Emergency procedures on the descending thoracic aorta in the endovascular era.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR), initially developed for the treatment of degenerative aneurysms of the descending thoracic aorta, has been applied to the entire spectrum of descending thoracic aortic pathology in both the elective and emergent settings. This single center study evaluates the effectiveness of TEVAR for the treatment of acute surgical emergencies involving the descending thoracic aorta, including traumatic aortic disruption (TAD), ruptured descending thoracic aneurysm (RDTA), and acute complicated Type B dissection (cTBD). METHODS: A retrospective review of the medical records of all patients undergoing emergent TEVAR at the University of Mississippi Medical Center between August 2007 and November 2010 was undertaken. Patients were studied for 30-day survival, complications, type of device used for the repair, and technical aspects of the procedure. RESULTS: A total of 44 patients (59% male) with an average age of 49 years (range, 16-87 years) underwent emergent TEVAR during the study period. The technical success rate was 100%, with no patient requiring emergent open surgery for conditions involving the descending thoracic aorta at our institution during the study period. The majority (73%) of the repairs were accomplished using commercially available thoracic stent grafts. Abdominal endograft proximal extension cuffs were used in 12 (38%) of the 32 patients undergoing repair of TAD. Twenty-one patients (48%) required coverage of the left subclavian artery, two (10%) of whom subsequently required subclavian artery revascularization. Procedure-related complications included two strokes, one spinal cord ischemia, one unintentional coverage of the left carotid artery, one episode of acute renal failure, and three access site injuries. One patient undergoing repair of TAD had collapse of the stent graft in the early postoperative period. He was successfully treated by placement of an additional stent graft. Seven patients (16%) died within 30 days of surgery. Three of the deaths occurred in patients who had successfully undergone repair of a TAD and died of associated injuries. CONCLUSIONS: Emergent TEVAR has become the treatment of choice for acute surgical emergencies involving the descending thoracic aorta. Short-term morbidity and mortality compare favorably with historic results for emergent open surgical procedures on the descending thoracic aorta. Survival is highest in patients undergoing repair of TAD. Using current endograft technology, nearly all emergent conditions of the descending thoracic aorta can be successfully treated with TEVAR.

Double-barrel technique for endovascular exclusion of an aortic arch aneurysm without sternotomy.

PURPOSE: To report the use of commercially available stents and a stent-graft in coaxial orientation to extend the proximal limits of endografting within the aortic arch. CASE REPORT: A 70-year-old man was found to have an asymptomatic 7-cm saccular aortic arch aneurysm, extending distally from the origin of the left carotid artery and involving the left subclavian artery; there was only 11 mm between the innominate artery orifice and the aneurysm. The patient was deemed to be high risk for open surgical repair due to a history of 2 prior sternotomies and the requirement for hypothermic circulatory arrest. A "double-barrel" stent-graft strategy combining retrograde placement of an innominate stent with thoracic stent-graft implantation into zone 0 was successfully executed. The patient has continued to fare well after 10 months on close follow-up. CONCLUSION: The "double-barrel" stent technique may extend the limits of thoracic endografting by preserving the aortic arch branches while avoiding the need for sternotomy. Using this technique, proximal fixation can be obtained well into the ascending aorta using commercially available devices.

Contemporary standards for the diagnosis and treatment of heparin-induced thrombocytopenia (HIT).

BACKGROUND: Heparin binding to platelet factor 4 (PF4) generates a new antigenic epitope. In an unpredictable fashion, as many as approximately 17% of patients treated with unfractionated heparin (UFH) and approximately 8% treated with low-molecular-weight heparin (LMWH) subsequently develop the anti-heparin-PF4 antibodies that mediate heparin-induced thrombocytopenia and thrombosis (HIT). Very few of those patients with circulating anti-heparin-PF4 antibodies, however, progress to develop clinical HIT (referred to previously as Type II HIT). Only 20% of those who harbor antibodies ( approximately 3% of those exposed to heparin) will manifest the thrombocytopenia subsequently. Even fewer patients (0.03% to 0.09% of those exposed to heparin) experience the marked platelet activation and morbid thromboses characteristic of the HIT syndrome. The pathogenesis of heparin-induced thrombocytopenia (HIT) remains elusive. The pathophysiologic understanding to date has revolved around pathogenic anti-heparin-PF4 antibodies that trigger platelet activation, release of platelet procoagulant microparticles, and resultant thrombosis. The clinical diagnosis of HIT is confusing because current assays to detect anti-heparin-PF4 antibodies do not correlate well with the disease. Currently available assays lack either adequate sensitivity and interlaboratory reproducibility (ie, functional serotonin release assays) or specificity (ie, enzyme-linked immunosorbent assays or ELISAs). CONCLUSIONS: Fortunately, the treatment for HIT is not confusing. The purposes of this review are as follows: (1) to examine the relevant clinical definition of HIT, (2) to explore our current understanding as to the pathogenesis of HIT, and (3) to present an algorithm for the identification and treatment of the HIT syndrome.

Slower onset of low shear stress leads to less neointimal thickening in experimental vein grafts.

Vein grafts respond to low flow and shear stress (tau(w)) by generating thicker walls and smaller lumens through the processes of neointimal hyperplasia and remodeling. Clinically, however, vein grafts with obviously low tau(w), such as those distal to high-grade proximal obstructions, are not infrequently found to be widely patent and pliable. One possible explanation for this phenomenon may be that vein grafts remodel more favorably in response to changes in shear that occur gradually over time compared to abruptly. This hypothesis was tested in an experimental animal model in this report. Two separate models of experimental vein graft failure were created, causing either immediate exposure to ultralow tau(w) (<1 dyne/cm2) or delayed exposure to ultralow tau(w). Under general anesthesia and using a sterile technique, the right external jugular (EJ) veins of 28 New Zealand white rabbits were surgically exposed and isolated. An end-to-side distal EJ/common carotid artery anastomosis was created, resulting in a widely patent arteriovenous fistula. For the immediate exposure group (n = 5), the EJ was suture-ligated just proximal to the thoracic inlet, distal to a small 10-50 microm venous tributary. This created a reversed vein segment immediately and abruptly exposed to high wall tension (2.0 +/- 0.3 x 10(4) dyne/cm) and ultralow tau(w) (0.15 +/- 0.08 dyne/cm2). For the delayed exposure group (n = 22), the EJ was ligated over a 0.035 guidewire, leaving a small aperture to sustain some measure of blood flow and tau(w). This predictably resulted in slightly less wall tension (1.4 +/- 0.2 x 10(4) dyne/cm) and higher tau(w) (0.68 +/- 0.21 dyne/cm2) than the immediate exposure group. During the first week, the small outflow aperture in the delayed exposure grafts thrombosed, eventually exposing them to the same low level of tau(w) as the immediate exposure grafts. Thus, the only difference in the two models was that delayed exposure grafts enjoyed a slower decline in tau(w) than immediate exposure grafts. Fourteen rabbits in the delayed exposure group were harvested over the first 7 days to define the patency curve of the restricted outflow channel. As expected, the small aperture had thrombosed in all animals by 7 days. The remaining 14 grafts were harvested after 4 weeks, and 13/14 remained patent. Examination of the hemodynamic parameters at the time of death confirmed that wall tension and tau(w) had equalized (wall tension 0.9 +/- 0.1 vs. 1.1 +/- 0.1 x 10(4) dyne/cm, tau(w) 0.45 +/- 0.12 vs. 0.30 +/- 0.08 dyne/cm2). Histological examination revealed less neointimal hyperplasia in the delayed exposure group compared to the immediate exposure group (wall thickness 266 +/- 16 vs. 180 +/- 24 microm, p = 0.025) as well as a slightly greater luminal diameter (0.30 +/- 0.02 vs. 0.40 +/- 0.02 cm, p = 0.038). The results of this experiment suggest that slow exposure to reduced tau(w) results in more favorable remodeling (less thickening) than abrupt exposure. This finding may explain the occasional clinical observation of a widely patent vein graft even in the face of proximal arterial obstruction and very low flow; the change in tau(w) presumably occurred slowly mitigating the remodeling response.

Ureteroarterial fistula with ruptured anastomotic pseudoaneurysm: successful management with vascular exclusion, extra-anatomic bypass and nephrectomy--a case report.

Ureteroarterial fistula is a rare but life-threatening condition most often arising as a consequence of combined vascular and urologic pathology. Only about 70 cases are reported in the English literature. Principles of repair include complete vascular isolation, extra-anatomic bypass, and urinary stream diversion away from major vascular conduits. The case presented herein is only the second reported instance of fistulization to an anastomotic pseudoaneurysm of an iliopopliteal bypass.

Modulation of vascular remodeling induced by a brief intraluminal exposure to the recombinant R7020 strain of Herpes simplex-1.

OBJECTIVE: Vascular remodeling in response to injury or low shear stress (or both) is characterized by neointimal hyperplasia and luminal contraction. When profound, the response leads to restenosis after percutaneous endovascular intervention as well as to de novo stenosis in vein grafts. It has recently been reported that exposure of vein patches to neurovirulence-attenuated Herpes simplex virus-1 (HSV-1) decreases neointimal hyperplasia and increases luminal area. This experiment tested the hypothesis that R7020, a more highly attenuated mutant of HSV-1, would modulate the vascular remodeling response of experimental vein grafts chronically exposed to low shear stress. METHODS: The external jugular veins of 31 New Zealand white rabbits were clamped and intraluminally exposed to vehicle (phospate-buffered saline solution, n = 11), R7020 2.5 x 10(8) plaque forming units [PFU]/mL (n = 8), or R7020 2.5 x 10(9) PFU/mL (n = 12) for 10 or 30 minutes at an average pressure of 80 mm Hg. After exposure, an end-to-side distal external jugular-to-common carotid artery anastomosis was created, resulting in a widely patent arteriovenous fistula. The external jugular was suture-ligated just proximal to the thoracic inlet, distal to a small 10- to 50-microm venous tributary, creating a reversed vein "graft" segment immediately and abruptly exposed to arterial pressure (48 +/- 3 mm Hg) and low shear stress (0.12 +/- .02 dyne/cm(2)). In the 29 animals (N = 31) that survived to harvest, 26 grafts were found to be patent and were analyzed further. Nine grafts were harvested within the first week after operation, snap frozen in liquid nitrogen, and assayed for the presence of the Herpes viral immediate-response protein ICP0 by Western blot analysis. The 17 remaining grafts were perfusion-fixed, excised, stained, and analyzed morphometrically by digital planimetry. RESULTS: In patent grafts, the hemodynamic environment of low shear stress was maintained (shear stress at harvest, 0.26 +/- .06 dyne/cm(2)). Western blot analysis revealed the presence of ICP0 in R7020-exposed vein grafts after 2, 3, 7, and 14 days; ICP0 was not detected in unexposed vein grafts or adjacent carotid arteries. After 4 weeks, vein grafts exposed to R7020 exhibited a statistically significantly increased ratio of luminal radius to wall thickness, indicating altered remodeling (vehicle, 6.7 +/- 1.3; R7020 2.5 x 10(8), 9.1 +/- 1.3; R7020 2.5 x 10(9) ratio, 11.3 +/- 1.4; P < .05 for high dose compared with vehicle). CONCLUSION: A brief exposure of the neurovirulence-attenuated HSV-1 strain R7020 results in an increased ratio of luminal radius to wall thickness in experimental vein grafts chronically exposed to low shear stress.

Gene therapy for the extension of vein graft patency: a review.

The mainstay of treatment for long-segment small-vessel chronic occlusive disease not amenable to endovascular intervention remains surgical bypass grafting using autologous vein. The procedure is largely successful and the immediate operative results almost always favorable. However, the lifespan of a given vein graft is highly variable, and less than 50% will remain primarily patent after 5 years. The slow process of graft malfunction is a result of the vein's chronic maladaptive response to the systemic arterial environment, its primary component being the uncontrolled proliferation of vascular smooth muscle cells (SMCs). It has recently been suggested that this response might be attenuated through pre-implantation genetic modification of the vein, so-called gene therapy for the extension of vein graft patency. Gene therapy seems particularly well suited for the prevention or postponement of vein graft failure since: (1) the stimulation of SMC proliferation appears to largely be an early and transient process, matching the kinetics of current gene transfer technology; (2) most veins are relatively normal and free of disease at the time of bypass allowing for effective gene transfer using a variety of systems; and (3) the target tissue is directly accessible during operation because manipulation and irrigation of the vein is part of the normal workflow of the surgical procedure. This review briefly summarizes the current knowledge of the incidence and basic mechanisms of vein graft failure, the vector systems and molecular targets that have been proposed as possible pre-treatments, the results of experimental genetic modification of vein grafts, and the few available clinical studies of gene therapy for vascular proliferative disorders.

Limb salvage after infrainguinal bypass graft failure.

OBJECTIVE: The purpose of this study was to examine the outcome of patients in whom an infrainguinal bypass graft failed. METHODS: This was a retrospective analysis of consecutive patients undergoing infrainguinal bypass grafting in a single institution over 8 years. RESULTS: Six hundred thirty-one infrainguinal bypass grafts were placed in 578 limbs in 503 patients during the study period. The indication for surgery was limb-threatening ischemia in 533 patients (85%); nonautologous conduits were used in 259 patients (41%), and 144 (23%) were repeat operations. After a mean follow-up of 28 +/- 1 months (median, 23 months; range, 0-99 months), 167 grafts (26%) had failed secondarily. The rate of limb salvage in patients with graft failure was poor, only 50% +/- 5% at 2 years after failure. The 2-year limb salvage rate depended on the initial indication for bypass grafting: 100% in patients with claudication (n = 16), 55% +/- 8% in patients with rest pain (n = 49), and 34% +/- 6% in patients with tissue loss (n = 73; P <.001). The prospect for limb salvage also depended on the duration that the graft remained patent. Early graft failure (<30 days; n = 25) carried a poor prognosis, with 2-year limb salvage of only 25% +/- 10%; limb salvage was 53% +/- 5% after intermediate graft failure (<2 years, n = 110) and 79% +/- 10% after late failure (>2 years, n = 15; P =.04). Multivariate analysis revealed shorter patency interval before failure (P =.006), use of warfarin sodium (Coumadin) postoperatively (P =.006), and infrapopliteal distal anastomosis (P =.01) as significant predictors for ultimate limb loss. CONCLUSION: The overall prognosis for limb salvage in patients with failed infrainguinal bypass grafts is poor, particularly in patients with grafts placed because of tissue loss and those with early graft failure.

Catheter-directed thrombolysis for deep venous thrombosis.

Venous thromboembolism (VTE) represents a significant clinical problem, affecting patients of all age groups, nationalities, and socioeconomic strata. Despite its prevalence, the paradigms for care are largely centered around primary or secondary prophylaxis, with less emphasis on actual treatment of the thrombus. With the recent rapid development of advanced endovascular techniques, it is now feasible to dissolve many thrombi using catheter-directed thrombolysis (CDT), and favorable clinical experience has been reported in over 600 patients. If performed safely, the purported benefits of CDT for DVT include a decreased incidence of persistent phlebitic symptoms, improved quality of life and, possibly, a decreased incidence of recurrent thrombotic events.

Theoretical hydraulic consequences of vein graft taper.

OBJECTIVE: Internal diameter is a strong predictor of patency of infrainguinal vein grafts. However, most vein grafts are tapered, with variable diameter along their length. It is unknown which diameter is most important in determining graft resistive properties, that is, its mean diameter, minimum diameter, or some geometric combination thereof. The purpose of this analysis was to examine the hydraulic consequences of vein graft tapering, with longitudinal impedance (Z(L)), a conduit-specific measure of pulsatile resistance along straight rigid tubes. METHODS: Proximal and distal graft pressure, pressure gradient (DeltaP), and blood flow (Q) were measured intraoperatively in a 100 cm bypass graft and digitally recorded for 10 seconds at 200 Hz. With the Womersley solution for fully developed fluid flow in a rigid tube, a series of DeltaP waveforms were generated for graft diameters ranging from 1.2 to 8.2 mm. With an axisymmetric form of the Navier-Stokes equations, a second series of DeltaP waveforms were computed for grafts with long smooth symmetric tapers ranging from 0% to 90%, with geometric mean diameter of 3.2, 4.2, and 5.2 mm (%Taper = 100 x [proximal diameter - distal diameter]/proximal diameter). For each set of DeltaP and Q, Z(L) was calculated as DeltaP/Q, plotted over a range of 8 Hz, and integrated over 4 Hz to yield integral Z(L). RESULTS: The architecture of the calculated DeltaP and Z(L) waveforms closely approximated their measured counterparts, validating the method. As expected, Z(L) was highly diameter-dependent in a nonlinear fashion. With a clinically relevant boundary of less than 50 x 10(3) dyne/cm(5) as "acceptable," the minimum acceptable diameter of nontapered 100 cm bypass conduits was 4.3 mm. Analysis of graft taper revealed that small amounts of taper in large conduits were well-tolerated. For example, introduction of 32% taper in a 5.2 mm graft (6.2 mm --> 4.2 mm) caused only an 8% increase in integral Z(L) (from 32 to 35 x 10(3) dyne/cm(5)). More pronounced taper in smaller conduits rendered them unacceptable. For example, 53% taper of a 4.2 mm graft (5.7 mm --> 2.7 mm) created a conduit with integral Z(L) of 70 x 10(3) dyne/cm(5), well above the acceptable limit. The relationship between Z(L) and percent taper was nonlinear and strongly dependent on mean diameter. CONCLUSIONS: The relationship between Z(L) and diameter in vein grafts is nonlinear; thus Z(L) increases rapidly in conduits smaller than 4 mm. Tapered vein grafts behave hydraulically like nontapered grafts, provided their geometric mean is greater than 4 mm and their degree of taper is less than 40%. Tapered veins are satisfactory conduits for long-segment bypass grafts, provided their mean diameter is acceptable.

Sustained inhibition of experimental neointimal hyperplasia with a genetically modified herpes simplex virus.

OBJECTIVE: Reported herein is a potential strategy for sustained smooth muscle cell (SMC) inhibition with a virulence-attenuated herpes simplex virus (HSV). Experiments were conducted in vitro to demonstrate selective SMC cytotoxicity and in vivo to demonstrate reduced neointimal hyperplasia (NIH) in a clinically relevant animal model. METHODS: In vitro: Cultured human umbilical artery smooth muscle cells (UASMC) and venous endothelial cells (HUVEC) were exposed to varying multiplicities of infection (MOI) of a gamma(1)34.5-deleted HSV-1 virus (R849). Cell survival was assessed at 48 and 72 hours with a colorimetric MTT viability assay. In vivo: New Zealand White rabbit external jugular veins (n = 21) were exposed to R849 (2.5 x 10(6) pfu/mL) or culture medium at 110 to 120 mm Hg for 10 minutes, then fashioned as vein patches on carotid arteries. Carotid arteries were ligated distally to decrease blood flow and stimulate a hyperplastic response (ultra-low shear stress model). After 2, 4, 12, and 24 weeks, patched segments were perfusion-fixed with glutaraldehyde and morphometrically examined for NIH formation. RESULTS: In vitro: At 48 hours, R849 exhibited preferential cytotoxicity to UASMC compared with HUVEC, with 11% +/- 10% of UASMCs and 49% +/- 8% of HUVECs surviving after infection with MOI = 25 (P <.05). Higher MOI resulted in poor survival of both cell lines. In vivo: Blood flow was similarly reduced in all animals both at surgery (0.9 +/- 0.1 mL/min vs 1.6 +/- 0.3 mL/min) and at harvest (2.7 +/- 0.4 mL/min vs 2.5 +/- 0.5 mL/min). R849-infected patches exhibited markedly less NIH than control patches did at 2 weeks (162 +/- 14 microm vs 49 +/- 6 microm; P <.05), 4 weeks (190 +/- 27 microm vs 67 +/- 8 microm; P <.05), and 12 weeks (233 +/- 18 microm vs 113 +/- 2 microm; P <.05). CONCLUSION: The virulence-attenuated HSV strain R849 demonstrates selective cytotoxicity for SMC and is capable of sustained inhibition of NIH in an experimental model of vein graft failure.

Ergotism associated with HIV antiviral protease inhibitor therapy.

Ergotism is a rare condition of acute vasospasm found classically in young and middle-aged women taking ergot alkaloid agents to treat migraine headache. We report the case of a young man with human immunodeficiency virus (HIV) positivity and describe the drug interaction between protease inhibitors and ergot alkaloid agents, which most likely predisposed to development of ergot toxicity. The HIV-positive population receiving antiviral therapy may be an under-recognized group at risk for ergotism through decreased hepatic metabolism of ergot preparations.

Long-term outcome of infrainguinal bypass grafting in patients with serologically proven hypercoagulability.

OBJECTIVE: The purpose of this study was to test the hypothesis that the long-term outcome of infrainguinal bypass grafting in patients with congenital or acquired hypercoagulability is inferior to the results in patients without documented clotting disorders. METHODS: The study was a retrospective analysis of consecutive patients from January 1994 to January 2001. RESULTS: Five hundred eighty-two infrainguinal bypass grafts were created in 456 patients. Indication for surgery was limb-threatening ischemia in 84%; prosthetic conduits were implanted in 38%. Seventy-four grafts were created in 57 patients with one or more serologically proven hypercoagulable states, including heparin-induced platelet aggregation (n = 37), anticardiolipin antibodies (n = 11), lupus anticoagulant (n = 8), protein C or S deficiency (n = 7), antithrombin III deficiency (n = 3), and factor V Leiden mutation (n = 1). Patients with hypercoagulability were younger (63 +/- 2 years versus 69 +/- 1 years; P =.007), more likely to have undergone prior revascularization attempts (38% versus 21%; P =.003), and more likely to have chronic anticoagulation therapy after surgery (46% versus 25%; P =.001). After 5 years (median follow-up, 19 months), patients with hypercoagulability had poorer primary patency (28% +/- 7% versus 35% +/- 5%; P =.004), primary assisted patency (37% +/- 7% versus 45% +/- 6%; P =.0001), secondary patency (41% +/- 7% versus 53% +/- 6%; P =.0001), limb salvage (55% +/- 8% versus 67% +/- 6%; P =.009), and survival (61% +/- 8% versus 74% +/- 4%; P =.02) rates. Multivariate analysis identified only prosthetic conduit choice (P =.0001), hypercoagulability (P =.0003), and limb salvage indication (P =.01) as independent predictors of graft failure. CONCLUSION: Patients with serologically proven hypercoagulability have inferior long-term patency, limb salvage, and survival rates after infrainguinal bypass. The high prevalence rate (13%) of diverse hypercoagulable states in this patient population supports serologic screening, especially in referral practices.

The changing face of abdominal aortic aneurysm management.

In summary, endovascular therapy represents a new and exiting paradigm in the treatment of abdominal aortic aneurysms. Its detractors have now largely been silenced, and a working knowledge of the devices and techniques is essential for all surgeons who care for patients with aneurysms. The first 25,000 stent-graft procedures have been attended by significant risks of implantation and endoleak, but the patients' acceptance of the technique has been heard loud and clear. The surgeon's task is not to convince the patient to undergo a more painful and invasive open procedure, but to advance the understanding, design, and implementation of this new technique such that its long-term results will someday rival those of the time-tested traditional operation.

Differential mechanical activation of mitogen-activated protein kinases in intact human blood vessels.

BACKGROUND: Vascular tissue remodels in response to a variety of hemodynamic factors, often transduced through activation of mitogen-activated protein kinases such as extracellular signal-related kinase (ERK1/2) and c-jun N-terminal kinase (JNK). This study tests the hypothesis that these kinases are involved in mechanical signal transduction in intact human arteries and veins. METHODS: Unused portions of human saphenous vein and radial artery were obtained fresh at the time of peripheral or coronary bypass. A sample of the vessel was immediately snap frozen (control(0)) and the remainder separated into three segments. One segment was placed in sterile medium and left undisturbed for 2 h (control(2)), one was perfused with sterile medium for 2 h at a steady rate of 150 ml/min, yielding shear stress values of 8-20 dyne/cm(2) (flow), and one was statically pressurized without flow at 110 mm Hg for 2 h (pressure). After treatment, samples were tested for phosphorylated ERK1/2 and JNK using Western blot. RESULTS: Two hours of culture produced mild increases in ERK1/2 activity in both vessel types. Stimulation with continuous rapid flow produced significantly increased ERK1 activity and a nearly 100% increase in ERK2 in veins. Static pressurization also stimulated ERK1/2, although slightly less than continuous flow. ERK1/2 phosphorylation was only mildly increased in flow-stimulated radial arteries, and exposure to normal systemic pressure showed no appreciable effect. Significant phosphorylation of JNK was not observed in either vessel. CONCLUSION: ERK1/2 phosphorylation is increased in human saphenous veins and radial arteries exposed to the hemodynamic conditions of arterial grafting. This pathway may be involved in the transduction of external stimuli leading to remodeling.