Effect of Local Ropivacaine on Hemodynamic Responses in Craniotomy Patients.

BACKGROUND: Increased intracranial pressure (ICP) with hemodynamic is of major concern to anesthesiologists and surgeons in craniotomy surgery. Thus, the management of hemodynamic stability is essential in neuro-anesthesia. This study was performed to investigate the effect of local infiltration of 0.5% ropivacaine on hemodynamic responses in craniotomy patients. MATERIAL AND METHODS: 64 ASA class I -II patients, scheduled for elective craniotomies, were enrolled in this prospective randomized double blind placebo controlled study. These patients were randomly divided into the ropivacaine group, who were administered with 0.5% ropivacaine (n = 32), and the placebo group administered with 0.9% normal saline (NaCl) (n = 32). Anesthesia was induced with 3 µg/kg fentanyl, 5 mg/kg thiopental and 0.5 mg/kg atracurium, and was maintained with isoflurane (0.8-1 = MAC) in 50% N2O, 1 mg/kg /30 minutes, 40% oxygen and 0.05 mg/kg /hour fentanyl. Five minutes prior to surgery, 10 mL of 0.5% ropivacaine was injected in the line of skin incision in the ropivacaine group, while 10 mL of normal saline was injected in placebo group. Thereafter, the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressures (MABP), and heart rate (HR) were measured before infiltration into the incision area, 30 seconds, 3 minutes, 5, 10, and 30 minutes after infiltration into the scalp. For higher BP and HR, an adjunct 0.5 mcg/kg of fentanyl was prescribed and administered. RESULTS: A significant difference was observed for SBP, DBP, MABP and HR, between the two groups at different times during craniotomy (p < 0.05). A significant decrease was observed for SBP, DBP, MABP and HR during craniotomy in 0.5% ropivacaine group as compared with placebo group (p < 0.05). CONCLUSION: Local anesthetic of 0.05% ropivacaine scalp infiltration is effective in clinical usage of regional anesthesia for producing good quality anesthesia, it seems to be a significant choice for management of optimal hemodynamic profile, providing a better hemodynamic stability during craniotomy.

Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.

BACKGROUND: There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. METHODS: IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. RESULTS: There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 µg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. CONCLUSIONS: Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01322009.

[Glibenclamide as a promising agent for prevention and treatment of cerebral edema]. / Glibenklamid - perspektivnoe sredstvo profilaktiki i lecheniia oteka golovnogo mozga.

The article presents a review of the literature on the use of a fundamentally new technique for prevention and treatment of cerebral edema. A drug glibenclamide, which is used to treat type 2 diabetes mellitus, is able to reduce cerebral edema and neuronal damage as evidenced by the results of preclinical trials in rodents and the first results of drug application in patients. The article describes the mechanism of glibenclamide action and discusses the potential for its application.

Methylprednisolone modulates intracranial pressure in the brain cellular edema induced by water intoxication.

Continuous monitoring of the intracranial pressure (ICP) detects impending intracranial hypertension resulting from the impaired intracranial volume homeostasis, when expanding volume generates pressure increase. In this study, cellular brain edema (CE) was induced in rats by water intoxication (WI). Methylprednisolone (MP) was administered intraperitoneally (i.p.) before the start of CE induction, during the induction and after the induction. ICP was monitored for 60 min within 20 h after the completion of the CE induction by fibreoptic pressure transmitter. In rats with induced CE, ICP was increased (Mean+/-SEM: 14.25+/-2.12) as well as in rats with MP administration before the start of CE induction (10.55+/-1.27). In control rats without CE induction (4.62+/-0.24) as well as in rats with MP applied during CE induction (5.52+/-1.32) and in rats with MP applied after the end of CE induction (6.23+/-0.73) ICP was normal. In the last two groups of rats, though the CE was induced, intracranial volume homeostasis was not impaired, intracranial volume as well as ICP were not increased. It is possible to conclude that methylprednisolone significantly influenced intracranial homeostasis and thus also the ICP values in the model of cellular brain edema.

Erectogenic and Aphrodisiac Property of Moringa oleifera: Involvement of Soluble Epoxide Hydrolase Enzyme.

Soluble epoxide hydrolase (sEH) inhibitors have been reported to improve penile erection; therefore, sEH could be useful for management of erectile dysfunction. Methanolic and aqueous extracts of 30 Indian medicinal plants were screened for their sEH inhibition potential. Fifteen extracts showed >50% inhibition when screened at 50 µg/mL in sEH inhibition assay. Methanolic extract of Moringa oleifera Lam. (Moringaceae) seeds (MEMO) was most potent with IC50 1.7 ± 0.1 µg/mL and was selected for in vitro studies on isolated rat corpus cavernosum smooth muscle and in vivo sexual behaviour studies on healthy and diabetic rats. Rats were divided into five groups, each containing six animals and treated orally with either water, vehicle (1% Tween-20), MEMO (45 and 90 mg/kg/day for 21 days), and standard drug, sildenafil (5 mg/kg/day for 7 days). An equal number of female rats were used, and the effect of MEMO and sildenafil was compared with that of vehicle. MEMO significantly relaxed isolated rat corpus cavernosum smooth muscle at 0.1-100 µg/mL in vitro and significantly increased (p < 0.05) sexual activity, intracavernous pressure/mean arterial pressure in normal and diabetic rats. The increase in erectile function of rats by MEMO could be because of its sEH inhibitory activity. Copyright © 2016 John Wiley & Sons, Ltd.

Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia.

UNLABELLED: Intravenous infusion of magnesium sulfate prevents seizures in patients with eclampsia and brain edema after traumatic brain injury. Neuroprotection is achieved by controlling cerebral blood flow (CBF), intracranial pressure, neuronal glutamate release, and aquaporin-4 (Aqp4) expression. These factors are also thought to be involved in the development of brain edema in acute liver failure. We wanted to study whether hypermagnesemia prevented development of intracranial hypertension and hyperperfusion in a rat model of portacaval anastomosis (PCA) and acute hyperammonemia. We also studied whether hypermagnesemia had an influence on brain content of glutamate, glutamine, and aquaporin-4 expression. The study consisted of three experiments: The first was a dose-finding study of four different dosing regimens of magnesium sulfate (MgSO4) in healthy rats. The second involved four groups of PCA rats receiving ammonia infusion/vehicle and MgSO4) /saline. The effect of MgSO(4) on mean arterial pressure (MAP), intracranial pressure (ICP), CBF, cerebral glutamate and glutamine, and aquaporin-4 expression was studied. Finally, the effect of MgSO4 on MAP, ICP, and CBF was studied, using two supplementary dosing regimens. In the second experiment, we found that hypermagnesemia and hyperammonemia were associated with a significantly higher CBF (P < 0.05, two-way analysis of variance [ANOVA]). Hypermagnesemia did not lead to a reduction in ICP and did not affect the brain content of glutamate, glutamine, or Aqp-4 expression. In the third experiment, we achieved higher P-Mg but this did not lead to a significant reduction in ICP or CBF. CONCLUSION: Our results demonstrate that hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in rats with PCA and hyperammonemia.

Effect of Tianhuang Granule on intracranial pressure and serum matrix metalloproteinase-9 in patients with acute cerebral hemorrhage.

OBJECTIVE: To study the effect and mechanism of Tianhuang Granule (, THG) on: hydrocephalus in the patients with acute cerebral hemorrhage (ACH) through intracranial pressure (ICP) monitoring, serum matrix metalloproteinase-9 (MMP-9) level observation, and National Institutes of Health Stroke Scale (NIHSS) scoring (for nerve function de ficit). METHODS: Sixty patients with ACH were equally randomized: into two groups by lottery, the control group and the THG group; all were treated with conventional therapy, but to the patients in the THG group, THG was given orally in addition for 28 days. Changes of ICP, MMP-9 expression, and NIHSS scores, as well as the degree of cerebral hematoma and hydrocephalus (by cranial CT scanning) in the patients, were estimated and compared. RESULTS: (1) ICP was lowered more significantly in the: THG group, showing a significant difference between groups on day 7 (P<0.05). (2) MMP-9 expression was down-regulated in the THG group more significantly and earlier than that in the control group. (3) The degrees of cerebral hematoma and hydrocephalus in the THG group on day 7 were reduced significantly as compared with those on day 3 (P<0.05), but in the control group, the day of significant reduction was delayed to day 14, and the degrees on day 7 and day 14 in the two groups were significantly different (P<0.05 and P<0.01). (4) NIHSS score was significantly lower in the THG group than that in the control group on day 14 and day 28 (P<0.05 and P<0.01). CONCLUSION: THG can effectively lower ICP, down-regulate MMP-9 expression, promote the absorption: of cerebral hematoma and hydrocephalus, and improve the nerve function, showing a clinical effectiveness than conventional therapy.

Effect of sex steroid hormones on brain edema, intracranial pressure, and neurologic outcomes after traumatic brain injury.

Recent studies have reported that estrogen and progesterone have a neuroprotective effect after traumatic brain injury (TBI); however, the mechanism(s) for this effect have not yet been elucidated. The aim of the present study was to investigate the role of sex steroid hormones on changes in brain edema, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) after TBI in ovariectomized (OVX) rats. In this study, 50 female rats were divided into 5 groups: control (intact), sham, and 3 TBI groups consisting of vehicle, estrogen (1 mg/kg), and progesterone (8 mg/kg). TBI was induced by the Marmarou method, and the hormones were injected i.p. 30 min after TBI. ICP was measured in the spinal cord, and CPP was calculated by subtracting the mean arterial pressure (MAP) from ICP. The results revealed that brain water content after TBI was lower (p < 0.001) in the estrogen and progesterone groups than in the vehicle group. After trauma, ICP was significantly higher in TBI rats (p < 0.001). The ICP in the estrogen and progesterone groups decreased at 4 and 24 h after TBI compared with vehicle (p < 0.001 and p < 0.05, respectively). The CPP in the estrogen and progesterone groups increased after 24 h compared with vehicle (p < 0.001). Also after TBI, the neurological score (veterinary coma scale) was significantly higher than vehicle at 1 h (p < 0.01) and 24 h (p < 0.001) in the group treated with estrogen. In conclusion, pharmacological doses of estrogen and progesterone improved ICP, CPP, and neurological scores after TBI in OVX rats, which implies that these hormones play a neuroprotective role in TBI.

Neuroprotective effects of erythropoietin during deep hypothermic circulatory arrest.

OBJECTIVE: Permanent mild-to-severe brain injury with neurologic sequelae remains a significant source of postoperative morbidity in cardiovascular surgery. There is increasing evidence that erythropoietin confers neuroprotective effects in various conditions of neuronal damage, such as hypoxia and cerebral ischaemia. Using a surviving porcine model, this study evaluates whether systemic treatment with erythropoietin induces brain protection in deep hypothermic circulatory arrest (DHCA). METHODS: Sixteen pigs (42+/-3 kg) randomly assigned into two groups (n=8) were subjected to 60 min of DHCA at an intracerebral temperature of 20 degrees C. The animals of the erythropietin group were treated perioperatively with 500 IU kg(-1) of recombinant human erythropoietin on 3 consecutive days beginning the day before surgery. Intracerebral monitoring was performed by subcortical microdialysis, brain tissue oxygenation, measurement of brain temperature and intracranial pressure. Neurologic recovery was evaluated daily. Perioperative S100 beta protein serum level was determined. The brains were harvested on the postoperative day 6 after perfusion fixation. Multiple brain regions were investigated histologically for hypoxic-ischaemic damage. RESULTS: The subcortical brain microdialysis detected significant increase of glycerol and lactate concentrations in both groups (P=0.0001) with considerably higher concentrations in the brain of control animals (P=0.011). There were no significant differences in neurological outcome (P=0.15). Erythropoietin-treated animals tended to a more complete and rapid neurological recovery. By contrast, none of the animals in the control group achieved complete neurological recovery. S100 beta protein as a putative marker of cerebral injury tended to be higher in the control group. Brain infarction was detectable in all control animals but only in two erythropoietin-treated animals. CONCLUSION: These results suggest some beneficial neuroprotective effects of erythropoietin in this model of global brain ischaemia induced by 1h of hypothermic circulatory arrest.

Impact of anesthetic agents on cerebrovascular physiology in children.

The role of the pediatric neuroanesthetist is to provide comprehensive care to children with neurologic pathologies. The cerebral physiology is influenced by the developmental stage of the child. The understanding of the effects of anesthetic agents on the physiology of cerebral vasculature in the pediatric population has significantly increased in the past decade allowing a more rationale decision making in anesthesia management. Although no single anesthetic technique can be recommended, sound knowledge of the principles of cerebral physiology and anesthetic neuropharmacology will facilitate the care of pediatric neurosurgical patients.

High-dose intraarterial verapamil in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

OBJECT: Because oral calcium channel blockers appear to reduce the severity of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH), interest in their application intraarterially has emerged for cases in which noninvasive means of alleviating vasospasm are unsuccessful. Studies to date have been limited to the administration of low intraarterial doses because of concerns about hemodynamic stability and changes in intracranial pressure. These doses, although effective in cases of milder vasospasm, were inadequate in severe cases. The authors present a series of 10 patients with cerebral vasospasm who underwent 12 procedures in which they received > or = 20 mg of intraarterial verapamil per procedure. METHODS: A retrospective review was undertaken of all patients who underwent endovascular treatment for cerebral vasospasm due to aneurysmal SAH by the senior author between February 2005 and October 2006. Ten patients were identified who had undergone a total of 12 procedures during which > or =20 mg of intraarterial verapamil had been administered. From angiography reports, anesthesia records, and nursing records, we obtained pre- and postverapamil mean arterial blood pressures (MABPs), heart rates, intracranial pressures (ICPs) (when available), and visible changes in the degree of vasospasm. RESULTS: No statistically significant changes in MABP, heart rate, or ICP were observed after administration of > or = 20 mg of intraarterial verapamil, and the degree of improvement in vasospasm was statistically significant based on our grading system. No correlation was found between the change in hemodynamic parameters and the total dose of verapamil. CONCLUSIONS: This study indicates that high-dose intraarterial verapamil may be used to treat cerebral vasospasm without compromising hemodynamic stability or increasing ICP.

Intravenous infusion of calcium antagonist, nicardipine, does not increase intracranial pressure: evaluation in a rat model of transient cerebral ischemia and reperfusion.

OBJECTIVE AND METHOD: Early use of parenteral antihypertensive drugs is recommended in acute ischemic stroke patients suffering hypertensive emergencies. Calcium antagonist has been widely employed, although there is controversy as to whether calcium antagonist can be administered safely to patients with intracranial hypertension. In a rat model of transient cerebral ischemia and reperfusion, we evaluated the effect of the calcium antagonist, nicardipine, on intracranial pressure (ICP). Using spontaneously hypertensive rats (SHRs), focal cerebral ischemia was induced by an intraluminal thread method. ICP was monitored continuously employing an intraparenchymal catheter. The mean arterial blood pressure (MABP) was reduced by infusing nicardipine intravenously. RESULTS: Following 6 hours of transient ischemia and reperfusion, MABP was decreased by about 10 or 20% as compared to the baseline MABP with low-dose or high-dose nicardipine administration, respectively. ICP was significantly increased following reperfusion, although it did not increase further with nicardipine infusion. CONCLUSION: Under conditions where ICP was high following reperfusion, nicardipine reduced blood pressure safely without increasing ICP in rats.

L-arginine causes amelioration of cerebrovascular dysfunction and brain inflammation during experimental heatstroke.

Cerebrovascular dysfunction ensuing from severe heatstroke includes intracranial hypertension, cerebral hypoperfusion, and brain inflammation. We attempted to assess whether L-arginine improves survival during experimental heatstroke by attenuating these reactions. Anesthetized rats, 70 min after the start of heat stress (43 degrees C), were divided into two major groups and given the following: vehicle solution (1 mL/kg body weight) or L-arginine (50-250 mg/kg body weight) intravenously. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiological and biochemical parameters were continuously monitored. When the vehicle-treated rats underwent heat stress, their survival time values were found to be 20 to 26 min. Treatment with i.v. doses of L-arginine significantly improved the survival rate during heatstroke (54-245 min). As compared with those of normothermic controls, all vehicle-treated heatstroke animals displayed higher levels of core temperature, intracranial pressure, and NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in hypothalamus. In addition, hypothalamic levels of IL-1beta and TNF-alpha were elevated after heatstroke onset. In contrast, all vehicle-treated heatstroke animals had lower levels of MAP, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of oxygen. Administration of L-arginine immediately after the onset of heatstroke significantly reduced the intracranial hypertension and the increased levels of NO metabolite, glutamate, glycerol, lactate-pyruvate ratio, and dihydroxybenzoic acid in the hypothalamus that occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta and TNF-alpha in the hypothalamus were suppressed by L-arginine treatment. In contrast, the hypothalamic levels of IL-10 were significantly elevated by L-arginine during heatstroke. The results suggest that L-arginine may cause attenuation of heatstroke by reducing cerebrovascular dysfunction and brain inflammation.

Effects of extract of ginkgo biloba on intracranial pressure, cerebral perfusion pressure, and cerebral blood flow in a rat model of subarachnoid haemorrhage.

The purpose of this study was to investigate in effect of extract of Ginkgo biloba (EGb) on cerebral blood perfusion in a subarachnoid haemorrhage (SAH) rat model. SAH lead to an increase in intracranial pressure and decrease in cranial perfusion pressure and regional cerebral blood flow in all groups. However, the intracranial pressure increases in EGb groups were less than that of the vehicle group (p < .01), whereas the reduction in cranial perfusion pressure and regional cerebral blood flow in the EGb group was less than that of the vehicle and SAH groups (p < .01). It was concluded that EGb attenuates the increase in intracranial pressure and reduction in cerebral blood perfusion after SAH.

Inhibition of neuronal nitric oxide synthase causes attenuation of cerebrovascular dysfunction in experimental heatstroke.

The present study was performed to assess the prophylactic effect of 7-nitroindazole (7-NI), an inhibitor of neuronal nitric oxide synthase (nNOS), in an animal model of heatstroke. Anesthetized rats, immediately before the start of heat stress, were divided into two major groups and given the following: vehicle solution (1 mL per kg body weight) or 7-NI (5-20mg/mL per kg body weight) intraperitoneally. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 21-25 min. Pretreatment with intraperitoneal doses of 7-NI significantly improved survival during heatstroke (55-164 min). As compared to those of normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of core temperature, intracranial pressure, nitric oxide metabolite (NO(2)(-)), glutamate, glycerol, lactate/pyruvate ratio, neuronal damage score and nNOS expression in the hypothalamus, and tumor necrosis factor-alpha (TNF-alpha) in the serum. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration of 7-NI before the start of heat exposure significantly reduced the hyperthermia, intracranial hypertension, nNOS-dependent NO(2)(-), glutamate, glycerol, lactate/pyruvate ratio, and neuronal damage score in the hypothalamus, as well as overproduction of TNF-alpha in the serum that occurred during heatstroke. The data show that reduction of nNOS-dependent NO(2)(-) with 7-NI causes attenuation of cerebrovascular dysfunction, hyperthermia, and TNF-alpha overproduction during heatstroke in the rat.

Valsartan treatment reverses erectile dysfunction in diabetic rats.

In order to investigate the effect of angiotensin receptor blockage (ARB) for the treatment on diabetic erectile dysfunction (ED), we used male Sprague-Dawley rats injected with 65 mg/kg streptozotocin to induce diabetes mellitus. The diabetic rats with ED were selected by hypodermic injection of apomorphine (APO) after 8 weeks of model setting. All rats were divided into four groups: G1 (normal control rats), G2 (diabetic rats treated with normal saline), G3 (diabetic rats treated with valsartan) and G4 (diabetic rats treated with spironolactone). After treatment with drugs for 8 weeks, the rate of erection for each group was evaluated after the injection of APO. The intracavernous pressure (ICP) of each rat was then recorded before and after the electrostimulation of the major pelvic ganglion. The rates of erection and the ICP after electrostimulation for diabetic rats treated with valsartan were significantly higher than that in diabetic rats treated with normal saline and spironolactone. The ARB may be an effective therapy for diabetics with ED.

Current controversies in the management of patients with severe traumatic brain injury.

BACKGROUND: Traumatic brain injury is a major cause of mortality and morbidity, particularly among young men. The efficacy and safety of most of the interventions used in the management of patients with traumatic brain injury remain unproven. Examples include the 'cerebral perfusion pressure-targeted' and 'volume-targeted' management strategies for optimizing cerebrovascular haemodynamics and specific interventions, such as hyperventilation, osmotherapy, cerebrospinal fluid drainage, barbiturates, decompressive craniectomy, therapeutic hypothermia, normobaric hyperoxia and hyperbaric oxygen therapy. METHODS: A review of the literature was performed to examine the evidence base behind each intervention. RESULTS: There is no class I evidence to support the routine use of any of the therapies examined. CONCLUSION: Well-designed, large, randomized controlled trials are needed to determine therapies that are safe and effective from those that are ineffective or harmful.

Hypertonic saline dextran improves outcome after hypothermic circulatory arrest: a study in a surviving porcine model.

BACKGROUND: Hypertonic saline dextran (HSD) has been shown to have neuroprotective properties. In the present study we have assessed its potential neuroprotective efficacy in the setting of hypothermic circulatory arrest in a surviving porcine model. METHODS: Twenty-four pigs were randomized to receive two 5-minute intravenous infusions (4 mL/kg) of either HSD (7.5 % saline, 6% dextran 70) or normal saline immediately after and 4 hours after a 75-minute period of hypothermic circulatory arrest at a brain temperature of 18 degrees C. RESULTS: The 7-day survival was 75% in the HSD group and 66% in the control group (p > 0.9). Brain total histopathologic score was lower in the HSD group (p = 0.01). Postoperative behavioral scores were higher in the HSD group on the second day after surgery (p = 0.03). Intracranial pressure was lower in the HSD group from 45 minutes to 8 hours after hypothermic circulatory arrest (p = 0.03). Cerebral perfusion pressure was higher in the HSD group from 45 minutes to 3 hours after hypothermic circulatory arrest (p = 0.06). Brain lactate concentration was lower in the HSD group when compared with controls (p = 0.05). Furthermore, brain glucose levels tended to be higher and brain lactate-pyruvate ratio and lactate-glucose ratio were lower in the HSD group. Brain tissue oxygen partial pressures were somewhat higher in the HSD group (p = 0.08). CONCLUSIONS: The use of HSD in experimental hypothermic circulatory arrest is associated with significantly better neurologic recovery, better histopathology, lower intracranial pressure, higher cerebral perfusion pressure, and better preservation of brain metabolism.