AB

ST

RA

CT

S

S18 Abstracts Heart, Lung and Circulation2008;17S:S1–S209

38Infusion of Reconstituted HDL leads to Acute Changes inHuman Atherosclerotic Plaque In Vivo

James Shaw 2,∗, Alex Bobik 2, Peter Blombery 1, DmitriSviridov 2, Stuart Lyon 1, Anthony Dart 1

1 Alfred Hospital, Victoria, Australia; 2 Baker Heart ResearchInstitute, Victoria, Australia

Background: High-density lipoprotein (HDL) is an inversepredictor of cardiovascular events. Recent studies haveshown a reduction in plaque volume and change in plaqueultrasound characteristics after four infusions of reconsti-tuted HDL. Whether rHDL infusion leads to acute changesin plaque composition in humans is not known.Methods and results: Patients with symptom limiting clau-dication planned for percutaneous superficial femoralartery (sfa) revascularisation were randomised to eitherplacebo or IV r HDL infusion (80 mg/kg given over 4 h).5–7 days following the infusion patients returned andrevascularisation was performed including atherectomy(Foxhollow CA) to excise plaque from the sfa. 18 patients(15 male) average age 69 ± 10 years (mean ± S.D.) wererecruited. 10 had a history of documented coronary arterydisease and all patients were on aspirin and 16 on statins.9 of the patients received r HDL and 9 placebo. In the SFAplaque there was significantly less Vascular Cell AdhesionMolecule staining (23 ± 9 vs. 41.8 ± 3, p < 0.05) evidence of

eral arterial tonometry (RH-PAT) measures digital pulsevolume changes during reactive hyperaemia and is analternative assessment of endothelial function. Centralpulse wave velocity (PWV) is considered the best estimateof aortic stiffness.Method: Pressure waveforms were acquired in 20 healthymales (24 ± 5 years) from the carotid and femoral arteryand PWV calculated as the quotient of foot-to-foot pres-sure wave delay and distance. Salbutamol (an endothelialdependant agent) was given 25 min after GTN (anendothelial independent agent) was administered. Salbu-tamol:GTN index is the ratio of change in augmentationindex (AIx) with salbutamol relative to that with GTN. PeakRH-PAT ratio is the ratio of the peak digital pulse volumeduring reactive hyperemia divided by that at baseline.Results: Peak RH-PAT ratio was inversely associated withsystolic, diastolic and mean blood pressures (all p < 0.05,r2 = 0.25, r2 = 0.26, r2 = 0.23, respectively). Radial salbuta-mol:GTN index was related to peak RH-PAT ratio (p < 0.05,r2 = 0.245) and PWV (p < 0.001, r2 = 0.52). Carotid salbuta-mol:GTN index was not associated with the peak RH-PATratio or with PWV.Conclusion: In contrast to the radial pressure waveform,changes in carotid AIx do not reflect indices of endothelialfunction. This may be explained by the influence of arterialstiffness during pressure propagation.

oxygen free radicals (29 ± 23 vs. 100 ± 20, p < 0.05 (arbitraryunits)) and amount of lipid in the plaque as measured withOil red O staining in the HDL treated subjects comparedto placebo. The level of HDL-C increased by 20% afterinfusion of rHDL, but decreased after placebo infusion.The capacity of isolated HDL to support cholesterol effluxfrom cultured macrophages also increased after infusionof rHDL, but decreased after placebo infusions.Conclusion: Intravenous infusion of a single dose of recon-stituted HDL in subjects with peripheral vascular diseaseled to acute changes in plaque with a reduction in mea-sures of inflammation, oxidised free radicals and lipidcontent in subjects with peripheral vascular disease. Thesechanges may contribute to the presumed cardioprotectiveeffects of HDL.

doi:10.1016/j.hlc.2008.05.039

39Radial, but not Carotid, Salbutamol: GTN Index is relatedto Endothelial Function

Kevin Cheng, Sarah Hope ∗, Phillip Mottram, IanMeredith, James Cameron

Monash Cardiovascular Research Centre, Monash Heart,Southern Health & Department of Medicine (MMC), MonashUniversity, Melbourne, Victoria, Australia

Background: The central aortic pressure waveform isbelieved influenced by endothelial function and aorticstiffness. Pulse wave analysis of the radial artery com-bined with pharmacological challenge has been used toassess endothelial function. Reactive hyperaemia periph-

doi:10.1016/j.hlc.2008.05.040

40Digital Reactive Hyperaemia Response is related withCentral Pulse Wave Velocity

Kevin Cheng, Sarah Hope ∗, Phillip Mottram, IanMeredith, James Cameron

Monash Cardiovascular Research Centre, Monash Heart,Southern Health & Department of Medicine (MMC), MonashUniversity, Melbourne, Australia

Background: Reactive hyperaemia peripheral arterialtonometry (RH-PAT) is a new technique of assessingendothelial function by non-invasively measuring digi-tal pulse volume changes during reactive hyperaemia.Pulse wave velocity (PWV) has been shown to be directlyrelated to endothelial function as assessed by flow medi-ated dilatation. Relationships between PWV and digitalRH-PAT response have not been explored.Method: In 20 healthy male subjects (24 ± 5 years) pressurewaveforms were acquired by Millar Mikro-tip tonometryof the carotid and femoral arteries. PWV was calculated asthe quotient of the foot-to-foot pressure wave delay anddistance. Endothelial function is expressed as the peakRH-PAT ratio (ratio of the digital pulse volume duringreactive hyperemia divided by that at baseline). Analysiswas by regression and correlation techniques.Results: Central PWV was directly related to age (p < 0.001,r2 = 0.46). Peak RH-PAT ratio was inversely related toPWV (p < 0.05, r2 = 0.29), systolic (p < 0.05, r2 = 0.25), dias-tolic (p < 0.05, r2 = 0.26) and mean (p < 0.05, r2 = 0.23) bloodpressures. Carotid augmentation index and time to inflec-tion were not associated with peak RH-PAT ratio.

AB

ST

RA

CT

S

Heart, Lung and Circulation Abstracts S192008;17S:S1–S209

Conclusion: Elevated PWV, systolic, diastolic, and meanblood pressures are associated with attenuated digitalreactive hyperaemia response in this cohort of healthyyoung male subjects. The inverse relationship betweenRH-PAT and PWV is consistent with current knowledgeand supports the potential of RH-PAT in assessment ofendothelial function.

doi:10.1016/j.hlc.2008.05.041

41Electrospun Elastin-based Vascular Grafts

Steven Wise 1,∗, Michael Byrom 2, Paul Bannon 2, AnthonyWeiss 1, Martin Ng 3

1 The University of Sydney, Sydney, NSW, Australia; 2 TheBaird Institute, Sydney, NSW, Australia; 3 The Heart ResearchInstitute, Sydney, NSW, Australia

Small-diameter synthetic vascular graft materials failto match the patency of human tissue conduits used incoronary artery and peripheral vascular bypass surgery.The foreign surface retards endothelialisation and ishighly thrombogenic, while the stiffness of availablesynthetics results in anastomotic wall tension and intimalhyperplasia. Elastin is a key elastic protein polymer inthe arterial extracellular matrix and its unique physicalproperties make it an ideal material for the constructionof novel bioengineered vascular bypass conduits. Usingsvm

MlnstpwRdhtsbo

flexible than existing commercial materials, Dacron andexpanded polytetrafluoroethylene.Conclusion: Our preliminary data indicate that elastin-based grafts, by mimicking the properties of nativevasculature, display mechanical properties and biocom-patibility that are highly suited to clinical vascularapplications including vascular grafting.

doi:10.1016/j.hlc.2008.05.042

42Elastin-coated ePTFE Vascular Conduit

Michael Byrom 1,∗, Steve Wise 3, Paul Bannon 1, AnthonyWeiss 3, Martin Ng 2

1 The Baird Institute, Sydney, Australia; 2 The Heart ResearchInstitute, Sydney, Australia; 3 University of Sydney, Sydney,Australia

For Copyright reasons this abstract is not reproduced inthis supplement.

doi:10.1016/j.hlc.2008.05.043

43This abstract has been withdrawn.

doi:10.1016/j.hlc.2008.05.044

4DP

ARH

1

VHCs

TdtAAdMuwtaadwRabipv

ynthetic human elastin we aimed to develop a novelascular conduit with favourable biocompatibility andechanical properties.

ethods: Composite solutions of elastin and polycapro-actone (PCL) were drawn into fibres using electrospin-ing. Fibres were directed to a rotating mandril andubsequently cross-linked. Fibre orientation was charac-erised by scanning electron microscopy. The mechanicalroperties and effects on endothelial cell proliferationere assessed.esults: Electrospun grafts were comprised of randomlyistributed fibres with uniform diameter. The number ofuman umbilical vein endothelial cells increased propor-

ionally relative to the amount of elastin. Strength andtiffness increased with PCL content, such that a 25:75lend of elastin:PCL had a tensile strength exceeding thatf the human aorta while remaining significantly more

4ysfunctional AT2R in Radial Arteries of Diabeticatients

nthony Zulli 2,∗, Robert Widdop 4, Simon Moten 1, Alexosalion 1, George Matalanis 1, Brian Buxton 3, Davidare 4

Austin Health, Department of Cardiac Surgery, Heidelberg,ictoria, Australia; 2 Austin Health, Department of Medicine,eidelberg, Victoria, Australia; 3 Austin Health, Department ofardiology, Heidelberg, Victoria, Australia; 4 Monash Univer-

ity, Department of Pharmacology, Clayton, Victoria, Australia

he role for the angiotensin II type 2 receptor in humaniseased arteries is unclear. Current evidence suggests

hat hypertension and age can change the function of theT2R from a vasodilator to a vasoconstrictor.ims: To determine whether the AT2R is dysfunctional iniseased human vessels, especially diabetics.ethods: Radial arteries were collected from 23 patients

ndergoing coronary artery bypass graft. AT2R functionas determined by inhibiting AT2R (with PD123319) prior

o an angiotensin II dose response curve. As well, radialrtery segments from four further patients (two diabeticsnd two age, blood pressure and medication matched non-iabetic controls) were then collected and preconstrictedith phenylephrine and AT2R stimulated with CGP42112.esults: Blocking AT2R with PD123319 resulted in eithern enhanced vasoconstrictive response to angiotensin IIy 67 % (n = 12, p < 0.05) in some arteries, but diminished

t by 33% (n = 11, p < 0.01) in other arteries. In diabeticatients, stimulation of AT2R caused a small increase inasoconstriction on top of the pre-existing tension (n = 2),