Evaluate the safety and efficacy of dura sealant patch in reducing cerebrospinal fluid leakage following elective cranial surgery (ENCASE II): study protocol for a randomized, two-arm, multicenter trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a frequent and challenging complication in neurosurgery, especially in the posterior fossa, with a prevalence of 8%. It is associated with substantial morbidity and increased healthcare costs. A novel dural sealant patch (LIQOSEAL) was developed for watertight dural closure. The objective of this study is to clinically assess the safety and effectiveness of LIQOSEAL as a means of reducing intra- as well as postoperative CSF leakage in patients undergoing elective posterior fossa intradural surgery with a dural closure procedure compared to the best currently available dural sealants. METHODS: We will conduct a two-arm, randomized controlled, multicenter study with a 90-day follow-up. A total of 228 patients will be enrolled in 19 sites, of which 114 will receive LIQOSEAL and 114 an FDA-approved PEG sealant. The composite primary endpoint is defined as intraoperative CSF leakage at PEEP 20 cm H2O, percutaneous CSF leakage within 90 days of, wound infection within 90 days of or pseudomeningocele of more than 20cc on MRI or requiring intervention. We hypothesize that the primary endpoint will not be reached by more than 10 patients (9%) in the investigational arm, which will demonstrate non-inferiority of LIQOSEAL compared to control. DISCUSSION: This trial will evaluate whether LIQOSEAL is non-inferior to control as a means of reducing CSF leakage and safety TRIAL REGISTRATION: ClinicalTrials.gov NCT04086550 . Registered on 11 September 2019.

MRI T2-Hyperintense Signal Structures in the Cervical Spinal Cord: Anterior Median Fissure versus Central Canal in Chiari and Control-An Exploratory Pilot Analysis.

BACKGROUND AND PURPOSE: Cervical spine axial MRI T2-hyperintense fluid signal of the anterior median fissure and round hyperintense foci resembling either the central canal or base of the anterior median fissure are associated with a craniocaudad sagittal line, also simulating the central canal. On the basis of empiric observation, we hypothesized that hyperintense foci, the anterior median fissure, and the sagittal line are seen more frequently in patients with Chiari malformation type I, and the sagittal line may be the base of the anterior median fissure in some patients. MATERIALS AND METHODS: Saggital line incidence and the incidence/frequency of hyperintense foci and anterior median fissure in 25 patients with Chiari I malformation and 25 contemporaneous age-matched controls were recorded in this prospective exploratory study as either combined (hyperintense foci+anterior median fissure in the same patient), connected (anterior median fissure extending to and appearing to be connected with hyperintense foci), or alone as hyperintense foci or an anterior median fissure. Hyperintense foci and anterior median fissure/patient, hyperintense foci/anterior median fissure ratios, and anterior median fissure extending to and appearing to be connected with hyperintense foci were compared in all, in hyperintense foci+anterior median fissure in the same patient, and in anterior median fissure extending to and appearing to be connected with hyperintense foci in patients with Chiari I malformation and controls. RESULTS: Increased sagittal line incidence (56%), hyperintense foci (8.5/patient), and anterior median fissure (4.0/patient) frequency were identified in patients with Chiari I malformation versus controls (28%, 3.9/patient, and 2.7/patient, respectively). Increased anterior median fissure/patient, decreasing hyperintense foci/anterior median fissure ratio, and increasing anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified in Chiari subgroups. A 21%-58% increase in observed anterior median fissure extending to and appearing connected to hyperintense foci in the entire cohort and multiple sagittal line subgroups compared with predicted occurred. CONCLUSIONS: In addition to the anticipated increased incidence/frequency of sagittal line and hyperintense foci in patients with Chiari I malformation, an increased incidence and frequency of anterior median fissure and anterior median fissure extending to and appearing to be connected with hyperintense foci/patient were identified. We believe an anterior median fissure may contribute to a saggital line appearance in some patients with Chiari I malformation. While thin saggital line channels are usually ascribed to the central canal, we believe some may be due to the base of the anterior median fissure, created by pulsatile CSF hydrodynamics.

Microsurgical treatment for unruptured intracranial aneurysms: a modern single surgeon series.

With the rise of endovascular treatments for the management of unruptured intracranial aneurysms (UIAs), advances in microsurgical techniques are underrepresented in modern surgical series, which largely consist of patients with aneurysms unfit for coiling. We report a modern series of microsurgical treatment for UIAs performed by a single surgeon as the preferred treatment modality. We retrospectively reviewed the charts of all patients with UIAs treated by the senior author with microsurgical clipping over an 11-year period. Procedure-related mortality, major neurologic morbidity (modified Rankin Score 3-5), complications, and persistent neurologic deficits were recorded. Risk factors for persistent neurologic deficits and major morbidity or mortality were analyzed using multivariate logistic regression analysis. We identified 329 patients with 400 UIAs treated in 353 surgeries. The average age was 52 years, 80% of patients were women, and 13% had a previous subarachnoid hemorrhage. The average aneurysm size was 7 mm and 92% were in the anterior circulation. The mean follow-up was 15 months (range 0.5-125). There was one procedure-related death (0.3%), and two patients suffered major morbidity (0.6%). Twenty procedures (5.6%) resulted in a persistent neurologic deficit. Risk factors for death and major morbidity were increasing age and posterior circulation, while risk factors for persistent neurologic deficits were increasing aneurysm size and posterior circulation. We conclude that microsurgical clipping is safe, effective, and should be given strong consideration as the primary treatment modality for younger patients with small to medium sized UIAs in the anterior circulation.

Calcifications associated with pediatric intracranial arterial aneurysms: incidence and correlation with pathogenetic subtypes.

BACKGROUND AND PURPOSE: Little is known about calcifications associated with pediatric intracranial arterial aneurysms (IAA). We sought to characterize calcifications associated with pediatric IAA according to aneurysm pathogenetic subtype. MATERIALS AND METHODS: Patients with IAA less than 20 years of age were retrospectively identified. Three fellowship-trained neuroradiologists independently reviewed each patient's CT studies for calcifications of the parent artery or aneurysm. Aneurysmal calcification (ANC) was correlated with characteristics of the patient (age, sex) and aneurysm pathogenetic subtype, size, morphology, rupture status, and location. RESULTS: Thirty-three patients (mean age 10 years) with 43 IAA were analyzed. There were no parent artery calcifications. Nine IAA were calcified. IAA in children with non-hemodynamic risk factors (arteriopathy, trauma, infection, tumor) were more commonly calcified than idiopathic IAA (p = 0.029). More than one third of the pediatric IAAs in this group (arteriopathy, infection trauma, tumor) were calcified. IAA ≥ 10 mm were more likely to be calcified (p = 0.03). IAA that were ruptured at presentation were less likely to be calcified (p = 0.03). ANC was not significantly associated with patient age (≤10 years vs. >10 years), sex, morphology (fusiform vs. saccular) or location (anterior vs. posterior circulation). CONCLUSION: Aneurysmal but not parent artery calcifications are associated with a significant minority of pediatric IAA. Pediatric ANCs are associated with underlying non-hemodynamic vascular risk factors (arteriopathy, infection, trauma, and tumor), size ≥10 mm and non-hemorrhagic presentation.

The acetazolamide challenge: techniques and applications in the evaluation of chronic cerebral ischemia.

The acetazolamide (ACZ) challenge test is a useful clinical tool and a reliable predictor of critically reduced perfusion. In patients with chronic steno-occlusive disease, the ability to maintain normal cerebral blood flow by reducing vascular resistance secondary to autoregulatory vasodilation is compromised. Identification of the presence and degree of autoregulatory vasodilation (reflecting the cerebrovascular reserve) is a significant prognostic factor in patients with chronic cerebrovascular disease. The pharmacologic challenge of a vasodilatory stimulus such as ACZ can also be used to optimize the treatment strategies for these patients. The pathophysiology, methods, and clinical applications of the ACZ challenge test are discussed in this article.

Preliminary findings of the minimally-invasive surgery plus rtPA for intracerebral hemorrhage evacuation (MISTIE) clinical trial.

INTRODUCTION: Compared to ischemic stroke, intracerebral hemorrhage (ICH) is easily and rapidly identified, occurs in younger patients, and produces relatively small initial injury to cerebral tissues--all factors suggesting that interventional amelioration is possible. Investigations from the last decade established that extent of ICH-mediated brain injury relates directly to blood clot volume and duration of blood exposure to brain tissue. Using minimally-invasive surgery plus recombinant tissue plasminogen activator (rtPA), MISTIE investigators explored aggressive avenues to treat ICH. METHODS: We investigated the difference between surgical intervention plus rtPA and standard medical management for ICH. Subjects in both groups were medically managed according to standard ICU protocols. Subjects randomized to surgery underwent stereotactic catheter placement and clot aspiration. Injections of rtPA were then given through hematoma catheter every 8 h, up to 9 doses, or until a clot-reduction endpoint. After each injection the system was flushed with sterile saline and closed for 60 min before opening to spontaneous drainage. RESULTS: Average aspiration of clots for all patients randomized to surgery plus rtPA was 20% of mean initial clot size. After acute treatment phase (aspiration plus rtPA), clot was reduced an average of 46%. Recorded adverse events were within safety limits, including 30-day mortality, 8%; symptomatic re-bleeding, 8%; and bacterial ventriculitis, 0%. Patients randomized to medical management showed 4% clot resolution in a similar time window. Preliminary analysis indicates that clot resolution rates are greatly dependent on catheter placement. Location of ICH also affects efficacy of aggressive treatment of ICH. CONCLUSION: There is tentative indication that minimally-invasive surgery plus rtPA shows greater clot resolution than traditional medical management.

Multidrug-resistant, progressive, invasive diffuse spinal aspergillosis: case report and review of the literature.

The authors describe a 65-year-old man who, after 7 years of complete remission from lung cancer, was found on routine oncologic follow imaging to have lesions on several vertebral bodies. Open biopsy of the affected thoracic vertebrae and surrounding soft tissue were negative for neoplasia. Bacteriology cultures revealed colonies of aspergillus fumigatus in all bone samples. Unlike most reported cases in which vertebral compromise rarely extends to more than two adjacent vertebrae, our patient had extensive compromise of the thoracic spine. This infection progressed despite treatment with antifungal regimens known to be effective, even in immunocompromised patients. Invasive aspergillosis of the spine is a rare and typically occurred in terminal patients. However, the spectrum of hosts and clinical presentations of invasive aspergillosis are increasing, due in part to better medical treatments that prolong the survival of patients with cancer, severe infections, and organ failure. In reviewing the literature, the authors discuss the currently available therapies for such infections of the spine, and highlight the growing incidence these and other formerly rare infections.

Evidence for the improved exposure of the ophthalmic segment of the internal carotid artery after anterior clinoidectomy: morphometric analysis.

BACKGROUND: Although resection of the anterior clinoid process (ACP) is valuable in the surgical treatment of aneurysms of the ophthalmic (C6) segment of the internal carotid artery (ICA), quantitative assessment of this adjunct is incomplete. Our morphometric study assesses the effectiveness of the anterior clinoidectomy for exposure of the C6 segment of the ICA. METHODS: Ten formalin-fixed adult cadaveric heads were dissected bilaterally and pterional craniotomies were performed bilaterally. Measurements before and after resection of the ACP included the length of C6 segment of the ICA on its lateral aspect; C6 segment length on its medial aspect; and medial length of the optic nerve from the optic chiasm to falciform ligament (before ACP resection) then to the annulus of Zinn (after ACP resection). FINDINGS: Height and width of the intradural ACP were 8.67 +/- 2.63 and 6.57 +/- 1.68 mm, respectively. After clinoidectomy, mean length of the lateral C6 segment of the ICA increased 60% and mean exposure of the medial C6 segment of the ICA increased 113% (p < 0.001). Exposure of the optic nerve increased 150% (p < 0.001) after clinoidectomy and sectioning of the falciform ligament. No correlations were found between the lengths of the ACP and entire C6 segment, or the ACP size and amount of the C6 segment covered by the clinoid. CONCLUSIONS: Exposure of the C6 segment of the ICA is markedly increased by increase of the mobility of the optic nerve with clinoidectomy and section of the falciform ligament.

Delayed profound local brain hypothermia markedly reduces interleukin-1beta gene expression and vasogenic edema development in a porcine model of intracerebral hemorrhage.

White matter (lobar) intracerebral hemorrhage (ICH) can cause edema-related deaths and life-long morbidity. In our porcine model, ICH induces oxidative stress, acute interstitial and delayed vasogenic edema, and up-regulates interleukin-1beta (IL-1beta), a proinflammatory cytokine-linked to blood-brain barrier (BBB) opening. In brain injury models, hypothermia reduces inflammatory cytokine production and protects the BBB. Clinically, however, hypothermia for stroke treatment using surface and systemic approaches can be challenging. We tested the hypothesis that an alternative approach, i.e., local brain cooling using the ChillerPad System, would reduce IL-1beta gene expression and vasogenic edema development even if initiated several hours after ICH. We infused autologous whole blood (3.0 mL) into the frontal hemispheric white matter of 20 kg pentobarbital-anesthetized pigs. At 3 hours post-ICH, we performed a craniotomy for epidural placement of the ChillerPad. Chilled saline was then circulated through the pad for 12 hours to induce profound local hypothermia (14 degrees C brain surface temperature). We froze brains in situ at 16 hours after ICH induction, sampled perihematomal white matter, extracted RNA, and performed real-time RT-PCR. Local brain cooling markedly reduced both IL-1beta RNA levels and vasogenic edema. These robust results support the potential for local brain cooling to protect the BBB and reduce injury after ICH.

Multiple, peripheral aneurysms of the anterior inferior cerebellar artery.

In this case report, a 49-year-old woman developed subarachnoid hemorrhage in the right cerebellopontine angle cistern and blood into the fourth ventricle from a ruptured peripheral aneurysm of the anterior inferior cerebellar artery (AICA) located at the meatal loop. Concomitantly, a contralateral peripheral aneurysm was found in the posterior inferior cerebellar artery (PICA). A second peripheral aneurysm, not identified by previous angiography, was found in the caudomedial branch of AICA. We describe this diagnostic dilemma, management, and review the clinical presentation and location of 84 other peripheral AICA aneurysms reported in the literature.

Evidence-based surgical treatment of carotid stenosis. Literature review.

Carotid stenosis is an important cause of transient ischemic attacks and stroke. The cause of carotid stenosis is most often atherosclerosis, which accounts for 10% to 20% of brain infarction cases. Despite the introduction of tissue-plasminogen activator and other promising experimental therapies for select patients with acute ischemic stroke prevention remains the best approach to reduce its impact. Stroke-prone patients can be identified and targeted for specific interventions. At this juncture, treatment of carotid stenosis is a well-established therapeutic target and a pillar of stroke prevention. Two main strategies exist for the treatment of carotid stenosis. The 1st is stabilization or halting the progression of the carotid plaque formation with medications and modifications of risk factors (e.g., hypertension, diabetes, smoking, obesity, high cholesterol). The 2nd approach is the elimination or reduction of carotid stenosis by carotid endarterectomy or angioplasty and stenting. Carotid endarterectomy is the mainstay of therapy for symptomatic, severe carotid stenosis. Although its role for asymptomatic patients appears more limited, it is distinct for severe stenosis. Carotid angioplasty and stenting are techniques in maturation with the attractiveness of being less invasive that face the challenge of at least replicating the results of surgery. In this article, we will discuss the surgical management of symptomatic and asymptomatic carotid stenosis based on the evidence provided by the literature.

Aneurysms of the ophthalmic (C6) segment of the internal carotid artery: treatment options and strategies based on a clinical series.

AIM: Treatment of ophthalmic segment aneurysms is technically demanding and still associated with a relatively high morbidity and mortality. The refinements of surgical techniques combined with the development of indirect methods of treatment have greatly improved the outcome in treating these lesions. We present our clinical experience and discuss treatment strategies. METHODS: Seventy-eight consecutive patients with 88 ophthalmic segment aneurysms were admitted to our service from January 1997 to June 2003. Forty-three patients presented with unruptured aneurysms and 35 presented with subarachnoid hemorrhage (SAH). Management strategies included surgical clipping alone in 53 patients, clipping and hemicraniectomy in 2, coiling in 17, external carotid artery-middle cerebral artery (ECA/MCA) by-pass in 2, and coil occlusion of the internal carotid artery in 2. Two patients underwent no treatment. RESULTS: In the group of 41 treated patients with unruptured aneurysms, 40 (97.6%) had good outcomes (GOS 1-2) and 1 patient had poor (GOS 3) outcome at discharge. Procedure-related morbidity was 15.7% (8/51 procedures), and permanent morbidity was 9.75% (4/41 patients). In the 35 patients who presented with SAH, mortality was 14.3% (5 patients); at discharge, 21 patients (60%) had good (GOS 1-2) and 9 (25.7%) poor (GOS 3) outcomes. The overall outcome was good (GOS 1-2) in 63 patients (80.8%) and poor (GOS 3-4) in 10 patients (12.8%). Overall mortality was 6.4% (5 patients all with SAH). CONCLUSIONS: Direct obliteration of the aneurysm utilizing advanced surgical techniques is our preferred treatment approach, whenever possible. In case of unclippable large or giant aneurysms, the surgical or endovascular occlusion of the proximal internal carotid artery with or without an extracranial-intracranial by-pass is an option. A highly skilled team including a cerebrovascular and an endovascular surgeon is essential to achieve good outcomes in treating these lesions.

Visceral leishmaniasis and HIV co-infection: a rare case of pulmonary and oral localization.

Visceral leishmaniasis (VL) has increased as a complicating infection in subjects with human immunodeficiency virus (HIV) in countries bordering the Mediterranean sea. The clinical course as well as organ involvement of VL are often atypical in HIV positive subjects. In this study a case of VL with pulmonary and oral mucose localisation in a patient with acquired immune deficiency syndrome (AIDS), is reported. These findings, together with the presence of the parasite in the peripheral blood smear, confirm that in HIV positive patients the impaired immune system allows the spreading and the atypical localisation of the Leishmania amastigotes more easily than in immuno-competent individuals. In endemic areas and in HIV positive subjects a systemic and careful parasitological follow-up is necessary to ensure that any clinical form of leishmaniasis is not overlooked.

Early carotid endarterectomy for critical carotid artery stenosis after thrombolysis therapy in acute ischemic stroke in the middle cerebral artery.

BACKGROUND AND PURPOSE: Tissue plasminogen activator (tPA) has been shown to be effective for acute ischemic stroke. However, if a high-grade cervical carotid stenosis remains despite tPA therapy, patients are at risk for recurrent stroke. Carotid endarterectomy (CEA) has been shown to be effective in symptomatic patients with high-grade cervical carotid stenosis in reducing the risk of stroke, but it is unknown whether CEA can be performed safely after tPA thrombolysis. We describe our experience with 5 patients who underwent early (<48 hours) CEA for residual high-grade cervical carotid stenosis after thrombolytic therapy for acute ischemic stroke in the middle cerebral artery territory. METHODS: All patients had a critical (>99%) carotid artery stenosis on the symptomatic side after tPA therapy. All patients received intravenous tPA; 3 patients also received intra-aortic tPA. Three patients received intravenous heparin infusion immediately after administration of tPA. All patients showed marked improvement in their National Institutes for Health Stroke Scale scores after treatment with tPA. CEA was then performed within 45 hours (6 hours in 1 patient, 23 hours in 2, 26 hours in 1, and 45 hours in 1). RESULTS: All 5 patients underwent successful CEA. There were no complications related to surgery. At discharge, 2 patients had a normal examination, and the remaining patients had mild deficits. In a long-term follow-up of 5 to 22 months, no patient had a recurrent cerebrovascular event. CONCLUSIONS: Early CEA can be performed safely and successfully in patients after tPA treatment for acute ischemic stroke in appropriately selected patients.

Expanding the boundaries of the transsphenoidal approach: a microanatomic study.

The anatomic features of a transsphenoidal approach are reviewed, focusing on the microsurgical anatomy of parasellar structures. Pertinent microsurgical anatomy is described in sufficient detail for the neurosurgeon to successfully extend a standard transsphenoidal approach for treatment of lesions involving the region of the tuberculum sellae, planum sphenoidale, supradiaphragmatic intradural space, and medial cavernous sinus. The parasellar region of 50 formalin-fixed cadaveric heads was examined by using magnification 3x to 40x. The arterial and venous systems of five cadaveric specimens were injected under pressure with colored silicone rubber. The sellar region of three specimens was examined histologically. Important anatomic landmarks identified in the roof of the sphenoid sinus include a carotid and trigeminal prominence, as well as a tubercular, clival, and opticocarotid recess. The diaphragma sella is actually comprised of two layers of dura, with a venous system (circular sinus) interposed between the layers. The dura mater of the pituitary gland separates the gland from the medial compartment of the cavernous sinus. The microanatomic detail necessary to extend the transsphenoidal approach to the supradiaphragmatic intradural space and medial compartment of the cavernous sinus is described. These data are presented to facilitate the clinical application of these extended approaches.

Treatment strategy for patients with unruptured intracranial aneurysms.

The increased sensitivity of neuroimaging techniques has enabled the more frequent diagnosis of unruptured aneurysms. Because the most devastating complication of an unruptured aneurysm is subarachnoid hemorrhage, it has been considered desirable to treat these aneurysms before they rupture. However, the optimal treatment strategy for patients with unruptured aneurysms remains controversial. The management decision requires knowledge of the natural history and an accurate assessment of the risks related to various treatment options. On December 10, 1998 the New England Journal of Medicine published an article by the International Study of Unruptured Intracranial Aneurysms Investigators. The study retrospectively assessed the natural history of unruptured aneurysms in 1449 patients; in addition, treatment-related mortality and morbidity were examined in a prospective cohort of 1172 patients. The major finding was that the rate of rupture for aneurysms smaller than 10 mm in diameter in patients with no history of subarachnoid hemorrhage was 0.05% per year, and that the mortality and morbidity associated with surgery greatly exceeded the risk of rupture in such patients. This report has generated tremendous controversy in the treatment of unruptured aneurysms and has influenced our decision making. The results of this study are critically analyzed and potential flaws presented. To develop recommendations for treatment, the literature was reviewed. The conclusion of this search is that there is insufficient evidence to recommend a standard of management. Therapeutic guidelines are provided, particularly for patients with small incidental aneurysms and no history of subarachnoid hemorrhage.

Intraoperative magnetic resonance imaging to determine the extent of resection of pituitary macroadenomas during transsphenoidal microsurgery.

OBJECTIVE: Well-established surgical goals for pituitary macroadenomas include gross total resection for noninvasive tumors and debulking with optic chiasm decompression for invasive tumors. In this report, we examine the safety, reliability, and outcome of intraoperative magnetic resonance imaging (iMRI) used to assess the extent of resection, and thus the achievement of preoperative surgical goals, during transsphenoidal microneurosurgery. METHODS: Our magnetic resonance operating room contains a Hitachi AIRIS II 0.3-T, vertical-field open magnet (Hitachi Medical Systems America, Inc., Twinsburg, OH). A motorized scanner tabletop moves the patient between the imaging and operative positions. For transsphenoidal surgery, the patient is positioned directly on the scanner tabletop so that the surgical field is located between 1.2 and 1.6 m from the magnet isocenter. At this location, the magnetic field strength is low (<20 G), thus permitting the use of many conventional surgical instruments. Thirty consecutive patients with pituitary macroadenomas underwent tumor resection in our magnetic resonance operating room by use of a standard transsphenoidal approach. After initial resection, the patient was advanced into the scanner for imaging. If residual tumor was demonstrated and deemed surgically accessible, the patient underwent immediate re-exploration. RESULTS: iMRI was performed successfully in all 30 patients. In one patient, iMRI was used to clarify the significance of hemorrhage from the sellar region and resulted in immediate conversion of the procedure to a craniotomy. In the remaining 29 patients, initial iMRI demonstrated that the endpoint for extent of resection had been achieved in only 10 patients (34%) after an initial resection attempt, whereas 19 patients (66%) still had unacceptable residual tumor. All 19 of these latter patients underwent re-exploration. Ultimately, re-exploration resulted in the achievement of the planned endpoint for extent of resection in all of the 29 completed transsphenoidal explorations. Operative time was extended in all cases by at least 20 minutes. CONCLUSION: iMRI can be used to safely, reliably, and objectively assess the extent of resection of pituitary macroadenomas during the transsphenoidal approach. The surgeon is frequently surprised by the extent of residual tumor after an initial resection attempt and finds the intraoperative images useful for guiding further resection.

Hypocapnic constriction in rabbit basilar artery in vitro: triggering by serotonin and dependence on endothelin-1 and alkalosis.

This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by serotonin, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic alkaline solution (25 mM NaHCO(3); pH 7.76; pCO(2) 14.2) or isocapnic alkaline solution (50 mM NaHCO(3); pH 7.73; pCO(2) 35.0) rarely altered basal tension. Serotonin (3 microM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension. Washout of the serotonin did not decrease tension in 54% of the tissues, as plateau tension was maintained for 2-2.5 h. The plateau tension of washed tissues was relaxed by 1-3 microM PD145065 (Ac-D-Bhg-L-Leu-Asp-L-Ile-L-Ile-L-Trp), BQ610 (homopiperidinyl-CO-Leu-D-Trp(CHO)-D-Trp), and BQ788 (N-cis-2, 6-dimethyl-piperidinocarbonyl-L-gamma-MeLeu-D-Trp (COOCH(3))-Nle), endothelin ET(A)/ET(B), endothelin ET(A), and endothelin ET(B) receptor antagonists, respectively. In contrast, serotonin-induced tension in normal solution (25 mM NaHCO(3); pH 7.42; pCO(2) 36.9) was maintained for only 40 min (mean). These results demonstrate that (1) constriction due to hypocapnia in vitro can be triggered by serotonin and is endothelin-1 mediated and (2) alkaline pH in the absence of decreased pCO(2) is sufficient to elicit the constriction triggered by serotonin.

Hypocapnic constriction in rabbit basilar artery in vitro: triggering by N(G)-monomethyl-L-arginine monoacetate and dependence on endothelin-1 and alkalosis.

This study tested whether hypocapnic constriction of the rabbit basilar artery in vitro can be triggered by a nitric oxide (NO) synthase inhibitor, and whether the resulting constriction is (1) due to the alkaline pH associated with hypocapnia, and (2) endothelin-1 mediated. Hypocapnic (25 mM NaHCO(3); pH 7.76; pCO(2) 14.2) or isocapnic alkaline solution (50 mM NaHCO(3); pH 7.73; pCO(2) 35.0) rarely altered basal tension. N(G)-monomethyl-L-arginine monoacetate (L-NMMA; 0.1 mM) challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal tension that was maintained for 2-2.5 h even following L-NMMA washout. L-NMMA challenge in normal solution (25 mM NaHCO(3); pH 7. 42; pCO(2) 36.9) also induced near maximal tension, although the tension was maintained for only 25 min (mean). Ac-D-Bhg-L-Leu-Asp-L-Ile-L-Ile-L-Trp (PD145065), homopiperidinyl-CO-Leu-D-Trp(CHO)-D-Trp (BQ610), and N-cis-2, 6-dimethyl-piperidinocarbonyl L-gamma-MeLeu-D-Trp (COOCH(3))-Nle (BQ788; 1-3 microM), endothelin ET(A)/ET(B), endothelin ET(A), and endothelin ET(B) receptor antagonists, respectively, completely relaxed the tension that resulted from L-NMMA challenge in hypocapnic or isocapnic alkaline solution. These results demonstrate that constriction due to hypocapnia in vitro can be triggered by an NO synthase inhibitor and is endothelin-1 mediated. Additionally, alkaline pH in the absence of decreased pCO(2) is sufficient to elicit the constriction.