Publications

Background The assumption that atherosclerosis accumulates in the proximal coronary arteries and that distal segments are spared has yet to be systematically shown in vivo. Methods We used intravascular ultrasound to analyze complete proximal, mid, and distal segments from 75 diseased left anterior descending arteries (LADs) and 61 diseased right coronary arteries (RCAs) (including either the posterolateral [PLA; n = 38] or posterior descending artery [PDA; n = 23]) to document that distal coronary arteries are more often free of disease vs proximal vessels. External elastic membrane, lumen, and plaque and media areas were measured every 0.4 mm (median), and plaque burden (plaque and media/external elastic membrane) and percentage of normal (plaque and media thickness <0.3 mm) cross sections/segment were determined. Results Left anterior descending artery plaque was heaviest in proximal and mid segments, diminishing significantly in distal segments; plaque burden was 46% ± 9% in proximal, 39% ± 8% in mid, and 31% ± 9% in distal LAD (P < .0001), with 93% (median) of distal LAD cross sections being normal compared with 21% of mid and 0% of proximal cross sections (P < .0001). Right coronary artery plaque gradient was less pronounced vs the LAD; plaque burden was 37% ± 13% in proximal, 40% ± 10% in mid, and 36% ± 10% in distal RCA, followed by 31% ± 11% in PDA and 33% ± 10% in PLA. This was supported by the median percentage of normal cross sections/segment: 0% proximal, 0% mid, and 23% distal RCA sections plus 100% PDA and 48% PLA sections. Conclusions Intravascular ultrasound data indicated a proximal-to-distal LAD plaque gradient; significant disease was uncommon in the distal LAD. Conversely, the proximal-to-distal RCA plaque gradient was less distinct than the LAD, although disease in the PDA was still reduced compared with proximal segments.

The efficacy of sirolimus-eluting stents (SES) compared to paclitaxel-eluting stents (PES) remains unknown. We evaluated the clinical outcomes after implantation of 2.25 mm diameter SES and PES.PES have been used as the stent of choice for all percutaneous coronary interventions as part of the prospective Taxus-Stent Evaluated At Rotterdam Cardiology Hospital (T-SEARCH) Registry. Ninety consecutive patients received at least one 2.25 mm PES (PES group), and were compared with 107 patients who received at least one 2.25 mm SES as part of the RESEARCH registry. The overall population presented high-risk characteristics commonly excluded from most studies. Populations were well-matched. There were 2 (2.2%) incidents of subacute stent thrombosis in the PES group (in a 2.25 mm stent), and none in the SES group. At one year, the cumulative incidence of major adverse cardiac events was 5.6% in the SES group, and 17.8% in the PES group (p = 0.007). After adjustments for other significant univariate variables, presentation with acute coronary syndrome (ACS) (adjusted OR 5.2 [95% CI 1.8-15.0], p = 0.002) and PES utilization (adjusted OR 3.7 [95% CI 1.3-10.5], p = 0.013) were found to be significant independent predictors of major adverse cardiac events (MACE).In an unselected population treated for very small vessel disease, SES were associated with better 12-month clinical outcomes and the use of PES was identified as an independent predictor of adverse events.

In heart-lung transplantation (HLT), the airways have been assumed to be denervated since cholinergic, adrenergic, and sensory nerves are severed. Challenge studies of such patients suggest that there is an increase in airway responsiveness to inhaled cholinergic agonists, which may be explained by denervation hypersensitivity of muscarinic receptors on airway smooth muscle. We have studied the cholinergic control of airways from lungs removed from five patients (8 to 31 yr of age) undergoing retransplantation because of rejection-related bronchiolitis, with time since transplantation ranging from 12 to 32 months. These airways were compared with airways obtained from eight heart donors (24 to 42 yr of age) and from five patients undergoing surgical lobectomy for bronchial carcinoma (54 to 72 yr of age). Bronchial rings (distal lobar and subsegmental) were mounted in organ baths and isometric contractile responses measured. Contractile responses to acetylcholine (ACh, 10 nM to 10 mM) and to electrical field stimulation (EFS) (40 V, 0.5 ms, 1 to 64 Hz for 15 s) were determined. Transplant and control airways showed the same response to ACh, with mean EC50 values of 61.0 ± 0.32 µM for HLT patients, 57.6 ± 0.24 µM for donor patients, and 48.7 ± 1.2 µM for lobectomy patients, suggesting no denervation hypersensitivity of muscarinic receptors. EFS, which activates postganglionic cholinergic nerves, caused similar frequency responses in both transplant and control airways, suggesting that postganglionic nerves are intact. [3H]quinuclidinyl benzilate binding to membranes prepared from lung was performed to determine muscarinic binding characteristics. There was a small but insignificant increase in receptor density (Bmax = 61.4 ± 7.5 in HLT and 46.1 ± 7.1 fmol/mg protein in control patients) and no difference in the binding affinity (Kd = 0.48 ± 0.08 in HLT and 0.37 ± 0.06 nM in control patients), indicating no alteration in muscarinic receptors with denervation. We conclude that surgically denervated human airways from lung transplant patients have normally functioning postganglionic nerves and no change in cholinergic responsiveness or receptors, presumably because parasympathetic neurons survive. Denervation hypersensitivity cannot account for the increased cholinergic responsiveness observed in these patients.

No abstract is provided for this article.

Summary Background Cytokines and chemokines produced by allergen‐reactive T‐helper type 2 (Th2) cells may be pivotal to the pathophysiology of allergic disorders. Objective This study was performed to assess the effect of 7 days of topical corticosteroid on nasal allergen challenge (NAC) in terms of eosinophils, cytokines and chemokines obtained by nasal lavage and filter paper methods. Methods Patients with grass pollen seasonal‐allergic rhinitis ( n =13) out of season received nasal challenge following matched placebo (twice daily into each nostril for 7 days) and fluticasone propionate (100 μg twice daily into each nostril for 7 days). Chemokine and cytokine levels were analysed using a sensitive automated bead immunoassay system at intervals up to 8 h after NAC. Results Levels of cytokines and chemokines from filter paper were generally higher than from nasal lavage. Fluticasone propionate caused a reduction in symptoms, total leukocyte counts and eosinophils, and abrogation of IL‐4, IL‐5, IL‐6 and IL‐13 responses in the filter paper taken in the late phase ( P &lt;0.05 for IL‐4 and IL‐13, P &lt;0.01 for IL‐5 and IL‐6). Levels of chemokines (eotaxin, RANTES, MCP‐1, MIP‐1α, IL‐8 and IP‐10) were also reduced in the late phase ( P &lt;0.01 at 8 h). However, levels of IL‐2, IL‐3, IL‐7, IL‐12 (p40 and p70), ‐15, TNF‐α, IFN‐γ and GM‐CSF were not affected. Conclusion Fluticasone propionate has selective inhibitory effects on Th2 cytokine synthesis following nasal challenge, while also decreasing release of chemokines, but not affecting levels of Th1 cytokines.

No abstract is provided for this article.

Purpose: The prevalence and clinical consequences of intimal flaps due to vessel trauma or plaque rupture in the proximal segments of native coronary arteries has not been sufficiently described. Methods: OFDI investigation was performed following stent implantation for the treatment of ST-segment elevation myocardial infarction (STEMI). We defined the flap-like structure (FS) as a disruption of endoluminal vessel surface, and classified as flaps or artefacts under the consensus from 3 observers. We assessed the prevalence of FS in the sub-segment between the guide catheter tip and distal left main stem, or maximally 20-mm distal to the guide catheter tip in proximal right coronary artery, beyond 5-mm proximal to the stented segment. All FSs were left untreated since operators per protocol were blinded to the OFDI images. Results: A total of 8,931 frames in 97 STEMI patients were analyzed in a frame-by-frame fashion. OFDI identified 8 FSs in 7 patients, none of which were evident angiographically. Five FSs in 5 patients (5.1%) appeared to be flaps where only intima was involved, whereas the remaining 3 FSs in 3 patients were caused by artefacts, namely residual blood and interface light reflectivity. The mean distance from the guide catheter tip to the most proximal frame with flap was 4.8±2.7 mm. The mean length, root thickness, and maximum flap area were 0.9 mm, 0.3 mm, and 0.1 mm2, respectively. There were no adverse cardiac events observed during hospitalization and in the following 6 months. A case example of OFDI-detected flap A case example of OFDI-detected flap Conclusions: Post-procedural OFDI identified intimal flaps in the proximal coronary arteries, even angiographically silent, in 5.1% of STEMI patients. The detectable FS had no clinical consequences. A precise interpretation of FS may help the decision making to avoid unnecessary stent implantation.

Bioresorbable scaffolds (BRSs) may potentially overcome the many pitfalls related to drug eluting stents (DESs). The primary objective of this study was to evaluate and effectiveness of the Mirage Microfiber Sirolimus Eluting Coronary Scaffold (MMSES) compared to the Bioresorbable Vascular Scaffold (BVSs) in the treatment of stenotic target lesions located in native coronary arteries. The secondary objectives of this study were to establish the long-term safety, effectiveness, and performance of the MMSES, assessed at multiple time points through assessment of clinical and/or angiographic, Optical coherence tomography (OCT), and intravascular ultrasound (IVUS) data. The high mechanical strength of polylactide (PLA) monofilament results in the high radial strength of MMSES. MMSES has a circular strut that is believed to accelerate the re-endothelialization process and minimize the risk for scaffold thrombosis. PLA monofilament technology offers great flexibility in manufacturing bioresorbable scaffolds. MMSES was made into various sizes that were virtually the same as those in DESs.