induce seizure activity were similar among groups. Plasma lidocaine concentrations at the onset of electroencephalographic seizure activity were also similar among groups (male = 10.7 +/- 5.5, nonpregnant female = 12.1 +/- 4.9, pregnant female = 10.8 +/- 4.1 micrograms/mL). In a subset of each group, brain lidocaine concentrations at the onset of seizure activity were also measured, and again no differences among groups were observed (male = 17.4 +/- 6.3, nonpregnant female = 16.8 +/- 4.5, pregnant female = 16.7 +/- 4.2 micrograms/100 g wet wt). The authors conclude that there are no pregnancy-specific alterations in either plasma or brain concentration thresholds for central nervous system toxicity of lidocaine in rats.

Animals↗
PubMed1992

Central nervous system toxicity of local anesthetic mixtures in the rat.

Local anesthetics are often administered as mixtures during regional anesthesia. This study investigated whether a synergistic or antagonistic interaction between amide/amide or amide/ester local anesthetic combinations is present with respect to central nervous system toxicity. For surgical preparation, rats were anesthetized with 0.8% halothane in 30% O2/balance N2O and mechanically ventilated. Mean arterial blood pressure and the electroencephalogram were continuously monitored. After surgery, the halothane was discontinued for 15 min. An intravenous infusion of solutions containing lidocaine alone, bupivacaine alone, or any of three mixtures of the two drugs was then begun and continued at a fixed rate until seizure activity was observed on the electroencephalogram. Total administered doses of both drugs were compared by isobolographic analysis. After a similar protocol, a second experiment was performed evaluating lidocaine, tetracaine, or any of three mixtures of those two drugs. In both experiments, normocapnia, normoxia, and normothermia were maintained for all rats. For mixtures of lidocaine/bupivacaine (P = 0.40) and lidocaine/tetracaine (P = 0.24), there was no evidence that a significant degree of either synergism or antagonism was present. At the onset of seizures, mean arterial pressure was lowest in the lidocaine-alone groups in both experiments. Increasing doses of either bupivacaine or tetracaine (with correspondingly decreasing doses of lidocaine) were associated with greater mean arterial pressure values at onset of seizures. We conclude that central nervous system toxic effects of amide/amide or amide/ester anesthetic combinations, such as might occur during accidental intravascular injection, are no more than when the drugs are administered alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗
PubMed1991

Effects of ketamine on outcome from temporary middle cerebral artery occlusion in the spontaneously hypertensive rat.

This experiment evaluated the potential for ketamine HCl, a non-competitive glutamate antagonist, to minimize injury resulting from temporary focal cerebral ischemia. Male spontaneously hypertensive rats were randomly assigned to receive either ketamine (n = 13) or halothane anesthesia (n = 12) during 2 h of reversible middle cerebral artery occlusion (MCAO). Ketamine was administered as a 50 mg/kg i.v. loading dose followed by a continuous 1.25 mg/kg/min i.v. infusion beginning 25 min prior to ischemia and continued until 30 min after reperfusion. An additional group of rats (ketamine-shams, n = 8) underwent craniectomy and ketamine administration (as above) but the middle cerebral artery was not ligated. Physiologic values were similar between groups with the exception of plasma glucose which was elevated in the halothane-MCAO group. After 4 days recovery, rats in all groups were neurologically evaluated. There were no differences between the two groups undergoing MCAO for neurologic grading or open field behavior, although both groups performed worse than did ketamine-shams (P less than 0.05). In contrast, motor performance revealed more severe deficits in the ketamine-MCAO rats vs either the halothane-MCAO or ketamine-sham groups (P less than 0.05). Cerebral infarct volume was then planimetrically measured after triphenyl tetrazolium chloride (TTC) staining of fresh brain sections. Mean +/- S.D. infarct volume was not different between the halothane-MCAO (134 +/- 51 mm3) and ketamine-MCAO (131 +/- 64 mm3) groups. Seven of 8 sham rats were free of TTC demarcated injury and in the remaining rat injury was minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of acute hypermagnesemia on the threshold for lidocaine-induced seizures in the rat.

The effects of acute changes in plasma magnesium concentration on the threshold for lidocaine-induced seizures were evaluated in mechanically ventilated rats receiving 70% nitrous oxide and 30% oxygen. In experiment 1, male rats were intravenously administered either 0.9% sodium chloride (group I) or 5.0% magnesium sulfate to elevate plasma magnesium levels to 5.8 +/- 0.1 (group II) or 10.5 +/- 1.0 mg/dl (group III). In experiment 2, pregnant rats were intravenously administered either 0.9% sodium chloride (normomagnesemia) or magnesium sulfate, resulting in a plasma magnesium concentration of 7.8 +/- 1.4 mg/dl. Thirty minutes later, a continuous intravenous infusion of lidocaine (2.3 mg/kg per minute) was begun in both experiments. Biparietal electroencephalographic activity was monitored continuously. At the onset of electroencephalographic seizure activity, arterial plasma magnesium and lidocaine concentrations were measured. In groups I and III (experiment 1), brain parenchymal magnesium was also assayed. There were no differences in plasma lidocaine concentrations (in experiments 1 or 2) between saline solution and hypermagnesemic groups at onset of seizures. Brain magnesium level was unaltered by magnesium sulfate infusion. We conclude that acute administration of magnesium sulfate alters neither brain magnesium level nor the plasma lidocaine concentration associated with onset of electroencephalographic seizures.

Acute Disease↗
PubMed1991

Reversible focal ischemia in the rat: effects of halothane, isoflurane, and methohexital anesthesia.

Barbiturates and the volatile anesthetic isoflurane reduce CMR to similar values. If the mechanism of barbiturate protection against focal ischemic injury is due to a reduction in cellular energy requirements, then isoflurane should similarly reduce ischemic injury. To evaluate this, spontaneously hypertensive rats underwent 2 h of reversible middle cerebral artery occlusion (MCAO) while receiving deep methohexital, isoflurane, or halothane anesthesia. Ninety-six hours postischemia, neurologic deficits were present but without a difference between groups. Mean +/- SD infarct volume, as assessed by triphenyl tetrazolium chloride staining and computerized planimetry, was significantly less in the methohexital group (n = 8; 166 +/- 74 mm3) than in either the halothane (n = 9; 249 +/- 71 mm3; p less than 0.04) or the isoflurane (n = 9; 243 +/- 62 mm3; p less than 0.03) groups. One possible explanation for the lack of protective effect for isoflurane might be related to its vasodilative properties, which could result in a cerebral vascular steal. To examine this possibility, rats anesthetized with methohexital or isoflurane underwent autoradiographic determination of CBF with or without MCAO. In isoflurane-anesthetized sham rats (n = 5; no ischemia), CBF was approximately three times greater than in methohexital-treated (n = 5) sham rats. During ischemia, although a regional reduction in flow was noted in both anesthetic groups, mean flow remained greater in the isoflurane group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗