Removal Of Intima Research Articles

POSSIBILITIES OF SURGICAL CORRECTION OF INTERNAL CAROTID ARTERY THROMBOSIS IN PATIENTS WITH ACUTE ISCHEMIC STROKE

Objective. To estimate the efficacy of surgical treatment of internal carotid artery (ICA) thrombosis in patients suffered from acute ischemic stroke (AIS). Material and methods. Author operated 25 patients suffered from AIS and ICA thrombosis from 01 Feb, 2014 till 31 Aug, 2016 in Neurosurgical Department of N.V. Sklifosovsky Research Institute for Emergency Medicine. Among them, 15 patients had total thrombosis of ICA and were operated on, 10 patients had partial mural thrombosis or floating thrombus (6 patients were operated on). There were 7 thrombectomies with the removal of intima, 13 superficial temporal artery (STA)-middle cerebral artery (MCA) bypasses, 1 ICA stent installation. Results. The excellent outcomes were seen in 7 (33.4%) patients, good outcomes — in 11 (52.3%) and satisfactory outcomes were observed in 3 (14.3%) patients. The improvement of functional deficit in the early post-operative period was 4.85 scores according to NIHSS, 1.2 scores according to Rankin scale and 2.3 scores according to Rivermead mobility index. The regress of neurological deficit was more significant among patients with severe focal disturbances; better outcomes were among patients operated on within first 3 days from an onset of the disease. There was no significant improvement among non-operated patients at the moment of discharge from hospital. Thrombectomy with the removal of intima performed in 2 (40%) patients with partial mural thrombosis was complicated by repeated thrombosis of ICA. The improvement of cerebral blood supply was verified in 16 (76.2%) operated patients according to the data of cerebral perfusion examination. Conclusions. The early surgical treatment is indicated for patients with acute total thrombosis of ICA. It is possible to perform STA-MCA bypass in case of inability to perform endovascular thrombextraction or open thrombectomy with the removal of intima. The conservative treatment is indicated for patients with partial mural thrombosis while urgent operation is necessary among patient with floating thrombus to decrease the risk of cerebral embolism.

Selective phosphodiesterase-5 inhibition reduces neointimal hyperplasia in rat carotid arteries after surgical endarterectomy

Long-term results of surgical vessel reconstruction are compromised by restenosis caused by neointimal hyperplasia. Recent studies suggest that reduced cyclic guanosine monophosphate signaling is associated with neointima formation. In a rat model of endarterectomy, we investigated the effect of pharmacologic inhibition of cyclic guanosine monophosphate degradation on neointima formation by using the selective phosphodiesterase-5 inhibitor vardenafil. Carotid endarterectomy was performed in male Sprague-Dawley rats by means of incision of the right common carotid artery with removal of intima. Four groups were studied: unoperated control rats (n = 4), sham-operated rats (n = 9), control rats with endarterectomy (n = 9), or endarterectomized rats treated with vardenafil (10 mg/kg/day) postoperatively (n = 9). After 3 weeks, vessel compartment areas were measured by means of conventional microscopy with hematoxylin and eosin staining. Immunohistochemical analysis was performed to confirm neointima formation and the local cyclic guanosine monophosphate content. Plasma levels of cyclic guanosine monophosphate were determined by means of enzyme immunoassay. Student's t test was used for statistical evaluation. Immunohistochemical analysis demonstrated intensive staining for transforming growth factor beta1 and alpha-smooth muscle actin in the control neointima. Vardenafil significantly reduced the stenosis grade (24.64% +/- 7.46% vs 54.12% +/- 10.30% in the control group, P < .05) and expression of transforming growth factor beta1, as well as alpha-smooth muscle actin, in the neointima. The immunohistochemical score for cyclic guanosine monophosphate was higher in the treated neointima (4.80 +/- 0.76 vs 2.84 +/- 0.40 in the control group, P < .05), and increased plasma cyclic guanosine monophosphate levels were found by means of enzyme immunoassay as well (84.65 +/- 12.77 pmol/mL vs 43.50 +/- 3.30 pmol/mL in the control group, P < .05). Treatment with vardenafil can be considered a new possibility to prevent neointimal hyperplasia after endarterectomy.

Opposite effects of vascular irradiation on inflammatory response and apoptosis induction in the vessel wall layers via the peroxynitrite-poly(ADP-ribose) polymerase pathway

We investigated in a surgical rat model of vascular injury the potential role of the peroxynitrite - poly(ADPribose) polymerase (PARP) pathway in inflammatory response and apoptosis induction after vascular gamma irradiation. Male Sprague-Dawley rats underwent left carotid endarterectomy with removal of intima: control (n = 10) and were irradiated with 15 Gray (n = 13) or 20 Gray (n = 10) postoperatively and compared with sham-operated rats (n = 10). Additional animals were solely irradiated with 15 Gy (n = 10) and with 20 Gy (n = 10) to distinguish between primary effects of vascular injury and secondary effects due to irradiation. After 21 days, neointima formation was significantly suppressed after irradiation (control: 0.07 mm(2) +/- 0.04 mm(2), 15 Gy: 0.003 mm(2) +/- 0.004 mm(2), 20 Gy: 0.001 mm(2) +/- 0.0006 mm(2), P< 0.0001). However, a significant inflammation of the vessel wall with focal wall necrosis was detected (control: 0.2 +/- 0.15, 15 Gy: 0.82 +/- 1.2, 20 Gy: 1.25 +/- 0.86, P= 0.003). Immunohistochemistry showed significant staining for nitrotyrosine, poly(ADP-ribose) and nuclear translocation of apoptosis-inducing factor in the neointima of the control group. In the irradiated groups these stainings were significantly higher in the media and adventitia compared to the non-irradiated groups. Activation of the peroxynitrite-PARP pathway was demonstrated during neointima proliferation in a rat model of surgical vascular injury. Vascular irradiation suppressed neointima formation, but induced significant activation of the peroxynitrite - PARP pathway in the outer vessel wall layers concomitant to inflammation and focal wall necrosis. This may contribute to adverse effects of vascular irradiation such as fibrosis and constrictive remodeling.

Poly(ADP-ribose) polymerase inhibition combined with irradiation: A dual treatment concept to prevent neointimal hyperplasia after endarterectomy

In a rat model of endarterectomy we investigated the potential role of the peroxynitrite-poly(ADP-ribose) polymerase (PARP) pathway in neointima formation and the effects of irradiation, pharmacologic inhibition of PARP, or combined pharmacologic inhibition of PARP and irradiation on vascular remodeling. Carotid endarterectomy was performed by incision of the left carotid artery with removal of intima in Sprague-Dawley rats. Six groups were studied: sham-operated rats (n = 10), control endarterectomized rats (n = 10), or endarterectomized rats irradiated with 15 Gy (n = 10), or treated with PARP inhibitor, INO-1001 (5 mg/kg/day) (n = 10), or with combined treatment with INO-1001 and irradiation with 5 Gy (n = 10) or with 15 Gy (n = 10). After 21 days, neointima formation and vascular remodeling were assessed. Neointima formation after endarterectomy was inhibited by postoperative irradiation with 15 Gy and was attenuated by PARP inhibition. However, in parallel to inhibition of neointimal hyperplasia, activation of the peroxynitrite-PARP pathway in the outer vessel wall layers was triggered by postoperative irradiation. Combined pharmacologic PARP inhibition and irradiation with 15 Gy significantly reduced both neointimal hyperplasia and activation of the peroxynitrite-PARP pathway in the outer vessel wall layers. Combination of PARP inhibition and irradiation with 5 Gy was less effective than both PARP inhibition or irradiation with 15 Gy alone. We conclude, that combined PARP inhibition and irradiation with 15 Gy may be a new dual strategy for prevention of restenosis after surgical vessel reconstruction: combining the strong antiproliferative effect of irradiation and ameliorating irradiation-induced side effects caused by excessive PARP activation.

Activation of the peroxynitrite-poly(adenosine diphosphate-ribose) polymerase pathway during neointima proliferation: A new target to prevent restenosis after endarterectomy

In a rat model of endarterectomy, we investigated the potential role of the peroxynitrite-poly(adenosine diphosphate[ADP]-ribose) polymerase (PARP) pathway in neointima formation and the effect of pharmacologic inhibition of PARP on vascular remodeling. Carotid endarterectomy was performed in male Sprague-Dawley rats by incision of the left carotid artery with removal of intima. Three groups were studied: sham-operated rats (n = 10), control rats with endarterectomy (n = 10) or rats with endarterectomy treated with the PARP inhibitor, INO-1001 (5 mg/kg daily) postoperatively (n =10). After 21 days, neointima formation and vascular remodeling were assessed. Immunohistochemistry analysis demonstrated activation of the peroxynitrite-PARP pathway with significant staining for nitrotyrosine, poly(ADP-ribose), and nuclear translocation of apoptosis-inducing factor (AIF) in the neointima of the control group. Treatment with INO-1001 significantly reduced the neointima area (0.024 mm2 +/- 0.019 mm2 vs 0.089 mm2 +/- 0.033 mm2 in the control group), the neointima/media thickness ratio (0.81 +/- 0.05 vs 2.76 +/- 1.57 in the control group), and the inflammation score (0.1 +/- 0.07 vs 0.3 +/- 0.12 in the control group) after endarterectomy. Pharmacologic inhibition of PARP with INO-1001 may be a new concept to prevent neointimal hyperplasia after endarterectomy.

Adjunct brachytherapy: a new concept to prevent intimal hyperplasia after surgical endarterectomy?

Endarterectomy represents a therapeutical option for patients with advanced coronary artery disease. The mid-term results are compromised by restenosis due to neointima formation. The aim of this study was to evaluate a new treatment concept - endarterectomy with consecutive gamma-irradiation - in a rat model. Male Sprague-Dawley rats underwent left carotid endarterectomy with removal of intima: control (n=10) or were irradiated with 15 Gray (Gy) (n=13) or 20 Gy (n=10) postoperatively and compared with sham-operated rats (n=10). After 3 weeks, carotid arteries were perfusion-fixed and vessel compartment areas were measured. Transmission electron microscopy and immunohistochemical staining were used to confirm neointima formation. Three weeks after endarterectomy, neointimal hyperplasia was found in the control group (0.07+/-0.04 mm(2)). After irradiation, a dose-dependent reduction of neointima was observed (0.003 mm(2) at 15 Gy and 0.0007 mm(2) at 20 Gy, P<0.0001). However, immunohistochemical staining revealed that thin re-endothelialization after irradiation was not inhibited. Gamma-irradiation significantly suppressed neointimal hyperplasia in a rat model of surgical endarterectomy. Despite inhibition of intimal hyperplasia, re-endothelialization after adjuvant brachytherapy was present. Adjuvant brachytherapy may be therefore a new concept to prevent restenosis after endarterectomy in patients.