Search PubMedSearch

Biomedical subjects

W S Kramer

Publications and source records attributed to W S Kramer.

3 recordsLinked to original sources

Pulsed laser and thermal ablation of atherosclerotic plaque: morphometrically defined surface thrombogenicity in studies using an annular perfusion chamber.

Although clinical trials using laser and thermal angioplasty devices have been underway, the effects of pulsed laser and thermal ablation of atherosclerotic plaque on surface thrombogenicity are poorly understood. This study examined the changes in platelet adherence and thrombus formation on freshly harvested atherosclerotic aorta segments from Watanabe-heritable hyperlipidemic rabbits after ablation by two pulsed laser sources (308-nm xenon chloride excimer and 2,940-nm erbium:yttrium-aluminum-garnet [YAG] lasers) and a prototype catalytic hot-tip catheter. Specimens were placed in a modified Baumgartner annular chamber and perfused with citrated whole human blood, followed by quantitative morphometric analysis to determine the percent surface coverage by adherent platelets and thrombi in the treated and contiguous control areas. Pulsed excimer laser ablation of plaque did not change platelet adherence or thrombus formation in the treated versus control zones. However, photothermal plaque ablation with a pulsed erbium:YAG laser resulted in a 67% reduction in platelet adherence, compared with levels in control areas (from 16.7 +/- 2.2% to 5.5 +/- 1.8%; p less than 0.005). Similarly, after plaque ablation using a catalytic thermal angioplasty device, there was a 74% reduction in platelet adherence (from 29.2 +/- 5.1% to 7.7 +/- 1.6%; p less than 0.005) and a virtual absence of platelet thrombi (from 8.6 +/- 2.3% to 0.03 +/- 0.03%; p less than 0.005). This reduced surface thrombogenicity after plaque ablation with either an erbium:YAG laser or a catalytic hot-tip catheter suggests that thermal modifications in the arterial surface ultrastructure or thermal denaturation of surface proteins, or both, may be responsible for reduced platelet adherence. These in vitro findings indicate that controlled thermal plaque ablation by catheter-based techniques may elicit endovascular responses that can reduce early thrombus formation during angioplasty procedures.

Angioplasty, Laser

Arginine-glycine-aspartic acid- and fibrinogen gamma-chain carboxyterminal peptides inhibit platelet adherence to arterial subendothelium at high wall shear rates. An effect dissociable from interference with adhesive protein binding.

Arg-Gly-Asp (RGD)- and fibrinogen gamma-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa). GP IIb-IIIa, vWF, and Fn are essential for normal platelet adherence to subendothelium. We added peptides to normal citrated whole blood before perfusion over human umbilical artery subendothelium and evaluated platelet adherence morphometrically at high (2,600 s-1) and low (800 s-1) wall shear rates. We also examined the effects of the peptides on platelet adhesion to collagen in a static system. At the high wall shear rate, RGDS and GQQHHLGGAKQAGDV caused dose-dependent reduction in the surface coverage with spread and adherent platelets. Amino acid transposition and conservative substitutions of RGD peptides and the AGDV peptide significantly inhibited platelet adherence at 2,600 s-1. By contrast, the modified RGD peptides and AGDV do not affect adhesive protein binding to platelets. None of the native or modified RGD- or fibrinogen gamma-chain peptides significantly inhibited either platelet adherence to subendothelium at 800 s-1 or platelet adhesion to collagen. Our findings demonstrate that peptides that interfere with adhesive protein binding to GP IIb-IIIa inhibit platelet adherence to vascular subendothelium with flowing blood only at high wall shear rates. Platelet adherence to subendothelium at high wall shear rates appears to be mediated by different recognition specificities from those required for fluid-phase adhesive protein binding or static platelet adhesion.

Amino Acid Sequence