Because an adequate blood supply to and within tissues is an essential factor for successful tissue regeneration, promoting a functional microvasculature is a crucial factor for biomaterials. In this ...study, we demonstrate that short self-assembling peptides form scaffolds that provide an angiogenic environment promoting long-term cell survival and capillary-like network formation in three-dimensional cultures of human microvascular endothelial cells. Our data show that, in contrast to collagen type I, the peptide scaffold inhibits endothelial cell apoptosis in the absence of added angiogenic factors, accompanied by enhanced gene expression of the angiogenic factor VEGF. In addition, our results suggest that the process of capillary-like network formation and the size and spatial organization of cell networks may be controlled through manipulation of the scaffold properties, with a more rigid scaffold promoting extended structures with a larger inter-structure distance, as compared with more dense structures of smaller size observed in a more compliant scaffold. These findings indicate that self-assembling peptide scaffolds have potential for engineering vascularized tissues with control over angiogenic processes. Since these peptides can be modified in many ways, they may be uniquely valuable in regeneration of vascularized tissues.
Purpose: In an earlier report, we documented the incidence and impact of aortic branch compromise complicating acute aortic dissection (AD) over a 21-year interbval (1965-1986).
In the current study, ...management of peripheral vascular complications (PVCs) of AD over the past decade was reviewed. Methods: Medical records of patients treated for AD over the interval January 1, 1990, to December 31, 1999, were reviewed. Patients with branch compromise confirmed with radiography or operation and patients with spinal cord ischemia that was based on results of a physical examination defined the study group. Comparisons between subgroups with and without PVC over a 30-year interval were analyzed with the
χ
2 test. Results: A total of 187 patients (101 proximal and 86 distal) were treated for AD over the study interval. A total of 53 (28%) of these patients had clinical evidence of organ or limb malperfusion (7 cerebral, 3 upper extremity, 5 spinal cord, 11 mesenteric, 12 renal, and 24 lower extremity sites inclusive), and one of three (17 patients) of these underwent specific peripheral vascular intervention. The remaining 65% (36) of the PVC group had complete or partial malperfusion resolution after central aortic therapy (medical or surgical) alone. Open techniques for treating PVC included aortic fenestration (9), femorofemoral grafting (2), and aortofemoral grafting (1). All had favorable outcomes with no mortality. Endovascular procedures in five patients included abdominal aortic fenestration (3) or stenting of the renal (2), mesenteric (2), and iliac (1) arteries with clinical success in three patients and two deaths. The in-hospital mortality rate for the entire group of 187 patients was 18% (15% for proximal aortic operation, 8% in medically treated patients). The presence of aortic branch compromise was not a statistically significant predictor of the patient mortality rate (23% with and 16% without;
P= .26). Overall mortality rate in the current study (18% vs 37%;
P= .000006) and the mortality rate with PVC (23% vs 51%;
P= .001), in particular with mesenteric ischemia (36% vs 87%;
P= .026), decreased significantly when compared with prior experience. Conclusions: The overall mortality rate from AD during the past decade has decreased significantly. Similar trends were noted in patients with PVCs, a previously identified high-risk subgroup. Increased awareness and prompt, specific management of PVCs, in particular when visceral ischemia is present, have contributed to improved outcomes in patients with AD. (J Vasc Surg 2001; 33: 1185-92.)
External pneumatic compression (EPC) is effective in preventing deep vein thrombosis (DVT) and is thought to alter endothelial thromboresistant properties. We investigated the effect of EPC on ...changes in nitric oxide (NO), a critical mediator in the regulation of vasomotor and platelet function. An in vitro cell culture system was developed to simulate flow and vessel collapse conditions under EPC. Human umbilical vein endothelial cells were cultured and subjected to tube compression (C), pulsatile flow (F), or a combination of the two (FC). NO production and endothelial nitric oxide synthase (eNOS) mRNA expression were measured. The data demonstrate that in the F and FC groups, there is a rapid release of NO followed by a sustained increase. NO production levels in the F and FC groups were almost identical, whereas the C group produced the same low amount of NO as the control group. Conditions F and FC also upregulate eNOS mRNA expression by a factor of 2.08 +/- 0.25 and 2.11 +/- 0.21, respectively, at 6 h. Experiments with different modes of EPC show that NO production and eNOS mRNA expression respond to different time cycles of compression. These results implicate enhanced NO release as a potentially important factor in the prevention of DVT.
Introduction: Evidence exists that an ideal bypass conduit should have a functional endothelial cell surface combined with mechanical properties similar to those of native arteries. We hypothesized ...that the effect of combined arterial levels of pulsatile shear stress, flow, and cyclic strain would enhance saphenous venous endothelial cell nitric oxide (NO) production, and that variations in these “ideal” conditions could impair this function. We studied NO production as a measure of endothelial function in response to different hemodynamic conditions.
Methods: Human adult saphenous venous endothelial cells were cultured in 10-cm silicone tubes, similar in diameter (5 mm) and compliance (6%) to a medium-caliber peripheral artery (eg, popliteal). Tube cultures were exposed to arterial conditions: a combined pressure (120/80 mm/Hg; mean, 100 mm/Hg), flow (mean, 115 mL/min) and cyclic strain (2%), with a resultant pulsatile shear stress of 4.8 to 9.4 dyne/cm
2 (mean, 7.1). Identical tube cultures were used to study variations in these conditions. Modifications of the system included a noncompliant system, a model with nonpulsatile flow, and a final group exposed to pulsatile pressure with no flow. NO levels were measured with a fluorometric nitrite assay of conditioned media collected at 0, 0.25, 0.5, 1, 2, and 4 hours. Experimental groups were compared with cells exposed to nonpulsatile, nonpressurized low flow (shear stress 0.1 dyne/cm
2) and static cultures.
Results: All experimental groups had greater rates of NO production than cells under static conditions (
P < .05). Cells exposed to ideal conditions produced the greatest levels of NO. Independent decreases in compliance, flow, and pulsatility resulted in significantly lower rates of NO production than those in the group with these conditions intact (vs noncompliant
P < .05, vs nonflow
P < .05, and vs nonpulsatile
P < .05).
Conclusions: Our results show that in the absence of physiologically normal pulsatility, cyclic strain, and volume flow, endothelial NO production does not reach the levels seen under ideal conditions. Pulsatile flow and compliance (producing flow with cyclic stretch) play a key role in NO production by vascular endothelium in a three-dimensional hemodynamically active model. This correlates biologically with clinical experience linking graft inflow and runoff and the mechanical properties of the conduit to long-term patency. (J Vasc Surg 2001;33:1199-205.)
Purpose: This report reviews our recent experience with nine patients who had intramural hematoma of the thoracic aorta.
Methods: This was a retrospective study of all patients who had intramural ...hematoma at our institution from 1989 to 1994. Patients who had identifiable intimal flap, tear, or penetrating aortic ulcer were excluded from the study.
Results: Among these nine elderly patients (mean age, 76 years), the most common presentation was chest or back pain. Intramural hematoma was diagnosed by a variety of high-resolution imaging techniques. The descending thoracic aorta alone was involved in seven patients, whereas the ascending aorta was affected in the other two patients. One patient had evidence of an aneurysm (5.0 cm diameter) in the region of the hematoma. All patients were initially managed nonsurgically with blood pressure control. Both patients who had ascending aortic involvement had progression of aortic hematoma, which resulted in death in one case and in successful surgery in the other. Six of the seven patients who had descending aortic involvement alone were successfully managed without aortic surgery. The patient who had intramural hematoma and associated aortic aneurysm, however, had severe, recurrent pain and underwent successful aortic replacement. Another patient had recurrent pain associated with hypertension, but was successfully managed nonsurgically with antihypertensive therapy. All eight survivors are doing well at a median follow-up of 19 months.
Conclusions: Intramural hematoma appears to be a distinct entity, although overlap with aortic dissection or penetrating aortic ulcer exists. Aggressive control of blood pressure with intensive care unit monitoring has been our initial management. Patients who have involvement of the descending thoracic aorta alone can frequently be managed without surgery in the absence of coexisting aneurysmal dilatation or disease progression. Our experience suggests that a more aggressive approach with early surgery is warranted in patients who have ascending aortic involvement or those who have coexisting aneurysm and intramural hematoma. (J Vasc Surg 1996;24;1022-9.)
Purpose: To determine the safety, effectiveness, and problems encountered with endovascular repair of abdominal aortic aneurysm (AAA). Initial experience with endoluminal stent grafts was examined ...and compared with outcome for a matched concurrent control group undergoing conventional operative repair of AAA.
Methods: Over a 3-year period, 30 patients underwent attempts at endovascular repair of infrarenal AAA. Of the 28 (93%) successfully implanted endografts, 8 were tube endografts, 8 bifurcated grafts, and 12 aortouniiliac grafts combined with femorofemoral bypass. Most of the procedures were performed in the past year because the availability of bifurcated and aortoiliac endografts markedly expanded the percentage of patients with AAA who might be treated with endoluminal methods. The follow-up period ranged from 1 to 44 months, with a mean value of 11 months.
Results: Endovascular procedures demonstrated significant advantages with respect to reduced blood loss (408 versus 1287 ml), use of an intensive care unit (0.1 versus 1.75 days), length of hospitalization (3.9 versus 10.3 days), and quicker recovery (11 versus 47 days). Although the total number of postoperative complications was identical for the two groups, the nature of the complications differed considerably. Local and vascular complications characteristic of endovascular repair could frequently be corrected at the time of the procedure and tended to be less severe than systemic or remote complications, which predominated among the open surgical repair group. On an intent-to-treat basis, 23 (77%) of the 30 AAAs were successfully managed with endoluminal repair. The seven (23%) failures were attributable to two immediate conversions caused by access problems, three persistent endoleaks, one late conversion caused by AAA expansion, and one late rupture.
Conclusions: Although less definitive than those for conventional operations, these early results suggest that endovascular AAA repair offers considerable benefits for appropriate patients. The results justify continued application of this method of AAA repair, particularly in the treatment of older persons at high risk. (J Vasc Surg 1998;27:992-1005.)
Purpose: This report summarizes our experience with epidural cooling (EC) to achieve regional spinal cord hypothermia and thereby decrease the risk of spinal cord ischemic injury during the course of ...descending thoracic aneurysm (TA) and thoracoabdominal aneurysm (TAA) repair.
Methods: During the interval July 1993 to Dec. 1995, 70 patients underwent TA (n = 9, 13%) or TAA (n = 61) (type I, 24 34%, type II, 11 15%, type III, 26 37%) repair using the EC technique. The latter was accomplished by continuous infusion of normal saline (4° C) into a T11-12 epidural catheter; an intrathecal catheter was placed at the L3-4 level for monitoring of cerebrospinal fluid temperature (CSFT) and pressure (CSFP). All operations (one exception, atriofemoral bypass) were performed with the clamp-and-sew technique, and 50% of patients had preservation of intercostal vessels at proximal or distal anastomoses (30%) or by separate inclusion button (20%). Neurologic outcome was compared with a published predictive model for the incidence of neurologic deficits after TAA repair and with a matched (Type IV excluded) consecutive, control group (n = 55) who underwent TAA repair in the period 1990 to 1993 before use of EC.
Results: EC was successful in all patients, with a 1442 ± 718 ml mean (range, 200 to 3500 ml) volume of infusate; CSFT was reduced to a mean of 24° ± 3° C during aortic cross-clamping with maintenance of core temperature of 34° ± 0.8± C. Mean CSFP increased from baseline values of 13 ± 8 mm Hg to 31 ± 6 mm Hg during cross-clamp. Seven patients (10%) died within 60 days of surgery, but all survived long enough for evaluation of neurologic deficits. The EC group and control group were well-matched with respect to mean age, incidence of acute presentations/aortic dissection/aneurysm rupture, TAA type distribution, and aortic cross-clamp times. Two lower extremity neurologic deficits (2.9%) were observed in the EC patients and 13 (23%) in the control group (p < 0.0001). Observed and predicted deficits in the EC patients were 2.9% and 20.0% (p = 0.001), and for the control group 23% and 17.8% (p = 0.48). In considering EC and control patients (n = 115), variables associated with postoperative neurologic deficit were prolonged (>60 min) visceral aortic cross-clamp time (relative risk, 4.4; 95% CI, 1.2 to 16.5; p = 0.02) and lack of epidural cooling (relative risk, 9.8; 95% CI, 2 to 48; p = 0.005).
Conclusion: EC is a safe and effective technique to increase the ischemic tolerance of the spinal cord during TA or TAA repair. When used in conjunction with a clamp-and-sew technique and a strategy of selective intercostal reanastomosis, EC has significantly reduced the incidence of neurologic deficits after TAA repair. (J Vasc Surg 1997;25:234-43.)
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