Ankur J. Shukla

Contemporary outcomes of intact and ruptured visceral artery aneurysms

OBJECTIVE The treatment outcomes of ruptured visceral artery aneurysms (rVAAs) have been sparsely characterized, with no clear comparison between different treatment modalities. The purpose of this paper was to review the perioperative and long-term outcomes of open and endovascular interventions for intact visceral artery aneurysms (iVAAs) and rVAAs. METHODS This was a retrospective review of all treated VAAs at one institution from 2003 to 2013. Patient demographics, aneurysm characteristics, management, and subsequent outcomes (technical success, mortality, reintervention) and complications were recorded. RESULTS The study identified 261 patients; 181 patients were repaired (77 ruptured, 104 intact). Pseudoaneurysms were more common in rVAAs (81.8% vs 35.3% for iVAAs; P < .001). The rVAAs were smaller than the iVAAs (20.7 mm vs 27.5 mm; P = .018), and their most common presentation was abdominal pain; 29.7% were hemodynamically unstable. Endovascular intervention was the initial treatment modality for 67.4% (75.3% for rVAAs, 61.5% for iVAAs). The perioperative complication rate was higher for rVAAs (13.7% vs 1% for iVAAs; P = .003), as was mortality at 30 days (13% vs 0% for iVAAs; P = .001), 1 year (32.5% for rVAAs vs 4.1% for iVAAs; P < .001), and 3 years (36.4% for rVAAs vs 8.3% for iVAAs; P < .001). Lower 30-day mortality was noted with endovascular repair for rVAAs (7.4% vs 28.6% open; P = .025). Predictors of mortality for rVAAs included age (odds ratio, 1.04; P = .002), whereas endovascular repair was protective (odds ratio, 0.43; P = .037). Mean follow-up was 26.2 months, and Kaplan-Meier estimates of survival were higher for iVAAs at 3 years (88% vs 62% for rVAAs; P = .045). The 30-day reintervention rate was higher for rVAAs (7.7% vs 19.5% for iVAAs; P = .019) but was similar between open and endovascular repair (8.2% vs 15%; P = NS). CONCLUSIONS rVAAs have significant mortality. Open and endovascular interventions are equally durable for elective repair of VAAs, but endovascular interventions for rVAAs result in lower morbidity and mortality. Aggressive treatment of pseudoaneurysms is electively recommended at diagnosis regardless of size.

Late collapse of a thoracic endoprosthesis

Thoracic stent graft collapse is a rare complication of thoracic endovascular aortic repair that is mostly asymptomatic and occurs ≤ 3 months of the procedure. We describe the case of a 36-year-old man who presented with symptomatic endograft collapse 38 months after an initial thoracic endovascular aortic repair that was performed for traumatic aortic transection. He had sudden and complete loss of bilateral lower extremity motor and sensory functions (spinal cord ischemia) and anal sphincter tone. The patient was successfully treated with redo thoracic endovascular aortic repair, followed by open conversion and device explantation.

Xanthine Oxidoreductase Function Contributes to Normal Wound Healing.

Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO. We hypothesize that XOR contributes to normal wound healing. Cutaneous wounds were created in C57Bl6 mice. XOR was inhibited with dietary tungsten or allopurinol. Topical hydrogen peroxide (H2O2, 0.15%) or allopurinol (30 µg) was applied to wounds every other day. Wounds were monitored until closure or collected at d 5 to assess XOR expression and activity, cell proliferation and histology. The effects of XOR, nitrite, H2O2 and allopurinol on keratinocyte cell (KC) and endothelial cell (EC) behavior were assessed. We identified XOR expression and activity in the skin and wound edges as well as granulation tissue. Cultured human KCs also expressed XOR. Tungsten significantly inhibited XOR activity and impaired healing with reduced ROS production with reduced angiogenesis and KC proliferation. The expression and activity of other tungsten-sensitive enzymes were minimal in the wound tissues. Oral allopurinol did not reduce XOR activity or alter wound healing but topical allopurinol significantly reduced XOR activity and delayed healing. Topical H2O2 restored wound healing in tungsten-fed mice. In vitro, nitrite and H2O2 both stimulated KC and EC proliferation and EC migration. These studies demonstrate for the first time that XOR is abundant in wounds and participates in normal wound healing through effects on ROS production.

Evolution of treatment for traumatic thoracic aortic injuries

OBJECTIVE To review the evolution of traumatic thoracic aortic injury (TTAI) treatment at a single institution. METHODS Retrospective analysis of all patients included in an institutional trauma registry and vascular surgery database who underwent treatment of TTAI between January 1999 and January 2011. RESULTS Ninety-one patients (69 males) were treated for TTAI. The mean age was 38.5 years (range, 16-79 years). Forty-one patients underwent open repair (OR) and 50 thoracic endovascular repair (TEVAR), 37 with thoracic stent grafts (TSG) alone, 11 with infrarenal aortic extender cuffs (AEC), and two with a combination of TSG and AEC. OR was performed exclusively until 2004; the last one was performed in January 2007. All TTAIs have since been treated with TEVAR. The left subclavian artery (LSA) was fully covered in 10 patients (20%) and partially covered in eight patients, with revascularization in only two cases. The use of AEC and avoidance of LSA coverage increased after 2007. Baseline characteristics and injury severity scores were similar between groups. The mortality rate was higher in the OR group (19.5% vs 6.0%; P = .06), although it did not reach statistical significance. The overall incidence of morbidities was similar between the two groups (42% OR vs 50% TEVAR). Two patients developed paraplegia (4.4%) after OR compared with none after TEVAR. In the TEVAR group, a pseudoaneurysm, an iliac artery thrombosis, and a retroperitoneal hematoma developed in one patient each. Overall, eight patients (16%) developed stent graft-related complications (SRC), with two developing early (within 30 days) complications. All complications were related to poor apposition, requiring 10 reinterventions. Four patients underwent open conversions with no mortality. Nine out of 10 SRCs were associated with the use of thoracic stent graft malapposition. No patient treated with AEC had endoleaks or SRC. CONCLUSIONS TEVAR for TTAI has superior survival outcomes and has replaced OR. SRC requiring reintervention is associated with malapposition and the use of TSG. Until TTAI-specific endografts become available, use of AEC may minimize malapposition and reduce reinterventions. Routine overstenting of the LSA is not necessary and may increase SRC.

P2Y2 nucleotide receptor mediates arteriogenesis in a murine model of hind limb ischemia

OBJECTIVE Arteriogenesis represents the maturation of preformed vascular connections in response to flow changes and shear stress. These collateral vessels can restore up to 60% of the native blood flow. Shear stress and vascular injury can induce the release of nucleotides from vascular smooth muscle cells and platelets that can serve as signaling ligands, suggesting they may be involved in mediating arteriogenesis. The P2Y2 nucleotide receptor (P2Y2R) has also been shown to mediate smooth muscle migration and arterial remodeling. Thus, we hypothesize that P2Y2R mediates arteriogenesis in response to ischemia. METHODS Hind limb ischemia was induced by femoral artery ligation (FAL) in C57Bl/6NJ or P2Y2R negative mice (P2Y2(-/-)). Hind limb perfusion was measured with laser Doppler perfusion imaging and compared with the sham-operated contralateral limb immediately and at 3, 7, 14, 21, and 28 days after ligation. Collateral vessel size was measured by Microfil casting. Muscle specimens were harvested and analyzed with immunohistochemistry for Ki67, vascular cell adhesion molecule, macrophages, and muscle viability by hematoxylin and essoin stain. RESULTS Hind limb ischemia induced by FAL in C57Bl/6NJ mice resulted in significant ischemia as measured by laser Doppler perfusion imaging. There was rapid recovery to nearly normal levels of perfusion by 2 weeks. FAL in P2Y2(-/-) mice resulted in severe ischemia with greater tissue loss. Recovery of perfusion was impaired, achieving only 40% compared with wild-type mice by 28 days. Collateral vessels in the P2Y2(-/-) mice were underdeveloped, with reduced vascular cell proliferation and smaller vessel size. The collaterals were ∼65% the size of wild-type collateral vessels (P = .011). Angiogenesis at 28 days in the ischemic muscle, however, was greater in the P2Y2(-/-) mice (P < .001), possibly related to persistent ischemia leading and angiogenic drive. Early macrophage recruitment was reduced by nearly 70% in P2Y2(-/-) despite significantly more myocyte necrosis. However, inflammation was greater at 28 days in the P2Y2(-/-) mice. CONCLUSIONS P2Y2R deficiency does not alter baseline collateral vessel formation but does significantly impair collateral maturation, with resultant persistent limb ischemia despite enhanced angiogenesis. These findings reinforce the importance of arteriogenesis in the recovery of perfusion in ischemic tissues compared with angiogenesis. They also support the role of P2Y2R in mediating this process. The mechanism by which P2Y2R mediates arteriogenesis may involve the recruitment of inflammatory cells to the ischemic tissues, which is essential to arteriogenesis. Approaches to target P2Y2R may yield new therapeutic strategies for the treatment of arterial occlusive disease.