Associations of thrombocytopenia, transaminase elevations, and transfusion with laboratory coagulation tests in women with preeclampsia: a cross-sectional study.

BACKGROUND: Women with preeclampsia may develop coagulopathy, predisposing to bleeding complications. Although guidelines and prior studies conflict, we hypothesized that in preeclampsia, abnormal coagulation test results are more common in women with thrombocytopenia or transaminase elevations and increase the transfusion risk. Our objectives were to investigate: 1. patterns of coagulation testing; 2. relationships between platelet count, transaminase level, and the risk of abnormal coagulation tests; 3. risk of bleeding complications; and 4. characteristics of patients with markedly abnormal coagulation parameters. METHODS: We conducted a cross-sectional study of deliveries of women with preeclampsia who had undergone activated partial thromboplastin time (aPTT) or international normalized ratio (INR) testing at one of two hospitals between 1994 and 2018. RESULTS: Of 10 699 women with preeclampsia, 3359 (32.7%) had coagulation testing performed and aPTT or INR elevations were present in 124 (3.7 %). Coagulation abnormalities were more common in women with thrombocytopenia or transaminase elevations (n=82) compared with those without (n=42) (6.7%, 95% CI 5.5 to 8.2 vs 1.8%, 95% CI 1.3 to 2.5). Transfusion was more common among women with abnormal coagulation parameters (n=124) compared with those without (n=39) (33.1 vs 7.0%, P <0.001). Among 26 patients with an aPTT ≥40 s or an INR ≥1.4, six required transfusion (all had placental abruption and disseminated intravascular coagulopathy). CONCLUSIONS: Coagulation testing was inconsistently performed in this cohort. Platelet counts and transaminase levels inadequately detected abnormal coagulation test results. Abnormal coagulation test results were associated with a markedly higher risk for red blood cell transfusion.

Effect of hyperglycemia on reperfusion-associated recovery of intracellular pH and high energy phosphates after transient cerebral ischemia in gerbils.

Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the relationship of intracellular tissue acidosis and delayed recovery of brain high-energy phosphates to increased damage during the reperfusion period. Mongolian gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2 h reperfusion. All gerbils were pretreated intraperitoneally with equivalent volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4 grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH, inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group, intracellular pH decreased with ischemia, but most significantly in hyperglycemic animals (6.45 +/- 0.15), in which it had not recovered to preischemic levels by the end of the reperfusion period (6.8 +/- 0.1 vs 7.04 +/- 0.1, p < 0.05). High-energy phosphates phosphocreatine-inorganic phosphate and phosphocreatine-adenosine triphosphate showed partial recovery in all groups throughout the reperfusion period; the recovery was not significantly altered by glucose status. Hyperglycemia worsened pH but not the recovery of high-energy phosphates in animals reperfused after 20 min of transient cerebral ischemia. This sustained acidosis may be a primary event in transient damage in hyperglycemic animals.

Delayed hyperglycemia and intracellular acidosis during focal cerebral ischemia in cats.

The effects of hyperglycemia on permanent focal brain ischemia is controversial; its effects on the size of the infarct are variable according to experimental conditions. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to assess brain pH and high-energy phosphate metabolites after focal middle cerebral artery (MCA) ischemia in hyperglycemic and normoglycemic cats. Sixteen adult cats underwent (MCA) occlusion under general anesthesia and nuclear magnetic resonance 31P spectroscopy to assess intracellular brain pH and energy metabolites throughout permanent ischemia. Animals were treated two hours after the onset of ischemia with either saline or glucose perfusions. Significant hyperglycemia (488 vs 105 mg/100 ml) was achieved in the experimental group. The response to hyperglycemia was dependent on the initial characteristics of the infants. A distinct pattern of phosphocreatine/inorganic phosphate recovery within 20 minutes of ischemia predicted a small infarct size. The addition of hyperglycemia did not affect acidosis, infarct size, or metabolite ratios in these animals. The lack of phosphocreatine/inorganic phosphate recovery within 20 minutes of ischemia was predictive of an eventual large infarct. In these animals, the delayed addition of hyperglycemia significantly lowered intracellular pH during the ischemic period (5.45 vs. 6.25, p = 0.25). These data support the theory that the response to hyperglycemia is very dependent on the initial metabolic state of the injured brain. This state can be predicted by early 31P spectroscopy data, which may, in turn, prove to be a useful marker for recoverable ischemic deficit in the cerebral region of interest.

Difluoromethylornithine decreases postischemic brain edema and blood-brain barrier breakdown.

Brain polyamines have been associated with posttraumatic vasogenic edema and blood-brain barrier (BBB) breakdown seen in some models of brain injury. We hypothesized that the inhibition of the enzyme responsible for polyamine production with the decarboxylase difluoromethylornithine (DFMO) may decrease BBB breakdown after a focal brain ischemic stroke. Thirty-two cats underwent 8 hours of middle cerebral artery occlusion and one of four treatments: sham operation (Sham), ischemia (Isc), ischemia/DFMO (Isc/DF), and ischemia/DFMO/putrescine (Isc/DF/PU). The regional brain specific gravity and the volume of Evans blue (EB) extravasation were measured at the time of death. The groups were monitored for temperature, heart rate, blood pressure, and arterial blood gases, and the values did not differ outside normal physiological ranges. EB results were expressed as the percentage of the hemisphere stained and showed the following: Sham, 2.23%; Isc, 32.8%; Isc/DF, 5.6%; Isc/DF/PU, 36.3%. As a measure of BBB, ischemia increased EB staining; DFMO pretreatment decreased the amount of EB staining to control levels; and the polyamine putrescine abolished the protective effect of DFMO (all significant at P = 0.05). DFMO pretreatment also resulted in a significant (P = 0.05) return to control values for specific gravity in the EB-stained regions (1.0328) of ischemic animals. This effect was present primarily in the white matter. Treatment with DFMO, an ornithine decarboxylase inhibitor, significantly decreased postischemic BBB breakdown and vasogenic edema in this model.

Hyperglycemia suppresses c-fos mRNA expression following transient cerebral ischemia in gerbils.

The c-fos proto-oncogene is activated by transient cerebral ischemia. This activation may signify a specific genetic response to ischemia affecting tolerance to ischemia and ultimate cell survival. Hyperglycemia, which enhances brain injury from transient ischemia, was studied for its effects on this gene system in gerbils by measuring c-fos mRNA 2 h after 20 min of bilateral carotid artery occlusion. Brain c-fos mRNA was increased by ischemia (11.7 +/- 5.0, p less than or equal to 0.05, fold increase) compared to nonischemic controls (1.0 +/- 1.3). Pretreatment with 1 g/kg of glucose partially reduced postischemic c-fos mRNA (6.3 +/- 1.6, p less than or equal to 0.05) while 4 g/kg of glucose completely suppressed postischemic c-fos expression (0.7 +/- 0.3, p less than or equal to 0.05). These data indicate that hyperglycemia suppresses normal postischemic gene expression and suggest the possibility that such suppression is a predictor or even a contributor to hyperglycemia-enhanced ischemic brain damage.

Unilateral carotid artery ligation in the Mongolian gerbil as a model for testing infarction-reducing therapies.

This study evaluates infarct size measurement as an indicator of cerebral ischaemia outcome in a placebo-controlled trial of potential cerebral protection in the unilateral carotid artery ligation in the Mongolian gerbil. Ibuprofen was used in an effort to manipulate infarct size as this agent has been shown to reduce ischaemia in myocardial infarction. Using measurements obtained through an infarct-sizing technique and a statistical power analysis of the method, the sample sizes needed to obtain significant results were projected for this model. In this case, it was not possible to demonstrate an effect of ibuprofen on infarct size although a tendency towards larger infarct size in ibuprofen-treated compared with placebo-treated gerbils was observed (36.1 +/- 10.1% versus 30.0 +/- 17.5%). The sample sizes needed to find significant changes in infarct size indicate that this model finds a practical use in studying therapies which will alter infarct size by at least 50%. For example, to detect a 30% change in infarct size, 33 successfully infarcted gerbils per group would be needed, but a 50% change would require a more tenable 13 infarcted gerbils per group. However, given the 40% infarction rate of occluded gerbils seen in this study, almost 33 gerbils per group would be required to detect a 50% change. In addition, somatosensory evoked potential was compared with neurological examination as a predictor of infarction. It would be helpful to be able to pre-screen for infarcted gerbils immediately after occlusion in order to direct infarcted gerbils into control and treated groups. Somatosensory evoked potential successfully predicted infarction with a 90% accuracy in 21 gerbils compared with neurological evaluation which was 100% accurate. But the somatosensory evoked potential prediction was made within 15 min of occlusion as opposed to the 6 h of observation during which the neurological evaluation was made.

Focal cerebral infarction in cats in the presence of hyperglycemia and increased insulin.

Although it has been well established that hyperglycemia increases cerebral damage following transient cerebral ischemia, its effect on permanent focal ischemia is controversial. We hypothesized that other factors associated with hyperglycemia, such as plasma insulin, may alter the brain's response to hyperglycemia. The objective of this study was to determine if hyperglycemia changes infarction size following 8 hr of middle cerebral artery occlusion in the anesthetized cat and to examine if changes in plasma insulin levels alter hyperglycemia's effects. Infarct size in hyperglycemic cats with increased plasma insulin (38.3 +/- 8.4, mean +/- SE) or in hyperglycemic cats without increased plasma insulin (30.5 +/- 7.6%) was not significantly different from that of ischemic controls (33.8 +/- 2.8%). However, the variability in infarct size tended to be greater (P = 0.0647) among all hyperglycemic cats compared to control animals. The source of the variability is unknown, but this observation is dependent on the exact nature of the focal ischemic insult (i.e., degree of collateral blood supply) and that this effect may vary greatly from individual to individual within a population.

Relationship between plasma glucose, brain lactate, and intracellular pH during cerebral ischemia in gerbils.

The dose-response relation between plasma glucose and brain lactate and the relation of these parameters to intracellular pH during severe cerebral ischemia have not been well characterized over a wide range of plasma glucose levels. Experiments to delineate these relations in the gerbil model of global ischemia were performed by using phosphorus-31 nuclear magnetic resonance spectroscopy to measure intracellular pH and a new method to measure brain lactate. Ischemia increased final brain lactate linearly 4 mumol/g for every 100 mg/dl increase in plasma glucose up to 650 mg/dl (p = 0.0001, r2 = 0.9); beyond 650 mg/dl, saturation of the glucose transport-glycolysis system occurred. Plasma glucose correlated better with ischemic intracellular pH than did brain lactate. However, when brain lactate levels are compared with intracellular pH during ischemia, the relation may be threshold rather than linear. A narrow transition zone, during which ischemic intracellular pH decreased precipitously with increasing brain lactate, was observed between 17 and 22 mumol/g; below 17 mumol/g, intracellular pH remained stable at 6.8-6.9, whereas above 22 mumol/g, intracellular pH decreased maximally to about 6.2. The marked decrease in intracellular pH that occurs when brain lactate surpasses 17 mumol/g suggests that this sudden drop in intracellular pH may account for the "lactate threshold" for increased cerebral ischemic damage.

In vivo 31phosphorus spectroscopy during transient cerebral ischaemia in the gerbil.

The depletion of the high energy phosphates; phosphocreatine and ATP, during cerebral ischaemia disrupts normal cellular function and can lead to cerebral infarction. Using in vivo nuclear magnetic resonance spectroscopy, the metabolic effects of the gerbil model of transient bilateral carotid artery occlusion were quantified. By examining the changes in the inorganic phosphate (Pi), phosphocreatine (PCr) and beta-ATP peaks, the PCr/Pi ratio, the PCr/beta-ATP ratio and intracellular pH (pHi) before, during and after an ischaemic insult were calculated. Preischaemic values for these parameters were: PCr/Pi = 2.466 +/- 0.130, PCr/beta-ATP = 1.691 +/- 0.053, pHi = 7.112 +/- 0.021. By the end of 20 min of global ischaemia, the PCr and beta-ATP peaks fell to levels similar to background in most animals. Calculated values were: PCr/Pi = 0.488 +/- 0.126, PCr/beta-ATP = 1.833 +/- 0.179, pHi = 6.551 +/- 0.258. With reperfusion, PCr/Pi increased rapidly back towards preischaemic levels but pHi improvement was delayed 10 min after that of PCr/Pi. By 1 h of reperfusion, both PCr/Pi and pHi were statistically equivalent to preischaemic values. During ischaemia, ATP was lost more rapidly than the storage form, PCr, but recovery of both was parallel. This suggested an intact ability to store such energy. These data indicate that the gerbil brain recovers normal high energy phosphate levels within an hour following a 20 min ischaemic insult, but that initial reperfusion does not immediately correct intracellular acidosis. Such a delay may prove a useful marker of those animals with more severe ischaemic injury.

The effect of total parenteral nutrition on vasogenic edema development following cold injury in rats.

Total parenteral nutrition (TPN) has been shown to decrease mortality and to increase the rate of recovery in head-injured patients. However, a recent short-term animal experiment has raised concern over the potential enhancement of vasogenic edema by TPN. The experiment described here was undertaken to examine longer-term effects of TPN infusion on vasogenic edema development. Twenty-four rats received an infusion of a TPN solution (35% glucose) or 0.9% saline at 4 ml/kg/hr for 4 or 26 hours following cold injury. In the 4-hour experiment, TPN increased the serum glucose level to 772 +/- 57 mg/dl compared to 160 +/- 14 mg/dl in the saline-treated animals (p = 0.0001) and increased serum osmolality to 312 +/- 3 mOsm/kg compared to 291 +/- 3 mOsm/kg in the saline-treated group (p = 0.0006). In the 26-hour experiment, TPN-infused rats were also hyperglycemic and hyperosmotic by 4 hours postinjury and remained hyperglycemic at 26 hours postinjury (serum glucose level 374 +/- 97 mg/dl compared to 141 +/- 3 mg/dl in saline-treated animals; p = 0.0371). Although by 26 hours the TPN-infused rats appeared hyperosmotic compared to the saline-treated rats, high variability in the TPN group prevented statistical confirmation of this observation (serum osmolality 337 +/- 35 mOsm/kg in the TPN group compared to 287 +/- 6 mOsm/kg in the saline group). A three-way analysis of variance with repeated measures was used to analyze the effect of infusion (saline vs. TPN), time (4 vs. 26 hours), and cold injury on the specific gravity of the five brain regions studied. Cold injury significantly increased edema development in the injured versus uninjured hemisphere for every region studied (p less than or equal to 0.0034, all five regions), and edema development increased significantly between 4 and 26 hours in three of the five regions (p less than or equal to 0.0207, all three regions). The infusion fluid was not a significant factor in any of the analyses. In conclusion, TPN infusion produced hyperglycemia and hyperosmolality in cold-injured rats but did not enhance vasogenic edema development in any brain region studied.

Polyamine inhibition preserves somatosensory evoked potential activity after transient cerebral ischaemia.

We tested the hypothesis that the increase in polyamines observed after cerebral ischaemia is related to deficits in electrocortical function as measured by somatosensory evoked potential (SEP). Adult Mongolian gerbils were anaesthetized with ketamine and prepared for monitoring SEP, cerebral blood flow (CBF) in parietal and frontal regions by H2 clearance, and for bilateral carotid artery occlusion (BCO). Seven animals served as controls and received saline. Another 7 animals were treated with the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO) (100 mg/kg I.P.) just prior to 40 min BCO followed by 4 h reperfusion. With BCO, both CBF and SEP declined significantly. In control animals, CBF fell from basal 37.8 +/- 4.7 cc/100 g/min to 2.9 +/- 1.2 cc/100 g/min and recovered to 22.7 +/- 3.5 cc/100 g/h over the 4 h reperfusion period. DFMO treatment did not alter this CBF pattern. SEP amplitude declined to 11.3 +/- 3.2% basal during occlusion. DFMO preserved SEP during ischaemia (35.5 +/- 16.8% basal) and remained significantly more preserved during reperfusion (p less than 0.05). These results suggest that polyamines are involved in the progressive decline in neuroelectrical function which occurs during occlusion/reperfusion in the Mongolian gerbil. The observation that polyamine inhibition preserves electrical function despite not altering blood flow indicates that the effects of polyamines are not manifested at the level of the vasculature but perhaps at the neuronal membrane.

Brain ornithine decarboxylase activity following transient cerebral ischaemia: relationship to cerebral oedema development.

Ornithine decarboxylase (ODC) activity, the first and generally rate-limiting enzyme for polyamine synthesis, is stimulated in permanent focal cerebral ischaemia in areas of incomplete ischaemia which are developing ischaemic brain oedema. As polyamines are ubiquitous ornithine-derived molecules which are obligatory in cold-induced vasogenic oedema, we studied the effect of transient dense cerebral ischaemia with reperfusion on ischaemic oedema development and ODC activity. Fifty-nine Mongolian gerbils were anaesthetized with ketamine hydrochloride (160 mg/kg i.p. plus supplementation as needed). Both common carotid arteries were isolated and a tracheotomy placed in position. EEG was monitored with needle electrodes and temperature maintained at 37-38 degrees C. Twenty-nine gerbils underwent 40 min of bilateral carotid artery occlusion followed by reperfusion times of 10 min, 1, 2, 4, 6 or 8 h. Non-ischaemic control groups were monitored for equal intervals. At sacrifice, the brain was rapidly removed and forebrain samples analysed for ODC activity (enzymatic assay) and cerebral oedema (gravimetric determination). Marked loss of EEG amplitude was noted in all gerbils subjected to bilateral carotid artery occlusion. Ischaemia produced significant levels of cortical oedema throughout the reperfusion period (maximal decrease in specific gravity at 4 h postischaemia; control: 1.0456 +/- 0.0013; ischaemia: 1.0355 +/- 0.0021, mean +/- SD; p less than 0.0001). Significant subcortical oedema was produced at 10 min, 2 and 4 h postischaemia. A biphasic response was observed in brain ODC activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of somatosensory evoked potential in the Mongolian gerbil: the effects of cerebral ischaemia.

Normal somatosensory evoked potential (SEP) as well as changes after incomplete cerebral ischaemia following bilateral carotid artery occlusion (BCO) were characterized in the Mongolian gerbil. BCO significantly decreased cerebral blood flow (CBF). Reperfusion CBF at 10 min and 2, 3 and 4 h was significantly below preischaemic control values. BCO decreased SEP amplitude but had no effect on EP-P3 central conduction time. BCO did significantly increase EP-P11 central conduction time. Reperfusion amplitudes at 10 min and 2, 3 and 4 h revealed a significant increase only at 4 h when compared to the ischaemic amplitude. EP-P11 central conduction time at 10 min reperfusion showed dramatic improvement compared to ischaemic values, although values at 2, 3 and 4 h reperfusion were not statistically different from ischaemic values. A separate group of animals prepared identically but without BCO showed no significant changes in either SEP or CBF over time. These studies establish the protocol necessary to measure SEP in the Mongolian gerbil. In the future SEP may be used as an integral tool in the study of the primary determinants of neurophysiological recovery following cerebral ischaemia.

Moderate hypothermia reduces postischemic edema development and leukotriene production.

Using the bilateral carotid artery occlusion model of cerebral ischemia in the gerbil, we studied the effect of moderate hypothermia (30 to 31 degrees C) on the postischemic production of prostanoids (cyclooxygenase pathway) and leukotrienes (lipoxygenase pathway) and accompanying changes in cerebral edema formation. Hypothermia capable of slowing central evoked potential conduction time was studied over the course of 40 minutes of cerebral ischemia and for up to 2 hours of reperfusion. The successful induction of cerebral ischemia was confirmed by somatosensory evoked potential amplitude changes. Measurements of 6-ketoprostaglandin F1 alpha (PGF1 alpha) and leukotriene B4 (LTB4) (radioimmunoassay) and cerebral edema (specific gravity) were made at early (10 minutes) and late (2 hours) reperfusion times. Although both white and gray matter showed no early significant difference in edema accumulation between normothermic and hypothermic gerbils at 10 minutes of reperfusion, hypothermic animals demonstrated significantly less white matter edema (specific gravity, 1.0397 +/- 0.0010 vs. 1.0341 +/- 0.0012, P less than 0.01) and gray matter edema (specific gravity, 1.0408 +/- 0.0009 vs. 1.0365 +/- 0.0008, P less than 0.01) by 2 hours of reperfusion. Production of PGF1 alpha was not significantly different between normothermic and hypothermic animals during the reperfusion period; however, hypothermic gerbils demonstrated significantly lower production of LTB4 at 10 minutes reperfusion time compared to normothermic animals (1.49 +/- 0.79 vs. 5.28 +/- 1.49 pg/mg of protein, P less than 0.05). This difference between the two groups in LTB4 levels was no longer detectable at 2 hours of reperfusion time.(ABSTRACT TRUNCATED AT 250 WORDS)

Motor performance in rats exposed to severe forebrain ischemia: effect of fasting and 1,3-butanediol.

Functional assessment of animals following experimental cerebral ischemia is often difficult due to the passive nature of many neurologic exams. We attempted to increase the objectivity of motor function evaluation by adapting quantifiable behavioral tests and actively testing rats' motor capability following a cerebral ischemic insult. It was hypothesized that active testing would reveal motor deficits which were not readily apparent upon casual observation and that such testing would provide a more sensitive means of experimental neurologic assessment. Wistar rats were exposed to reversible severe forebrain ischemia using the four-vessel occlusion technique. Motor function was evaluated using the total motor score (sum of scores for screen test, balance beam test, and prehensile-traction test) over the 48 hours which followed 20 minutes of cerebral ischemia. To manipulate neurologic outcome, rats were fed or fasted the day prior to ischemia and then pretreated with either 1,3-butanediol or saline. Fasted saline-treated animals demonstrated improved total motor performance compared with fed animals by 48 hours after ischemia. There was no improvement in motor performance by fasted vs. fed rats from among the butanediol-treated animals. Pretreatment with butanediol resulted in significantly better total motor performance among fasted rats 24 hours after ischemia; however, by 48 hours postischemia, no difference was detectable. This is the first demonstration of motor deficits produced by four-vessel occlusion in rats. The motor tests devised appear to be adequately sensitive to detect changes in motor function that are not apparent with passive observation in this model.

Morphometric evaluation of brain infarcts in rats and gerbils.

The Levine rat preparation, the gerbil stroke model, and appropriate control animals were used to determine if the 2,3,5-triphenyltetrazolium chloride (TTC) would selectively identify noninfarcted versus infarcted cerebral tissue. The TTC is frequently used to quantify infarcted myocardial tissue and has been shown to have great specificity, reproducibility, and efficacy. The TTC produces a red product upon reaction with the respiratory enzymes (dehydrogenases) present in non-infarcted tissues. Irreversibly damaged tissues, lacking dehydrogenases, do not form red reaction products. Six gerbil brains and seven rat brains were incubated with the TTC, and the unreacted areas were macroscopically identified. The brains were fixed and sectioned for routine hematoxylin and eosin staining to determine the specificity of the TTC. The TTC was found to react selectively only with non-infarcted cerebral tissue. The gross brain sections were evaluated by macroscopic morphometric analysis, and the unreacted area was always ipsilateral to ligation and correlated with histologic identification of infarct. The brains from neurologically intact animals demonstrated neither macroscopic nor histological evidence of infarction. This technique allows macroscopic quantification of infarct size by planimetry. The average area of infarct for the neurologically impaired rats was 34.7% and it was 31.4% for the impaired gerbils. The percentage of surface area of each infarcted slice was found to correlate with the severity of the neurologic deficit. We conclude that TTC staining is effective for macroscopically delineating cerebral infarcts in rats and gerbils, thus permitting quantification of infarct size.

Glycolytic inhibition by 2-deoxyglucose reduces hyperglycemia-associated mortality and morbidity in the ischemic rat.

Numerous laboratories have shown that hyperglycemia increases cerebral ischemic damage. This presumably results from increased lactate production and accumulation during ischemia. Although increased tissue lactic acidosis is associated with increased ischemic brain damage, this damage has not been directly linked to glycolytic flux. Because 2-deoxyglucose (2-DG) is a competitive inhibitor of glycolysis we tested its ability to reduce hyperglycemia-exacerbated ischemic brain damage. Severe forebrain ischemia was produced by the four-vessel occlusion model in rats. Four rats received 3 g/kg glucose and saline while a second group (n = 5) was injected with 3 g/kg glucose plus 1.6 g/kg 2-DG. A third group (n = 5) was treated with 1 g/kg glucose plus saline and a fourth group (n = 5) received 1 g/kg glucose and 1.6 g/kg 2-DG. All rats were injected i.p. 10 minutes prior to the ischemic insult with the same volume/kg body weight. All rats receiving the high dose of glucose alone (3 g/kg) were dead within 24 hours postischemia. Rats who received 2-DG in addition to 3 g/kg glucose showed only 40% mortality (p = 0.119 Fisher's Exact). 2-DG completely eliminated convulsions during the initial two hours of recovery which was significant (p = 0.008), however, all rats in both groups showed some convulsions by 24 hours postischemia. Among rats receiving the low glucose dose (1 g/kg), none of the rats receiving 2-DG died or convulsed by 24 hours postischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Butanediol induced cerebral protection from ischemic-hypoxia in the instrumented Levine rat.

To determine if 1,3-Butanediol (BD), which protects mice from hypoxia, would extend the tolerance of rats to ischemic-hypoxia, the Levine rat (unilateral carotid ligation and conscious hypoxic exposure) was modified to record mean arterial pressure (BP), heart rate (HR), central venous pressure (CVP), spontaneous respiration and EEG. Age and weight matched, male, Sprague-Dawley rats were anesthetized under halothane (1-2%), ligated, instrumented, and recovered 2 hrs before hypoxia (4.5% oxygen). Thirty minutes prior to hypoxia, groups of rats received, BD (47 mmoles/kg i.v.; n = 7), equal volumes of saline (S) (n = 6) or no-infusion (NI) (n = 7). Since no significant difference was observed between S and NI they were combined into a single control group (C). In a parallel group administered BD, resultant beta- hydroxybutarate ( BHB ) levels increased from 0.13 +/- 0.02 to 0.84 +/- 0.03 mM and temperature declined only 1.5 degrees C. The EEG of all ischemic-hypoxic rats invariably became isoelectric before cessation of spontaneous respiration and eventual loss of BP. BD significantly (p less than 0.01, Student's t) increased ischemic-hypoxic tolerance (time to isoelectric EEG) from 875 +/- 56 for the control group to 1338 +/- 67 seconds for the BD group, without changing the interval from isoelectric EEG to loss of BP. Further, EEG activity persisted at a lower mean BP (p less than 0.01) in the BD group (44 +/- 5 mm Hg) than in the control group (66 +/- 4 mm Hg). In summary, isoelectric EEG invariably precedes ventilatory failure and cardiovascular collapse. BD increases ischemic-hypoxic tolerance in the conscious rat by extending, at a lower mean BP, the time to isoelectric EEG.