Distal embolization at the site of a stenotic distal anastomosis of a saphenous vein graft,leading to dye entrapment

This case report describes the entrapment of contrast media after recanalization of a recently occluded saphenous vein graft with balloon predilation, thrombectomy and stent implantation. Recanalization of the respective coronary artery was performed, and the entrapped contrast media within the saphenous vein graft progressed to the left circumflex artery.     

MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation

PurposeLong-term failure of vein grafts due to neointimal hyperplasia remains an important problem in coronary artery bypass graft surgery. Endothelial to mesenchymal transition (EndMT) contributes to vein graft vascular remodeling. However, there is little study on microRNA-mediated EndMT contributions to neointimal formation in vein graft. We hypothesized that microRNA-92a (miR-92a) might play an important role in determining EndMT contributions to neointimal formation.MethodsmiR-92a and EndMT-related proteins detected by qRT-PCR and Western blot in vitro and in vivo. Adeno-associated virus 6 (AAV6) delivery gene therapy was used to inhibit neointimal formation in vivo. The intimal hyperplasia of vein grafts was measured by HE staining, the expression of EndMT-related protein in vein grafts was measured by immunofluorescence. Immunohistochemistry and luciferase assay were used to detect potential targets of miR-92a.ResultsThe expression of miR-92a was found to be upregulated in neointimal hyperplasic lesions after vein grafting. Using cultured human umbilical vein endothelial cells (HUVECs), we show that TGF-β1 treatment of HUVECs significantly increased miR-92a expression and induced EndMT, characterized by suppression of endothelial-specific markers (CD31 and VE-cadherin) and an increase in mesenchymal-specific markers (a-SMA and vimentin), while inhibition of miR-92a expression blunted EndMT in cultured HUVECs. Furthermore, AAV6 mediated miR-92a suppression gene therapy effectively resulted in decreased EndMT and less neointimal formation in vein grafts in vivo. We further identified that integrin alpha 5 (ITGA5) is a potential target gene involved in the development of neointima formation in these vein grafts.ConclusionThis data suggests that neointimal formation does not solely rely on vascular smooth muscle cell phenotypic switching but is also related to EndMT, and miR-92a-mediated EndMT is an important mechanism underlying neointimal formation in vein grafts.     

Evaluation of bifurcation stenting techniques at Catharina Hospital,Eindhoven in 2013

Aims

Percutaneous coronary intervention (PCI) of bifurcation lesions can be performed using various techniques. The aim of this study was to analyse the outcome of various techniques of bifurcation stenting in all patients undergoing bifurcation stenting at one large intervention centre in 2013, taking into account that more complex lesions might more often warrant a two-stent technique.

Methods and results

This retrospective study included 260 consecutive patients who underwent non-primary PCI of a bifurcation lesion at the Catharina Hospital, Eindhoven, in 2013. Patients were classified into two groups: one-stent technique (provisional stenting), and two-stent techniques (culotte, crush and T?stenting). The primary endpoint was the rate of restenosis at 1 year. The secondary endpoints were procedural complications (side branch occlusion, periprocedural infarction, and death) and major adverse cardiac events (MACE) at 1 year. Periprocedural complications occurred in 15 patients (5.8?%) with no difference between the groups (p = 0.27). After 1 year, restenosis occurred in 3.2?% of the patients in the one-stent technique group and 7.3?% in the two-stent technique group (p = 0.20). MACE at 1 year did not differ between the groups at 11.9?% and 12.2?% respectively (p = 1.00).

Conclusions

This study shows that there is no significant difference between restenosis rate, or any other outcome parameter, with the different techniques of bifurcation stenting. Since provisional stenting is the simplest, most straightforward and cheapest approach, if technically feasible this technique has our preference as the initial approach, and an upgrade can be considered if the result is insufficient.

     

Hemodynamic factors at the distal end-to-side anastomosis of a bypass graft with different POS:DOS flow ratios

A pulsatile flow in vitro model of the distal end-to-side anastomosis of an arterial bypass graft was used to examine the effects that different flow ratios between the proximal outlet segment (POS) and the distal outlet segment (DOS) have on the flow patterns and the distributions of hemodynamic factors in the anastomosis. Amberlite particles were tracked by flow visualization to determine overall flow patterns and velocity measurements were made with Laser Doppler anemometry (LDA) to obtain detailed hemodynamic factors along the artery floor and the graft hood regions. These factors included wall shear stress (WSS), spatial wall shear stress gradient (WSSG), and oscillatory index (OSI). Statistical analysis was used to compare these hemodynamic factors between cases having different POS:DOS flow ratios (Case 1-0:100, Case 2-25:75, Case 3-50:50). The results showed that changes in POS:DOS flow ratios had a great influence on the flow patterns in the anastomosis. With an increase in proximal outlet flow, the range of location of the stagnation point along the artery floor decreased, while the extent of flow separation along the graft hood increased. The statistical results showed that there were significant differences (p<0.05) for the mean WSS between cases along the graft hood, but no significant differences were detected along the artery floor. There were no significant differences for the spatial WSSG along both the artery floor and the graft hood. However, there were significant differences (p<0.05) in the mean OSI between Cases 1 and 2 and between Cases 1 and 3 both along the artery floor and along the graft hood. Comparing these mechanical factors with histological findings of intimal hyperplasia formation obtained by previous canine studies, the results of the statistical analysis suggest that regions exposed to a combination of low mean WSS and high OSI may be most prone to the formation of intimal hyperplasia.     

The effect of proximal artery flow on the hemodynamics at the distal anastomosis of a vascular bypass graft: computational study

The formation of distal anastomotic intimal hyperplasia (IH), one common mode of bypass graft failure, has been shown to occur in the areas of disturbed flow particular to this site. The nature of theflow in the segment of artery proximal to the distal anastomosis varies from case to case depending on the clinical situation presented. A partial stenosis of a bypassed arterial segment may allow residual prograde flow through the proximal artery entering the distal anastomosis of the graft. A complete stenosis may allow for zero flow in the proximal artery segment or retrograde flow due to the presence of small collateral vessels upstream. Although a number of investigations on the hemodynamics at the distal anastomosis of an end-to-side bypass graft have been conducted, there has not been a uniform treatment of the proximal artery flow condition. As a result, direct comparison of results from study to study may not be appropriate. The purpose of this work was to perform a three-dimensional computational investigation to study the effect of the proximal artery flow condition (i.e., prograde, zero, and retrograde flow) on the hemodynamics at the distal end-to-side anastomosis. We used the finite volume method to solve the full Navier-Stokes equations for steady flow through an idealized geometry of the distal anastomosis. We calculated the flow field and local wall shear stress (WSS) and WSS gradient (WSSG) everywhere in the domain. We also calculated the severity parameter (SP), a quantification of hemodynamic variation, at the anastomosis. Our model showed a marked difference in both the magnitude and spatial distribution of WSS and WSSG. For example, the maximum WSS magnitude on the floor of the artery proximal to the anastomosis for the prograde and zero flow cases is 1.8 and 3.9 dynes/cm2, respectively, while it is increased to 10.3 dynes/cm2 in the retrograde flow case. Similarly, the maximum value of WSSG magnitude on thefloor of the artery proximal to the anastomosis for the prograde flow case is 4.9 dynes/cm3, while it is increased to 13.6 and 24.2 dynes/cm3, respectively, in the zero and retrograde flow cases. The value of SP is highest for the retrograde flow case (13.7 dynes/cm3) and 8.1 and 12.1 percent lower than this for the prograde (12.6 dynes/cm3) and zero (12.0 dynes/cm3) flow cases, respectively. Our model results suggest that the flow condition in the proximal artery is an important determinant of the hemodynamics at the distal anastomosis of end-to-side vascular bypass grafts. Because hemodynamic forces affect the response of vascular endothelial cells, the flow situation in the proximal artery may affect IH formation and, therefore, long-term graft patency. Since surgeons have some control over the flow condition in the proximal artery, results from this study could help determine which flow condition is clinically optimal.     

Morphology of a neonatal umbilical vein graft under prolonged experimental conditions

The authors carried out a comparative histological and electron microscopic study of the bioprosthesis of the umbilical vein (Biograft manufactured by Meadox) and bioprosthesis obtained according to the method by M. I. Kuzin and coworkers. A far greater preservation of the new bioprosthesis was observed at long-term periods both at the histological and ultrastructural levels. Some morphological phenomena reflecting the time course of the vessel graft rearrangement were delineated 18 to 24 months after transplantation, particularly the development of "collateral" vessels in the perivenous space. The suggestion was made about an important role of Wharton's substance in the formation of the vessels.     

Prolonged systemic delivery of tirofiban in a thrombus-laden saphenous vein graft

Results from previous trials have shown conflicting results from local delivery of thrombolytic agents to diminish thrombus burden before intervention in native coronary arteries and saphenous vein grafts. We described a patient with an acute coronary syndrome who was treated for 24 hours with systemic tirofiban (Aggrastat), a glycoprotein IIb/IIIa inhibitor, for the treatment of a degenerated saphenous vein graft with a TIMI grade 4 thrombus (large-sized thrombus). Angiographic evaluation 48 hours later revealed complete resolution of the thrombus with normal coronary blood flow.     

Transitional flow at the venous anastomosis of an arteriovenous graft: potential activation of the ERK1/2 mechanotransduction pathway

We present experimental and computational results that describe the level, distribution, and importance of velocity fluctuations within the venous anastomosis of an arteriovenous graft. The motivation of this work is to understand better the importance of biomechanical forces in the development of intimal hyperplasia within these grafts. Steady-flow in vitro studies (Re = 1060 and 1820) were conducted within a graft model that represents the venous anastomosis to measure velocity by means of laser Doppler anemometry. Numerical simulations with the same geometry and flow conditions were conducted by employing the spectral element technique. As flow enters the vein from the graft, the velocity field exhibits flow separation and coherent structures (weak turbulence) that originate from the separation shear layer. We also report results of a porcine animal study in which the distribution and magnitude of vein-wall vibration on the venous anastomosis were measured at the time of graft construction. Preliminary molecular biology studies indicate elevated activity levels of the extracellular regulatory kinase ERK1/2, a mitogen-activated protein kinase involved in mechanotransduction, at regions of increased vein-wall vibration. These findings suggest a potential relationship between the associated turbulence-induced vein-wall vibration and the development of intimal hyperplasia in arteriovenous grafts. Further research is necessary, however, in order to determine if a correlation exists and to differentiate the vibration effect from that of flow related effects.     

Iatrogenic chorioretinal venous anastomosis in the treatment of central retinal vein occlusion

This paper discusses the clinical application of an iatrogenic chorioretinal venous anastomosis for experimental treatment of non-ischemic central retinal vein occlusions (CRVO). The creation of an iatrogenic chorioretinal venous anastomosis offers a potential means of by-passing the obstructed central retinal vein and allowing venous blood to exit the retinal circulation through the choroid. A successful anastomosis may allow improved venous drainage and faster resolution of macular edema. This procedure may also prevent the conversion of a non-ischemic CRVO to the ischemic type. The natural history of a CRVO, the procedure for anastomosis creation, the patients most likely to benefit, and complications of chorioretinal anastomosis are discussed.     

Localization of DNA repair synthesis by human cell extracts to a short region at the site of a lesion

Double-stranded bacteriophage M13 DNA molecules were constructed containing a single specifically placed 2-(acetylamino)fluorene adduct or a single 4'-hydroxymethyl-4,5',8-trimethylpsoralen monoadduct. These circular DNA molecules were used to analyze in vitro DNA repair synthesis by cell extracts from normal human lymphoid cell lines. Both types of lesions stimulate DNA repair synthesis at the site of the adduct. DNA repair synthesis induced by the 2-(acetyl-amino)fluorene adduct took place in the damaged strand and was confined to a region within a 31-base pair restriction fragment around the adduct.     

Autogenous vein graft repair of digital nerve defects in the finger: a retrospective clinical study

Twenty-two digital nerve repairs were performed in the finger using autogenous vein grafts. Eighty-two percent of the repairs were available for follow-up. Results of sensibility return were assessed using moving two-point discrimination, Semmes-Weinstein monofilaments, and vibratory testing. Two-point discrimination averaged 4.6 mm for 11 acute digital nerve repairs using vein conduits 1 to 3 cm in length. Delayed digital nerve repair with vein conduits yielded poor results. Semmes-Weinstein values demonstrated comparable levels of return of slowly adapting fiber/receptors to the quickly adapting fiber/receptors, as evidenced by moving two-point discrimination tests. Vibratory sensibility was present in all. A review of previous experiences with end-to-end digital neurorrhaphies and digital nerve grafting suggests that repair of 1- to 3-cm gaps in digital nerves with segments of autologous vein grafts appears to give comparable results to nerve grafting. Further laboratory and clinical research is necessary to better define the role of interpositional vein conduits for repair of peripheral nerves.     

Postsurgical changes of the opening angle of canine autogenous vein graft.

The opening angles of 30 canine autogenous vein grafts were measured to determine the postsurgical change of residual strain in the vein graft. Canine femoral veins were grafted to femoral arteries in the end-to-end anastomosis fashion. When harvested, the vein grafts were cut into short segments and the segments were cut open radially. The opened-up configurations were taken as the zero-stress states of the vessels. Opening angle, defined as the angle between the two lines from the middle point to the tips of the inner wall, was used to describe the zero-stress states. Results show that the opening angles (mean +/- SD) are 63.0 +/- 30.6 deg for normal femoral veins, and -0.4 +/- 4.6, 6.1 +/- 19.4, 25.4 +/- 20.1, and 47.8 +/- 11.4 deg for vein grafts at 1 day, 1 week, 4 and 12 weeks postsurgery, respectively. The postsurgical changes in opening angle reveal nonuniform transmural tissue remodeling in the vascular wall. The relations between the changes in opening angle and the changes in the morphology of the vein grafts are discussed. Intimal hyperplasia is correlated to the opening angle and is suggested to be the main factor for the postsurgical increase in opening angle. The longitudinal strain in the vein graft is found to decrease postsurgically.     

Effects of inertia and gravity on liquid plug splitting at a bifurcation

Liquid plugs may form in pulmonary airways during the process of liquid instillation or removal in many clinical treatments. During inspiration the plug may split at airway bifurcations and lead to a nonuniform final liquid distribution, which can adversely affect treatment outcomes. In this paper, a combination of bench top experimental and theoretical studies is presented to study the effects of inertia and gravity on plug splitting in an airway bifurcation model to simulate the liquid distributions in large airways. The splitting ratio, Rs, is defined as the ratio of the plug volume entering the upper (gravitationally opposed) daughter tube to the lower (gravitationally favored) one. Rs is measured as a function of parent tube Reynolds number, Rep; gravitational orientations for roll angle, phi, and pitch angle, gamma; parent plug length LP; and the presence of pre-existing plug blockages in downstream daughter tubes. Results show that increasing Rep causes more homogeneous splitting. A critical Reynolds number Rec is found to exist so that when Rep < or = Rec, Rs = 0, i.e., no liquid enters the upper daughter tube. Rec increases while Rs decreases with increasing the gravitational effect, i.e., increasing phi and gamma. When a blockage exists in the lower daughter, Rec is only found at phi = 60 deg in the range of Rep studied, and the resulting total mass ratio can be as high as 6, which also asymptotes to a finite value for different phi as Rep increases. Inertia is further demonstrated to cause more homogeneous plug splitting from a comparison study of Rs versus Cap (another characteristic speed) for three liquids: water, glycerin, and LB-400X. A theoretical model based on entrance flow for the plug in the daughters is developed and predicts Rs versus Rep. The frictional pressure drop, as a part of the total pressure drop, is estimated by two fitting parameters and shows a linear relationship with Rep. The theory provides a good prediction on liquid plug splitting and well simulates the liquid distributions in the large airways of human lungs.     

Effects of nerve growth factor on nerve regeneration through a vein graft across a gap.

The limited availability of donor sites for nerve grafts and their inherent associated morbidity continue to stimulate research toward finding suitable alternatives. In the following study, the effect of direct administration of nerve growth factor (NGF) into a nerve conduit across a gap was tested in a rat sciatic nerve model. A 1-cm segment of the right sciatic nerve in Sprague-Dawley rats was resected, and the gap was then bridged using one of three methods: group I (NGF-treated group, n = 12), a vein graft filled with NGF (100 ng in 0.3-ml phosphate buffered saline); group II (control group, n = 12), a vein graft filled with phosphate buffered saline only; group III (standard nerve graft, n = 11), a resected segment of the sciatic nerve. All animals were evaluated at 3 and 5 weeks by behavioral testing and at 5 weeks by electrophysiologic testing. At 3 weeks, sensory testing showed that the latency to a noxious stimulus in group I animals (8.0 +/- 5.4 sec, mean +/- SD) was significantly lower than that of group II animals (13.2 +/- 6.5 sec), indicating that sensory recovery was superior in the animals receiving NGF. The mean latency of animals in group III was 12.9 +/- 6.5 sec, but the difference between the latencies of group I and group III did not reach statistical significance. At 5 weeks, there was no difference in sensory testing between groups. Motor function in groups I and III as measured by walk pattern analysis was superior to that of group II at 5 weeks (toe spread ratios 0.66 +/- 0.09, 0.48 +/- 0.07, and 0.69 +/- 0.09 for groups I, II, and III, respectively). Mean motor conduction velocities across the 1-cm gap were 8.6 +/- 4.7 m/sec, 2.5 +/- 0.7 m/sec, and 6.9 +/- 2.9 m/sec in groups I, II, and III respectively. The difference between groups I and III was not statistically significant, but the motor conduction velocity of group II was significantly slower than that of either group I or III (p < 0.002). The positive effects of NGF on regeneration of nerves across a gap seen in this study suggest that it may be useful for treating peripheral nerve injuries in combination with autogenous vein grafts.