Extent and distribution of in-stent intimal hyperplasia and edge effect in a non-radiation stent population.

Intimal hyperplasia within the body of the stent is the primary mechanism for in-stent restenosis; however, stent edge restenosis has been described after brachytherapy. Our current understanding about the magnitude of in vivo intimal hyperplasia and edge restenosis is limited to data obtained primarily from select, symptomatic patients requiring repeat angiography. The purpose of this study was to determine the extent and distribution of intimal hyperplasia both within the stent and along the stent edge in relatively nonselect, asymptomatic patients scheduled for 6-month intravascular ultrasound (IVUS) as part of a multicenter trial: Heparin Infusion Prior to Stenting. Planar IVUS measurements 1 mm apart were obtained throughout the stent and over a length of 10 mm proximal and distal to the stent at index and follow-up. Of the 179 patients enrolled, 140 returned for repeat angiography and IVUS at 6.4 +/- 1.9 months and had IVUS images adequate for analysis. Patients had 1.2 +/- 0.6 Palmaz-Schatz stents per vessel. There was a wide individual variation of intimal hyperplasia distribution within the stent and no mean predilection for any location. At 6 months, intimal hyperplasia occupied 29.3 +/- 16.2% of the stent volume on average. Lumen loss within 2 mm of the stent edge was due primarily to intimal proliferation. Beyond 2 mm, negative remodeling contributed more to lumen loss. Gender, age, vessel location, index plaque burden, hypercholesterolemia, diabetes, and tobacco did not predict luminal narrowing at the stent edges, but diabetes, unstable angina at presentation, and lesion length were predictive of in-stent intimal hyperplasia. In a non-radiation stent population, 29% of the stent volume is filled with intimal hyperplasia at 6 months. Lumen loss at the stent edge is due primarily to intimal proliferation.

A radiolabeled staphylococcal protein A assay for detection of anti-erythrocyte IgG in warm agglutinin autoimmune hemolytic anemia of dogs and man.

A cell wall protein from Staphylococcus aureus, Protein A, (SpA) has been shown to have the ability to bind the Fc region of most mammalian IgG molecules. This study uses this unusual property as the basis for a quantitative assay for erythrocyte (RBC) bound antibodies. Test serum is incubated in a suspension of normal RBC's. The cells are then washed and incubated with 125Iodine-labeled SpA (125I-SpA). After incubation cells are pelleted and bound radiolabeled SpA counted. This procedure has been performed using canine anti-goat RBC (DagRBC) serum and human anti-D serum (positive controls) to establish the kinetics of the SpA reaction in the above system. The results indicate that SpA binds to red blood cells as a function of membrane bound antibody. RBC's incubated with indirect Coombs positive sera bound 42.6% and 43.3% of the 125I-SpA, as compared to 19.2%, the upper limit of the 95% confidence interval (n = 9) for normal sera. Furthermore, significant binding was observed for certain indirect Coombs negative (direct Coombs positive) sera indicating that the SpA assay is more sensitive than the indirect Coombs test. The SpA system should provide the clinician with an inexpensive, sensitive, quantitative assay for the diagnosis of warm agglutinin autoimmune hemolytic anemia, as well as other autoimmune disorders involving membrane bound IgG.

Adenosine induced atrial fibrillation precipitating polymorphic ventricular tachycardia.

An 86-year-old female developed supraventricular tachycardia 36 hours after a myocardial infarction (MI). She developed atrial fibrillation and polymorphic ventricular tachycardia (PVT) following administration of 12 mg of adenosine. The PVT caused hemodynamic instability with no response to cardioversion, but termination with procainamide. The heart is vulnerable to hemodynamically unstable, possibly lethal, PVT early after MI under some circumstances. This vulnerability may be exposed following administration of adenosine. Extra caution is warranted when using adenosine in the post-MI period.

Novel perfusion sleeve for use during balloon angioplasty: initial clinical experience.

The perfusion sleeve (PS) is an "over-the-balloon" catheter designed to add perfusion capability to standard PTCA catheters. To evaluate the clinical effectiveness of this device, eight patients underwent standard PTCA with the PS retracted in the guide (Inflation 1-Control) and after deployment of the PS (Inflation 3-Control). Between standard inflations the PS was advanced and aligned with the already positioned PTCA balloon which was inflated for up to 15 minutes (Inflation 2-Perfusion). TIMI III flow was present in 5/7 and TIMI II flow in 2/7 patients during Inflation 2-Perfusion. Absolute ST segment shift (mm) on the ECG was significantly less at 3 minutes and prior to balloon deflation with the PS in place (1.0 +/- 1.4 and 1.1 +/- 1.1 mm) compared to Inflation 1-Control and Inflation 3-Control (2.6 +/- 1.3 and 2.3 +/- 0.3 mm) respectively (P < or = 0.05). Use of the PS in conjunction with standard PTCA is feasible, provides perfusion during prolonged balloon inflations and reduces the magnitude of ischemia.

A novel nucleotide-based thrombin inhibitor inhibits clot-bound thrombin and reduces arterial platelet thrombus formation.

A novel thrombin inhibitor based on single-stranded (ss) deoxynucleotides with the sequence GGTTGGTGTGGTTGG (thrombin aptamer) has been recently discovered. In this study, we tested its efficacy in inhibiting clot-bound thrombin activity and platelet thrombus formation in an ex vivo whole artery angioplasty model. The thrombin aptamer showed a specific dose-dependent inhibition of thrombin-induced platelet aggregation (0.5 U/mL) in human platelet-rich plasma, with an IC50 of approximately 70 to 80 nmol/L. In an in vitro clot-bound thrombin assay system, heparin, used at clinically relevant concentrations of 0.2 U/mL and 0.4 U/mL, was ineffective in inhibiting clot-bound thrombin (6.5% and 34.9% inhibition at 0.2 U/mL and 0.4 U/mL, respectively). In contrast, the thrombin aptamer at an equivalent anticoagulant concentration inhibited clot-bound thrombin (79.7% inhibition). In an ex vivo whole artery angioplasty model, the thrombin aptamer markedly suppressed the generation of fibrinopeptide A (FPA), whereas heparin at 2 U/mL was ineffective. Compared with a scrambled ssDNA control, the thrombin aptamer reduced platelet deposition by 34.5% +/- 5% (mean +/- SEM, n = 4, P = .09) at low shear rates (approximately 200 s-1) and 61.3% +/- 11% (mean +/- SEM, n = 4, P = .05) at high shear rates (approximately 850 s-1). Thrombin aptamers based on ssDNA molecules represent a new class of thrombin inhibitors with potent anticoagulant and antithrombotic properties.

Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model.

BACKGROUND: Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis. METHODS AND RESULTS: In a new ex vivo whole artery angioplasty model, we examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 +/- 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 +/- 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin. CONCLUSIONS: At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation. The 7E3 results suggest that approximately 70% of platelet deposition at the site of balloon injury is GPIIb/IIIa dependent and that the remaining 30% results from non-GPIIb/IIIa-mediated platelet-subendothelial adhesion. Finally, the ex vivo whole artery system is a useful model for studying platelet-vessel wall interactions under physiologically defined parameters.