Distal Arterial Flow Research Articles

La phlébite bleue

Herein we report a case of phlegmasia cerulea dolens, a form of venous thrombosis complicated by arterial ischaemia.A 69-year-old man presented a bilateral trophic condition of the lower limbs that had appeared 3 weeks earlier. The patient had a history of metastatic urothelial bladder carcinoma and arteritis. Clinical examination revealed right leg ulcers with massive bilateral oedema of the lower limbs, cyanosis and local ischaemia. Doppler ultrasound revealed bilateral and proximal deep vein thrombosis (sural and superficial femoral veins of the right leg; sural and iliac veins of the left leg) without any distal arterial flow. We concluded on a diagnosis of bilateral phlegmasia cerulea dolens.Phlegmasia cerulea dolens is a particular type of deep venous thrombosis in which a proximal venous thrombus is combined with arterial ischaemic signs due to brutal and massive oedema and slowing down of arterial flow. In most cases, the lower limbs are involved, with malignancy being the most common cause. It should be suspected in the presence of the classical triad of "pain, oedema and cyanosis", with confirmation by Doppler ultrasound. There is no general consensus regarding standard management. Traditionally, systemic anticoagulation has been the mainstay of treatment for this condition. Endovascular surgery may be a possibility in some cases. Prompt diagnosis and rapid treatment initiation are paramount in order to improve the prognosis of this severe condition with ominous prospects.

Endovascular treatment of superior mesenteric artery pseudoaneurysms using covered stents in six patients.

The objective of our study was to evaluate our experience with the use of endovascular treatments for superior mesenteric artery (SMA) pseudoaneurysms using covered stents. Between 2002 and 2011, six patients (mean age, 41.7 years; range, 23-65 years) with SMA pseudoaneurysms were treated percutaneously with the placement of covered stents at our institution. The causes of SMA pseudoaneurysms were penetrating trauma (n = 2), blunt trauma (n = 1), and previous surgical procedures (n = 3). The mean diameter of the SMA pseudoaneurysms was 16 mm (range, 4-24 mm). Technical success and clinical success were retrospectively analyzed. Immediate technical success, defined as exclusion of the pseudoaneurysm and lack of active extravasation, was achieved in all six patients. Secondary balloon angioplasty was needed in one patient with residual narrowing. There was a small dissection of the proximal SMA necessitating placement of a second bare stent across the dissection. A second covered stent (Fluency stent, 8 mm) was placed in the same patient because of recurrent bleeding due to a type II endoleak 5 days after the first covered stent had been placed. This patient had no subsequent episodes of bleeding or bowel ischemia. Follow-up CT in the remaining five patients (mean, 21 months; range, 1-58 months) confirmed stent patency and preserved distal arterial flow to the bowel without episodes of bleeding or bowel ischemia during follow-up (mean, 27 months; range, 11-58 months). Percutaneous endovascular treatment using a covered stent may be a safe and feasible tool for SMA pseudoaneurysms.

Hyperemia-free delineation of epicardial and microvascular impairments using a basal index.

The assessment of functional coronary lesion severity using intracoronary hemodynamic parameters like the pressure-derived fractional flow reserve and the flow-derived coronary flow reserve are known to rely critically on the establishment of maximal hyperemia. We evaluated a hyperemia-free index, basal pressure drop coefficient (bCDP), that combines pressure and velocity for simultaneous assessment of the status of both epicardial and microvascular circulations. In 23 pigs, simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual-sensor tipped guidewire in the settings of both normal and abnormal microcirculation with the presence of epicardial lesions of area stenosis (AS) < 50% and AS > 50%. The bCDP, a parameter based on fundamental fluid dynamics principles, was calculated as the transtenotic pressure-drop divided by the dynamic pressure in the distal vessel, measured under baseline (without hyperemia) conditions. The group mean values of bCDP for normal (84 ± 18) and abnormal (124.5 ± 15.6) microcirculation were significantly different. Similarly, the mean values of bCDP from AS < 50% (72.5 ± 16.1) and AS > 50% (136 ± 17.2) were also significantly different (p < 0.05). The bCDP could significantly distinguish between lesions of AS < 50% to AS > 50% under normal microcirculation (52.1 vs. 85.8; p < 0.05) and abnormal microcirculation (84.9 vs. 172; p < 0.05). Further, the bCDP correlated linearly and significantly with the hyperemic parameters FFR (r = 0.42, p < 0.05) and CDP (r = 0.50, p < 0.05). The bCDP is a promising clinical diagnostic parameter that can independently assess the severity of epicardial stenosis and microvascular impairment. We believe that it has an immediate appeal for detection of coronary artery disease if validated clinically.

Long-Term Vascular, Motor, and Sensory Donor Site Outcomes after Ulnar Forearm Flap Harvest

Use of the ulnar forearm flap (UFF) is limited by concerns for ulnar nerve injury and impaired perfusion in the donor extremity. Twenty UFFs were performed over a 6-year period. All patients underwent postoperative bilateral upper extremity arterial duplex studies. A subset of postoperative patients (n = 10) also had bilateral upper extremity sensory and motor evaluations, and functional evaluation via the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH). Motor function was tested by digital and key grip dynamometry. Ulnar nerve sensation was tested by evaluation of one- and two-point perceived pressure thresholds and two-point discrimination using the Pressure-Specified Sensory Device (Sensory Management Services, LLC, Baltimore, MD). All UFFs were viable postoperatively. Mean follow-up was 28.8 months for vascular studies and 45.3 months for motor, sensory, and QuickDASH evaluations. Although mid and distal radial artery flow velocities were significantly higher in donor versus control extremities evaluated at less than 1 year postoperatively, there was no significant difference in extremities evaluated at later time points. Digital pressures, grip strength, key pinch strength, and ulnar sensation were equivalent between donor and control extremities. The mean QuickDASH score was 17.4 ± 23.8. The UFF can be harvested reliably and long-term follow-up shows no evidence of impaired vascular, motor, or sensory function in the donor extremity.

PP072. Features of intrarenal blood flow in patients with preeclampsia (PE)

The pregnancy-associated complication preeclampsia is a leading cause of maternal and fetal morbidity and mortality. The classical clinical manifestations of preeclampsia are elevated blood pressure and proteinuria due to renal damage. In severe cases of preeclampsia, the only effective treatment is delivery, irrespective of gestational age. To investigate renal perfusion in PE patients by ultrasound Doppler examination and to assess the possibility of strategy to identify renal blood flow changes to predict preeclampsia before the onset of disease. We studied 31 pregnant women of 21-46 years without renal disease: 19 PE (gr.1) and 12 volunteers (gr.2 ). PE was defined as a combination of proteinuria >0.3g/24h and blood pressure >140/90mmHg. We used Vivid7. We measured systolic (Vps), diastolic (Ved) velocities in renal and segmental arteries, and in at 5 pulse beats of interlobar and arcuate arteries. The resistance parameter (RI)=(Vps-Ved )/Vps. Table 1. The intrarenal blood flow in distal arteries. There was no difference in velocities and RI in renal and segmental arteries in both groups. We noted decrease of arterial and increase of the venous flow (color Doppler) of distal arteries in gr.1 seems to be a marker of renal ischaemia. All volunteers have the same parameters from signals of all pulse beats in one area - in arcuate and interlobar arteries. The RI in gr.1 varied in all distal arteries pulse beats in comparison with gr.2, where RI was identical. The "patchy" decreasing of RI suggests the presence of thromo-occlusive lesions leading to arteriovenous blood flow bypassing. The doppler ultrasonography may be used as a method of early diagnostic PE.

Mechanism underlying enhanced angiogenesis of PDE III inhibitor (Cilostazol) in limb ischemia of diabetes

Cilostazol is used for peripheral arterial disease with evidence level A by AHA. Previous study suggested it may work even in diabetes, however, the mechanism was not fully proven. Methods 30 mice were divided into 3 groups (Control; C, Diabetes; D, and Diabetes with Cilostazol; L). After ligation of femoral artery, each 5 mice were sacrificed at 1 and 4 weeks postoperatively. Soleus muscle was resected. Evaluations were made by 1) distal arterial flow, 2) capillary density (CD), 3) expression of HIF1 alpha, VEGFR2 and eNOS by IHC and western blotting. Results At 1 week: As level of ischemia shown by flow (C: 90% of preoperative flow, D: 58%, L: 66%), HIF1 alpha expression was higher in D and L than C (p<0.001 and p<0.005). However, in VEGFR2 expression, there was no difference between C and D, whereas there was significant difference between C and L (p<0.05). There was no difference in eNOS expression and CD in 3 groups. At 4 weeks: CD decreased in D (p<0.05) whereas increased in L (p<0.01). Significant difference in VEGFR2 was only seen between D and L (p<0.05). On the other hand, in eNOS expression, D was significantly lower from C and L (p<0.005 and p<0.05). Conclusion 1. HIF1 alpha did not promote VEGFR2 expression in DM. 2. Cilostazol improved VEGFR2 expression in spite of HIF1 alpha dysfunction. 3. Mechanism of Cilostazol on ischemic diabetic angiogenesis was possibly due to enhancement of eNOS expression rather than VEGER2.

New prototype of femoral arterial SmartCannula with anterograde and retrograde flow

Femoral artery cannulation is routinely used in circulatory support scenarios for cardiorespiratory support in patients with acute cardiac and/or pulmonary decompensation. During prolonged perfusion, this may cause acute ischemia of the leg and, in the worst case, even amputation. The aim of this experimental study was to test a newly designed arterial cannula allowing proximal and distal blood flow. Veno-arterial cardiopulmonary bypass was established in three calves (67.6 ± 5.1 kg). The venous line was secured by cannulation of the external jugular vein. The arterial line of each animal was secured by cannulation of iliac arteries on both legs. On one side, we used a modified SmartCannula (SmartCannula 18Fr 130 mm) and, on the other side, a standard rectilinear BioMedicus cannula system was used, 19 Fr for retrograde and an 8 Fr BioMedicus shunt for anterograde flow toward the leg. An ultrasonic flow probe was used to quantify the perfusion of the distal leg. At 0.5, 1.0, 1.5, and 2.0 l/min, the anterograde leg blood flow increased steadily for each cannula, but remained higher in the self-expanding cannula. That is, the 8 F rectilinear cannula achieved a blood flow of 0.02 ± 0.01, 0.1 ± 0.04, 0.22 ± 0.09, and 0.21 ± 0.02 l/min, respectively, and the 18 F self-expanding cannula achieved 0.06 ± 0.02, 0.15 ± 0.03, 0.24 ± 0.07 and 0.36 ± 0.04 l/min. The modified self-expanding cannula exhibited superior distal arterial flow compared to the routinely used rectilinear shunt system. This has a potential to reduce ischemic events of the inferior extremity in prolonged perfusion.

Surgical Treatment of a Large Fusiform Distal Anterior Cerebral Artery Aneurysm With In Situ End-to-Side A3—A3 Bypass Graft and Aneurysm Trapping: Case Report and Review of the Literature

Large fusiform aneurysms of the distal anterior cerebral territory are extremely rare and can be particularly challenging to treat. The circumferential pathology of fusiform lesions renders stand-alone clip or coil ablation unsatisfactory, and the deep, narrow corridor augments the difficulty of surgical approaches. In this setting, bypass procedures may be used to both treat the aneurysm definitively and preserve distal parent artery flow. We report a rare case of a large fusiform A3 aneurysm treated with trapping and concomitant end-to-side A3:A3 bypass. A 52-year-old man was evaluated after losing consciousness and experiencing a fall. A noncontrast computed tomography scan revealed a focal area of hemorrhage above the body of the corpus callosum, and computed tomography angiography showed a fusiform aneurysm of the right A3 artery. To treat the aneurysm definitively and preserve distal vessel flow, the patient was taken to surgery in anticipation of aneurysm ablation and cerebrovascular bypass. A large, fusiform right A3 aneurysm was identified. Intraoperative flow measurement demonstrated poor collateral circulation. The aneurysm was trapped with clips, and a right-to-left A3:A3 end-to-side in situ bypass was performed. Aneurysm occlusion and preserved distal vessel flow were confirmed with intraoperative angiography. Large fusiform aneurysms in the distal anterior cerebral artery region are rare, and the anatomy of these lesions and their vascular location render stand-alone surgical management technically challenging. End-to-side A3:A3 bypass combined with aneurysm trapping represents a feasible treatment strategy for lesions in this location.

Influence of heart rate on fractional flow reserve, pressure drop coefficient, and lesion flow coefficient for epicardial coronary stenosis in a porcine model

A limitation in the use of invasive coronary diagnostic indexes is that fluctuations in hemodynamic factors such as heart rate (HR), blood pressure, and contractility may alter resting or hyperemic flow measurements and may introduce uncertainties in the interpretation of these indexes. In this study, we focused on the effect of fluctuations in HR and area stenosis (AS) on diagnostic indexes. We hypothesized that the pressure drop coefficient (CDP(e), ratio of transstenotic pressure drop and distal dynamic pressure), lesion flow coefficient (LFC, square root of ratio of limiting value CDP and CDP at site of stenosis) derived from fluid dynamics principles, and fractional flow reserve (FFR, ratio of average distal and proximal pressures) are independent of HR and can significantly differentiate between the severity of stenosis. Cardiac catheterization was performed on 11 Yorkshire pigs. Simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire for HR < 120 and HR > 120 beats/min, in the presence of epicardial coronary lesions of <50% AS and >50% AS. The mean values of FFR, CDP(e), and LFC were significantly different (P < 0.05) for lesions of <50% AS and >50% AS (0.88 ± 0.04, 0.76 ± 0.04; 62 ± 30, 151 ± 35, and 0.10 ± 0.02 and 0.16 ± 0.01, respectively). The mean values of FFR and CDP(e) were not significantly different (P > 0.05) for variable HR conditions of HR < 120 and HR > 120 beats/min (FFR, 0.81 ± 0.04 and 0.82 ± 0.04; and CDP(e), 95 ± 33 and 118 ± 36). The mean values of LFC do somewhat vary with HR (0.14 ± 0.01 and 0.12 ± 0.02). In conclusion, fluctuations in HR have no significant influence on the measured values of CDP(e) and FFR but have a marginal influence on the measured values of LFC. However, all three parameters can significantly differentiate between stenosis severities. These results suggest that the diagnostic parameters can be potentially used in a better assessment of coronary stenosis severity under a clinical setting.

Radial artery cannulation decreases the distal arterial blood flow measured by power doppler ultrasound

Department of Anaesthesiology and Intensive Care, Hamamatsu University School of Medicine, Hamamatsu, Japan

Hemodynamic Impact of Anastomosis Size and Angle in Side-to-End Arteriovenous Fistulae: A Computer Analysis

An arteriovenous fistula (AVF) is the first choice vascular access for hemodialysis. The AVF pathway can be seen as consisting of seven segments: proximal artery, distal artery, arterial collaterals, proximal vein, distal vein, venous collaterals, and the anastomosis. While most studies describe access complications without considering the impact of the anastomosis (7th segment), the present mathematical study investigated the hemodynamic impact of anastomosis size and angle on pressure drop and flow distribution. A side-to-end AVF model was developed, consisting of an anastomosis with a given cross-sectional area (substudy 1) and angle (substudy 2). Starting from two reference cases (one for each substudy) with fixed flow distribution, pressure drop over the anastomosis was calculated for an arterial inflow in the range 600 to 1200 mL/min. The same reference cases, subsequently with fixed pressure boundary conditions, were further used to assess flow distribution over the proximal vein and distal artery. Pressure drop decreased with a larger anastomosis cross-sectional area and an angle wider than 43 degrees , while it was almost stable for smaller angles. Although proximal arterial inflow increased for larger anastomosis areas, the overall flow distribution shifted almost totally to the proximal vein. When the anastomosis angle exceeded 58 degrees , the proximal arterial inflow was not sufficient to deliver enough flow, leading to distal arterial flow reversal. Despite the underestimation of the hemodynamic impact of the anastomosis size and angle in the literature, this study showed major influences on the pressure drop over the anastomosis and, with it, on flow distribution towards the arterial and venous outflow.

Catheter-induced aorto-coronary artery dissection: Utility and appearance on CT coronary angiogram

Aorto-coronary artery dissection (CCAD) is rare but potentially fatal complication of catheter coronary angiography. Management is dependent on the state of distal arterial flow and the extension of retrograde aortic dissection. This manuscript describes the use and appearance of CCAD on ECG-gated multi-detector CT coronary angiogram in the acute setting.

Amplatzer Vascular Plug for Arteriovenous Hemodialysis Access Occlusion: Initial Experience

The Amplatzer Vascular Plug (AVP; AGA Medical, Golden Valley, MN) is a recently developed self-expanding metallic device indicated for peripheral vascular embolizations. Herein, we describe use of this device in the treatment of vascular complications related to arteriovenous hemodialysis fistulas and grafts. This HIPAA compliant retrospective study was approved by the institutional review board with informed consent waived. Six patients with problematic arteriovenous access underwent access occlusion using the AVP. Procedure indications included vascular steal syndrome in five patients, and enlarging vascular aneurysms in one patient. Contraindications for surgical correction were determined by the referring surgeon. AVP embolizations were performed using devices oversized by 50% introduced through vascular sheaths positioned within vein segments just beyond the arteriovenous anastomoses. Noninvasive evaluation of the involved extremity was performed pre- and post-embolization in addition to clinical follow-up examinations. Measured outcomes included success of angiographic occlusion, improvement in distal arterial flow, AVP number, AVP diameter, time to access occlusion, and clinical symptomatic improvement. Technical success was 100%, with complete arteriovenous access occlusion accomplished in all cases, with an average of 1.5 AVPs used per patient. Mean time to access occlusion was 19.3 minutes. Angiographic improvement in distal arterial flow was immediately evident and resolution of clinical symptoms occurred in all patients, with mean long-term follow-up of 16 months. No procedure-related complications were encountered. The Amplatzer Vascular Plug provides a minimally invasive and efficacious method for embolization of problematic arteriovenous hemodialysis access.

Buerger's Disease; Any Current Advances?

Buerger's Disease; Any Current Advances?

Applications and Advantages of Power Motion-Mode Doppler in Acute Posterior Circulation Cerebral Ischemia

Evaluation of posterior circulation with single-gate transcranial Doppler (TCD) is technically challenging and yields lower accuracy parameters in comparison to anterior circulation vessels. Transcranial power motion-mode Doppler (PMD-TCD), in addition to spectral information, simultaneously displays in real-time flow signal intensity and direction over 6 cm of intracranial space. We aimed to evaluate the diagnostic accuracy of PMD-TCD against angiography in detection of acute posterior circulation stenoocclusive disease. Consecutive patients presenting to the emergency room with symptoms of acute (<24 hours) cerebral ischemia underwent emergent neurovascular evaluation with PMD-TCD and angiography (computed tomographic angiography, magnetic resonance angiography, or digital subtraction angiography). Previously published diagnostic criteria were prospectively applied for PMD-TCD interpretation independent of angiographic findings. A total of 213 patients (119 men; mean age 65+/-16 years; ischemic stroke 71%, transient ischemic attack 29%) underwent emergent neurovascular assessment. Compared with angiography, PMD-TCD showed 17 true-positive, 8 false-negative, 6 false-positive, and 182 true-negative studies in posterior circulation vessels (sensitivity 73% [55% to 91%], specificity 96% [93% to 99%], positive predictive value 68% [50% to 86%], negative predictive value 95% [92% to 98%], accuracy 93% [90% to 96%]). In 14 patients (82% of true-positive cases), PMD display showed diagnostic flow signatures complementary to the information provided by the spectral display: reverberating or alternating flow, distal basilar artery flow reversal, high-resistance flow, emboli tracks and, bruit flow signatures. PMD-TCD yields a satisfactory agreement with urgent brain angiography in the evaluation of patients with acute posterior circulation cerebral ischemia. PMD display can depict flow signatures that are complimentary to and can increase confidence in standard single-gate TCD spectral findings.

Unrecognized hand ischemia after intraarterial drug injection: successful management of a "near miss" event

BackgroundComplications arising from accidental intraarterial drug injections have been described in the past. However, given the multitude of injected substances and complex pathophysiology, guidelines regarding diagnosis and management of patients with intraarterial injections remain vague. As such it remains unclear, when to expect limb ischemia and whether and for how long to monitor patients after intraarterial injections.Case reportWe present the case of a "near miss event" in an i.v. drug abuser presenting to the emergency department 3 hours after injection of water dissolved zolpidem (Ambien™) tablets into the right ulnar artery. Chief complaint was forearm pain. Clinical examination at the time revealed no concern for limb ischemia and patient was discharged. The patient returned unplanned 18 hours after injection with an ischemic right hand. Angiography revealed no flow in the distal ulnar artery and minimal flow in the palmar arch. Emergent intraarterial thrombolysis with Urokinase was performed and restored hand perfusion. Clinical follow-up 3 months after injury showed full recovery with regular recapillarisation and normal Allen test.ConclusionThis case report highlights the need to rigorously monitor patients with suspected intraarterial injections for potential delayed onset of limb ischemia. This is to our knowledge the first described case report of a successful revascularization after prolonged ischemia with delayed onset after zolpidem injection. We recommend close monitoring of these patients for at least 24 hours in addition to starting prophylactic anticoagulation.

Flow‐dependent regulation of angiopoietin‐2

Endothelial cells are constantly exposed to high or low shear stress in arteries and veins by the flowing blood. Angiopoietin-2 (Ang-2) is acting as a critical regulator of vessel maturation and endothelial cell quiescence. In this study, flow-dependent regulation of Ang-2 was analyzed in vitro and in vivo. Ang-2 mRNA, protein expression and release was upregulated by 24 h of low (1 dyne/cm(2)), but downregulated by high flow (30 dyne/cm(2)) in human endothelial cells. Increased endothelial NO synthase expression and NO formation was not affecting regulation of Ang-2 by low or high flow. Low and high flow increased VEGF-A expression. Inhibition of VEGFR-2 prevented upregulation of Ang-2 by low flow, but not downregulation of Ang-2 by high flow. Furthermore, upregulation of Ang-2 by VEGF was reduced by application of high flow. Forkhead box O (FOXO) transcription factor FOXO1 has been shown to regulate Ang-2 expression in endothelial cells. FOXO1 binding activity was reduced by high flow. Nuclear localization of transcription factor FOXO1 was not changed by low flow, but reduced by high flow. In vivo, Ang-2 was higher expressed in veins compared to arteries. Arterial ligation augmented Ang-2 expression in distal arterial low flow areas. Our results support a VEGF-dependent induction of Ang-2 in low flow areas, and FOXO1-dependent downregulation of Ang-2 in high flow areas. These data suggest a new mechanism of flow-dependent regulation of vessel stability and differentiation.

Abstract 442: Flow-Dependent Regulation of Angiopoietin-2

Background: Endothelial cells are constantly exposed to high or low shear stress in arteries and veins by the flowing blood. Angiopoietin-2 (Ang-2) is acting as a critical regulator of vessel maturation and endothelial cell quiescence. In this study, we determined the effect of low and high laminar shear stress on the expression and release of angiopoietin (Ang-)2 in human endothelial cells, studied the role of nitric oxide and protein kinases in this context, determined the impact of VEGF on Ang-2, studied the expression, activity and translocation of the forkhead box O transcription factor FOXO1 by low and high shear stress, and analyzed the vessel- and flow-dependent expression of Ang-2 in vivo . Methods and Results: Primary cultures of human umbilical vein endothelial cells (HUVEC) were subjected to laminar shear stress at different physiological levels of laminar shear stress of 1, 5, 10, 15, and 30 dyne/cm 2 in a cone-and-plate viscometer. Ang-2 mRNA, protein expression and release was upregulated by 24 h of low (1 dyne/cm 2 ), but downregulated by high flow (30 dyne/cm 2 ) in human endothelial cells. Increased endothelial NO synthase expression and NO formation was not affecting regulation of Ang-2 by low or high flow. Tie2 protein expression, but not Tie2 phosphorylation was induced by high flow. Furthermore, low and high flow increased VEGF-A expression. Inhibition of VEGFR-2 prevented upregulation of Ang-2 by low flow, but not downregulation of Ang-2 by high flow. Upregulation of Ang-2 by VEGF was reduced by application of high flow. Forkhead box O (FOXO) transcription factor FOXO1 has been shown to regulate Ang-2 expression in endothelial cells. FOXO1 binding activity was reduced by high flow. Nuclear localization of transcription factor FOXO1 was not changed by low flow, but reduced by high flow. In vivo , Ang-2 was higher expressed in veins compared to arteries. Arterial ligation augmented Ang-2 expression in distal arterial low flow areas. Conclusion: Our results support a VEGF-dependent induction of Ang-2 in low flow areas, and FOXO1-dependent downregulation of Ang-2 in high flow areas. These data suggest a new mechanism of flow-dependent regulation of vessel stability and differentiation.

Percutaneous selective pulmonary artery bands (Joeys) in a pulmonary overcirculation model

Control of distal pulmonary artery (PA) pressure and flow is a critical step in palliating infants with complex congential heart disease. Surgical procedures to protect or isolate the pulmonary circulation carry significant risk and can be unpredictable. Interventional control of pulmonary pressure/flow with an intravascular device (band) could reduce risk and improve regulation of pulmonary flow. Internal pulmonary bands were created from woven nitinol to create an internal orifice estimated to reduce distal pulmonary arterial pressure by 50%. Two designs were tested, a single eccentric lumen and two symmetrical lumens. The devices were approximately 7-mm long and the external diameter varied to suit the pulmonary arterial lumen size. A total of 15 devices were implanted in seven lambs with a stented ductus arteriosus to create high pulmonary pressure/flow. Four lambs were followed with devices and stent in place for a mean of 37 +/- 13 days. Fourteen of 15 devices were successfully implanted. One was acutely removed since the size was too large. Both device designs created greater than a 50% reduction in distal pulmonary pressure. Main PA pressure was 70/38, mean 50 +/- 13 mm Hg, and distal PA pressure 25/16, mean 20 +/- 7 mm Hg (P < 0.05). Angiography demonstrated protection of the internal banded pulmonary segments from overcirculation. Late follow-up showed that the device lumen(s) remained patent. Histology showed the vessel media to be intact but there was intimal proliferation where the device approximated the wall. There were no thrombotic emboli detected. Percutaneous internal banding of the pulmonary arteries was feasible and successful in lambs with high pulmonary flow/pressure analogous to infants with complex congenital heart disease.

Heparin-Binding Epidermal Growth Factor–Like Growth Factor, Collateral Vessel Development, and Angiogenesis in Skeletal Muscle Ischemia

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent mitogen for smooth muscle cells and has been implicated in atherosclerosis, tissue regeneration after ischemia, vascular development, and tumor angiogenesis. We examined the hypothesis that HB-EGF participates in angiogenesis and collateral growth in ischemia. During 3 weeks after femoral artery ligation, no attenuation occurred in recovery of hindlimb perfusion or distal saphenous artery flow in HB-EGF-null (HB-EGF(-/-)) versus wild-type mice. Lumen diameters of remodeled collaterals in gracilis muscle were similar by morphometry (87+/-8 versus 94+/-6 microm) and angiography, although medial thickening was reduced. Gastrocnemius muscle underwent comparable angiogenesis (41% and 33% increase in capillary-to-muscle fiber ratio). Renal renin mRNA, arterial pressure, and heart rate during anesthesia or conscious unrestrained conditions were similar between groups. These latter findings validate comparisons of perfusion data and also suggest that differences in arterial pressure and/or renin-angiotensin activity are not masking an otherwise inhibitory effect of HB-EGF absence. Four days after ligation, EGF receptor phosphorylation increased in muscle by 104% in wild-type but by only 30% in HB-EGF(-/-) mice. This argues against compensation by other EGF receptor ligands. Our results suggest that HB-EGF is not required for arteriogenesis or angiogenesis in hindlimb ischemia.