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ABSTRACTS S18 Abstracts Heart, Lung and Circulation 2008;17S:S1–S209 38 Infusion of Reconstituted HDL leads to Acute Changes in Human Atherosclerotic Plaque In Vivo James Shaw 2,, Alex Bobik 2 , Peter Blombery 1 , Dmitri Sviridov 2 , Stuart Lyon 1 , Anthony Dart 1 1 Alfred Hospital, Victoria, Australia; 2 Baker Heart Research Institute, Victoria, Australia Background: High-density lipoprotein (HDL) is an inverse predictor of cardiovascular events. Recent studies have shown a reduction in plaque volume and change in plaque ultrasound characteristics after four infusions of reconsti- tuted HDL. Whether rHDL infusion leads to acute changes in plaque composition in humans is not known. Methods and results: Patients with symptom limiting clau- dication planned for percutaneous superficial femoral artery (sfa) revascularisation were randomised to either placebo or IV r HDL infusion (80 mg/kg given over 4 h). 5–7 days following the infusion patients returned and revascularisation was performed including atherectomy (Foxhollow CA) to excise plaque from the sfa. 18 patients (15 male) average age 69 ± 10 years (mean ± S.D.) were recruited. 10 had a history of documented coronary artery disease and all patients were on aspirin and 16 on statins. 9 of the patients received r HDL and 9 placebo. In the SFA plaque there was significantly less Vascular Cell Adhesion Molecule staining (23 ± 9 vs. 41.8 ± 3, p < 0.05) evidence of oxygen free radicals (29 ± 23 vs. 100 ± 20, p < 0.05 (arbitrary units)) and amount of lipid in the plaque as measured with Oil red O staining in the HDL treated subjects compared to placebo. The level of HDL-C increased by 20% after infusion of rHDL, but decreased after placebo infusion. The capacity of isolated HDL to support cholesterol efflux from cultured macrophages also increased after infusion of rHDL, but decreased after placebo infusions. Conclusion: Intravenous infusion of a single dose of recon- stituted HDL in subjects with peripheral vascular disease led to acute changes in plaque with a reduction in mea- sures of inflammation, oxidised free radicals and lipid content in subjects with peripheral vascular disease. These changes may contribute to the presumed cardioprotective effects of HDL. doi:10.1016/j.hlc.2008.05.039 39 Radial, but not Carotid, Salbutamol: GTN Index is related to Endothelial Function Kevin Cheng, Sarah Hope , Phillip Mottram, Ian Meredith, James Cameron Monash Cardiovascular Research Centre, Monash Heart, Southern Health & Department of Medicine (MMC), Monash University, Melbourne, Victoria, Australia Background: The central aortic pressure waveform is believed influenced by endothelial function and aortic stiffness. Pulse wave analysis of the radial artery com- bined with pharmacological challenge has been used to assess endothelial function. Reactive hyperaemia periph- eral arterial tonometry (RH-PAT) measures digital pulse volume changes during reactive hyperaemia and is an alternative assessment of endothelial function. Central pulse wave velocity (PWV) is considered the best estimate of aortic stiffness. Method: Pressure waveforms were acquired in 20 healthy males (24 ± 5 years) from the carotid and femoral artery and PWV calculated as the quotient of foot-to-foot pres- sure wave delay and distance. Salbutamol (an endothelial dependant agent) was given 25 min after GTN (an endothelial independent agent) was administered. Salbu- tamol:GTN index is the ratio of change in augmentation index (AI x ) with salbutamol relative to that with GTN. Peak RH-PAT ratio is the ratio of the peak digital pulse volume during reactive hyperemia divided by that at baseline. Results: Peak RH-PAT ratio was inversely associated with systolic, diastolic and mean blood pressures (all p < 0.05, r 2 = 0.25, r 2 = 0.26, r 2 = 0.23, respectively). Radial salbuta- mol:GTN index was related to peak RH-PAT ratio (p < 0.05, r 2 = 0.245) and PWV (p < 0.001, r 2 = 0.52). Carotid salbuta- mol:GTN index was not associated with the peak RH-PAT ratio or with PWV. Conclusion: In contrast to the radial pressure waveform, changes in carotid AI x do not reflect indices of endothelial function. This may be explained by the influence of arterial stiffness during pressure propagation. doi:10.1016/j.hlc.2008.05.040 40 Digital Reactive Hyperaemia Response is related with Central Pulse Wave Velocity Kevin Cheng, Sarah Hope , Phillip Mottram, Ian Meredith, James Cameron Monash Cardiovascular Research Centre, Monash Heart, Southern Health & Department of Medicine (MMC), Monash University, Melbourne, Australia Background: Reactive hyperaemia peripheral arterial tonometry (RH-PAT) is a new technique of assessing endothelial function by non-invasively measuring digi- tal pulse volume changes during reactive hyperaemia. Pulse wave velocity (PWV) has been shown to be directly related to endothelial function as assessed by flow medi- ated dilatation. Relationships between PWV and digital RH-PAT response have not been explored. Method: In 20 healthy male subjects (24 ± 5 years) pressure waveforms were acquired by Millar Mikro-tip tonometry of the carotid and femoral arteries. PWV was calculated as the quotient of the foot-to-foot pressure wave delay and distance. Endothelial function is expressed as the peak RH-PAT ratio (ratio of the digital pulse volume during reactive hyperemia divided by that at baseline). Analysis was by regression and correlation techniques. Results: Central PWV was directly related to age (p < 0.001, r 2 =0.46). Peak RH-PAT ratio was inversely related to PWV (p < 0.05, r 2 = 0.29), systolic (p < 0.05, r 2 = 0.25), dias- tolic (p < 0.05, r 2 = 0.26) and mean (p < 0.05, r 2 = 0.23) blood pressures. Carotid augmentation index and time to inflec- tion were not associated with peak RH-PAT ratio.

Radial, but not Carotid, Salbutamol: GTN Index is related to Endothelial Function

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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.