Ryan O. Lakin

The contemporary management of splenic artery aneurysms

OBJECTIVES The management of patients with splenic artery aneurysms (SAAs) is variable since the natural history of these aneurysms is poorly delineated. The objective of this study was to review our experience with open repair, endovascular therapy, and observation of SAAs over a 14-year interval. METHODS Between January 1, 1996 and December 31, 2009, 128 patients with SAAs were evaluated. Sixty-two patients underwent surgical repair (n = 13) or endovascular coil/glue ablation (n = 49), while 66 patients underwent serial observation. The original medical records and computed tomography (CT) imaging were reviewed. Statistical analyses were performed using χ(2) or Fishers exact test for categorical patient characteristics and t-test for continuous variables. Kaplan-Meier estimates for survival were calculated. Mortality was verified via the Social Security Death Index. RESULTS Patients (61 ± 11 years, 69% female) were investigated for abdominal symptoms (49%) or had the incidental finding of SAA (mean size, 2.4 ± 1.4 cm). Seven patients (5.5%) presented with rupture and were treated emergently with two perioperative mortalities (29%). Patients requiring surgical or endovascular treatment were more likely male (40% vs 21%, P = .031), younger (58 vs 64 years; P = .004), and current smokers (18% vs 5%; P = .035). Increased aneurysm calcification was associated with decreased SAA size (P = .013). The mean aneurysm size at initial diagnosis was 1.67 cm for patients undergoing observation and 3.13 cm for the treated group (P < .001). Endovascular repair was safe and durable with a mean 1.5-mm regression in SAA size over 2 years. The mean rate of growth for observed SAA was 0.2 mm/y. Ten-year survival was 89.4% (95% confidence interval: 82.0, 97.4) for all patients (observed group, 94.9%; treated group, 85.1%; P = .18). No late aneurysm-related mortality was identified. CONCLUSIONS Ruptured SAAs are lethal. Large SAAs can undergo endovascular ablation safely with durable SAA regression. Smaller SAAs (<2 cm) grow slowly and carry a negligible rupture risk.

Arteriovenous grafts have higher secondary patency in the short term compared with autologous fistulae

BACKGROUND To estimate patency of arteriovenous fistulas (AVFs) and grafts (AVGs) for dialysis access. METHODS Records of all adult patients who had a dialysis access placed from January 2008 to June 2011 were retrospectively reviewed. RESULTS A total of 494 patients with 655 accesses (390 AVFs, 265 AVGs) were examined. We found that AVG fared worse in assisted primary patency. But AVG had superior secondary patency up to 1.2 years (hazard ratio [HR] .6, confidence interval [CI]: [.4 to .8]) and was no different than AVF after 1.2 years. (HR 1.6, CI: [.9 to 3.1]). On univariate analysis, dialysis catheters negatively impacted assisted primary patency (HR 1.4, CI: [1.09 to 1.77]). CONCLUSIONS AVG can be maintained with higher rates of secondary patency in the short term and are no different in the long term. This result suggests that in patients with limited life expectancy an AVG may be an effective alternative to an AVF to reduce both catheter time and associated complications.

Techniques to harvest diseased human peripheral arteries and measure endothelial function in an ex vivo model.

OBJECTIVE Endothelial dysfunction has been studied in animal models. However, direct evidence of endothelial function from human vessels is limited. Our objectives were to optimize methods in harvesting human arteries from amputation specimens, determine endothelial function, and measure responsiveness to l-arginine, a nitric oxide precursor. METHODS Fresh amputation specimens were transferred expeditiously from the operating room to the bench laboratory for dissection and arterial harvest in an Investigational Review Board-approved protocol. Popliteal and tibial vessels were examined in pilot experiments leading to the use of the anterior tibial artery in consecutive experiments. Human lower extremity anterior tibial artery segments were harvested from 14 amputation specimens. Specimens were rapidly collected and divided for endothelial-dependent relaxation (EDR) studies in a tissue bath apparatus, immunohistochemistry, and intravascular ultrasound-derived virtual histology. A total of 47 ring segments were studied. The data were compared with two-way analysis of variance. RESULTS Human lower extremity arteries exhibited low responsiveness to acetylcholine (EDR, 24.9%; acetylcholine, 10(-4)). L-arginine supplementation enhanced EDR by 38.5% (P < .0001). N-nitro-L-arginine methyl ester abrogated EDR (P < .0001) in vessels exposed to L-arginine. Arterial responsiveness was intact in all vessels (endothelial independent relaxation to sodium nitroprusside, 113.2% ± 28.1%). Histology and immunohistochemistry confirmed intact endothelium by morphometric analysis, cluster of differentiation 31, endothelial nitric oxide synthase, and arginase II staining. Intravascular ultrasound-derived virtual histology indicated atheroma burden was 11.9 ± 4.7 mm(3)/cm, and plaque stratification indicated fibrous morphology was predominant (59.9%; necrotic core, 16.9%; calcium, 11.2%). Variations in plaque morphology did not correlate with endothelial function or responsiveness to L-arginine. CONCLUSIONS Human lower extremity arteries demonstrate low baseline endothelial function in patients requiring amputation. Endothelial dysfunction is improved by L-arginine supplementation in an ex vivo model. These results support strategies to increase local levels of nitric oxide in human vessels.

In Vivo Assessment of Endothelial Function in Human Lower Extremity Arteries

OBJECTIVE Endothelial function has been measured in preclinical studies in human brachial and coronary arteries but not in lower extremity arteries affected by atherosclerosis. We describe a novel, first-in-man evaluation of endothelial function of the superficial femoral arteries (SFAs) in patients with peripheral arterial disease (PAD). METHODS Enrolled were 25 patients with PAD requiring lower extremity angiography. Endothelial-dependent relaxation was measured using intravascular ultrasound (IVUS) imaging and a Doppler flow wire after the infusion of acetylcholine (Ach). IVUS-derived virtual histology of the same vessel was calculated. Endothelial-independent relaxation was measured with an infusion of nitroglycerin (200 μg). Levels of nitric oxide and serum nitric oxide metabolites were determined by laboratory analysis. RESULTS Patients (48% male; mean age, 62 years) had a history of hypertension (80%), coronary disease (36%), and diabetes (40%). The mean SFA diameter was 5.2 ± 1 mm (range, 3.2-6.9 mm). Patients tolerated Ach infusion with no adverse events. Endothelial-dependent relaxation increased over baseline for all patients with Ach infusion of 10(-6) to 10(-4). At Ach 10(-4), diameter (0.5%) and area (1.8%) changes in the diseased SFAs were modest and insignificant; however, average peak velocity of blood flow significantly increased 26%, 46%, and 63% with an Ach 10(-6) to 10(-4) infusion. Calculations of limb volumetric flow (68% at Ach 10(-4)) were significantly increased after Ach infusion. Lower extremity nitric oxide levels were slightly lower than systemic venous levels (P = .04). Nitroglycerin infusion indicated normal smooth muscle responsiveness (3% diameter, 9% area, and 116% velocity change over baseline). IVUS-virtual histology plaque stratification indicated predominantly fibrous morphology (46%; necrotic core, 29%; calcium, 18%). Atheroma burden was 14.9 ± 5.5 mm(3)/cm and did not correlate with endothelial responsiveness. CONCLUSIONS Endothelial function can be measured directly in human lower extremity arteries at the sites of vascular disease. Despite extensive atherosclerosis, endothelial function is still intact. These data support the application of regional endothelial-specific biologic therapies in patients with PAD.

The use of dextran and carbon dioxide for optical coherence tomography in the superficial femoral artery

The following case report describes using carbon dioxide (CO2) as contrast media for intravascular optical coherence tomography (OCT) imaging in the superficial femoral artery. For initial OCT imaging, 20 mL of iodinated contrast was used during automated pullback. This was followed by 20 mL of hand-injected dextran 40 in normal saline, and finally hand-injected 50 mL of CO2. CO2 gave comparable erythrocyte clearance and imaging quality compared with dextran and iodinated contrast. To our knowledge, this is the first reported case using both dextran and CO2 with OCT imaging of the superficial femoral artery. Using CO2 is a viable option in patients with contraindications to contrast or dextran use.

The LargPAD Trial: Phase IIA evaluation of l-arginine infusion in patients with peripheral arterial disease

Objective: Endothelial function is improved by l‐arginine (l‐arg) supplementation in preclinical and clinical studies of mildly diseased vasculature; however, endothelial function and responsiveness to l‐arg in severely diseased arteries is not known. Our objective was to evaluate the acute effects of catheter‐directed l‐arg delivery in patients with chronic lower extremity ischemia secondary to peripheral arterial disease. Methods: The study enrolled 22 patients (45% male) with peripheral arterial disease (mean age, 62 years) requiring lower extremity angiography. Endothelium‐dependent relaxation of patent but atherosclerotic superficial femoral arteries was measured using a combination of intravascular ultrasound (IVUS) imaging and a Doppler FloWire (Volcano Corporation, Rancho Cordova, Calif) during the infusion of incremental acetylcholine (10−6 to 10−4 molar concentration) doses. Patients received 50 mg (n = 3), 100 mg (n = 10), or 500 mg (n = 9) l‐arg intra‐arterially, followed by repeat endothelium‐dependent relaxation measurement (limb volumetric flow). IVUS‐derived virtual histology of the culprit vessel was also obtained. Endothelium‐independent relaxation was measured using a nitroglycerin infusion. Levels of nitrogen oxides and arginine metabolites were measured by chemiluminescence and mass spectrometry, respectively. Results: Patients tolerated limb l‐arg infusion well. Serum arginine and ornithine levels increased by 43.6% ± 13.0% and 23.2% ± 10.3%, respectively (P < .005), and serum nitrogen oxides increased by 85% (P < .0001) after l‐arg infusion. Average vessel area increased by 6.8% ± 1.3% with l‐arg infusion (acetylcholine 10−4; P < .0001). Limb volumetric flow increased in all patients and was greater with l‐arg supplementation by 130.9 ± 17.6, 136.9 ± 18.6, and 172.1 ± 24.8 mL/min, respectively, for each cohort. Maximal effects were seen with l‐arg at 100 mg (32.8%). Arterial smooth muscle responsiveness to nitroglycerin was intact in all vessels (endothelium‐independent relaxation, 137% ± 28% volume flow increase). IVUS‐derived virtual histology indicated plaque volume was 14 ± 1.3 mm3/cm, and plaque stratification revealed a predominantly fibrous morphology (46.4%; necrotic core, 28.4%; calcium, 17.4%; fibrolipid, 6.6%). Plaque morphology did not correlate with l‐arg responsiveness. Conclusions: Despite extensive atherosclerosis, endothelial function in diseased lower extremity human arteries can be enhanced by l‐arg infusion secondary to increased nitric oxide bioactivity. Further studies of l‐arg as a therapeutic modality in patients with endothelial dysfunction (ie, acute limb ischemia) are warranted.