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Background The delivery of complex neuroendovascular devices requires a robust proximal access platform. This demand has previously been met with a 6Fr long-sheath (8Fr guide) that is placed in the proximal ICA (high cervical) or vertebral artery (V1/2) segments. We share our experience with the first 088 8Fr guide catheter designed specifically for direct intracranial access. Methods We retrospectively reviewed a prospectively-maintained IRB-approved institutional database of the senior authors to identify all cases where the TracStar LDP (Imperative Care, Campbell, CA) was utilized. Case details were recorded including patient demographics, case type, and distal location achieved with navigation of the guide catheter. Technical success was defined as safe placement of the guide catheter to at least the petrous (anterior circulation) or vertebral artery (V3) segments (posterior circulation) or the transverse sinus for venous stenting procedures. Results Over the 14-month study period, 127 femoral access cases were identified where the TracStar LDP guide catheter was utilized for aneurysm treatment (80% of cases, 102/127 ), intracranial angioplasty/stenting (13% of cases, 17/127), venous sinus stenting (3% of cases, 4/127), and other pathologies (3% of cases, 4/127). All cases utilized a direct select catheter technique for placement (no exchange). Posterior circulation placement occurred in 14% of cases (18/127). Technical success was achieved in 97% of cases (123/127). Of the 4 cases with technical failure, 75% (3/4) were in the posterior circulation and were attributed to tortuous proximal subclavian access or a small caliber vertebral origin. No symptomatic or flow-restricting vessel dissections occurred in any of the cases. Conclusion The TracStar LDP is a safe and effective means for establishing direct 088 intracranial access. This can be achieved in a wide range of cases with extremely high rates of technical success. Disclosures J. Campos: None. Z. Hsu: None. D. Zarrin: None. K. Golshani: None. N. Beaty: 2; C; Medtronic Neurovascular, Stryker Neurovascular. M. Bender: None. G. Colby: 2; C; Medtronic Neurovascular, MicroVention-Terumo, Stryker Neurovascular. L. Lin: 2; C; Medtronic Neurovascular, MicroVention-Terumo, Stryker Neurovascular. A. Coon: 2; C; Avail MedSystems, Imperative Care, InNeuroCo, Medtronic Neurovascular, MicroVention-Terumo, Q’apel, Rapid Medical, Stryker Neurovascular.

OBJECTIVEThe second-generation Pipeline embolization device (PED), Flex, has several design upgrades, including improved opening and the ability to be resheathed, in comparison with the original device (PED classic). The authors hypothesized that Flex is associated with a lower rate of major complications.METHODSA prospective, IRB-approved, single-institution database was analyzed for all patients with anterior circulation aneurysms treated by flow diversion. The PED classic was used from August 2011 to January 2015, and the Pipeline Flex has been used since February 2015.RESULTSA total of 568 PED procedures (252 classic and 316 Flex) were performed for anterior circulation aneurysms. The average aneurysm size was 6.8 mm. Patients undergoing treatment with the Flex device had smaller aneurysms (p = 0.006) and were more likely to have undergone previous treatments (p = 0.001). Most aneurysms originated along the internal carotid artery (89% classic and 75% Flex) but there were more anterior cerebral artery (18%) and middle cerebral artery (7%) deployments with Flex (p = 0.001). Procedural success was achieved in 96% of classic and 98% of Flex cases (p = 0.078). Major morbidity or death occurred in 3.5% of cases overall: 5.6% of classic cases, and 1.9% of Flex cases (p = 0.019). On multivariate logistic regression, predictors of major complications were in situ thrombosis (OR 4.3, p = 0.006), classic as opposed to Flex device (OR 3.7, p = 0.008), and device deployment in the anterior cerebral artery or middle cerebral artery as opposed to the internal carotid artery (OR 3.5, p = 0.034).CONCLUSIONSFlow diversion of anterior circulation cerebral aneurysms is associated with an overall low rate of major complications. The complication rate is significantly lower since the introduction of the second-generation PED (Flex).

BackgroundAn estimated 2%–3% of the population harbour an intracranial aneurysm. Concomitant atherosclerotic cervical carotid disease is not uncommon. The management of these two entities remains a challenge within the field.Case presentationWe report a single case of concomitant carotid stenosis and two ipsilateral unruptured intracranial aneurysms treated with a single-staged cervical carotid stenting and cerebral aneurysm embolisation with the Pipeline embolisation device.DiscussionNo consensus currently exists to guide endovascular treatment of intracranial aneurysms associated with asymptomatic ipsilateral stenosis. Here, we present a case of asymptomatic moderate carotid stenosis with two ipsilateral intracranial aneurysms and suggest carotid artery stenting takes procedural priority over aneurysm embolisation in single-stage treatment. The rationale for the sequence of neurointerventions is based on the tracking a robust distal access system beyond a stenotic proximal carotid lesion and stabilisation of the ulcerated plaque to avoid thromboembolic complications associated with plaque irritation during aneurysm embolisation. Additional cases and longer follow-up will be needed to further assess the efficacy of this technique.

Intracranial aneurysms in the pediatric population are rare entities. The authors recently treated a 9-month-old infant with a 19-mm recurrent, previously ruptured, and coil-embolized left middle cerebral artery (MCA) pseudoaneurysm, which was treated definitively with single-stage Pipeline-assisted coil embolization. The patient was 5 months old when she underwent resection of a left temporal Grade 1 desmoplastic infantile ganglioglioma at an outside institution, which was complicated by left MCA injury with a resultant 9-mm left M1 pseudoaneurysm. Within a month, the patient had two aneurysmal rupture events and underwent emergency craniectomy for decompression and evacuation of subdural hematoma. The pseudoaneurysm initially underwent coil embolization; however, follow-up MR angiography (MRA) revealed aneurysm recanalization with saccular enlargement to 19 mm. The patient underwent successful flow diversion–assisted coil embolization at 9 months of age. At 7 months after the procedure, follow-up MRA showed complete aneurysm occlusion without evidence of in-stent thrombosis or stenosis. Experience with flow diverters in the pediatric population is still in its early phases, with the youngest reported patient being 22 months old. In this paper the authors report the first case of such a technique in an infant, whom they believe to be the youngest patient to undergo cerebral flow diversion treatment.

BackgroundAdjunctive coiling may improve occlusion outcomes when combined in a single stage with cerebral aneurysm flow diversion. This technique has not been well described.ObjectiveTo present a series of aneurysm patients treated by single-stage flow diversion with adjunctive coiling, describing technical considerations and outcomes.MethodsThis was a retrospective cohort study using an IRB-approved database of procedures performed at a single institution. Treatment selection was based on large aneurysm size, morphological irregularity, branch vessel location, and wide neck.ResultsA total of 72 Pipeline with adjunctive coiling (PAC) procedures were performed on 69 patients. Average aneurysm size was 11.0 mm and 86% were wide-necked. Three progressively complex techniques were performed approximately equally: 27 sequential (38%), 23 jailed single-intermediate (32%), and 22 bifemoral jailed microcatheter (31%) cases. Aneurysm dome (P=0.0223) and neck size (P=0.001) increased with procedural complexity and there was a trend toward increased procedure length, radiation exposure, and stent thrombosis. A ‘light’ coil pack was used with an average packing density of 14% that did not vary by technique. Of the three major complications (4.2%), none were observed with the sequential approach (0%), one with the jailed single-intermediate (4.3%), and two with bifemoral cases (9.1%) (P=0.116). Complete occlusion was achieved in 85% of PAC cases at 6 months and 96% at 12-month follow-up angiography.ConclusionsThere are multiple approaches to flow diversion with adjunctive coiling, each with technical challenges, suitable to different types of aneurysms. Flow diversion with coiling can expedite and improve occlusion outcomes without a significant increase in morbidity.

Background: An estimated 0.1% of the population harbors brain arteriovenous malformations (AVMs). Diagnosis and workup of AVMs include thorough evaluation for characterization of AVM angioarchitecture and careful assessment for concomitant aneurysms. The presence of coexisting aneurysms is associated with an increased risk of intracranial hemorrhage, with a published risk of 7% per year compared to patients with AVMs alone with a risk of 3%. Comprehensive AVM management requires recognition of concomitant aneurysms and prioritizes treatment strategies to mitigate the aggregate risk of intracranial hemorrhage associated with AVM rupture in patients with coexisting aneurysms. Endovascular treatment of these flow-related aneurysms can offer a cure, while avoiding open surgery. Successful flow-diverting embolization techniques, efficacy, and outcomes have been previously described for a variety of aneurysm types and locations. However, use of a flow diverter has not been previously described for the treatment of high-flow aneurysms on AVM-feeding vessels. Case Presentation: We report 2 cases of large AVMs within eloquent cortex associated with flow-related aneurysms in patients presenting initially with suspected intracerebral hemorrhage secondary to AVM rupture. Discussion: No consensus currently exists to guide treatment of intracranial aneurysms associated with AVMs. Surgical management addressed AVM embolization initially, as the vasculopathology with the highest rupture risk. Subsequently, Pipeline embolization of the associated aneurysms with adequate antiplatelet treatment was performed before scheduled radiosurgery to decrease the risk of AVM rupture or rebleed. This represents a novel and promising use of the Pipeline Embolization Device. Additional cases and longer follow-up will be needed to further assess the efficacy of this technique.

BackgroundIntracranial access techniques in modern neurointerventions have shifted towards more robust access platforms. The long guide sheath is one of the building blocks of triaxial systems used in intracranial embolizations. Here we present our experience with the AXS Infinity LS long sheath in the triaxial platform for the implantation of the Pipeline embolization device (PED).MethodsWe retrospectively identified patients who underwent PED Flex treatment with the AXS Infinity LS at a single institution. Procedural data collected included parent artery tortuosity, patient demographics, vasodilator use, aneurysm characteristics, equipment utilized, and catheter-related complications.ResultsA total of 95 cases were completed using the AXS Infinity LS for the triaxial platform foundation in PED Flex treatment of cerebral aneurysms. Mean patient age was 56.2±12.2 years (range 21–86). Average aneurysm size was 6.9±6.2 mm (range 1–38). There were 89 anterior circulation cases (94%) and 6 posterior circulation cases (6%). Significant cervical ICA tortuosity was present in 11/89 (12%) and moderate to severe cavernous ICA tortuosity was present in 29/89 (33%). Mean fluoroscopy time was 40.0±19.8 min. In 14/95 cases (15%), vasospasm prophylaxis or treatment with intra-arterial verapamil infusion was performed. Catheter access-related complications included asymptomatic iatrogenic dissection in one case (1%) from the distal intracranial catheter and groin hematoma in one case (1%). No parent vessel wall abnormalities were visualized in the region of the Infinity long sheath on final control angiography in all 95 cases.ConclusionThe AXS Infinity LS is the newest long guide sheath available for modern neurointerventional procedures. We have shown its utility in augmenting the triaxial access platform in PED Flex cases by providing enhanced distal tip trackability with added support in the aortic arch and proximal great vessels.

Background: Coaxial catheter support systems provide a safe and stable foundation in endovascular treatment of intracranial aneurysms. Increasingly, robust distal intracranial support is sought during complex neurointerventions. The AXS Catalyst 5 distal access catheter (Cat5) is a new intracranial catheter designed for improved trackability and stability. We report the first experience using Cat5 for aneurysm treatment by flow diversion. Methods: A single-center aneurysm database was reviewed for cases of aneurysm treatment with the Pipeline embolization device (PED) that utilized Cat5. Data were collected for patient demographics, aneurysm characteristics, procedural details, catheter positions, vessel tortuosity, and catheter related complications. Results: One hundred and ten cases of aneurysm flow diversion were successfully performed using Cat5. Patient age ranged from 21 to 86 years (mean 57 ± 12.5 years) with 84% women. Aneurysm size ranged from 2 to 28 mm (mean 5.7 ± 5.0 mm), with 97% in the anterior circulation. Twenty-four aneurysms (22%) were located beyond the ICA termination. Significant cervical carotid tortuosity was present in 26% of cases, and moderate to severe cavernous tortuosity (cavernous grade ≥2) in 45% of cases. Cat5 was tracked to the intended distal position in all cases with 100% technical success of PED implantation. No iatrogenic catheter-related vessel injury occurred, and major neurological morbidity occurred in 1 patient (1%). Summary: The Cat5 is a novel, multi-durometer cranial distal access catheter designed for use in tri-axial systems. We have demonstrated the utility of Cat5 in 110 successful cases of flow diversion with a wide range of complexity. This catheter is a new tool in the neurointerventionalist's armamentarium to achieve robust and atraumatic distal access.

BACKGROUND AND PURPOSE: Neurointerventional surgery may expose patients and physician operators to substantial amounts of ionizing radiation. Although strategies for reducing patient exposure have been explored in the medical literature, there has been relatively little published in regards to decreasing operator exposure. The purpose of this study was to evaluate the efficacy of shielding systems in reducing physician exposure in a modern neurointerventional practice. MATERIALS AND METHODS: Informed consent was obtained from operators for this Health Insurance Portability and Accountability Act–compliant, institutional review board–approved study. Operator radiation exposure was prospectively measured during 60 consecutive neurointerventional procedures from October to November 2013 using a 3-part lead shielding system. Exposure was then evaluated without lead shielding in a second 60-procedure block from April to May 2014. A radiation protection drape was randomly selected for use in half of the cases in each block. Two-way analysis of covariance was performed to test the effect of shielding systems on operator exposure while controlling for other covariates, including procedure dose-area product. RESULTS: Mean operator procedure dose was 20.6 μSv for the entire cohort and 17.7 μSv when using some type of shielding. Operator exposure significantly correlated with procedure dose-area product, but not with other covariates. After we adjusted for procedure dose-area product, the use of lead shielding or a radiation protection drape significantly reduced operator exposure by 45% (F = 12.54, P < .0001) and 29% (F = 7.02, P = .009), respectively. The difference in protection afforded by these systems was not statistically significant (P = .46), and their adjunctive use did not provide additional protection. CONCLUSIONS: Extensive lead shielding should be used as much as possible in neurointerventional surgery to reduce operator radiation exposure to acceptable levels. A radiation protection drape is a reasonable alternative when standard lead shielding is unavailable or impractical to use without neglecting strategies to minimize the dose.

Background: Flow diversion with the Pipeline embolization device (PED) is an effective neuro­endovascular method and increasingly accepted for the treatment of cerebral aneurysms. Acute in situ thrombosis is a known complication of PED procedures. There is limited experience in the flow diversion literature on the use of abciximab (ReoPro) for the management of acute thrombus formation in PED cases. Methods: Data were collected retrospectively on patients who received intra-arterial (IA) ReoPro with or without subsequent intravenous (IV) infusion during PED flow diversion treatment of intracranial aneurysms. Results: A total of 30 cases in patients with a mean age of 56.7 years (range 36–84) and a mean aneurysm size of 8.6 mm (range 2–25) were identified to have intraprocedural thromboembolic complications during PED treatment. IA ReoPro was administered in all cases, with 20 cases receiving increments of 5-mg boluses and 10 cases receiving a 0.125 mg/kg IA bolus (half cardiac dosing). Complete or partial recanalization was achieved in 100% of the cases. IV ReoPro infusion at 0.125 μg/kg/min for 12 h was administered postprocedurally in 22 cases with a residual thrombus. Postprocedurally, 18 patients were transitioned from clopidogrel (Plavix) to prasugrel (Effient). The majority of the cases (23/30; 77%) were discharged home. Periprocedural intracranial hemorrhage was noted in 2 cases (7%) and radiographic infarct was noted in 4 cases (13%), with an overall mortality of 0% at the time of initial discharge. Clinical follow-up was available for 28/30 patients. The average duration of follow-up was 11.7 months, at which time 23/28 (82%) of the patients had a modified Rankin Scale score of 0. Conclusions: IA ReoPro administration is an effective and safe rescue strategy for the management of acute intraprocedural thromboembolic complications during PED treatment. Using a dosing strategy of either 5-mg increments or a 0.125 mg/kg IA bolus (half cardiac dosing) can provide high rates of recanalization with low rates of hemorrhagic complications and long-term morbidity.

This study reports our initial clinical experience treating very small intracranial aneurysms using only Target® Nano™ coils. Retrospective angiographic and clinical analysis was performed on a non-randomized single arm registry of all intracranial aneurysms treated with only Target® Nano™ coils (1 mm and 1.5 mm diameter only) during a 12 month period at two academic hospitals. Fourteen patients with 14 intracranial aneurysms were treated. The maximum diameter of saccular aneurysms treated ranged from 1.5 to 3.5 mm; minimum aneurysm diameter was 1.1 to 2 mm. The immediate complete aneurysm occlusion rate was 86% (12/14), and a small residual within the aneurysm was seen in 14% (2/14) of cases. Packing density from coils ranged between 24% and 83% (mean 51%). The immediate complication rate was 0% (0/14). The angiographic/MR angiography follow-up period was 22 to 70 weeks (mean 37 weeks) with an overall complete occlusion rate of 9/11 (81%), recurrence in 18% (2/11), and lack of follow-up in three cases, two due to death during hospitalization and one procedure not yet due for imaging follow-up. Both patients who died presented with brain aneurysm ruptures prior to treatment. Both recurrences were retreated with repeat coiling procedures. Our initial results using only Target® Nano™ coils for the endovascular treatment of very small intracranial aneurysms have demonstrated initial good safety and efficacy profiles.

Background Flow diversion is an effective and increasingly accepted method for endovascular treatment of cerebral aneurysms. Acute in-situ thrombosis during Pipeline embolization device (PED) deployment has potential for devastating morbidity. There is limited experience in the flow diversion literature on the usage of Abciximab (ReoPro) to address this issue. Methods Data were collected retrospectively on patients who encountered in-situ thrombosis during Pipeline flow diversion of anterior and/or posterior circulation intracranial aneurysms. Data collected include aneurysms characteristics, Abciximab dosing and administration regimen, post-procedural antiplatelet therapy, and clinical/radiographical follow up. Results Twenty-five patients (mean age 56 years; range 36–75 years) with 26 unruptured aneurysms (mean size 8.7 mm; range 2-25 mm) were identified to have in-situ thrombosis during PED deployment. Intraarterial (IA) ReoPro was administered in all cases, with 15 patients receiving increments of 5mg boluses and 10 patients receiving 0.125mg/kg bolus. Immediate or partial resolution of in-situ thrombosis was observed in 100% of the patients. Intravenous (IV) ReoPro infusion was administered post-procedurally in 18 patients. 19 patients were transitioned to Prasugrel (Effient) from Clopidogrel (Plavix) post procedurally. Average length of stay was 4.5 days (range 1-30 days), with 21/26 (81%) patients discharged to home. Intracranial hemorrhage was noted in 2 patients (8%). At six-months clinical follow up, 20/25 (80%) patients had mRS of 0. Angiographic follow up was available for 18 patients at a mean duration of 9.6 months, at which time aneurysm occlusion rate was 94% (16/17 patients). Conclusions IA and IV ReoPro administration is a effective and safe strategy for the management of acute in-situ thrombosis during PED, with high rates of immediate thrombosis resolution and relatively low rates of hemorrhagic complications and long term morbidity. Disclosures: B. Jiang: None. J. Campos: None. N. Beaty: None. E. Westbroek: None. M. Bender: None. R. Tamargo: None. J. Huang: 2; C; Longeviti. G. Colby: 1; C; Stryker. 2; C; Microvention, Medtronic. A. Coon: 2; C; Medtronic, Microvention, Sequent, Stryker. L. Lin: None.

BACKGROUND Prospective studies of unruptured aneurysms have shown very low rates of rupture for small aneurysms (

Deconstructive approaches may be necessary to treat a variety of neurovascular pathologies. Recently, a new device has become available for endovascular arterial occlusion that may have unique applications in neurovascular disease. The Micro Vascular Plug (MVP, Reverse Medical, Irvine, California, USA) has been designed for vessel occlusion through targeted embolization.To report the results from our initial experience with eight consecutive patients in whom the MVP was used to achieve endovascular occlusion of an artery in the head and neck.Eight consecutive patients treated over a nine-month period were included. The patients' radiographic and electronic medical records were retrospectively reviewed. Specifically demographic information, clinical indication, site of arterial occlusion, size of MVP, time to vessel occlusion, clinical complications, use of other secondary embolic agents, and clinical outcome were recorded. Follow-up information when available is presented.The MVP was used in eight patients for the treatment of neurovascular disease. Indications for treatment included post-traumatic head/neck bleeding (n=3), carotid-cavernous fistula (1), vertebral-vertebral fistula (1), giant fusiform vertebral aneurysm (1), stump-emboli after carotid dissection (1), and iatrogenic vertebral artery penetrating injury (1). One device was used in five patients, two in two patients, and one patient with extensive vertebral-vertebral venous fistula required three plugs to effectively trap the fistula from proximal and distal aspects. Vessel occlusion was obtained in2 min in each case and there were no procedural complications. Four patients were followed up and no incidence of plug migration or vessel recanalization was seen.To the best of our knowledge, this is the first series reporting the use of MVP in neurovascular disease. Use of this device may be associated with shorter procedural times and cost savings in comparison with the use of microcoils for vessel occlusion. Our experience shows that MVP can have unique applications in neurovascular pathologies and it complements other occlusive devices.

Gel-exclusion chromatography coupled with HPLC instrumentation can be used to determine the molecular weight of highly purified sodium hyaluronate in solution. The method is very reproducible, precise, and rapid, and allows molecular weight determinations up to 2 million to be done in the presence of considerable impurities. This technique offers considerable advantages over traditional light-scattering, sedimentation equilibrium, and viscometry methods for molecular weight determinations, in that HPLC-gel exclusion is rapid and not subject to errors arising from impurities. Simultaneous with molecular weight measurements, sodium hyaluronate concentrations can be determined with a lower range of 0.1 to 0.3 mg/ml dependent upon the sensitivity of the refractive index-detecting system. Unlike the carbazole reaction, this technique is unaffected by low-molecular-weight impurities such as monosaccharides or substances with relative molecular weights less than 18,000.

This review of the mammalian extracellular matrix polysaccharides covered the glycosaminoglycans (GAGs) and their association into proteoglycans. As they necessarily pertain to the chromatographic and electrophoretic separations of these molecules, the structural features of the five principal GAGs were briefly reviewed. Much of the current structural work as well as the separation technology has been concerned with the sulfation state and copolymeric sequences of the individual classes of GAGs. The separation methods discussed included electrophoresis by agarose, acrylamide and cellulose acetate, high-performance liquid chromatography (HPLC), ion-exchange, gel permeation and biospecific affinity methods. Since detection systems are an integral part of chemical separation technology, current thoughts about the best methods to assay GAGs or detect column fractions were discussed. These included polysaccharide-specific detection systems such as Alcian blue dye, 1,9-dimethylmethylene blue, bovine serum albumin—Coomassie blue, as well as non-specific carbohydrate detection systems such as the carbazole or indole hydrochloride methods. Instrumentation used in the detection of chromatography fractions for these molecules was discussed, since the usual ultraviolet detector, standard with HPLC equipment, is often unsatisfactory. The most sensitive specific detection method for GAGs is the use of monoclonal antibodies, which are only now becoming commercially available. The use of these antibodies, combined with HPLC separation, appears to be the best available biochemical technology for studying the extracellular matrix polysaccharides. Finally, the assocation between proteoglycans, GAGs and mammalian disease processes was reviewed, Emphasizing mucopolysaccharidoses and arthrities. The early detection of both of these diseases is desired for effective counselling and treatment. Many of the methods discussed here have been applied, but others are yet to be tried in efforts to further that goal.

The kinetic time course of citrate-induced activation and polymerization (into filaments) of the protomeric form of acetyl-CoA carboxylase were compared to assess the concertedness of the two processes. Rapid-quench techniques were employed to measure the kinetics of activation of the carboxylase-catalyzed reaction by citrate. When enzyme was preincubated with citrate prior to initiating the steady state turnover reaction with acetyl-CoA in the rapid-quench device, the observed rate of carboxylation of acetyl-CoA was apparently linear from the moment of mixing. However, when enzyme was mixed with citrate to initiate the reaction, a lag (t1/2 = 0.7 s) occurred in the approach to steady state carboxylation rate. This lag was independent of enzyme concentration over a 230-fold range and was marginally dependent upon citrate concentration. Over the same range of enzyme concentration, polymerization of carboxylase protomers, as determined by right angle light scattering, was enzyme concentration-dependent in a manner predicted by a single protomer activation step, followed by a rate-limiting dimerization of active protomer and subsequent polymerization. Polymerization is a second order process, with a second order rate constant of 597,000 M-1 s-1. There appear to be two steps that limit polymerization of the inactive carboxylase protomer: a rapid citrate-induced conformational change, which is independent of enzyme concentration and leads to an active protomeric form of the enzyme and the dimerization of the active protomer, which constitutes the first step of polymerization and is enzyme concentration-dependent. Dimerization is the rate-limiting step of acetyl-CoA carboxylase polymerization. On the basis these results, it is concluded that activation of catalysis and the polymerization of carboxylase protomers are not concerted. Furthermore, activation of carboxylation leading to the formation of an active protomer was faster than polymerization under all conditions, and therefore precedes polymerization. It was also shown that the activation constant (Kact) for citrate is altered in a predictable manner by the accumulation of the reaction product, malonyl-CoA, the Kact increasing with malonyl-CoA concentration. Depolymerization of fully polymerized acetyl-CoA carboxylase is caused by malonyl-CoA or ATP.Mg (and HCO3-). Both malonyl-CoA and ATP.Mg (and HCO3-) compete with citrate in the maintenance of a given state of the protomer-polymer equilibrium apparently by carboxylating the enzyme to form enzyme-biotin CO2- which destabilizes the polymeric form.