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1.
J Neurol Surg B Skull Base ; 85(4): 412-419, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38966294

ABSTRACT

Background Advances in skull base surgery have increased the need for a detailed understanding of skull base anatomy and its intrinsic relationship to surrounding structures. This has resulted in an improvement in patient outcomes. The frontotemporal orbitozygomatic (FTOZ) transcavernous approach (TCA) is an excellent option for treating complex lesions involving multiple compartments of the skull base, including the sellar and parasellar, third ventricle, orbit, and petroclival region. Objective This article aimed to provide a detailed cadaveric dissection accompanying a thorough procedure description, including some tips and pitfalls of this technique. Methods Microsurgical dissection was performed in four freshly injected cadaver heads at the Cranial Base Neuroanatomy Laboratory, Cleveland Clinic Florida. The FTOZ TCA was performed on both sides of the four specimens. The advantages and disadvantages were discussed based on the anatomic nuances of this approach. Results The FTOZ TCA represented a wide access to the anterior, middle, and posterior fossa. When combined with an anterior clinoidectomy, it allowed for significant and safe internal carotid artery mobilization. This approach created numerous windows, including opticocarotid, carotid-oculomotor, supratrochlear, infratrochlear, anteromedial, anterolateral, and posteromedial triangles. The only drawback was the length of the dissection and the level of surgical acumen required to perform it. Conclusion Despite its technical difficulty, the FTOZ TCA should be considered for the surgical management of basilar apex aneurysms and tumors surrounding the cavernous sinus, sellar/parasellar, retrochiasmatic, and petroclival region. Continuous training and dedicated time in the skull base laboratory can help achieve the necessary skills required to perform this approach.

2.
Acta Neurochir (Wien) ; 166(1): 297, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39004670

ABSTRACT

PURPOSE: The trigeminocardiac reflex (TCR) has traditionally been characterized by a sudden decrease in heart rate, asystole, or hypotension during the manipulation of the trigeminal nerve (MTN) or its branches. While this classical TCR is well-documented, there is limited literature on alternative forms of TCR, such as the development of intraoperative hypertension (HTN) or tachycardia, and the underlying pathogenesis. Furthermore, a gap exists in understanding the correlation between intraoperative blood pressure readings and postoperative outcomes, particularly regarding pain relief in patients with trigeminal neuralgia (TN). Our study aims to examine intraoperative blood pressure trends during microvascular decompression (MVD) for TN and assess their impact on postoperative outcomes. METHODS: We selected 90 patients who underwent MVD for TN treatment. Blood pressure and heart rate were recorded both preoperatively and during the procedure, specifically during the MTN period, using an arterial line. The Barrow Neurological Institute (BNI) Pain Scale was calculated for all patients both pre- and post-operatively to evaluate pain relief after surgery. RESULTS: The mean age of the patients was 61.0 ± 12.35 years, with 64.4% being females. Classical TCR (hypotension) was observed in only 2.2% of patients, whereas 80% of patients developed hypertension (≥ 140/90) during MTN. The mean preoperative systolic blood pressure was 128 ± 22.25, and the mean intraoperative systolic blood pressure during MTN was 153.1 ± 20.2. An analysis of covariance, utilizing either preoperative BNI or duration of symptoms as covariate variables, revealed a statistically significant association between intraoperative HTN and postoperative BNI. A linear regression model demonstrated that intraoperative HTN following MTN significantly predicted a lower postoperative BNI score (p = 0.006). CONCLUSIONS: Intraoperative HTN during MTN, an observed yet underexplored phenomenon, demonstrated a correlation with improved postoperative outcomes. Furthermore, it is recommended to conduct additional investigations into potential neurovascular conflicts in patients not manifesting intraoperative HTN following MTN. A comprehensive understanding of TCR, encompassing its various forms, is vital for optimizing surgical management. This study underscores the imperative for further research to unravel the mechanisms linking intraoperative HTN to surgical outcomes in TN patients.


Subject(s)
Hypertension , Microvascular Decompression Surgery , Trigeminal Neuralgia , Humans , Trigeminal Neuralgia/surgery , Female , Middle Aged , Male , Microvascular Decompression Surgery/methods , Hypertension/surgery , Aged , Treatment Outcome , Intraoperative Complications/etiology , Blood Pressure/physiology , Reflex, Trigeminocardiac/physiology
3.
Neurosurg Rev ; 47(1): 334, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39009883

ABSTRACT

PURPOSE: The past two decades have witnessed the rise of keyhole microscopic minimally invasive surgeries, including the transciliary supraorbital approach (TCA) and transpalpebral approach (TPA), commonly known as the transorbital approach. This study aims to elucidate the nuances, specific indications, and advantages of each approach. METHODS: A series of dissections were conducted on five formalin-fixed, alcohol-preserved cadaver heads. The TCA was performed on one side, and the TPA on the other. Virtual measurements of working angles for both approaches were recorded. Additionally, three clinical cases were presented to illustrate the practical application of the techniques. RESULTS: For TCA, the craniotomy dimensions were 1.7 cm x 2.5 cm (Cranial-Caudal (CC) x Lateral-Lateral (LL)), while for TPA, they measured 2.1 cm x 2.9 cm (CC x LL). The measurements of anterior clinoid processes (ACP) were obtained and compared between approaches. In the TCA, the mean ipsilateral ACP measurement was 62 mm (Range: 61 -63 mm), and the mean contralateral ACP measurement was 71.2 mm (Range: 70 -72 mm). In TPA, these measurements were 47.8 mm (Range: 47 -49 mm) and 62.8 mm (Range: 62 -64 mm), respectively. TCA exhibited an average cranial-caudal angle of 14.9°, while TPA demonstrated an average of 8.3°. CONCLUSION: The anterior cranial fossa was better exposed by a TCA, which also featured shorter operative times, enhanced midline visualization, and a quicker learning curve. Conversely, the middle fossa was better exposed by a TPA, making it an excellent option for middle fossa pathologies, including those in the anterior temporal lobe. After sphenoid bone wing drilling, the TPA offers superior visualization from the lateral to the medial aspect and enhances the CC angle. Additionally, the TPA reduces the risk of postoperative frontalis palsy based on anatomic landmarks. However, the TPA requires a greater cranial osteotomy, and due to unfamiliarity with eyelid anatomy, the learning curve for most neurosurgeons is lengthier for this procedure.


Subject(s)
Cadaver , Craniotomy , Skull Base , Humans , Craniotomy/methods , Skull Base/surgery , Skull Base/anatomy & histology , Male , Female , Minimally Invasive Surgical Procedures/methods , Middle Aged , Orbit/anatomy & histology , Orbit/surgery , Neurosurgical Procedures/methods , Aged , Adult , Microsurgery/methods
5.
Heliyon ; 9(9): e19756, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37809543

ABSTRACT

Idiopathic intracranial hypertension (IIH) is characterized by raised intracranial pressure with unknown etiology. The most common neurological manifestations are headache and visual loss. Often, other cranial nerve impairments are also found, most commonly in the VI nerve. Trigeminal neuralgia (TN) is a debilitating condition that is most frequently caused by neurovascular pathology, but TN secondary to IIH is a rare and poorly described topic. Possible explanations of TN in these patients include the distortion of the local anatomy at CN entry zones and fluid displacement causing distortion of the Meckel's cave. In the case below we describe the clinical course of an obese female patient with TN-like pain who underwent a ventriculoperitoneal shunt to treat IIH and experienced complete resolution of both conditions.

6.
World Neurosurg ; 2023 Jun 27.
Article in English | MEDLINE | ID: mdl-37385444

ABSTRACT

OBJECTIVE: Chiari I malformation results from a mismatch between the posterior fossa bones and neural components. Management usually relies on surgical treatment. Despite being the most common assumed positioning, the prone position can be challenging in high body mass index (BMI) patients (>40 kg/m2). METHODS: Between February 2020 and September 2021, 4 consecutive patients with class III obesity underwent posterior fossa decompression. The authors describe nuances of the positioning and perioperative details. RESULTS: No perioperative complications were reported. These patients are at a lower risk of bleeding and increased intracranial pressure as a consequence of low intra-abdominal pressure and venous return. In this context, the semi-sitting position, with the aid of accurate monitoring for venous air embolism, seems to be an advantageous surgical position in this group of patients. CONCLUSIONS: We present our results and technical nuances on positioning high BMI patients for posterior fossa decompression using a semi-sitting position.

7.
Curr Oncol ; 30(5): 4946-4956, 2023 05 12.
Article in English | MEDLINE | ID: mdl-37232831

ABSTRACT

Introduction: Glioblastoma (GBM) patients have a 20-30 incidence of venous thromboembolic events. EGFR is a widely used prognostic marker for many cancers. Recent lung cancer studies have described relationships between EGFR amplification and an increased incidence of thromboembolic complications. We aim to explore this relationship in glioblastoma patients. Methods: Two hundred ninety-three consecutive patients with IDH wild-type GBM were included in the analysis. The amplification status of EGFR was measured using fluorescence in situ hybridization (FISH). Centromere 7 (CEP7) expression was recorded to calculate the EGFR-to-CEP7 ratio. All data were collected retrospectively through chart review. Molecular data were obtained through the surgical pathology report at the time of biopsy. Results: There were 112 subjects who were EGFR-amplified (38.2%) and 181 who were non-amplified (61.8%). EGFR amplification status was not significantly correlated with VTE risk overall (p = 0.2001). There was no statistically significant association between VTE and EGFR status after controlling for Bevacizumab therapy (p = 0.1626). EGFR non-amplified status was associated with an increased VTE risk in subjects greater than 60 years of age (p = 0.048). Conclusions: There was no significant difference in occurrence of VTE in patients with glioblastoma, regardless of EGFR amplification status. Patients older than 60 years of age with EGFR amplification experienced a lower rate of VTE, contrary to some reports on non-small-cell lung cancer linking EGFR amplification to VTE risk.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Glioblastoma , Lung Neoplasms , Venous Thromboembolism , Humans , ErbB Receptors/genetics , ErbB Receptors/metabolism , Retrospective Studies , Glioblastoma/complications , Glioblastoma/genetics , Glioblastoma/metabolism , Venous Thromboembolism/genetics , In Situ Hybridization, Fluorescence , Prognosis
8.
Clin Neurol Neurosurg ; 230: 107757, 2023 07.
Article in English | MEDLINE | ID: mdl-37196458

ABSTRACT

OBJECTIVE: Patients with idiopathic normal pressure hydrocephalus (iNPH) who undergo ventriculoperitoneal shunt (VPS) placement often belong to an older demographic, putting them at increased risk of postoperative delirium and related complications. Recent literature documenting the use of Enhanced Recovery After Surgery (ERAS) protocols in various disciplines of surgery has shown improved clinical outcomes, faster discharge, and lower readmission rates. Early return to a familiar environment (i.e., discharged home) is a well-known predictor of reduced postoperative delirium. However, ERAS protocols are uncommon in neurosurgery, especially intracranial procedures. We developed a novel ERAS protocol for patients with iNPH undergoing VPS placement to gain further insight regarding postoperative complications, specifically delirium. METHODS: We studied 40 patients with iNPH with indications for VPS. Seventeen patients were selected at random to undergo the ERAS protocol, and twenty-three patients underwent the standard VPS protocol. The ERAS protocol consisted of measures to reduce infection, manage pain, minimize invasiveness, confirm procedural success with imaging, and shorten the length of stay. Pre-operative American Society of Anesthesiologists (ASA) grade was collected for each patient to indicate baseline risk. Rates of readmission and postoperative complications, including delirium and infection, were collected at 48 h, 2 weeks, and 4 weeks postoperatively. RESULTS: There were no perioperative complications among the 40 patients. There was no postoperative delirium in any of the ERAS patients. Postoperative delirium was observed in 10 of 23 non-ERAS patients. There was no statistically significant difference between the ASA grade between the ERAS and non-ERAS groups. CONCLUSIONS: We described a novel ERAS protocol for patients with iNPH receiving VPS focusing on an early discharge. Our data suggest that ERAS protocols in VPS patients might reduce the incidence of delirium without increasing the risk of infection or other postoperative complications.


Subject(s)
Delirium , Enhanced Recovery After Surgery , Hydrocephalus, Normal Pressure , Humans , Ventriculoperitoneal Shunt/adverse effects , Hydrocephalus, Normal Pressure/surgery , Hydrocephalus, Normal Pressure/complications , Postoperative Complications/etiology , Delirium/complications , Delirium/surgery , Length of Stay , Retrospective Studies
9.
Clin Neurol Neurosurg ; 229: 107750, 2023 06.
Article in English | MEDLINE | ID: mdl-37146367

ABSTRACT

BACKGROUND: The neurosurgical management of idiopathic intracranial hypertension (IIH) remains controversial. Although shunting and newer endovascular stenting techniques are part of the neurosurgical armamentarium to treat medically refractory IIH symptoms, optic nerve sheath fenestration has traditionally been performed by ophthalmologists. OBJECTIVE: We present a detailed cadaveric dissection that simulates the endoscopic endonasal optic nerve sheath decompression (EONSD) technique along with the literature review. METHODS: EONSD was performed in four freshly injected cadaveric specimens. Additionally, a systematic review from different electronic databases has been done. RESULTS: Bilateral EONSD was performed in all specimens without significant technical difficulties. Based on our experience, there is no need to expose the periorbita or orbital apex. The primary anatomic landmarks were the optic canal, the lateral opticocarotid recess, the tuberculum, the limbus, and the clinoid segment of the internal carotid artery. Based on the systematic review, 68 patients (77.9% female) underwent EONSD, with a mean age of 33.4 ± 6.9 years in adult patients. Follow-up ranged from 3 to 58 months across different studies. The pooled meta-analysis showed headache, papilledema, and visual disturbance improvement in 78% [95%CI 0.65-0.90], 72% [95%CI 0.61-0.83], and 88% [95%CI 0.80-0.96] of cases who underwent EONSD, respectively. The subgroup analysis showed there was no statistically significant difference between unilateral and bilateral EONSD in terms of different measured outcomes. CONCLUSION: EONSD is a feasible surgical procedure that may obviate the need for shunting in patients with IIH. Although clinical studies showed that EONSD is a safe and effective technique, further studies are required to establish the preferences of either unilateral or bilateral approaches.


Subject(s)
Intracranial Hypertension , Papilledema , Pseudotumor Cerebri , Adult , Humans , Female , Male , Pseudotumor Cerebri/surgery , Optic Nerve/surgery , Papilledema/surgery , Decompression, Surgical/methods , Cadaver , Intracranial Hypertension/surgery
10.
World Neurosurg ; 175: e151-e158, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36931342

ABSTRACT

OBJECTIVE: To describe and evaluate the steps required to perform a combined endoscopic endonasal/transoral transclival transodontoid approach for anterior decompression of the craniovertebral junction. METHODS: The endoscopic endonasal transclival transodontoid approach combined with endoscopic transoral decompression was performed on 4 cadaveric specimens. Evaluation of this combined technique; a review of the literature; and the nuances, advantages, and pitfalls are reported. RESULTS: Adequate wide anterior decompression was achieved in all specimens. This combined approach allowed the preservation of the anterior arch of C1 without injuring the eustachian tube anatomy and avoiding internal carotid artery manipulation. CONCLUSIONS: Mastery of both techniques allows for a safe and comfortable surgical corridor. The transoral and transnasal approaches should not be considered as either/or techniques, but rather as a complement to each other. However, as with all new or developing techniques, there is a steep learning curve, which requires ample training in the skull base laboratory.


Subject(s)
Nose , Odontoid Process , Humans , Nose/surgery , Endoscopy/methods , Head , Decompression , Odontoid Process/surgery
11.
Int J Neurosci ; : 1-7, 2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36724879

ABSTRACT

INTRODUCTION: The incidence of brain tumors has increased in elderly population overtime. Their eligibility to a major surgery remains a questionable subject. This study evaluated prognostic factors and 30-days morbidity and mortality in octogenarian population who underwent craniotomy for resection of brain tumor. MATERIALS AND METHODS: A total of 154 patients were divided into two different groups: patients above 80 years old and patients below 65 years old. In both groups, patients were stratified based on diagnosis with benign tumors [meningioma] and malignant tumors [high-grade gliomas and metastases]. Multivariable logistic regression model with backward elimination method was utilized to identify the independent risk factors for 30-days readmission and post-operative complications. RESULTS: The analysis revealed no significant difference in 30-day readmission (p = 0.7329), 30-day mortality (0.6854) or in post-operative complication (p = 0.3291) between age ≥ 80 and age ≤ 65 groups. A longer length of stay (LOS) was observed in the older patients (p = 0.0479). There was a significant difference in the pre-post KPS between the two groups (p < 0.0001). ASA (p = 0.0315) and KPS (p = 0.071) were found as important prognostic factors associated with post-operative mortality in both groups. CONCLUSION: Octogenarians can withstand craniotomy without any significant increase in 30-day readmission, 30-day mortality and post-operative complications as compared to patients younger than age 65. The ASA score (>3) and/or KPS (<70) were the most important prognostic factors for 30-days readmission and mortality.

12.
World Neurosurg ; 171: 84, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36526228

ABSTRACT

Trigeminal nerve balloon compression (TNBC)1-3 can provide immediate therapeutic relief to patients suffering from trigeminal neuralgia. This is a particularly effective treatment option for patients who are not eligible for surgical procedures (i.e., elderly patients or patients with multiple comorbidities) or for patients who have had an insufficient response to microvascular decompression. TNBC can also be used as a bridge treatment before stereotactic radiosurgery. Use of intraoperative computed tomography-like images using a C-arm system (DYNA-CT) imaging facilitates the TNBC procedure.4,5 Three-dimensional DYNA-CT imaging with needle guidance allows for precise needle advancement and insertion through the foramen ovale. DYNA-CT enables the direct visualization and avoidance of vascular structures such as the carotid or internal maxillary arteries and results in decreased procedure times and complications. The authors present a step-by-step video demonstrating the use of intraoperative DYNA-CT needle guidance for TNBC (Video 1). A Siemens Artis Zee Biplane system is used for the procedure. A comprehensive description of all elements of the procedure is provided including balloon preparation, needle trajectory planning, needle advancement, 3-dimensional confirmation of the needle's depth and path, balloon placement, balloon inflation, and balloon removal. Tips and optimal strategies are presented. Advantages of using DYNA-CT for needle guidance include the reduction of fluoroscopy dose and fluoroscopy time. The average dose area product during conventional percutaneous balloon compression in prior studies was 1137 mGycm2, with a mean fluoroscopic time of 62 seconds.6 In our experience, the mean fluoroscopy dose is 274 mGycm2 and the total fluoroscopic time is about 45 seconds. Furthermore, during the DYNA-CT acquisition, the neurointerventional team stays outside the room during the DYNA-CT, which reduces the cumulative radiation to the operator. DYNA-CT needle guidance facilitates precise advancement of the needle into the foramen ovale and positioning of the balloon in the Meckel cave during TNBC. It is a safe and feasible technique that allows for the visualization and avoidance of important structures such as the internal carotid artery or the internal maxillary artery, resulting in decreased procedure times and complications.


Subject(s)
Balloon Occlusion , Trigeminal Neuralgia , Triple Negative Breast Neoplasms , Humans , Aged , Trigeminal Neuralgia/surgery , Rhizotomy/methods , Tomography, X-Ray Computed/methods
13.
Respir Care ; 2022 Nov 08.
Article in English | MEDLINE | ID: mdl-36347565

ABSTRACT

BACKGROUND: Mobility is human body movement in all its forms, including bed-to-chair transfer, walking, daily tasks, participating in work and social functions, exercising, and using public transport. The mobility of people living with COPD is affected negatively by the disease symptoms. However, limited data are available on the life-space mobility in people with COPD on long-term oxygen therapy (LTOT). This study aimed to explore the life-space mobility in subjects with COPD on LTOT and verify whether life-space mobility is associated with comorbidities and symptoms, activity in daily life, exercise capacity performance, and quality of life. METHODS: This cross-sectional study enrolled 61 subjects with COPD on LTOT (73.0 ± 8.8 y, FEV1 41.7 ± 16.0% predicted, on LTOT for 2.8 ± 3.3 y). Life-space mobility (Life-Space Assessment), LTOT usage time, comorbidities (Charlson comorbidity index), need for support from a caregiver, exercise capacity (6-min step test), dyspnea (modified Medical Research Council scale), activities of daily living (ADLs, Katz scale), and health-related quality of life (EuroQol 5-Dimension Questionnaire) were assessed. RESULTS: Mobility restriction was identified in 90% of participants. Life-space mobility was negatively associated with the number of comorbidities (rs = -0.31, P = .02), dyspnea symptom (rs = -0.60, P < .001), and positively associated with basic ADLs performance (rs = 0.59, P < .001) and exercise capacity (rs = 0.49, P < .001). Dyspnea and exercise capacity were independent predictors of vital space mobility. CONCLUSIONS: Subjects with COPD on LTOT had limited life-space mobility. Interventions to reduce dyspnea and improve exercise capacity should be prioritized to increase this population's domestic and community mobility.

14.
Curr Oncol ; 29(10): 7396-7410, 2022 10 04.
Article in English | MEDLINE | ID: mdl-36290858

ABSTRACT

Introduction: Resection of intra-axial tumors (IaT) in eloquent brain regions risks major postoperative neurological deficits. Awake craniotomy is often used to navigate these areas; however, some patients are ineligible for awake procedures. The trans-sulcal approach (TScal) was introduced to reduce parenchymal trauma during tumor resection. We report our experiences utilizing TScal for resection of deep IaT located in eloquent areas. Materials and Methods: This is a single-center retrospective analysis of patients who underwent IaT resection in eloquent areas via TScal from January 2013 to April 2021. Seventeen cases were reviewed, and relevant data was collected. Fluorescence-guided surgery with 5-aminolevulinic acid (ALA) and intraoperative ultrasound was performed in some cases. Results: Seventeen patients (10 males, 7 females) averaging 61.2 years-old (range, 21-76) were included in this study. Average length of stay was 4.8 days, and only 2 patients (11.8%) required hospital readmission within 30 days. Gross total resection (GTR) was achieved in 15 patients (88.2%), while subtotal resection occurred in 2 patients (11.8%). Eleven patients (64.7%) reported full resolution of symptoms, 4 patients (23.5%) reported deficit improvement, and 2 patients (11.8%) experienced no change from their preoperative deficits. No patient developed new permanent deficits postoperatively. Discussion: GTR, preoperative deficit reduction, and complications were comparable to awake craniotomy and other TScal studies. Ancillary intraoperative techniques, such as brain mapping, 5-ALA and intraoperative ultrasound, are afforded by TScal to improve resection rates and overall outcomes. Conclusions: TScal can be an option for patients with deep lesions in eloquent areas who are not candidates for awake surgeries.


Subject(s)
Aminolevulinic Acid , Brain Neoplasms , Male , Female , Humans , Middle Aged , Brain Neoplasms/surgery , Brain Neoplasms/pathology , Retrospective Studies , Craniotomy/methods , Brain/pathology
15.
Surg Neurol Int ; 13: 187, 2022.
Article in English | MEDLINE | ID: mdl-35673653

ABSTRACT

Background: Several approaches are described for giant meningiomas of the anterior skull base. Recently, endonasal endoscopic approaches have been described as a minimally invasive (MI) alternative. However, the extension of dissection of the nose cavity and the risks of CSF leak do not fit in the MI prerogatives. We present an operative video illustrating a MI transcortical approach through a nummular craniotomy for a giant meningioma of the anterior fossa. Case Description: We report an 83-year-old female patient. On neurological examination, she was drowsy and hemiparetic on the left side. MRI scan demonstrated a giant anterior fossa lesion (7.6 × 6.2 × 6 cm). An 1.5 diameter craniotomy was placed in the right frontal region after MRI 3D reconstruction analysis. The first step was to debulk the core of the tumor with the ultrasonic aspirator. An important aspect is that the surgeon needs to rotate its positions around the patient in a 360° fashion for a total resection. The final step was to inspect the surgical cavity with the endoscope to check for any remaining tumor. The patient was discharged home 1 day after the surgery with no new deficits. Conclusion: Giant meningiomas of the anterior fossa are a different entity. When they reach the cortical surface, the surgical approach can be different from the common skull base meningiomas. We demonstrate that a MI transcortical approach can be a safe alternative for giant meningiomas, especially for high-risk patients, as the elderly ones.

16.
Can J Physiol Pharmacol ; 87(12): 1102-9, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20029547

ABSTRACT

U74389F is a compound in a family of 21-aminosteroids devoid of classical glucocorticoid action that inhibit lipid peroxidation. These compounds improve neurologic function and tissue survival after head or spinal cord injury. Dexamethasone inhibits development of intimal hyperplasia (IH) and improves attenuated nitric oxide (NO) production of the rabbit aorta subsequent to balloon catheter injury. We tested the hypothesis that U74389F is protective in a catheter-induced endothelial-denuded and arterial injury model. A 4-Fr Fogarty balloon (BALL) embolectomy catheter was passed through the thoracic aorta of New Zealand White rabbits treated with 15 mg/kg U74389F (LAZ) 2 days before and 1 week after injury. Animals were killed at 4 weeks after surgical intervention, and formation of IH was determined by calculating the intimal/medial ratio (I/M). The treatment groups of animals were injured untreated (BALL), injured treated (BALL/LAZ), uninjured treated (CONTROL/LAZ), and sham-operated treated (SHAM/LAZ). Scanning electron microscopy revealed that after injury lazaroid treatment produced an improvement of the neoendothelium (alignment in the direction of blood and fewer intercellular gaps) as compared with injured but untreated aortas. Relaxation to acetylcholine (NO formation) was impaired in aortic rings from catheterized animals; lazaroid treatment improved the relaxation to 10-6 mol/L acetylcholine but not to lower concentrations. I/M for SHAM/LAZ, BALL, and BALL/LAZ was 0.02 +/- 0.02, 21.6 +/- 1.6, and 17.2 +/- 2.5, respectively; BALL vs. BALL/LAZ, p < 0.06. An increased contractile response to 120 mmol/L KCl was observed after lazaroid treatment. This is the first report of lazaroid-mediated improvement in the neoendothelial morphology, improved neoendothelial NO generation, and augmented hypopolarizing contractile response, but no attenuation in the development of IH.


Subject(s)
Antioxidants/pharmacology , Catheterization/adverse effects , Endothelium, Vascular/injuries , Pregnatrienes/pharmacology , Tunica Intima/injuries , Animals , Antioxidants/therapeutic use , Aorta/drug effects , Aorta/injuries , Aorta/pathology , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Hyperplasia/drug therapy , Male , Microscopy, Electron, Scanning , Nitroglycerin/pharmacology , Pregnatrienes/therapeutic use , Rabbits , Tunica Intima/drug effects , Tunica Intima/pathology
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