Wire-frame integrity of patch-like Gore devices following atrial septal defect closure.

OBJECTIVES: To assess the structural integrity of the patch-like Gore Septal Occluder (GSO) used for device closure of secundum-type atrial septal defects (ASD II) in pediatric patients. BACKGROUND: GSO has shown to be effective and safe for ASD device closure in children and adolescents. METHODS: Single-center, retrospective mid- to long-term follow-up of all children and adolescents with a GSO in situ (≥12 months). Periprocedural data and follow-up data were evaluated, including chest X-rays to assess the GSO's wire-frame morphology. RESULTS: Ninety-one consecutive patients were enrolled with a median age and weight of 5 years (range 2-18) and 20 kg (range 11-95) at implantation. ASD anatomy included 64 single and 27 multi-fenestrated defects, with 39 patients having small retro-aortic rims (≤4 mm). Median follow-up period was 42.5 months (range 12-74). Chest X-rays were available in 80 children: in 74 of them, the GSO's visualization on X-ray enabled us to reliably assess the wire-frame structure. Wire-frame fracture (WFF) was ultimately detected in five of the 74 patients (6.8%); however, those occluders appeared stably anchored and well aligned to both sides of the septum, and no free wire fragments had escaped the GSO matrix. Thus, no further treatment was required. CONCLUSIONS: Our data confirm that the GSO is safe and effective for ASD closure. Despite its lightweight construction, the GSO seems to offer reliable mechanical durability. Wire-frame fractures occur, but the free wire-ends appear to have remained stable within the GSO matrix without any clinical sequelae so far.

Cardiac thrombus with risk of fulminant pulmonary embolism in paediatric antiphospholipid syndrome.

Antiphospholipid Syndrome (APS) describes a systemic disease caused by autoantibodies to membrane components. Involving coagulation pathways, complement factors and immune cells, it results in thrombosis in any blood vessel. Its clinical presentation varies considerably depending upon the organ affected. Paediatric data on APS remain sparse. Most case reports focus on catastrophic APS with multiple small-vessel occlusions and a life-threatening course. Here, we report on a 15-year-old patient with deep vein thrombosis and a right ventricular tumour posing the risk of a fulminant pulmonary embolism. The tumour was surgically removed. Histology revealed it to be a thrombus. The patient fully recovered and is currently treated with long term anticoagulation.

Bronchial compression following pulmonary artery stenting in single ventricle lesions: how to prevent, and how to decompress.

OBJECTIVES: To assess airway compression during pulmonary artery (PA) intervention in single ventricle (SV) palliation. BACKGROUND: SV lesions with a prominent neo-aortic root are considered a high risk for branch PA and/or bronchial stenosis. PA stenting is well established, but may result in ipsilateral bronchial compression. METHODS: Single-centre retrospective analysis of 19 palliated SV patients with branch PA stenosis and close proximity to the ipsilateral main bronchus who underwent cardiac catheterisation at a median age and weight of 8.5 years (0.5-25) and 16.5 kg (6-82) between 12/2011 and 05/2015. RESULTS: Two of the 19 patients suffered an almost-closed left-main bronchus (LMB) following PA stenting. Fortunately, LMB decompression succeeded in both those patients by re-shaping the PA stents by compressing the chest while splinting the LMB with an inflated balloon. To prevent the other 17 patients from suffering this serious complication, we adopted a thorough preparation strategy: 13 patients underwent safe simultaneous bronchoscopy and cardiac catheterisation; in the remaining 4 patients CT-angiography enabled accurate risk evaluation prior to re-catheterisation. CONCLUSIONS: In SV lesions accompanied by branch PA stenosis, thorough preparation via cross-sectional imaging is mandatory, including simultaneous bronchoscopy and cardiac catheterisation in selected cases, to rule out any airway compression before considering endovascular stent implantation. If a PA stent's compression has already caused severe bronchial obstruction, our balloon-splinted decompression technique should be considered.

Transcatheter closure of atrial septal defects in children and adolescents: single-center experience with the GORE® septal occluder.

OBJECTIVES: Device closure of atrial septal defects (ASD II) is an alternative to surgery. ASD morphology and intracardiac relationships may influence device selection. Biocompatibility, techniques for closing large or multiple defects, and the risk of erosion are main issues in children BACKGROUND: The GORE® Septal Occluder (GSO) is a non-self-centering device with a flat and conformable nitinol-frame covered with expanded polytetrafluoroethylene. We hereby evaluate our initial experience in children to demonstrate feasibility, efficacy, and safety. METHODS: Single-center retrospective intention-to-treat analysis of GSO procedures in children and adolescents with hemodynamically significant ASD. All procedures were conducted under general anesthesia, fluoroscopy and transesophageal echocardiography. All defects were sized using stop-flow-technique. GSOs of 20-30 mm disc-diameter were implanted. RESULTS: GSO implantation was attempted in 45 with technical success in 41 patients, median age 6 (range 3-17) years, bodyweight 19 (12-95) kg. Median balloon-sized diameter was 13 (8-19) mm resulting in a GSO-to-ASD-ratio of 2 (1.7-2.5). Deficient retro-aortic rims (<3 mm) were found in 12 patients, and 10 of these 12 defects could be closed. We observed no complications. Four extensive or multiple ASDs were not treated successfully with GSO. After retrieval, one was closed with a different device; three patients needed surgical therapy. The median follow-up of four (range 0.2-22) months was uneventful in all patients CONCLUSIONS: We found the GSO device closure of ASDs in children to be effective. However, our initial experience is limited to short- and mid-term-follow-up of a low number of patients.

[Vacuum assisted closure therapy for the treatment of sternal wound infections after heart transplantation: preliminary results]. / VAC-Therapie zur Behandlung von sternalen Wundinfektionen nach Herztransplantation: Erste Ergebnisse.

Sternal wound infection after heart transplantation is a feared and potentially life threatening complication with reported incidences between 2.5 % and 3.6 %. However, optimal therapy of sternal wound infections in heart transplant recipients remains a matter of controversy, particularly the effect of immunosuppression in those patients is still unclear. We examined 5 heart transplanted patients (4 men and 1 woman with a median age of 46 +/- 21.4 years (ranging from 14 to 59 years) in terms of inflammation and treatment response during VAC therapy. Infection begin was median 18.2 days (+/- 10 days, ranging from 5 to 28 days) after transplantation. VAC therapy lasted on average 12.2 +/- 2 days, ranging from 10 to 19 days. A median of 3 changes (range from 3 to 5) were necessary until the definitive closure. We examined C-reactive protein, leucocyte count and fibrinogen 2 days pre VAC, during VAC treatment and 2 days after definitive closure. All five patients showed an increase of leucocytes at every VAC change. Furthermore, we saw an adequate reaction to the VAC in terms of granulation tissue growth and resolution of infection. Transplanted patients had an increase of leucocytes at every VAC change. Furthermore all patients showed an adequate response of VAC treatment in terms of granulation tissue in growth and infection decline. Therefore a reduction of immunosuppressive therapy is not necessary, which in turn would increase the risk of rejection.

[Cost effectiveness of V.A.C. therapy after post-sternotomy mediastinitis]. / Kosteneffektivität der V.A.C.-Therapie nach Poststernotomie Mediastinitis.

Since November 2001 all patients with postoperative sternum bone infections were treated with V.A.C. therapy. The mean length of stay at intensive care unit was reduced from 9 to 1 day and reduces costs for 33 714.- USD per patient. Additionally patients who had to be closed with pectoralis muscle flap had significant reduced length of stay at ICU (1 vs 4 days, cost effectiveness 14 984.- USD per patient). The V.A.C. therapy after post-sternotomy mediastinitis significantly reduces morbidity and mortalità and is cost effective.

Mid-term results of conservative, conventional and endovascular treatment for acute traumatic aortic lesions.

BACKGROUND: To analyze our results after conservative, conventional and endovascular treatment for acute traumatic aortic lesions during the last decade. METHODS: From June 1993 to September 2004, a total of 19 patients with traumatic aortic lesions were referred to our department. All patients sustained injuries from blunt deceleration trauma. In hemodynamically stable patients, initial evaluation was by multi-slice CT scan. The diagnosis of traumatic aortic injury was confirmed and an individual treatment strategy was determined. In hemodynamically unstable patients, emergency thoracotomy was performed. RESULTS: An emergency thoracotomy was performed in seven (37%) patients. Mortality in this group was 100%. In the remaining group of 12 (63%) patients without hemodynamic instability at time of admission, in-hospital mortality was 0%. Treatment was surgical in five patients (26%), endovascular in five (26%) and conservative in two patients (11%). Mean follow-up was 63 months (5-108 months). No patient died during follow-up. In patients treated by endovascular stent-graft placement no signs of endoleaks could be detected. CONCLUSIONS: Hemodynamic stability and an individual treatment strategy are prerequisites for survival of acute traumatic aortic lesions. Endovascular stent-graft placement has emerged as an innovative and minimally invasive therapeutic option in this polytraumatic high-risk patient cohort.

Successful type II endoleak closure by subclavian-to-carotid artery transposition after stent-graft placement of a distal aortic arch aneurysm.

Endovascular stent-graft placement has become a safe and effective treatment modality for various diseases of the distal aortic arch as well as of the descending aorta. However, its effectiveness may be limited by various kinds of endoleaks resulting in persistent or recurrent perfusion of the aneurysm sac. Subsequently, systemic pressurization leads to expansion of the aneurysm sac, exposing the patient to a recurrent risk of aneurysm rupture. We report on the case of a 57-year-old male who underwent emergency stent-graft placement in March 2001 due to a contained rupture of a distal aortic arch aneurysm involving the origin of the left subclavian artery. Due to the emergency condition, a subclavian-to-carotid artery transposition had not been performed prior to stent-graft placement. During follow-up the patient developed a type II endoleak originating from the left subclavian artery with consecutive enlargement of the aneurysm sac. The endoleak was successfully treated by subclavian-to-carotid artery transposition.

Cannulation of the axillary artery: the decision between direct cannulation and cannulation via side graft.

BACKGROUND: The axillary artery has emerged as promising alternative cannulation site when the ascending aorta is unsuitable for cannulation. However, in order to minimize vascular injury, the decision to cannulate the artery directly or via graft has to be considered carefully. METHODS: Seventy patients underwent axillary artery cannulation during a two-year period. Indications for operation were acute aortic dissection type A in 25(36 %), ascending aortic or arch aneurysm in 32 (46 %), redo surgery in 6 (9 %), and severely atherosclerotic aorta in 3 (4.3 %) patients. Depending on the diameter of the vessel and the rigidity of the wall, the artery was either cannulated directly or via an 8-mm prosthetic Dacron graft. RESULTS: Direct cannulation was performed in 46 patients (66 %) and cannulation via graft in the remaining 24 patients (34 %). The complication rate associated with axillary artery cannulation was 3.8 %. These two patients developed retrograde type A dissection and further dissection into the descending aorta caused by forceful insertion of a 20-French cannula in a very elastic and small artery. CONCLUSIONS: Cannulation of the axillary artery is an attractive approach with a wide indication spectrum. However, the decision to cannulate directly or via graft should be based on the diameter and elasticity of the vessel, to minimize the complications of vascular injury and subsequent dissection.

Clonidine added to bupivacaine enhances and prolongs analgesia after brachial plexus block via a local mechanism in healthy volunteers.

BACKGROUND AND OBJECTIVE: The addition of clonidine to local anaesthetics enhances pain relief after peripheral nerve block, but the site of action is unproven. METHODS: Seven healthy volunteers underwent three brachial block procedures using bupivacaine 0.25% 1 mg kg(-1) + epinephrine 1:200,000 (=local analgesic) in a randomized, double-blind cross-over fashion: (a) control treatment: local analgesic with 0.9% sodium chloride solution for the block and an intramuscular injection of saline; (b) intramuscular treatment: local analgesic with 0.9% NaCl for block and an intramuscular injection of clonidine 2 microg kg(-1) and (c) block treatment: local analgesic with clonidine 2 microg kg(-1) for block and an intramuscular injection of saline. RESULTS: The onset and duration of complete blockade (sensory/motor/temperature) was evaluated in the four nerve regions of the hand and forearm. Additionally, sedation score, blood pressure, heart rate and plasma clonidine concentrations were determined. The median duration of complete sensory blockade was 270 min (range 0-600) for block treatment compared to 0 min (range 0-480) for intramuscular treatment (P < 0.05) and 0 min (range 0-180) for control treatment (P < 0.05). Motor and temperature blockade exhibited similar results. Administration of clonidine was associated with sedation and a decrease in heart rate and blood pressure independent of the route of administration. Plasma clonidine concentrations were lower for block compared to the intramuscular treatment. CONCLUSIONS: The admixture of clonidine to bupivacaine plus epinephrine prolongs and enhances brachial plexus blockade. Lower clonidine plasma concentrations for block treatment strongly suggest a local effect.

Interventional treatment methods in patients with Marfan Syndrome.

Marfan syndrome is an autosomal dominant heritable connective tissue disorder which involves primarily the skeletal, ocular and cardiovascular system. The incidence of MS is on average 1: 10000 with 25-30% of cases caused by sporadic mutations.The leading cause of premature death in these patients is progressive dilatation and subsequent dissection of the ascending thoracic aorta resulting in cardiac tamponade, and left ventricular failure due to aortic regurgitation. Life expectancy is primarily determined by the severity of cardiovascular involvement, and has improved substantially over the last 20 years due to the advances in surgical and medical management.The optimum management of Marfan patients includes a lifelong surveillance with particular emphasis placed on aortic behaviour. Preventive replacement of various portions of the aorta has been a major contribution for improved life expectancy in these patients. The different surgical and interventional treatment options currently available will be further outlined in this review.

[Ebstein's anomaly: long-term results after modified reconstruction of tricuspid valve without ventricle plication]. / Ebstein-Anomalie: Langzeitverlauf nach Trikuspidalklappenrekonstruktion ohne Ventrikelplikatur.

Ebstein's anomaly is a rare congenital heart defect in which the hinges of the septal and/or posterior leaflets are displaced downward to the right ventricle. The anterior leaflet is usually not displaced but is enlarged and sail-like and valve closure is likewise displaced downwards. Since 1988 we have operated on 22 patients with Ebstein's anomaly using a modified repair technique of the tricuspid valve. This technique restructures the valve mechanism at the level of the true tricuspid annulus by using the most mobile leaflet for valve closure without plication of the atrialized chamber. We evaluated our long-term results with regard to functional capacity (New York Heart Association functional class), tricuspid valve function, rhythm disturbances and re-operation rate. We quantified the right ventricular function by measuring flow velocity integral of the pulmonary artery (VTIPA). All patients survived the operation. There were two hospital deaths (9%) and the late mortality was 4.5%. The mean followup period was 9 years (range, 1.5 to 13 years) for 19 patients. So far no re-operation has been necessary. Preoperatively, the majority of all patients were in NYHA classes III and IV (79%). After the first postoperative follow-up examination (2.9 months), 17 patients were in NYHA class II. Long-term follow-up examinations showed an additional improvement of 11 patients to NYHA class I. Echocardiographic studies demonstrated a significant improvement of tricuspid valve function. No tricuspid valve stenosis was observed. Significant improvement of VTI(PA) was observed. Analysis of the postoperative deaths demonstrated that all patients were in NYHA class III or IV and had a cardiothoracic ratio of 0.65 or more. A severe reduction in functional capacity seems to be an additional risk factor for mortality beside a cardiothoracic ratio greater than 0.65. We conclude that reconstruction of the tricuspid valve without ventricle plication not only achieves good functional results immediately after the operation but that follow-up examinations demonstrate stable or improved functional capacity in the long term. We postulate that incorporation of the atrialized chamber into the right ventricle may contribute to right ventricular contraction and thereby account for the improved functional capacity of the patients.

Endoluminal stent-graft placement in patients with acute aortic dissection type B.

OBJECTIVES: This study was performed to evaluate the feasibility, safety and effectiveness of endovascular stent-grafting in treating Stanford type B acute aortic dissection. We describe our first clinical experiences and initial results with stent-grafting across the primary entry tear in patients with acute aortic dissection type B. METHODS: Between March 2000 and August 2001, nine patients with acute type B dissection were treated endoluminally by stent-graft implantation. There were seven male and two female patients with a mean age of 63 years (between 48 and 85 years). In all nine patients aortic dissection was diagnosed by multislice computed tomography (CT) angiography. All nine patients had a maximal aortic diameter of 5.5 cm or more and recurrent pain, one patient showed hemoptysis. This patient with signs of a contained rupture was treated under emergency condition, the eight remaining patients were in hemodynamic stabile condition at the time of intervention. The GORE Excluder stent-graft system was used in eight patients (mean 1.8 stents/patient) and the TALENT stent-graft system in one patient, which were introduced transfemorally. RESULTS: The primary entry tear could be sealed successfully in all nine patients. Complete thrombosis of the false thoracic aortic lumen was obtained in two patients, in the remaining seven patients the false lumen was obliterated in the area of the thoracic aorta but perfused via re-entries in the abdominal region. No severe intraoperative complications occurred. One patient developed bilateral incomplete paraplegia with motor and sensory deficits affecting completely the right leg and partially the left leg, 14 h after intervention. A cerebrospinal fluid drainage was initiated by inserting a lumbar catheter. All nine patients, including the patient with the transient paraplegia, could be discharged from the hospital in excellent condition and without remaining neurologic deficits. Control CT scans showed a reduction of the false lumen from 2.34+/-0.58 to 0.7+/-0.44 cm and an increase of the true lumen from 1.56+/-0.5 to 4.10+/-0.6 cm in the thoracic aortic region. Mean ICU stay was 1.8 days, mean postoperative hospital stay was 7.6 days. CONCLUSIONS: Stent-grafting of acute type B dissections may represent a very effective and promising new method by closure of the primary entry tear, thereby minimizing the risk of rupture of the thoracic aorta and optimizing distal perfusion by decompression of the true lumen.

Influence of hypotensive and normotensive anesthesia on platelet aggregability and hemostatic markers in orthognathic surgery.

This prospective randomized study investigated the influence of normotensive and hypotensive general anesthesia on platelet aggregability, intraoperative blood loss and parameters of plasmatic coagulation during extensive orthognathic surgery. A total of 30 patients were randomly allocated for either normotensive anesthesia maintained by continuous infusion of propofol and remifentanil (NORMO, n=10) or hypotensive anesthesia, whereby hypotension was induced by increasing the infusion rate of remifentanil (HYPO-R, n=10) or by administration of nitroglycerin (HYPO-N, n=10). Whole blood platelet aggregability was significantly reduced during hypotension compared to normotensive anesthesia (P<.01, HYPO-N and HYPO-R vs. NORMO). Mean arterial blood pressure during hypotension correlated well with adenosinediphosphate- (R=.712, P<.001) and collagen-induced platelet aggregability (R=.685, P<.001). Within hypotensive study groups, postoperative fibrinogen levels were significantly different, whereas intraoperative platelet aggregability, postoperative platelet count, prothrombin time, activated partial thromboplastin time and antithrombin levels were not different. Normotensive anesthesia, however, caused significant decreases in platelet count (-29%), prothrombin time (-24%), fibrinogen (-41%) and antithrombin (-28%) and a significant prolongation in activated partial thromboplastin time (+21%) and thrombin time (+18%). There was a trend to reduced intraoperative blood loss in hypotensive study groups; however, differences were not significant. In conclusion, induced hypotension--independent of substances used for induction of hypotension--reduces intraoperative platelet aggregability, subsequently protecting the coagulation system against subclinical consumption coagulopathy. Induced hypotension-caused platelet dysfunction does not lead to an increased intraoperative blood loss, but quite on the contrary shows a trend to reduced intraoperative blood loss, possibly by preventing platelet-induced subclinical consumption coagulopathy.

Disease mechanisms revealed by transcription profiling in SOD1-G93A transgenic mouse spinal cord.

Mutations of copper,zinc-superoxide dismutase (cu,zn SOD) are found in patients with a familial form of amyotrophic lateral sclerosis. When expressed in transgenic mice, mutant human cu,zn SOD causes progressive loss of motor neurons with consequent paralysis and death. Expression profiling of gene expression in SOD1-G93A transgenic mouse spinal cords indicates extensive glial activation coincident with the onset of paralysis at 3 months of age. This is followed by activation of genes involved in metal ion regulation (metallothionein-I, metallothionein-III, ferritin-H, and ferritin-L) at 4 months of age just prior to end-stage disease, perhaps as an adaptive response to the mitochondrial destruction caused by the mutant protein. Induction of ferritin-H and -L gene expression may also limit iron catalyzed hydroxyl radical formation and consequent oxidative damage to lipids, proteins, and nucleic acids. Thus, glial activation and adaptive responses to metal ion dysregulation are features of disease in this transgenic model of familial amyotrophic lateral sclerosis.

Protein oxidative damage in a transgenic mouse model of familial amyotrophic lateral sclerosis.

The Gly93-->Ala mutation in the Cu,Zn superoxide dismutase (Cu,Zn-SOD) gene (SOD1) found in some familial amyotrophic lateral sclerosis (FALS) patients has been shown to result in an aberrant increase in hydroxyl radical production by the mutant enzyme that may cause oxidative injury to spinal motor neurons. In the present study, we analyzed the extent of oxidative injury to lumbar and cervical spinal cord proteins in transgenic FALS mice that overexpress the SOD1 mutation [TgN(SOD1-G93A)G1H] in comparison with nontransgenic mice. Total protein oxidation was examined by spectrophotometric measurement of tissue protein carbonyl content by the dinitrophenylhydrazine (DNPH) assay. Four ages were investigated: 30 (pre-motor neuron pathology and clinical disease), 60 (after initiation of pathology, but pre-disease), 100 (approximately 50% loss of motor neurons and function), and 120 (near complete hindlimb paralysis) days. Protein carbonyl content in 30-day-old TgN(SOD1-G93A)G1H mice was twice as high as the level found in age-matched nontransgenic mice. However, at 60 and 100 days of age, the levels were the same. Then, between 100 and 120 days of age, the levels in the TgN(SOD1-G93A)G1H mice increased dramatically (557%) compared with either the nontransgenic mice or transgenic animals that overexpress the wild-type human Cu,Zn-SOD [TgN(SOD1)N29]. The 100-120-day increase in spinal cord protein carbonyl levels was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoretic separation and western blot immunoassay, which enabled the identification of heavily oxidized individual proteins using a monoclonal antibody against DNPH-derivatized proteins. One of the more heavily oxidized protein bands (14 kDa) was identified by immunoprecipitation as largely Cu,Zn-SOD. Western blot comparison of the extent of Cu,Zn-SOD protein carbonylation revealed that the level in spinal cord samples from 120-day-old TgN(SOD1-G93A)G1H mice was significantly higher than that found in age-matched nontransgenic or TgN(SOD1)N29 mice. These results suggest that the increased hydroxyl radical production associated with the G93A SOD1 mutation and/or lipid peroxidation-derived radical species (peroxyl or alkoxyl) causes extensive protein oxidative injury and that the Cu,Zn-SOD itself is a key target, which may compromise its antioxidant function.

Anticancer activity of glaucarubinone analogues.

A series of glaucarubinone analogues, obtained from natural sources as well as synthesized by us, were studied both in vitro and in vivo. The focus of the in vitro assessment was to define solid tumor-selective compounds by quantitating differential cytotoxic activity between murine and human solid tumor cells and either murine leukemia or normal cells. Subsequent in vivo studies were aimed at determining the therapeutic efficacy of these analogues against the murine models. Structure-activity analysis consequent to both the in vitro and in vivo studies demonstrated that few changes could be made in the parent glaucarubinone structure (outside of the C-15 position) without abrogating either cytotoxicity or potency. However, significant changes could be made at the C-15 position which modified, either enhanced or diminished, in vitro differential cytotoxicity, potency, human solid tumor selectively, and differential cytotoxicity to a MDR-expressing murine mammary tumor.

Comparative neuroprotective properties of the benzodiazepine receptor full agonist diazepam and the partial agonist PNU-101017 in the gerbil forebrain ischemia model.

Recent studies have demonstrated the neuroprotective properties of the novel imidazoquinoline benzodiazepine receptor partial agonist, PNU-101017, in the gerbil forebrain ischemia model. The compound effectively reduces delayed post-ischemic (5 min bilateral carotid occlusion) hippocampal CA1 neuronal degeneration even when its administration is withheld until 4 h after reperfusion and the effect is unrelated to hypothermia. The purpose of the present study was to determine the comparative abilities of PNU-101017 versus the full agonist diazepam to attenuate post-ischemic CA1 damage. Male gerbils were treated either 30 min before ischemia induction or immediately after reperfusion with an initial dose of PNU-101017 (30 mg/kg i.p.) or diazepam (10 mg/kg i.p.) with a second dose being given at 2 h after reperfusion. Possible hypothermic effects of either compound were prevented by external heating. In vehicle (0.05 N HCl)-treated gerbils, the loss of hippocampal CA1 neurons at 5 days was 85%. PNU-101017 pretreatment reduced the loss to 50% (p<0.05 vs. vehicle) whereas pretreatment with diazepam attenuated damage to only 17% (p<0.001 vs. vehicle). Delaying treatment with PNU-101017 until just after reperfusion still resulted in a reduction in CA1 degeneration statistically that was indistinguishable from that seen with pretreatment. In contrast, diazepam post-treatment did not significantly decrease CA1 neuronal loss. These results suggest that a benzodiazepine receptor partial agonist may have greater neuroprotective practicality than a full agonist for the treatment of global cerebral ischemia. The mechanistic basis for this difference may relate to the partially pro-excitatory neuronal response to endogenous GABA before and after neuronal insult.