Brilliant blue FCF is a nontoxic dye for saphenous vein graft marking that abrogates response to injury.

BACKGROUND: Injury to saphenous vein grafts during surgical preparation may contribute to the subsequent development of intimal hyperplasia, the primary cause of graft failure. Surgical skin markers currently used for vascular marking contain gentian violet and isopropanol, which damage tissue and impair physiologic functions. Brilliant blue FCF (FCF) is a nontoxic dye alternative that may also ameliorate preparation-induced injury. METHODS: Porcine saphenous vein (PSV) was used to evaluate the effect of FCF on physiologic responses in a muscle bath. Cytotoxicity of FCF was measured using human umbilical venous smooth muscle cells. Effect of FCF on the development of intimal hyperplasia was evaluated in organ culture using PSV. Intracellular calcium fluxes and contractile responses were measured in response to agonists and inhibitors in rat aorta and human saphenous vein. RESULTS: Marking with FCF did not impair smooth muscle contractile responses and restored stretch injury-induced loss in smooth muscle contractility of PSV. Gentian violet has cytotoxic effects on human umbilical venous smooth muscle cells, whereas FCF is nontoxic. FCF inhibited intimal thickening in PSV in organ culture. Contraction induced by 2'(3')-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate and intracellular calcium flux were inhibited by FCF, oxidized adenosine triphosphate, KN-62, and brilliant blue G, suggesting that FCF may inhibit the purinergic receptor P2X7. CONCLUSIONS: Our studies indicated that FCF is a nontoxic marking dye for vein grafts that ameliorates vein graft injury and prevents intimal thickening, possibly due to P2X7 receptor inhibition. FCF represents a nontoxic alternative for vein graft marking and a potentially therapeutic approach to enhance outcome in autologous transplantation of human saphenous vein into the coronary and peripheral arterial circulation.

Surgical vein graft preparation promotes cellular dysfunction, oxidative stress, and intimal hyperplasia in human saphenous vein.

INTRODUCTION: Human saphenous vein (HSV) is the most widely used bypass conduit for peripheral and coronary vascular reconstructions. However, outcomes are limited by a high rate of intimal hyperplasia (IH). HSV undergoes a series of ex vivo surgical manipulations prior to implantation, including hydrostatic distension, marking, and warm ischemia in solution. We investigated the impact of surgical preparation on HSV cellular function and development of IH in organ culture. We hypothesized that oxidative stress is a mediator of HSV dysfunction. METHODS: HSV was collected from patients undergoing vascular bypass before and after surgical preparation. Smooth muscle and endothelial function were measured using a muscle bath. Endothelial preservation was assessed with immunohistochemical staining. An organ culture model was used to investigate the influence of surgical preparation injury on the development of IH. Superoxide levels were measured using a high-performance liquid chromatography-based assay. The influence of oxidative stress on HSV physiologic responses was investigated by exposing HSV to hydrogen peroxide (H2O2). RESULTS: Surgical vein graft preparation resulted in smooth muscle and endothelial dysfunction, endothelial denudation, diminished endothelial nitric oxide synthase staining, development of increased IH, and increased levels of reactive oxygen species. Experimental induction of oxidative stress in unmanipulated HSV by treatment with H2O2 promoted endothelial dysfunction. Duration of storage time in solution did not contribute to smooth muscle or endothelial dysfunction. CONCLUSIONS: Surgical vein graft preparation causes dysfunction of the smooth muscle and endothelium, endothelial denudation, reduced endothelial nitric oxide synthase expression, and promotes IH in organ culture. Moreover, increased levels of reactive oxygen species are produced and may promote further vein graft dysfunction. These results argue for less injurious means of preparing HSV prior to autologous transplantation into the arterial circulation.

Intimal thickness associated with endothelial dysfunction in human vein grafts.

BACKGROUND: Intimal hyperplasia is a complex process thought to be initiated by injury and is the leading cause of vein graft failure. In the present investigation, we hypothesized that the basal intimal thickness in the human saphenous vein is a predictor of endothelial dysfunction and, potentially, intimal hyperplasia. METHODS: Human saphenous veins were obtained during coronary artery bypass surgery. The segments were contracted with phenylephrine and relaxed with carbachol to determine the endothelial-dependent relaxation. The vein segments were fixed in 10% buffered formalin and grown for 14 d in high-serum culture and then fixed in formalin. The fixed tissues were stained with Verhoeff-Van Gieson, and the average intimal and medial thicknesses were calculated using light microscopy and a computerized image analysis system. RESULTS: The human saphenous veins displayed varying amounts of basal intimal thickness (range 18.80-241.3 µm). The endothelial-dependent relaxation of the veins was highly variable, with values ranging from 0% to 27.59%. Human saphenous veins with a basal intimal thickness greater than 120 µm had significantly less endothelial-dependent relaxation (8.90% ± 6.32%) than those with a basal intimal thickness less than 120 µm (21.97% ± 10.64%). Endothelial dysfunction correlated with a basal intimal thickness greater than 120 µm (P = 0.02). The basal intimal thickness also correlated with increased intimal thickness after 14 d in organ culture (P = 0.0001). CONCLUSIONS: A basal intimal thickness greater than 120 µm is a predictor of endothelial dysfunction. Also, because a greater basal intimal thickness correlated with an increased intimal thickness after organ culture, the basal intimal thickness might predict vein graft failure owing to intimal hyperplasia.

Three-dimensional C-arm computed tomography reformation combined with fluoroscopic-guided sacroplasty for sacral metastases.

The aim of this retrospective study was to evaluate a sacroplasty technique, using three-dimensional C-arm CT reformation combined with fluoroscopic guidance for patients with severe painful sacral metastases. We studied the data of seven patients (average age 55.7 years) treated through trans-sacroiliac joint approach with the technique. Patients with additional thoracolumbar osteolytic metastases (five out of seven) also received concomitant vertebroplasty accordingly. Subjective significant pain relief was reported with visual analogue scale reduction ≥4 in all seven patients at 1 month after procedure, six out of seven at 3 months, and five out of six at 6 months. Pain recurrence was reported in two patients at 3 and 6 months follow-up, respectively, associated with their clinical evidence of tumor progression. One patient died from underlying disease unrelated with the procedure. Sacroplasty under three-dimensional C-arm CT reformation combined with fluoroscopic guidance was a feasible, safe, and minimally invasive procedure that could provide both the precise control of needle placement and cement injection with one imaging system.

Height restoration and wedge angle correction effects of percutaneous vertebroplasty: association with intraosseous clefts.

OBJECTIVE: To evaluate effects of vertebroplasty on restoration of vertebral body height and wedge angle and relief from pain in patients with osteoporotic compression fractures. METHODS: A retrospective study of 156 patients (232 levels) who had undergone vertebroplasty was conducted. Treated vertebrae with cleft included 49 patients (49 levels) and that without cleft 107 patients (183 levels). Effects on restoration of vertebral body height and wedge angle, and pain scores between pre- and post-procedure were statistically analyzed by using a paired-sample t test, and Kruskal Wallis test. RESULTS: The height and wedge angle of the fractured vertebral body, and pain score, improved significantly after vertebroplasty. On a vertebra-by-vertebra analysis, the vertebral body height and wedge angle in the cleft group, were statistically significantly better post-procedure (P < 0.01); in the non-cleft group, there was nosignificant improved (P > 0.05). Pain relief was not statistically significant different between the two groups (P > 0.05). CONCLUSION: Most patients experienced pain relief after vertebroplasty. After vertebroplasty, the height and wedge angle were significantly improved in the cleft group (p < 0.01), with no significant improvement in the non-cleft group (p > 0.05). Key Points • Vertebra with cleft is attributed to improvement of the spinal deformity • Vertebra without cleft was not associated with improvement of the spinal deformity • Vertebroplasty is an effective treatment strategy for osteoporotic compression fractures.

Preliminary study on a single balloon cross-midline expansion via unipedicular approach in kyphoplasty.

BACKGROUND: Recently, bilateral transpedicular kyphoplasty with a single balloon was performed for osteoporotic vertebral body compression fractures (OVCFs) to reduce the fees of the operation, but the time of operation and radiation exposure are longer. The aim of this study was to determine the safety and effectiveness of a single balloon cross-midline expansion via unipedicular approach in kyphoplasty for OVCFs. METHODS: Thirty-six patients with painful OVCFs (61 vertebrae) were enrolled in this research. Unilateral transpedicular puncture was performed under the fluoroscopy monitoring of an oblique angle down the pedicle. A single balloon was introduced through unipedicular approach. The final balloon position was in the midline of the vertebral body with the balloon cross-midline expansion and bone cement filled. Clinical outcomes were determined by comparison of the preoperative and postoperative visual analogue scale (VAS) and Oswestry disability index (ODI). Radiographic assessment included restoration of vertebral height and correction of kyphosis. Follow-up was conducted for 6 - 12 months (mean 9.2 months). RESULTS: Thirty-six consecutive patients with 61 vertebrae were successfully operated on with a mean operation time of 37.4 minutes per vertebra. All patients had dramatic pain relief and functional recovery within 96 hours after the procedure with no surgery or device-related complications. VAS score improved from 7.27 +/- 1.02 preoperatively to 2.71 +/- 0.75 postoperatively (P < 0.01). ODI score was decreased from (71.14 +/- 10.94)% preoperatively to (26.56 +/- 6.35)% postoperatively. The average loss of anterior body height was (14.33 +/- 2.76) mm before procedure and (10.03 +/- 1.83) mm after procedure (P < 0.01), while the average loss of middle body height was (10.15 +/- 2.70) mm before procedure and (5.89 +/- 1.83) mm after procedure (P < 0.01). The kyphotic deformity was corrected from (23.43 +/- 5.00) degree to (16.16 +/- 2.77) degree (P < 0.01). The pain relief and functional recovery were substantial and maintained to the last follow-up without any re-collapse or adjacent level fracture. CONCLUSIONS: A single-balloon cross-midline expansion via unipedicular approach in kyphoplasty for OVCFs is an effective and safe procedure with less cost, less operation time and less radiation exposure when compared with the conventional kyphoplasty technique.

[Percutaneous kyphoplasty with double or single balloon in treatment of osteoporotic vertebral body compressive fracture: a clinical controlled study].

OBJECTIVE: To evaluate the clinical efficacy of percutaneous bipediculary kyphoplasty with double or single balloon I treatment of osteoporosis vertebral compressive fractures. METHODS: Fifty-one patients with painful osteoporotic vertebral compressive fracture involving 69 vertebrae. 19 males and 32 females, aged 72.5 (63 - 85), underwent percutaneous kyphoplasty with double inflatable balloon (29 cases, 38 vertebrae) or single inflatable balloon (22 cases, 31 vertebrae) under X-ray fluoroscopy monitoring. The fractured vertebral bodies were punctuated, balloon was put into the subsided areas and then distended, and bone cement was injected into the cavity. The vertebral height and Cobb angle, preoperative and postoperative, were measured by radiography. Follow-up was conducted for 6 - 12 months. RESULTS: All patients tolerated the procedure well with dramatic pain relief within 96 hours after the procedure. No clinical complication was found. Visual analog scale score was improved from 7.8 preoperatively to 2.6 postoperatively (P < 0.01). Oswestry disability index was decreased from 73% preoperatively to 26% postoperatively. In the double balloon group, the heights loss of the anterior and middle portions of the vertebral body reduced from 14.7 mm and 10.5 mm to 10.1 mm and 5.5 mm respectively (both P < 0.01), and the Cobb angle was corrected from 22.4 degrees to 12.3 degrees (P < 0.01). In the single balloon group, the heights loss of the anterior and middle portions of the vertebral body reduced from 14.7 mm and 10.6 mm to 10.4 mm and 6.5 mm respectively (both P < 0.01), and the. Cobb angle was corrected averagely from 21.2 degrees to 11.6 degrees (P < 0.01). The mean vertebral height restoration rates were 72.8% and 70.1% in the double and single balloon groups respectively. The mean Cobb angle correct degrees were 10.1 degrees and 9.5 degrees in double and single balloon groups respectively. There were no significant differences in the average height restoration rate and Cobb angle correction between the double and single balloon groups (72.8% vs 70.1%, and 10.0 degrees vs 9.5 degrees both P > 0.05). The pain relief and functional recovery were substantial and maintained to the last follow up. CONCLUSION: Percutaneous bipediculary kyphoplasty with double or single balloon for painful osteoporotic vertebral body compressive fractures is effective and safe.

Calcification of Human Saphenous Vein Associated with Endothelial Dysfunction: A Pilot Histopathophysiological and Demographical Study.

While the pathophysiology and clinical significance of arterial calcifications have been studied extensively, minimal focus has been placed on venous calcification deposition. In this study, we evaluated the association between calcium deposition in human saphenous vein (HSV), endothelial function, and patient demographic risk factors. Fifty-four HSV segments were collected at the time of coronary artery bypass graft (CABG) surgery. The presence or absence of calcium deposits was visualized using the Von Kossa staining method. Endothelial function was determined by measuring muscle tissue contraction with phenylephrine and relaxation with carbachol in a muscle bath. Additional segments of vein underwent histologic evaluation for preexisting intimal thickness and extracellular matrix (ECM) deposition. Patient demographics data were obtained through our institution's electronic medical record, with patient consent. Calcium was present in 16 of 54 samples (29.6%). Veins with calcium deposits had significantly greater intimal-to-medial thickness ratios (p = 0.0058) and increased extracellular collagen deposition (p = 0.0077). Endothelial relaxation was significantly compromised in calcified veins vs. those without calcium (p = 0.0011). Significant patient risk factors included age (p = 0.001) and preoperative serum creatinine (p = 0.017). Calcified veins can be characterized as having endothelial dysfunction with increased basal intimal thickness and increased ECM deposition. Patient risk factors for calcium deposits in veins were similar to those for arteries, namely, advanced age and kidney disease. Further studies are needed to determine the effect of preexisting vein calcification on short- and long-term graft patency.

[The effects of coronary abnormalities on reconstruction of right ventricular outflow tract in patients with complex congenital heart disease].

OBJECTIVE: To explore the effects of coronary abnormalities on reconstruction of right ventricular outflow tract in patients with complex congenital heart disease. METHODS: Eighty patients, including tetralogy of Fallot 14 cases and double outlet right ventricle (DORV) 4 cases with anomalous coronary artery, underwent surgical treatment from April 1989 to May 2004. The coronary diseases included single left or right coronary artery in 11 cases, left anterior descending coronary artery originating from right coronary artery in 6 cases, vascular plexus on right outflow tract in 1 case. One-stage correction was undergone in 17 cases, palliative procedure in 1 case. The reconstruction methods were as follows: mobilizing coronary artery and expanding incision under coronary artery with pericardial patches in 4 cases; repairing ventricular septal defect (VSD) via the incision beneath the coronary artery and expanding right ventricular outlet tract (RVOT) and pulmonary via longitudinal incision over the coronary artery in 3 cases. VSD were repaired via right atrium and minimal incision on RVOT plus incision on pulmonary were made to expand RVOT. Trunk of pulmonary were anastomosis with RVOT in 3 cases. Homograft valved aorta were used in 3 cases. RESULTS: One case died of serious low cardiac output syndrome postoperatively. There was no critical complication of hemorrhage and respiratory tract. Oxygen saturation rose from 68.0% to 82.0% after treated by palliative procedure. Seventeen cases were followed from 10 months to 8 years, 1 case suddenly died with no clear cause. Three cases were with residual leak, 3 with residual obstruction. CONCLUSIONS: Surgical procedure should be selected according to the characteristics of coronary disease with complex congenital heart disease.

Brilliant blue FCF as an alternative dye for saphenous vein graft marking: effect on conduit function.

IMPORTANCE: Surgical skin markers are used off-label to mark human saphenous veins (HSVs) to maintain orientation before implantation as aortocoronary or peripheral arterial bypass grafts. These surgical skin markers impair functional responses of the HSV tissue. OBJECTIVES: To investigate the effect of brilliant blue dye 1 (brilliant blue FCF [for food coloring]; hereinafter, FCF) as a nontoxic alternative marking dye and to determine whether FCF has pharmacological properties. DESIGN, SETTING, AND PARTICIPANTS: Segments of HSVs were collected in university hospitals from patients undergoing coronary artery bypass grafting procedures immediately after harvest (unmanipulated) or after typical intraoperative surgical graft preparation (after manipulation). Rat inferior venae cavae were used to determine the pharmacological properties and cellular targets of FCF. Endothelial and smooth muscle functional responses were determined in a muscle bath, and intimal thickening in HSVs was determined after 14 days in organ culture. MAIN OUTCOMES AND MEASURES: Contractile responses were measured in force and converted to stress. Smooth muscle function was expressed as maximal responses to potassium chloride depolarization contractions. Endothelial function was defined as the percentage of relaxation of maximal agonist-induced contraction. Neointimal thickness was measured by histomorphometric analysis. RESULTS: Human saphenous veins stored in the presence of FCF had no loss of endothelial or smooth muscle function. Unmanipulated HSVs preserved in the presence of FCF demonstrated a significant increase in endothelial-dependent relaxation (mean [SEM], 25.2% [6.4%] vs 30.2% [6.7%]; P = .02). Application of FCF to functionally nonviable tissue significantly enhanced the smooth muscle responses (mean [SEM], 0.018 [0.004] × 105 N/m² vs 0.057 [0.016] × 105 N/m²; P = .05). Treatment with FCF reduced intimal thickness in organ culture (mean [SEM], -17.5% [2.1%] for unmanipulated HSVs vs -27.9% [3.7%] for HSVs after manipulation; P < .001). In rat inferior venae cavae, FCF inhibited the contraction induced by the P2X7 receptor agonist 2'(3')-O-(4-benzoyl)benzoyl-adenosine-5'-triphosphate (mean [SEM], 14.8% [2.2%] vs 6.5% [1.8%]; P = .02) to an extent similar to the P2X7 receptor antagonist oxidized adenosine triphosphate (mean [SEM], 5.0% [0.9%]; P < .02 vs control) or the pannexin hemichannel inhibitor probenecid (mean [SEM], 7.3% [1.6%] and 4.7% [0.9%] for 0.5mM and 2mM, respectively; P < .05). CONCLUSIONS AND RELEVANCE: Treatment with FCF did not impair endothelial or smooth muscle function in HSVs. Brilliant blue FCF enhanced endothelial-dependent relaxation, restored smooth muscle function, and prevented intimal hyperplasia in HSVs in organ culture. These pharmacological properties of FCF may be due to P2X7 receptor or pannexin channel inhibition. Brilliant blue FCF is an alternative, nontoxic marking dye that may improve HSV conduit function and decrease intimal hyperplasia.

Pressure control during preparation of saphenous veins.

IMPORTANCE: Long-term patency of human saphenous veins (HSVs) used as autologous conduits for coronary artery bypass grafting (CABG) procedures remains limited because of vein graft failure (VGF). Vein graft failure has been reported to be as high as 45% at 12 to 18 months after surgery and leads to additional surgery, myocardial infarction, recurrent angina, and death. Preparation of HSVs before implantation leads to conduit injury, which may promote VGF. OBJECTIVES: To investigate whether pressure distension during vein graft preparation leads to endothelial injury and intimal thickening and whether limiting intraluminal pressure during pressure distension by using a pressure release valve (PRV) preserves endothelial function and prevents neointima thickening. DESIGN, SETTING, AND PARTICIPANTS: Segments of HSVs were collected in a university hospital from 13 patients undergoing CABG procedures immediately after harvest (unmanipulated [UM]), after pressure distension (after distension [AD]), and after typical intraoperative surgical graft preparation (after manipulation [AM]). Porcine saphenous veins (PSVs) from 7 healthy research animals were subjected to manual pressure distension with or without an in-line PRV that prevents pressures of 140 mm Hg or greater. Endothelial function of the HSVs and PSVs was determined in a muscle bath, endothelial integrity was assessed, and intimal thickening in PSVs was evaluated after 14 days in organ culture. MAIN OUTCOMES AND MEASURES: Endothelial function was measured in force, converted to stress, and defined as the percentage relaxation of maximal phenylephrine-induced contraction. Endothelial integrity was assessed by immunohistologic examination. Neointimal thickness was measured by histomorphometric analysis. RESULTS: Pressure distension of HSVs led to decreased mean (SEM) endothelial-dependent relaxation (5.3% [2.3%] for AD patients vs 13.7% [2.5%] for UM patients; P < .05) and denudation. In the AM group, the function of the conduits was further decreased (-3.2% [3.2%]; P < .05). Distension of the PSVs led to reduced endothelial-dependent relaxation (7.6% [4.4%] vs 61.9% [10.2%] in the control group; P < .05), denudation, and enhanced intimal thickening (15.0 [1.4] µm vs 2.2 [0.8] µm in the control group; P < .05). Distension with the PRV preserved endothelial-dependent relaxation (50.3% [9.6%]; P = .32 vs control), prevented denudation, and reduced intimal thickening (3.4 [0.8] µm; P = .56 vs controls) in PSVs. CONCLUSIONS AND RELEVANCE: Use of a PRV during graft preparation limits intraluminal pressure generated by manual distension, preserves endothelial integrity, and reduces intimal hyperplasia. Integration of this simple device may contribute to improved long-term vein graft patency.