Faculty Bibliography

Hyperkalemia affects the myocardial tissue producing electrocardiographic abnormalities, such as prolongation of the P-R interval, tall peaked T waves, a reduction in the amplitude and an increase in the duration of P wave, and atrial and ventricular arrhythmias, including variable degree heart blocks. Elderly patients are particularly predisposed to developing hyperkalemia and the associated abnormalities due to an age-related reduction in glomerular filtration rate and pre-existing medical problems. Therefore, the impact of aging on potassium homeostasis must be taken into consideration, and preventive measures, such as early recognition of possible hyperkalemia in the geriatric population treated with certain medications or supplements must be investigated. The threshold for cardiac arrhythmias in the elderly can be lower than the general population. We report 3 unusual cases of mild hyperkalemia in elderly patients presenting with hypotension, syncope and variable degree heart blocks which resolved spontaneously with the correction of hyperkalemia.

AIMS/OBJECTIVE:There is little in vivo data in regards to the impact of adventitial neovascularisation on vascular remodelling and plaque composition. Using a porcine model of coronary atherosclerosis, we aimed to determine the impact of adventitial neovascularisation on plaque composition and vascular remodelling evaluated by IVUS. METHODS AND RESULTS/RESULTS:Coronary atherosclerosis was induced by adventitial delivery of lipids and a high cholesterol diet. At termination all vessels were analysed using IVUS to determine the degree of remodelling of each individual segment containing atherosclerotic lesions. Then, each segment was correlated with its correspondent histological frame for plaque composition and neovessel density. A total of 57 atherosclerotic lesions at different stages of development were analysed. The total neovessel count (TNC) correlated to the degree of plaque burden (15.6+/-7.2 TNC in <40% stenosis versus 35.7+/-14.0 TNC in >60% stenosis, p<0.01) and to the amount of intra-plaque collagen (32.4+/-14.1%, lower TNC tertile versus 47.5+/-8.9% upper TNC tertile, p< 0.01). The amount of intra-plaque SMC content inversely correlated with the TNC (49.7+/-18.9% versus 36.4+/-14.4%, lower versus upper tertiles, p<0.05). Plaques with the highest TNC showed higher remodelling indexes by IVUS (0.89+/-0.32 in lower TNC tertile versus 1.36+/-0.73 in upper TNC tertile, p<0.05) and higher macrophage cell content (161.42+/-157.6 in lower TNC tertile versus 340.6+/-127.2 in upper TNC tertile, p<0.05) compared to non-remodelled segments. CONCLUSIONS:Adventitial neovascularisation is more prominent in positively remodelled segments and appears to be associated to SMC loss, increase collagen deposition and localised macrophage infiltration.

OBJECTIVES/OBJECTIVE:In this study, we hypothesized that an antihuman-CD34 antibody immobilized on the surface of commercially available sirolimus-eluting stents (SES) could enhance re-endothelialization compared with SES alone. BACKGROUND:Previous experience with antihuman-CD34 antibody surface modified Genous stents (GS) (OrbusNeich Medical, Fort Lauderdale, Florida) has shown enhanced stent endothelialization in vivo. METHODS:In the phase 1 study, stents were deployed in 21 pig coronary arteries for single stenting (9 vessels: 3 GS, 3 SES, and 3 bare-metal stents) and overlapping stenting with various combinations (12 vessels: 4 GS+GS, 4 SES+SES, and 4 GS+SES) and harvested at 14 days for scanning electron and confocal microscopy. In phase 2, immobilized anti-CD34 antibody coating was applied on commercially available SES (SES-anti-CD34, n = 7) and compared with GS (n = 8) and SES (n = 7) and examined at 3 and 14 days by scanning electron/confocal microscopy analysis. RESULTS:In phase 1, single stent implantation showed greatest endothelialization in GS (99%) and in bare-metal stent (99%) compared with SES (55%, p = 0.048). In overlapping stents, endothelialization at the overlapping zone was significantly greater in GS+GS (95 +/- 6%) and GS+SES (79 +/- 5%) compared with the SES+SES (36 +/- 14%) group (p = 0.007). In phase 2, SES-anti-CD34 resulted in increased endothelialization compared with SES alone at 3 days (SES-anti-CD34 36 +/- 26%; SES 7 +/- 3%; and GS 76 +/- 8%; p = 0.01), and 14 days (SES-anti-CD34 82 +/- 8%; SES 53 +/- 20%; and GS 98 +/- 2%; p = 0.009). CONCLUSIONS:Immobilization of anti-CD34 antibody on SES enhances endothelialization and may potentially be an effective therapeutic alternative to improve currently available drug-eluting stents.

The interaction of platelets with the polymeric surface of drug eluting stents has not been fully described in the literature. Our aim was to analyze the patterns of activation and deposition of platelets exposed to two different stent platforms; (a) the polymeric surface of the paclitaxel eluting stent (Taxus((R)) stent, PES,) and (b) the metallic surface of a stent with identical structural design (Express((R)) stent, BMS). Platelet activation was tested by deploying stents in an in vitro flow chamber model. Anticoagulated blood of 25 healthy volunteers was circulated (flow rate 10 ml/min for 60 min) into the flow chamber system. P-selectin expression, glycoprotein IIb/IIIa activation (PAC-1 binding) and platelet-monocyte complexes (PMC) formation were evaluated at 0, 10, 30 and 60 min. Surface platelet deposition was assessed by surface electron microscopy in stents implanted in the in vitro system for 60 min and in stents implanted in normal porcine coronary arteries for 24 h. Platelet activation evaluation showed a higher P-Selectin expression (92.9% of baseline in PES versus 68.3 % in BMS, P = 0.01) and higher PMC formation (125.7 % of baseline in PES versus 75.6% in BMS, P < 0.01) in the PES compared to the BMS control group. PAC-1 binding levels did not differ among groups. In the in vitro study, SEM analysis of the stent surface showed no statistical differences on platelet deposition between the groups. In addition, presence of proteinaceous material was more frequently seen on the BMS group (moderate to complete coverage = 80% in BMS versus 26% in PES, P < 0.01). In the in vivo study, complete platelet coverage was similar between groups (PES = 7% versus BMS = 8%, P = NS). However, there was an overall trend towards less platelet deposition on the BMS surface (mild and moderate coverage = 83%, 9% in BMS versus 49%, 44% in PES, P < 0.001 for both) but thrombus formation was not observed in either group. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface. The biological implications of these findings on the patterns of vascular healing need to be further studied in vivo. Condensed Abstract The interaction of human platelets with the surface of drug eluting stents has not been fully characterized. Patterns of platelet activation and adhesion were evaluated in vitro and in vivo after exposing platelets to the surface of the paclitaxel-eluting stent and identical bare metal stent. The degree of PMC formation and P-selectin expression was increased in PES compared to BMS. In the in vivo study, complete platelet coverage was similar between groups. There was an overall trend towards less platelet deposition on the BMS surface, however, thrombus formation was not observed on either surface. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface.

BACKGROUND:Metabolic syndrome (MS) is associated with a prothrombotic state and predicts the subsequent development of type 2 diabetes mellitus. We hypothesized that similar to diabetes, subjects with MS may have increased platelet reactivity, and reduced response to aspirin. We, therefore, compared platelet reactivity and response to aspirin among subjects with MS and healthy volunteers. METHODS:Fifty subjects with MS, defined by Adult Treatment Panel III criteria (age 44+/-9 years, 80% women, body mass index 35+/-8 kg/m2) were compared to 50 healthy controls who met none of the MS criteria (age 40+/-7 years, 80% women, body mass index: 24+/-3 kg/m2). Blood samples were taken before and 24 hours after 325 mg aspirin (single dose). Platelet function was evaluated by aggregation in response to 1.5 mmol/L arachidonic acid, 1 microg/mL collagen, and 5 and 20 micromol/L adenosine diphosphate; the VerifyNow Aspirin assay (Accumetrics Inc, San Diego, CA); Impact-R Cone and Plate(let) Analyzer (shear-dependent test) (DiaMed, Cresier, Switzerland) and flow cytometric determination of P-selectin expression and activated glycoprotein IIb/IIIa expression; and reticulated platelets (reflecting platelet turnover). RESULTS:Subjects with MS had higher baseline P-selectin levels (14.5+/-5 vs 11.3+/-4 mean fluorescence intensity, P=.002), reticulated platelets (2.8%+/-3% vs 1.2%+/-1%, P=.04) and platelet deposition under flow (Impact-R 7.5%+/-2% vs 5.9%+/-2%, P=.003). Subjects with MS also had lower response to aspirin, as evaluated by the change in all platelet aggregation assays and the VerifyNow score. CONCLUSIONS:Subjects with MS appear to have increased baseline platelet reactivity and turnover and a lower antiplatelet response to aspirin. Further research is required to elucidate platelet properties in subjects with MS and find ways to modify them.