Fabio A. Kudo

Venous Identity Is Lost but Arterial Identity Is Not Gained During Vein Graft Adaptation

Objectives—Ephrin ligands and Eph receptors are signaling molecules that are differentially expressed on arteries and veins during development. We examined whether Eph-B4, a venous marker, and Ephrin-B2, an arterial marker, are regulated during vein graft adaptation in humans and aged rats. Methods and Results—Eph-B4 transcripts and immunodetectable protein are downregulated in endothelial and smooth muscle cells of patent vein grafts in both humans and in aged rats, whereas Ephrin-B2 transcripts and protein are not strongly induced. Other markers of arterial identity, including dll4 and notch-4, are also not induced during vein graft adaptation in aged rats. Because VEGF-A is upstream of the Ephrin–Eph pathway, and expression of VEGF-A is induced only at early time points after exposure of the vein to the arterial environment, we inhibited VEGF-A in vein grafts using an siRNA-based approach. Vein grafts treated with siRNA directed against VEGF-A demonstrated a thicker intima-media containing α-actin, consistent with arterialization, but did not contain Eph-B4 or Ephrin-B2. Conclusions—Venous identity is preserved in the veins of aged animals, but is lost during adaptation to the arterial circulation; arterial markers are not induced. Markers of vessel identity are plastic in adults and their selective regulation may mediate vein graft adaptation to the arterial environment in aged animals and humans.

Postoperative renal function after elective abdominal aortic aneurysm repair requiring suprarenal aortic cross-clamping.

PurposeTo examine postoperative renal function after suprarenal aortic cross-clamping performed without renal hypothermia in patients undergoing elective abdominal aortic aneurysm (AAA) surgery.MethodsBetween 1991 and 2000, 18 patients underwent surgery for a juxtarenal AAA, which required a suprarenal aortic cross-clamp. All AAAs were repaired with a proximal anastomosis just below the renal arteries. We divided the patients into two groups according to the duration of the renal ischemia: <45 min (n = 12) and ≥45 min (n = 6). The postoperative changes in renal function were analyzed.ResultsThere were no hospital deaths and none of the patients needed permanent hemodialysis. The postoperative peak in the serum creatinine level after suprarenal cross-clamping for ≥45 min was significantly higher than that after cross-clamping for <45 min. The percentage changes in serum creatinine and blood urea nitrogen were correlated positively with the duration of renal ischemia, and were significantly greater in the group with renal ischemia of <45 min than in the group with prolonged renal ischemia (≥45 min).ConclusionsSuprarenal aortic cross-clamp without performing renal hypothermia is safe and able to be tolerated well by the patient during elective AAA surgery, although careful attention must be paid to limiting the period of renal ischemia.

Use of bioresorbable membrane to prevent postoperative small bowel obstruction in transabdominal aortic aneurysm surgery.

PurposeTo evaluate the efficacy of Seprafilm (Genzyme, Cambridge, MA, USA), a bioresorbable membrane, in preventing or reducing early postoperative small bowel obstructions after transabdominal abdominal aortic aneurysm (AAA) surgery.MethodsFifty-one patients underwent aortic reconstruction via a midline transperitoneal approach for infrarenal AAAs. Twenty-one patients underwent surgery with Seprafilm (Seprafilm group) and the remaining 30 patients did not (control group). The incidence of early small bowel obstruction was examined, and the time before liquid and solid diet were resumed was also compared to assess postoperative paralytic ileus.ResultsPatients in the Seprafilm group resumed a liquid diet on postoperative day (POD) 2.4 ± 1.1 and a solid diet on POD 4.0 ± 1.3, whereas the patients in the control group resumed a liquid diet on POD 3.3 ± 1.9 and a solid diet on POD 5.4 ± 3.4. These values were not significantly different between the two groups; however, the incidence of early postoperative small bowel obstruction was significantly lower (P < 0.05) in the Seprafilm group (0/21) than in the control group (6/30).ConclusionThese findings suggest that Seprafilm may help to prevent early postoperative small bowel obstructions after transabdominal AAA surgery.

Stripping operation with preservation of the calf saphenous veins for primary varicose veins: hemodynamic evaluation.

PURPOSE To study early changes in venous hemodynamics in stripping operation with preservation of the calf saphenous veins. PATIENTS AND METHODS From October 1999 to December 2000, 110 extremities of 73 patients were treated for primary varicose veins. Based on preoperative ascending venography, 40 extremities underwent the groin-to-knee stripping of the GSV, 20 underwent the proximal division of the LSV, and 50 received combinations of both surgeries. To evaluate venous hemodynamic changes, air plethysmography was performed before operation and 7-14 days after operation. RESULTS The venous volume, venous filling index and residual volume fraction were improved after surgery, but the ejection fraction did not change. The overall incidence of nerve injury was 4.5% (five limbs). CONCLUSIONS In stripping operations, the preservation of the calf saphenous veins, which is shown to be advantageous in reducing saphenous or sural nerve injuries, does not adversely affect early venous hemodynamic improvement.

Improved healing of small-caliber, long-fibril expanded polytetrafluoroethylene vascular grafts by covalent bonding of fibronectin

PurposeTo evaluate the intermediate performance of small-caliber, long-fibril expanded polytetrafluoroethylene (ePTFE) vascular grafts pretreated with covalent bonding of fibronectin in dogs.MethodsSmall-caliber (4 mm), long-fibril (60 µm), ePTFE vascular grafts, 10 cm in length, were pretreated by covalent bonding of fibronectin. Bilateral iliac grafting was done in dogs using a fibronectin-bonded graft on one side and a nonbonded control graft on the other side. The grafts were retrieved 12 weeks after implantation, and subjected to histomorphometric analysis.ResultsAlthough the patency rates of the fibronectin-bonded and control grafts were the same (3/7, 43%), the fibronectin-bonded grafts showed almost complete neointimal healing, whereas the nonbonded control grafts showed only partial neointimal healing, proximally and distally.ConclusionsSmall-caliber, long-fibril ePTFE vascular grafts with covalent bonding of fibronectin achieved almost complete neointimal healing by the time of retrieval at 12 weeks. This indicates that, with further modifications, our new technique for covalent bonding of fibronectin has great potential in the development of small-caliber arterial prosthetic grafts.

Successful Endovascular Stent-Graft Treatment for an Aortoesophageal Fistula Caused by a Descending Thoracic Aortic Aneurysm : Report of a Case

Conventional surgery for aortoesophageal fistula (AEF) is technically difficult, and is associated with high morbidity and mortality. We report a case of primary AEF caused by a descending thoracic aortic aneurysm, which was successfully treated with an endovascular stent-graft technique. The patient has been followed up for 3 years with no signs of infection.

Age-Related Neointimal Hyperplasia Is Associated With Monocyte Infiltration After Balloon Angioplasty

Carotid angioplasty is associated with adverse events in elderly patients; it is unclear whether this is related to an altered inflammatory axis. The carotid arteries of young (6 months) or aged (22-24 months) Fischer 344 rats were balloon injured. Aged rats had reduced lumen area (0.18 ± 0.03 vs 0.24 ± 0.01 mm(2), p = .02) and increased neointimal thickening (0.15 ± 0.04 vs 0.08 ± 0.03 mm(2), p = .006). Aged rats had increased circulating monocytes (96 ± 21 vs. 54 ± 7; p = .002) as well as increased numbers of monocytes at the post-angioplasty site. Aged rats had sustained monocyte chemotactic protein-1 expression after angioplasty but young rats did not. Aged arteries also exhibited defective vasorelaxation and abnormal eNOS localization. Aged (≥80 years) human patients with high-grade carotid stenosis had increased number of monocytes (9.1% ± 0.4%) compared with younger (65-80 years) patients (8.1% ± 0.3%, p = .013). Aged rats develop neointimal hyperplasia after carotid angioplasty with increased numbers of monocytes, and elderly humans with carotid stenosis have increased numbers of circulating monocytes. These preliminary results may suggest a role for monocytes in the response to carotid angioplasty.

Left renal vein anomaly associated with abdominal aortic aneurysm surgery: Report of a case

Retroaortic left renal vein occurs infrequently and poses potential hazards to the surgeon during abdominal aortic surgery. We herein report the case of a 77-year-old man with a retroaortic left renal vein who underwent an abdominal aortic aneurysm (AAA) repair. The retroaortic left renal vein was diagnosed preoperatively by contrast-enhanced computed tomography (CT). The patient underwent a successful abdominal aortic replacement with an uneventful postoperative course without any renal complications. The CT scan was useful for both evaluating the AAA and for establishing the presence of the venous anomaly. Major venous anomalies (retroaortic left renal vein, left renal vein collar, left-sided inferior vena cava, and caval duplication) should thus be taken into consideration in AAA operations.

Repair of False Para-anastomotic Aortic Aneurysms Using an Endovascular Stent Graft Technique in a Patient with Severe Pulmonary Disease: Report of a Case

Abstract Conventional surgery for para-anastomotic aortic aneurysms is technically challenging, and is associated with high morbidity and mortality. This report describes the case of a patient with severe pulmonary diseases in whom false para-anastomotic aortic aneurysms were successfully repaired using an endovascular stent graft technique.

Age-related Notch-4 quiescence is associated with altered wall remodeling during vein graft adaptation.

BACKGROUND The link of aging to specific mechanisms of vascular biology is not well understood. We have previously shown that aging is associated with increased vein graft wall thickness and that this process involves the VEGF-Delta/Notch-ephrin/Eph cascade. Therefore, we examined whether Dll-4 or Notch-4 are differentially expressed, according to age, during vein graft adaptation. MATERIALS AND METHODS Vein grafts were performed in 6-mo and 24-mo Fischer 344 rats. Gene expression was analyzed by quantitative real-time PCR, and the distribution of Dll-4 and Notch-4 was observed by immunofluorescence. RESULTS The expression of Dll-4 and Notch-4 was reduced in vein grafts performed in aged rats compared with the expression in young adult rats. Both Dll-4 and Notch-4 were distributed in vein graft endothelium as well as the outer adventitia, with reduced amounts in the outer adventitia of aged vein grafts. Aged veins had reduced eNOS membrane targeting and colocalization with caveolin-1 as well as reduced eNOS protein expression in comparison to young adult veins. In an exchange model between young and aged animals, heterogeneous vein grafts (Yo(Ag) and Ag(Yo)) showed significantly thicker neointima compared with young (Yo(Yo)) controls, and had Notch-4-positive cells, but not Dll-4-positive cells, diminished in the adventitia. Vein grafts that were air-denuded of endothelium did not show any adaptation to the arterial environment and also lacked both Dll-4 and Notch-4 expression at 3 wk. CONCLUSIONS During vein graft adaptation to the arterial environment, both Dll-4 and Notch-4 expression are down-regulated in an aged, but not a young, background. Loss of Notch-4 is associated with loss of attenuation of neointima. The delta-Notch signaling pathway may be active during vein graft adaptation.