Osamu Masuo

Cilostazol Activates Function of Bone Marrow-Derived Endothelial Progenitor Cell for Re-endothelialization in a Carotid Balloon Injury Model

Background Cilostazol(CLZ) has been used as a vasodilating anti-platelet drug clinically and demonstrated to inhibit proliferation of smooth muscle cells and effect on endothelial cells. However, the effect of CLZ on re-endothelialization including bone marrow (BM)-derived endothelial progenitor cell (EPC) contribution is unclear. We have investigated the hypothesis that CLZ might accelerate re-endothelialization with EPCs. Methodology/Principal Findings Balloon carotid denudation was performed in male Sprague-Dawley rats. CLZ group was given CLZ mixed feed from 2weeks before carotid injury. Control group was fed normal diet. CLZ accelerated re-endothelialization at 2 weeks after surgery and resulted in a significant reduction of neointima formation 4 weeks after surgery compared with that in control group. CLZ also increased the number of circulating EPCs throughout the time course. We examined the contribution of BM-derived EPCs to re-endothelialization by BM transplantation from Tie2/lacZ mice to nude rats. The number of Tie2-regulated X-gal positive cells on injured arterial luminal surface was increased at 2 weeks after surgery in CLZ group compared with that in control group. In vitro, CLZ enhanced proliferation, adhesion and migration activity, and differentiation with mRNA upregulation of adhesion molecule integrin αvβ3, chemokine receptor CXCR4 and growth factor VEGF assessed by real-time RT-PCR in rat BM-derived cultured EPCs. In addition, CLZ markedly increased the expression of SDF-1α that is a ligand of CXCR4 receptor in EPCs, in the media following vascular injury. Conclusions/Significance CLZ promotes EPC mobilization from BM and EPC recruitment to sites of arterial injury, and thereby inhibited neointima formation with acceleration of re-endothelialization with EPCs as well as pre-existing endothelial cells in a rat carotid balloon injury model. CLZ could be not only an anti-platelet agent but also a promising tool for endothelial regeneration, which is a key event for preventing atherosclerosis or restenosis after vascular intervention.

Results of endovascular treatment of internal carotid artery stenoses with a newly developed balloon protection catheter.

OBJECTIVEA new balloon protection catheter to prevent distal emboli during internal carotid artery percutaneous transluminal angioplasty and stenting was developed, and its efficacy was evaluated in both an experimental model and clinical cases. METHODSThe balloon protection catheter was navigated over a steerable 0.014-inch guidewire to negotiate tight stenoses and sharp bends, which would cause difficulties for the passage of a flow-directed balloon catheter. Percutaneous transluminal angioplasty and stenting were performed for 85 consecutive patients with 87 stenotic lesions of the cervical internal carotid artery, with two different methods using this protection system. Distal protection was provided only after dilation for the initial 38 lesions (Group I), but the latter 49 lesions were treated in both the pre- and postdilation periods (Group II). The effects of using the balloon protection catheter with the embolic debris clearance technique were evaluated with pre- and postoperative magnetic resonance imaging for each group. RESULTSThe balloon protection catheter was introduced beyond the stenosis in all cases. In Group I, one symptomatic embolic stroke was caused by distal embolization resulting from atheromatous plaque, and high-intensity areas appeared on diffusion-weighted magnetic resonance imaging scans in 47% of cases. In contrast, in Group II, there were no strokes related to the procedure, although one patient with multiple risk factors died suddenly on the second day after stenting. Diffusion-weighted imaging scans demonstrated small, high-intensity areas in 19% of cases in Group II. The overall morbidity/mortality rate in our series was 2.3%. CONCLUSIONOur new balloon protection catheter was reliably navigated across internal carotid artery stenoses and reduced distal embolism in clinical cases.

Endovascular treatment for pseudo-occlusion of the internal carotid artery.

OBJECTIVE:The surgical benefit to pseudo-occlusion of the internal carotid artery (ICA) is controversial. Because the benefit of carotid endarterectomy for pseudo-occlusion of the ICA remains uncertain, we examined the use of carotid stenting as a possible alternative treatment for this condition. METHODS:Twenty cases of carotid pseudo-occlusion (17 symptomatic, three asymptomatic) were treated with carotid artery stenting. Nineteen patients were treated with various embolic protection techniques. Our clinical results, including angiographic follow-up data, perioperative complications, and data on the effectiveness of the embolic protection methods were studied for ICA pseudo-occlusion. RESULTS:All pseudo-occlusions were successfully dilated, and the stenotic ratio was reduced from 95 to 6.7% on average. No neurological deterioration was encountered in any of the cases, although one patient died of cardiac event 1 day after treatment. None of the patients experienced stroke during the mean 24.8 month follow-up period, although one patient died from myocardial infarction. Among the 17 cases in which follow-up angiography was performed at 6 months after stenting, only one patient demonstrated restenosis. This patient was successfully treated with repeated percutaneous transluminal angioplasty. The rate of restenosis in our series was 5.9%, and the morbidity/mortality rate within 30 days was 5%. CONCLUSION:The clinical results of carotid stenting for ICA pseudo-occlusion under embolic protection were fairly good from the viewpoints of periprocedural neurological morbidity, angiographic follow-up results, and stroke prevention. Carotid stenting can be considered an alternative to carotid endarterectomy in patients with ICA pseudo-occlusion.

Hemorrhagic complications after endovascular therapy for atherosclerotic intracranial arterial stenoses.

OBJECTIVE:Hemorrhagic complications were analyzed in 106 procedures of 99 patients treated with percutaneous transluminal angioplasty (PTA) or stenting for intracranial arterial stenoses. METHODS:Ninety-nine patients with intracranial arterial stenosis were treated with PTA or stenting 106 times from January 1995 to December 2003. Fifty-seven patients had intracranial internal carotid artery stenosis, 23 had middle cerebral artery stenosis, and 19 had vertebrobasilar stenosis. Evaluation of hemodynamic compromise via single-photon emission computed tomography was performed 50 times for 50 patients before the treatment. RESULTS:Four hemorrhagic complications occurred in 106 procedures. Two of these cases involved intracerebral hemorrhage after PTA or stenting in the treated vascular territory 30 minutes and 16 hours after the treatment, respectively. One case showed subarachnoid hemorrhage, which appeared 6 hours after treatment. Hemodynamic compromise was found on single-photon emission computed tomography in these three cases. The last case with a hemorrhagic complication was a hemorrhagic infarction after recanalization of stent thrombosis, which appeared 3 days after stenting. Hyperperfusion syndrome was strongly suggested as the cause of hemorrhage in the two cases associated with intracerebral hemorrhage. CONCLUSION:The rate of hemorrhagic complication directly related to the procedure of PTA or stenting was 3%, and hyperperfusion syndrome was suggested as the cause of hemorrhage in two cases (2%), from the perspective of clinical characteristics and single-photon emission computed tomographic findings.

Memory impairment and spatial disorientation following a left retrosplenial lesion.

We treated a patient in whom a left retrosplenial lesion resulted in memory impairment and spatial disorientation. A 31 year old, right handed man was admitted to our hospital after the sudden onset of headache. He was alert, attentive and cooperative, and showed no motor or sensory deficits. Although intelligence was preserved, memory was obviously deficient. The patient proceeded in wrong directions after he left his hospital room and subsequently his home. Neuroimaging revealed a subcortical hematoma in the left cingulate isthmus, while single-photon emission computed tomography demonstrated decreased perfusion in the splenium and left parietal lobe.

Endovascular recanalization of the completely occluded internal carotid artery using a flow reversal system at the subacute to chronic stage.

OBJECTnThe efficacy and pitfalls of endovascular recanalization were evaluated in cases of internal carotid artery (ICA) occlusion in the subacute to chronic stage.nnnMETHODSnFourteen cases (15 lesions) of symptomatic ICA occlusion with hemodynamic compromise or recurrent symptoms were treated at the subacute to chronic stage using an endovascular technique. The Parodi embolic protection system was used during the recanalization procedure to prevent embolic stroke by reversing the flow from the distal ICA to the common carotid artery.nnnRESULTSnRecanalization of the occluded ICA was possible in 14 of 15 lesions. The occlusion points were 10 cervical ICAs and 4 petrous/cavernous ICAs in successfully recanalized cases. Ischemic symptoms disappeared completely after the treatment, and new ischemic symptoms did not appear related to the treated lesion. Single photon emission computed tomography findings demonstrated the improvement of hemodynamic compromise in all cases. One case showed right middle cerebral artery branch occlusion during the procedure, but this patients neurological symptoms were stable due to preexisting hemiparesis. Endovascular recanalization was possible and effective in improving hemodynamic compromise. However, there are still several problems with this technique, such as hyperperfusion syndrome after recanalization, cerebral embolism during treatment, durability after treatment, and identification of the occlusion point before treatment.nnnCONCLUSIONSnEndovascular recanalization using an embolic protection device can be considered as an alternative treatment for symptomatic ICA occlusion with hemodynamic compromise or refractoriness to antiplatelet therapy, even in the subacute to chronic stage of the illness.

Carotid artery stenting for stenosis with intraluminal thrombus

Since intraluminal thrombus in the context of carotid artery stenosis is rarely encountered, treatment for this condition remains controversial. The present paper describes six cases of carotid artery stenosis with thrombus and discusses the efficacy and complications of carotid artery stenting (CAS). From April 2002 to May 2004, six patients with carotid artery stenosis and intraluminal thrombus receiving medical therapy underwent CAS at our institution. CAS was performed with distal protection alone (method 1) in three patients, and three other patients underwent CAS with reversed-flow system and distal protection (method 2). Two of six patients experienced worsening neurologic symptoms despite medical therapy. All six patients were successfully treated with CAS and showed satisfactory patency of the artery. Embolic lesions were detected on diffusion-weighted MRI after the procedure in all patients treated with method 1 but not in patients treated with method 2. Complications included stent thrombosis (n=1) and in-stent thrombus (n=1). All six patients achieved a modified Rankin Scale 1 or 2 classification at 30 days after stenting. In conclusion, CAS was feasible for stenosis even with intraluminal thrombus. Use of method 2 for this condition may reduce the incidence of thromboembolic events although our series was small in number.

Endovascular treatment of unruptured cerebral aneurysms

76 consecutive patients with 78 unruptured cerebral aneurysms underwent endovascular therapy from July 1999 to May 2004 in our institute. For the wide-necked aneurysms, the remodeling technique, double microcatheter technique, or stent-assisted coil embolization was used, while a parent artery occlusion or covered stent was applied for the giant or fusiform aneurysms. Immediate angiographical results demonstrated 33 complete occlusions, 26 neck remnants, and 14 dome fillings. Four cases were treated with parent occlusion or stenting only, and one case was not treated with embolization but with clipping due to the rupture of the aneurysm during coil embolization. Immediate angiographic findings demonstrated that in aneurysms between 5 to 10 mm, the rate of complete occlusion was 48%, that of neck remnants 33%, and that of dome fillings 27%. In aneurysms between 11 to 25 mm, the rate of complete occlusion was 14%, that of neck remnants 28%, and that of dome fillings was 58%. In the angiographic follow-up results, all aneurysms smaller than 5 mm showed complete occlusion. In aneurysms between 5 to 10 mm, 74% of the aneurysms showed complete occlusion, and 21% showed neck remnants, and 5% showed dome filling. In aneurysms between 10 to 24 mm, 25% showed complete occlusion, while 75% showed dome filling. The overall mortality rate was 0% and the morbidity rate was 3.7% (2 major strokes, 1 minor stroke) at 30-days after embolization. In the clinical follow-up study, one case of a large basilar tip aneurysm caused a fatal rupture 28 months after the initial embolization. Endovascular therapy was performed on the unruptured aneurysms and was found to be an acceptable treatment, except for durability in cases of large aneurysms.

De Novo Cerebral Aneurysm Formation Associated With Proximal Stenosis

BACKGROUNDnHemodynamic insults--high wall shear stress (WSS) combined with high positive WSS gradient (WSSG)--have been proposed to link to cerebral aneurysm initiation. We report 4 cases of aneurysms with proximal stenosis, including 1 de novo aneurysm, that might be associated with hemodynamic insults caused by the proximal stenosis.nnnCLINICAL PRESENTATIONnIn 4 clinical cases, the diameter stenosis was 37% to 49% (mean, 42%) located 2.7 to 4.7 mm (mean, 3.7 mm) from the apex. We performed computational fluid dynamics simulations for 2 cases: a ruptured basilar terminus aneurysm with proximal stenosis (which had an angiogram taken 15 years previously that showed no aneurysm and no stenosis) and a cavernous carotid artery aneurysm with proximal stenosis. In both cases, the stenosis caused unphysiologically high WSS (> 7 Pa) at the apex, nearly doubling the WSS and WSSG values. To investigate the relationship between stenosis and distal hemodynamic elevation, we created a series of T-shaped vascular models by varying the degree and location of stenosis. We found that stenosis > 40% by diameter located within 10 mm from the apex caused unphysiologically high WSS and WSSG. All 4 clinical cases satisfied these conditions.nnnCONCLUSIONnProximal stenosis could produce high WSS and high positive WSSG at the apex, thus potentially inducing de novo aneurysm formation.nnnABBREVIATIONSnBT, basilar terminusCFD, computational fluid dynamicsICA, internal carotid arteryWSS, wall shear stressWSS, wall shear stress gradient.

Carotid endarterectomy and simultaneous percutaneous transluminal angioplasty for tandem internal carotid stenoses

Abstract We treated three patients with tandem internal carotid stenoses in single procedures including carotid endarterectomy (CEA) for the proximal stenosis and percutaneous transluminal angioplasty (PTA) for the distal stenosis. We devised a Y-shaped shunt tube for the CEA, through which a balloon catheter was introduced to perform PTA guided by mobile digital subtraction angiography. No cerebrovascular events occurred during follow-up. Our approach avoids the risk of a second procedure while effectively treating tandem stenoses.