Martin K. O'Donohoe

Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence.

Symptomatic carotid stenosis is associated with a 3‐fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque‐related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined 18F‐fluorodeoxyglucose positron‐emission tomography (FDG‐PET)/computed tomography, we investigated the relation between inflammation‐related FDG uptake and stroke recurrence.

Myointimal thickening in experimental vein grafts is dependent on wall tension

This study examines the relative contributions of intraluminal pressure, blood flow, wall tension, and shear stress to the development of myointimal thickening in experimental vein grafts. To study these different hemodynamic parameters, several experimental models were created in 30 New Zealand White rabbits separated into six groups: common carotid interposition vein grafts harvested at 4 weeks (VG-4) or 12 weeks (VG-12), common carotid-linguofacial vein arteriovenous fistulas harvested at 4 weeks (AVF-4) or 12 weeks (AVF-12), AVFs with partial outflow obstruction harvested at 4 weeks (AVFobs), and combination VG-AVFs in series harvested at 4 weeks (VGAVF). Blood pressure and flow in the graft or vein were measured by use of a transducer-tipped pressure catheter and electromagnetic flow meter. At harvest, veins were perfusion-fixed and proximal, middle, and distal sections were subjected to computerized morphometric analysis. Vein grafts were characterized by a high mean pressure (VG-4, 51 +/- 4; VG-12, 62 +/- 3 mm Hg), low mean flow (VG-4, 17 +/- 1; VG-12, 16 +/- 4 ml/min), large luminal area (VG-4, 19.7 +/- 2.4; VG-12, 19.3 +/- 3.9 mm2), high wall tension (VG-4, 17.0 +/- 1.5; VG-12, 19.5 +/- 2.4 x 10(3) dyne/cm), low shear stress (VG-4, 0.75 +/- 0.13; VG-12, 0.96 +/- 0.38 dyne/cm2), and a high degree of myointimal thickening (VG-4, 5.89 +/- 0.90; VG-12, 4.72 +/- 0.83 mm2). Arteriovenous fistulas were characterized by a low mean pressure (AVF-4, 5 +/- 1, AVF-12, 6 +/- 2 mm Hg), elevated blood flow (AVF-4, 82 +/- 16; AVF-12, 82 +/- 17 ml/min), small luminal area (AVF-4, 2.43 +/- 0.58; AVF-12, 7.14 +/- 2.68), low wall tension (AVF-4, 0.62 +/- 0.19; AVF-12, 0.89 +/- 0.24 x 10(3) dyne/cm), elevated shear stress (AVF-4, 108 +/- 32; AVF-12, 71 +/- 50 dyne/cm2), and decreased myointimal area (AVF-4, 1.18 +/- 0.26; AVF-12, 1.90 +/- 0.55 mm2). The addition of outflow obstruction to AVFs (AVFobs) resulted in elevated pressure (48 +/- 2 mm Hg), decreased flow (17 +/- 4 ml/min), larger luminal area (8.71 +/- 2.31 mm2), elevated wall tension (10.3 +/- 1.7 x 10(3) dyne/cm), and a degree of myointimal thickening approaching that of vein grafts (3.79 +/- 0.66 mm2).(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic Ace Inhibition Reduces Intimal Hyperplasia in Experimental Vein Grafts

Intimal hyperplasia is an important factor in the pathophysiology of vein graft failure. Local renin-angiotensin systems recently have been shown to modulate the development of intimal hyperplasia in arteries after intimal injury. The effect of chronic angiotensin-converting enzyme (ACE) inhibition on the development of intimal hyperplasia in experimental vein grafts was examined in this study. Ten New Zealand White rabbits received 10 mg/kg of captopril daily in their drinking water. One week later the right carotid artery was divided and bypassed with the reversed right external jugular vein in these rabbits and in 10 matched controls. Captopril was continued for 28 days after operation, when all the grafts were harvested. Five grafts from each group were perfusion fixed, and the intimal thickness in the proximal, middle, and distal segments was determined. Rings from the remaining grafts (n = 20 in each group) were studied in vitro under isometric tension, and their responses to norepinephrine (NE), histamine (HIST), serotonin (S-HT), angiotensin I (AI), and angiotensin II (All) was measured. The intimal thickness of the proximal, middle, and distal segments of the captopril-treated grafts were significantly less than controls, being reduced in all segments by approximately 40% (p < 0.0001). With regard to vasoreactivity, the captopril-treated grafts were hypersensitive to 5-HT (control ED50 5.5 ± 0.5 ± 10-7 mol/L vs. captopril-treated 1.1 ± 0.2 ± 10-6 mol/L; p < 0.005) although the maximal response was significantly reduced (control 1.6 ± 0.3 g vs. captopril-treated 0.8 ± 0.1 g; p < 0.05). There were no differences in sensitivity between control and captopril-treated rings with respect to NE, HIST, AI, or AIL Four of the ten captopril-treated segments, however, failed to respond to AI, and the maximal active tension of the responders was significantly reduced (control 0.47 ± 0.06 g vs. 0.20 ± 0.05 g; p < 0.02). These results suggest that ACE is involved in the modulation of vein graft intimal hyperplasia, and that ACE inhibitors may have therapeutic applications in patients undergoing vein bypass procedures.

Use of Colour Duplex Ultrasound as a First Line Surveillance Tool Following EVAR is Associated with a Reduction in Cost Without Compromising Accuracy

INTRODUCTION CT scanning remains the postoperative surveillance imaging modality of choice following EVAR. Concerns regarding cost, exposure to ionising radiation and intravenous contrast have led to a search for a less expensive, equally efficacious and safer method of monitoring EVAR patients after endograft deployment. This study evaluated the cost saving obtained if CDUS was employed as a first line surveillance tool following EVAR, as well as comparing the two entities in terms of efficacy. PATIENTS & METHODS Postoperative surveillance CTs and CDUS scans in the 145 patients who have undergone EVAR from 1st June 2003 to 1st July 2010 were compared for the detection of endoleak and determination of residual sac size. RESULTS Adopting a protocol where CDUS was employed as the first line surveillance tool following EVAR would result in a reduction in the number of postoperative CTs required in 2010 from 235 to 36. Based on 2010 costings, this would equate to an estimated reduction in expenditure from €117,500 to €34,915 a saving of €82,585. CDUS had a sensitivity of 100% and a specificity of 85% in the detection of endoleaks compared to CT. The positive predictive value was 28% and negative predictive value 100%. The Pearson Coefficient correlation of 0.96 indicates a large degree of correlation between CDUS and CT when measuring residual aneurysm size following EVAR. CONCLUSION CDUS can replace CT as the first line surveillance tool following EVAR. This is associated with a significant reduction in the cost of surveillance without any loss of imaging accuracy.

Alterations in serotonergic receptor expression in experimental vein grafts

Rabbit external jugular veins, normally unresponsive to serotonin (5-HT), develop a constrictive response when grafted into the arterial circulation. The mechanisms responsible for this alteration were examined in this study. The right external jugular vein was grafted into the right carotid artery in 37 New Zealand white rabbits. The vein grafts were harvested at 3, 7, 9, 14, and 28 days after operation; contralateral external jugular veins were harvested at 9 days in six animals. Rings of these vessels were mounted under isometric tension, and dose-response curves to 5-HT were obtained. None of the grafts harvested at day 3 responded to 5-HT. All the grafts harvested from day 7 through day 28 constricted to 5-HT. The maximal response increased from 258 +/- 30 mg at 7 days to 734 +/- 108 mg at 28 days. No change occurred in the sensitivity to 5-HT with time. The increase in maximal response was paralleled by a linear increase in percent intimal area (intimal area/intimal + media areas) from 11.6% +/- 2.1% at 3 days to 48.7% +/- 1.9% at 28 days. Preincubation with ketanserin, a 5-HT2 and alpha 1-adrenergic antagonist, produced a concentration-dependent rightward shift in the 5-HT dose-response curve. The median effective dose for 5-HT increased progressively from 1.9 +/- 0.3 x 10(-6) mol/L (in the absence of ketanserin) to 6.1 +/- 1.7 x 10(-5) mol/L (ketanserin 8 x 10(-7) mol/L; p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

The management of mycotic femoral pseudoaneurysms in intravenous drug abusers.

Mycotic femoral pseudoaneurysms, particularly in the drug-abusing population, pose a difficult problem to the vascular surgeon. Management ranges from ligation with debridement to extra-anatomical bypass. This study reviewed the management of mycotic femoral pseudoaneurysms presenting in intravenous drug abusers to an inner city tertiary referral center. Between 2001 and 2006, 11 cases presenting in nine patients were treated. The mean age was 30.7 years with a male-to-female ratio of 1:2. Eight patients had a positive viral status for the human immunodeficiency virus and/or hepatitis C. Two patients re-presented with a contralateral pseudoaneurysm. A combination of groin pain and swelling was the most common presentation. Two patients presented with significant hemorrhage. The diagnosis was confirmed by ultrasound in the majority of cases. Nine cases were managed with arterial ligation and debridement of the necrotic tissue. The two remaining cases were managed with ultrasound-guided thrombin injection and arterial puncture closure. On follow-up, one patient required a below-knee amputation following reinjection into the postoperative wound site. One further patient underwent a fifth metatarsal amputation due to ischemia. Ligation and debridement are well tolerated in the majority of drug-abusing patients diagnosed with mycotic femoral pseudoaneurysms.

Quantitation of vascular outflow by measurement of impedance

One of the most important determinants of graft patency is the degree and character of vascular outflow. This study was designed to evaluate input impedance as a functional assessment of the outflow bed of vascular grafts. Four distinct outflow environments were created for external jugular vein conduits in 42 New Zealand white rabbits. Vein grafts (n = 14) were fashioned as end-to-side common carotid interposition bypass grafts. Arteriovenous fistulas (n = 15) were created by side-to-side anastomosis of the distal common carotid artery and linguofacial vein. Arteriovenous fistulas with outflow obstruction (n = 7) were fistulas with a metal clip partially obstructing the distal outflow channel (1 mm lumen). Vein graft/arteriovenous fistula combinations (n = 6) consisted of a vein graft and arteriovenous fistula in series. Pressure and flow in the external jugular vein were measured, and input impedance spectra were calculated by Fourier methods. By use of a PC-based acquisition and processing system, impedance results for 20 cardiac cycles could be obtained in approximately 10 minutes. The results revealed that vein grafts typically demonstrated high resistance to steady state flow (Rin = 235 +/- 50 x 10(3) dyne . sec/cm-5) and steadily decreasing impedance to pulsatile flow resulting in a characteristic impedance (Z0; average of fourth to tenth harmonics) of 35.5 +/- 8.0 x 10(3) dyne . sec/cm-5. Phase angle values were usually negative, especially at low harmonics (first harmonic phase angle = -1.11 +/- 0.10 radians) indicating that flow led pressure. In contrast, arteriovenous fistula Rin was minimal (6.3 +/- 1.4 x 10(3) dyne . sec/cm-5; p less than 0.05 compared to vein graft, and the impedance was flat across the frequency spectrum (Z0 = 8.5 +/- 1.5 x 10(3) dyne . sec/cm-5; p less than 0.05) with pressure and flow nearly in phase (first harmonic phase angle = -0.05 +/- 0.10 radians). Creation of outflow obstruction in arteriovenous fistulas resulted in significantly elevated Rin (136 +/- 41 x 10(3) dyne/sec . cm-5; p less than 0.05 compared to arteriovenous fistula and Z0 (23 +/- 9 x 10(3) dyne . sec/cm-5, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Increased concentrations of angiotensin-converting enzyme in the intimal hyperplasia of experimental vein grafts.

Summary: Local renin and angiotensin-converting enzyme (ACE) activity were recently implicated in development of intimal hyperplasia after vascular injury, but little is known about the local responses of angiotensin I/II (AI/AII) and local ACE activity in vein graft physiology. The activity of the local ACE system of experimental vein grafts was examined in this study. The right carotid artery was divided and bypassed in 21 New Zealand White rabbits, using the right external jugular vein. The left external jugular vein was used as a control. Veins and vein grafts were harvested after 14 days. Rings from both vessels were studied in vitro under isometric tension, and dose–response curves to AI and AII were obtained. AI responses were also measured in the presence of captopril. The tissue concentrations of ACE in both vessels were estimated by spectrophotometry and were localized by immunohistochemistry. The responses of the veins to AI and AII were multiphasic, whereas the responses of vein grafts were sigmoid-shaped. Incubation of vein grafts with captopril significantly decreased the sensitivity to AI (p < 0.0001). Immunohistochemical localization identified ACE in the endothelial layer of the veins and vein grafts, but also at a greater density in the intimal hyperplasia of the vein graft. The concentration of ACE was 1.92 ± 0.16 U/g (wet weight; mean ± SEM, n = 9) in vein grafts and 1.39 ± 0.05 U/g in the veins (38% increase, p < 0.05, n = 9). These results indicate that increased levels of ACE in experimental vein grafts are associated with altered responses to AI and AII and that ACE is predominantly localized to the intimal hyperplastic layer. The increased concentration of ACE in vein grafts suggests that local angiotensin systems may modulate the proliferative response that follows grafting and may explain the efficacy of ACE inhibition in controlling intimal hyperplasia.

Saphenous vein endothelium-dependent relaxation in patients with peripheral vascular disease

In vitro vasomotor responses of saphenous veins of 15 patients undergoing peripheral vascular bypass procedures were studied. Vessels were harvested by standard techniques, sectioned into 4 mm rings, and suspended in organ baths under isometric tension. Stimulation with cumulative doses of norepinephrine revealed a −logED50 of 6.85±0.12 M and maximal tension of 8.64±1.77 g. Patient characteristics suggesting high maximal response (by univariate analysis) included male sex (male 11.69±2.49 g versus female 5.08±1.69 g; p=0.058). Intact and denuded rings were additionally tested for endothelium-dependent relaxation following submaximal norepinephrine precontraction. The vessels relaxed in response to acetylcholine (maximal relaxation 31.1±10.7% at 1 × 10−6 M), calcium ionophore A23187 (85.3±11.8% at 1 × 10−5 M), and sodium nitroprusside (150.8±15.2% at 1 × 10−5 M), but only acetylcholine relaxation was completely endothelium-dependent. Calcium ionophore A23187 relaxation was partially dependent on the endothelium while sodium nitroprusside relaxation was entirely endothelium-independent. Negligible relaxation was observed in response to adenosine diphosphate (ADP) (12.1±12.8% at 1 × 10−5 M) while histamine and serotonin caused additional contraction only. We concluded that, in patients undergoing vascular surgical procedures, the saphenous vein (1) demonstrates variable contractile function which appears to be greater in males following spinal anesthesia, and (2) exhibits moderate endothelium-dependent relaxation in response to acetylcholine and calcium ionophore A23187 but not to ADP, histamine, or serotonin.

Serum lipids associated with inflammation-related PET-FDG uptake in symptomatic carotid plaque

Objective: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on 18fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. Methods: In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUVmax) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUVROImax); (3) averaged mean SUV across 10 ROIs (SUVmean). Results: Sixty-one patients were included. Plaque inflammatory FDG SUVmax was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol (p = 0.009), and triglycerides (p = 0.01), and with lower high-density lipoprotein (HDL) (p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUVmean (Spearman rho 0.44, p = 0.009), SUVROImax (rho 0.33, p = 0.01), and SUVmax (rho 0.35, p = 0.06). Total cholesterol was associated with SUVmean (rho 0.33, p = 0.009), with trends for SUVmax (rho 0.24, p = 0.059) and SUVROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUVmax (rho 0.32, p = 0.01) and SUVROImax (rho 0.35, p = 0.005). HDL was associated with lower SUVmax (rho −0.37, p = 0.004) and SUVROImax (rho −0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL (p = 0.008) and total cholesterol (p = 0.04) were independently associated with SUVmax. Conclusion: Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.