Three‐months optical coherence tomography analysis of a biodegradable polymer,sirolimus‐eluting stent

Objective

We aimed to assess early neointimal healing by optical coherence tomography (OCT) 3 months after implantation of the ultrathin Orsiro® sirolimus‐eluting stent with biodegradable polymer.

Background

New generations of drug‐eluting stents with biodegradable polymer have been developed to avoid the continued vascular irritation of durable polymers.

Methods

In this prospective, open‐label study, 34 patients received an Orsiro® sirolimus‐eluting stent with biodegradable polymer. In a subgroup of patients (n = 15), the intervention was performed under OCT guidance. All patients underwent OCT‐examination at three months. The primary endpoint was 3‐month neointimal healing (NIH) score, calculated by weighing the presence of filling defects, malapposed and uncovered struts. Secondary endpoint was maturity of tissue coverage at 3 months.

Results

At 3 months, NIH score was 13.7 (5.4‐22), covered struts per lesion were 90% (84‐97%), malapposed struts were 2.7% (0.8‐5.4%) and rate of mature tissue coverage was 47% (42‐53%). No target lesion failure occurred up to 12 months. Patients with OCT‐guided stent implantation demonstrated a trend toward earlier stent healing as demonstrated by superior NIH scores (angio guided: 17.6% [8.8‐26.4]; OCT‐guided: 9.8% [4.0‐15.5]; mean difference ?8, [95%CI: ?18.7‐2.9], P = 0.123). This group had significantly more covered struts per lesion (angio‐guided: 86% [82‐90]; 95% [92‐99]; mean difference 9% [95%CI: 3‐15], P = 0.001).

Conclusion

The Orsiro® sirolimus‐eluting stent with biodegradable polymer shows early vascular healing with a high rate of strut coverage at 3‐month follow‐up. OCT guided stent implantation had a positive impact on early vascular healing.

     

Blood pressure responses to hypertension treatment and trends in cognitive function in patients with initially difficult-to-treat hypertension: a retrospective subgroup analysis of the Observational Study on Cognitive Function and SBP Reduction (OSCAR) study

J Clin Hypertens (Greenwich). 2012;14:78–84. ©2012 Wiley Periodicals, Inc.The Observational Study on Cognitive Function and SBP Reduction (OSCAR) provided opportunities to examine the influence of eprosartan on trends in cognitive performance in a large population of patients with difficult‐to‐treat hypertension (DTTH). A total of 4649 patients diagnosed retrospectively with DTTH, defined as systolic/diastolic blood pressure (SBP/DBP) ≥140/90 mm Hg despite use of at least 3 antihypertensive drugs during the month preceding the baseline visit comprised the intention‐to‐treat (ITT) cohort. The patients were given eprosartan‐based antihypertension therapy (EBT; 600 mg/d). Blood pressure and cognitive function parameters included significant (P<.001) differences for DTTH vs non‐DTTH patients such as older age, body mass index, SBP and pulse pressure (PP), and lower Mini‐Mental State Examination (MMSE) score. After EBT for 6 months, SBP/DBP in DTTH was 138.8±12.2/81.9±7.4 (ΔSBP−26±15.7; ΔDBP−11.4±9.8); PP was 57.0±10.8 (ΔPP−14.5±13.8) (all P<.001 vs baseline and non‐DTTH group). A total of 2576 patients (87.4%) responded to EBT (ie, SBP <140 mm Hg and/or ΔSBP ≥15 mm Hg, or DBP <90 mm Hg and/or ΔDBP ≥10 mm Hg); 1426 DTTH patients (48.4%) achieved normalized SBP/DBP (ie, SBP <140 mm Hg and DBP <90 mm Hg). ΔPP in DTTH‐isolated systolic hypertension (ISH) was −18.0±13.3 mm Hg (P=.003 vs DTTH‐systolic‐diastolic hypertension). End‐of‐EBT mean MMSE was 27.5±3.0 (P<.001 vs baseline). Blood pressure responses after EBT coincided with stabilization/improvement of MMSE in this retrospective investigation in DTTH patients. The average improvement in MMSE in DTTH patients was similar to that in non‐DTTH patients. EBT effects on PP may be relevant to the evolution of MMSE in DTTH‐ISH patients.

The Observational Study on Cognitive Function and SBP Reduction (OSCAR) was designed to examine the safety and tolerability of once‐daily therapy with eprosartan in a very large community‐dwelling population of patients with arterial hypertension recruited in 28 countries and managed in routine primary care. This study provided opportunities to examine the influence of the angiotensin receptor blocker (ARB) eprosartan on trends in cognitive performance in a large population of patients with high blood pressure (BP).The principal findings of OSCAR have been reported previously. ¹ A 6‐month period of antihypertensive therapy based on eprosartan was associated with a significant reduction in mean systolic BP (SBP) and a significant improvement in mean Mini‐Mental State Examination (MMSE) score (P<.0001 for both outcomes). In multiple linear regression, cognitive decline was demonstrated to be independently and inversely correlated with SBP reduction (odds ratio, 0.77; 95% confidence interval [CI], 0.73–0.82).The intention‐to‐treat (ITT) cohort of OSCAR comprised 25,745 adult patients with hypertension. This large number of patients enabled us to identify several large subgroups for further investigation, with the intention of adding to what are still sometimes limited epidemiologic data on specific types of patients.Recent revisions to extant European hypertension guidelines and first reports of new treatment options for this condition ² , ³ , ⁴ are indications that resistant hypertension is a pressing clinical priority. Poorly controlled high BP may be a factor in cognitive decline in older patients. Observations from several thousand patients in a real‐world survey may be instructive for the better management of this condition. Accordingly, we report here our findings in a retrospectively identified cohort of almost 3000 patients from the OSCAR population classified as having difficult‐to‐treat hypertension (DTTH) at baseline.     

Extravascular lung water determined with single transpulmonary thermodilution correlates with the severity of sepsis-induced acute lung injury

OBJECTIVE: To find out if the extravascular lung water index (EVLWI) and the derived permeability indexes determined by the single transpulmonary thermodilution technique are associated with markers of acute lung injury in human septic shock. DESIGN: Prospective, observational study. SETTING: Mixed intensive care unit of a 900-bed university hospital. PATIENTS: Thirty-eight consecutive adult patients with septic shock and acute lung injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The variables were assessed over a 72-hr period and included hemodynamics, EVLWI, and pulmonary vascular permeability indexes determined with the single indicator transpulmonary thermodilution technique, lung compliance, oxygenation ratio (Pao2/Fio2), lung injury score, cell counts, and the plasma concentration of endothelin-1. At day 1, EVLWI was elevated (>or=7 mL/kg) in 28 (74%) patients and correlated with lung compliance (r=-.48, p=.002), Pao2/Fio2 (r=-.50, p=.001), lung injury score (r=.46, p=.004), roentgenogram quadrants (r=.39, p=.02), and platelet count (r=-.43, p=.007). At day 3, EVLWI correlated with compliance (r=-.51, p=.002), Pao2/Fio2 (r=-.49, p = .006), and lung injury score (r=.53, p=.003). At day 3, EVLWI and pulmonary vascular permeability indexes were higher in nonsurvivors (p<.05). The plasma concentration of endothelin-1 (mean+/-sd) was significantly higher in patients with elevated EVLWI (>or=7 mL/kg) (3.85+/-1.40 vs. 2.07+/-0.38 pg/mL, respectively). Twenty-two (59%) patients died before day 28. CONCLUSIONS: In human septic shock, EVLWI demonstrated moderate correlation with markers of acute lung injury, such as lung compliance, oxygenation ratio, roentgenogram quadrants, and lung injury score. In nonsurvivors, EVLWI and permeability indexes were significantly increased at day 3. Thus, EVLWI might be of value as an indicator of prognosis and severity of sepsis-induced acute lung injury.     

Morphologic characteristics of chernobyl-related childhood papillary thyroid carcinomas are independent of radiation exposure but vary with iodine intake

BACKGROUND: The Chernobyl accident caused an unprecedented increase in papillary thyroid carcinoma (PTC) incidence with a surprisingly short latency and unusual morphology. We have investigated whether unexpected features of the PTC incidence after Chernobyl were radiation specific or influenced by iodine deficiency. METHODS: PTCs from children from Belarus, Ukraine, and the Russian Federation exposed to fallout from Chernobyl were compared with PTCs from children not exposed to radiation from the same countries, from England and Wales (E&W) and from Japan. The degree and type of differentiation, fibrosis, and invasion were quantified. RESULTS: There were no significant differences between PTCs from radiation-exposed children from Belarus, Ukraine, and the Russian Federation and PTCs from children from the same countries who were not exposed to radiation. Childhood PTCs from Japan were much more highly differentiated (p < 0.001), showed more papillary differentiation (p < 0.001) and were less invasive (p < 0.01) than "Chernobyl" tumors, while tumors from E&W generally showed intermediate levels of degree and type of differentiation and invasion. There was a marked difference between the sex ratios of children with PTCs who were radiation exposed and those who were not exposed (F:M exposed vs. unexposed 1.5:1 vs. 4.2:1; chi(2) = 7.90, p < or = 0.01005). CONCLUSIONS: The aggressiveness and morphological features of Chernobyl childhood PTCs are not associated with radiation exposure. The differences found between tumors from the Chernobyl area, E&W, and Japan could be influenced by many factors. We speculate that dietary iodine levels may have wide implications in radiation-induced thyroid carcinogenesis, and that iodine deficiency could increase incidence, reduce latency, and influence tumor morphology and aggressiveness.     

Investigation of the Metabolites of (S,S)-[11C]MeNER in Humans, Monkeys and Rats

Introduction  (S,S)-[¹¹C]MeNER ((S,S)-2-(α-(2-[¹¹C]methoxyphenoxy)benzyl)morpholine) is a positron emission tomography (PET) radioligand recently applied in clinical studies of norepinephrine transporters (NETs) in the human brain in vivo. In view of further assessment of the suitability of (S,S)-[¹¹C]MeNER as a NET radioligand, its metabolism and the identity of the in vivo radiometabolites of (S,S)-[¹¹C]MeNER are of great interest. Materials and Methods  Thus, PET studies were used to measure brain dynamics of (S,S)-[¹¹C]MeNER, and plasma reverse-phase radiochromatographic analysis was performed to monitor and quantify its rate of metabolism. Eighteen healthy human volunteers, five cynomolgus monkeys, and five rats were studied. Results and Discussion  In human subjects, the plasma radioactivity representing (S,S)-[¹¹C]MeNER decreased from 88 ± 5% at 4 min after injection to 82 ± 7% at 40 min, while a polar radiometabolite increased from 3 ± 3% to 16 ± 7% at the same time-points, respectively. A more lipophilic radiometabolite than (S,S)-[¹¹C]MeNER decreased from 9 ± 5% at 4 min to 1 ± 2% at 40 min. In monkeys, plasma radioactivity representing (S,S)-[¹¹C]MeNER decreased from 97 ± 2% at 4 min to 74 ± 7% at 45 min, with a polar fraction as the major radiometabolite. A more lipophilic radiometabolite than (S,S)-[¹¹C]MeNER, constituted 3 ± 2% of radioactivity at 4 min and was not detectable later on. In rats, 17 ± 4% of plasma radioactivity was parent radioligand at 30 min with the remainder comprising mainly a polar radiometabolite. (S,S)-[¹¹C]MeNER in rat brain and urine at 30 min after injection were 90% and 4%, respectively. On a brain regional level, parent radioligand ranged from 87.5 ± 3.9% (57.2 ± 14.2% SUV [standard uptake values, %injected radioactivity per mL multiplied with animal weight (in g)]; cerebellum) to 92.9 ± 1.8% (36.1 ± 4.7% SUV; striatum), with differential distribution of the radiometabolite in the cerebellum (6.7 ± 0.3% SUV) and the striatum (2.5 ± 0.3% SUV). Liquid chromatography-mass spectrometry analysis of rat urine identified a hydroxylation product of the methoxyphenoxy ring of (S,S)-MeNER as the main metabolite. In the brain, the corresponding main metabolite was the product from O-de-methylation of (S,S)-MeNER. PET measurements were performed in rats as well as in wild-type and P-gp-knock-out mice. In rats, the brain peak level of radioactivity was found to be very low (65%SUV). In mice, there was only a small difference in peak brain accumulation between P-gp knock-out and wild-type mice (145 vs. 125%SUV) with the following rank order of regional brain radioactivity: cerebellum × thalamus > cortical regions > striatum. Conclusion  It can be concluded that radiometabolites of (S,S)-[¹¹C]MeNER are of minor importance in rat and monkey brain imaging. The presence of a transient lipophilic radiometabolite in peripheral human plasma may induce complications with brain imaging, but its kinetics appear favorable in relation to the slow kinetics of (S,S)-[¹¹C]MeNER in humans.     

Renal fractional flow reserve: a hemodynamic evaluation of moderate renal artery stenoses.

The objective of this study was to perform a hemodynamic evaluation of moderate (50-90%) renal artery stenosis (RAS) under conditions of rest and maximum hyperemia. Identifying patients with RAS who have hemodynamically significant stenoses and are most likely to benefit from revascularization is clinically important. Current methods used to evaluate RAS, including angiography, have limitations. Physiologic evaluation of RAS may have a role in identifying patients with hemodynamically significant stenosis. Patients with suspected renovascular hypertension due to aorto-ostial RAS were included in the study. Hyperemia was induced by administration of intrarenal papavarine. Translesional pressure gradients were measured and renal fractional flow reserve (FFR) was calculated using a 0.014' pressure guidewire. Thirteen patients and 14 arteries with moderately severe (50-90%) RAS were studied. The mean translesional pressure gradient rose from a baseline of 6.3 +/- 3.9 to 17.5 +/- 10.8 mm Hg with maximal hyperemia. The renal FFR ranged from 0.58 to 0.95. There was a poor correlation between angiographic stenosis measurement and the renal FFR (r = -0.18; P = 0.54) and the hyperemic translesional mean pressure gradient (r = 0.22; P = 0.44). There was an excellent correlation between renal FFR and the resting mean translesional pressure gradient (r = -0.76; P = 0.0016) and the hyperemic mean translesional pressure gradient (r = -0.94; P < 0.0001). Selective renal arterial papavarine administration induces maximum hyperemia, permitting the calculation of renal FFR in renal arteries with aorto-ostial stenoses. The renal FFR correlates well with other hemodynamic parameters of lesion severity, but poorly with angiographic measures of lesion severity.     

Differential effects of ivabradine and ryanodine on pacemaker activity in canine sinus node and purkinje fibers

Effects of Ivabradine and Ryanodine on Cardiac Pacemakers . Introduction: It is generally accepted that at least 2 major mechanisms contribute to sinus node (SN) pacemaking: a membrane voltage (mainly I_f) clock and a calcium (Ca) clock (localized submembrane sarcoplasmic reticulum Ca²⁺ release during late diastolic depolarization). The aim of this study was to compare the contributions of each mechanism to pacemaker activity in SN and Purkinje fibers (PFs) exhibiting normal or abnormal automaticity. Methods and Results: Conventional microelectrodes were used to record action potentials in isolated spontaneously beating canine SN and free running PF in control and in the presence of 0.1 μM isoproterenol. Ryanodine (0.1–3 μM) and ivabradine (3 μM) were used to inhibit sarcoplasmic reticulum Ca²⁺ release or I_f, respectively. To induce automaticity at low membrane potentials, PFs were superfused with BaCl₂. In SN, ivabradine reduced the rate whereas ryanodine had no effect. Isoproterenol significantly accelerated automatic rate, which was decreased by ivabradine and ryanodine. In normally polarized PFs, ryanodine had no effects on the automatic rate in the absence or presence of isoproterenol, whereas ivabradine inhibited both control and isoproterenol‐accelerated automaticity. In PF depolarized with BaCl₂, ivabradine decreased BaCl₂‐induced automatic rate while ryanodine had no effect. Conclusion: In canine SN, I_f contributes to both basal automaticity and β‐adrenergic‐induced rate acceleration while the ryanodine‐inhibited Ca clock appears more involved in β‐adrenergic regulation of pacemaker rate. In PF, normal automaticity depends mainly on I_f. Inhibition of basal potassium conductance results in high automatic rates at depolarized membrane potentials with SN‐like responses to inhibition of membrane and Ca clocks. (J Cardiovasc Electrophysiol, Vol. 23, pp. 650–655, June 2012)     

Computer-Aided Design of Boron Nitride-Based Membranes with Armchair and Zigzag Nanopores for Efficient Water Desalination

Recent studies have shown that the use of membranes based on artificial nanoporous materials can be effective for desalination and decontamination of water, separation of ions and gases as well as for solutions to other related problems. Before the expensive stages of synthesis and experimental testing, the search of the optimal dimensions and geometry of nanopores for the water desalination membranes can be done using computer-aided design. In the present study, we propose and examine the assumption that rectangular nanopores with a high aspect ratio would demonstrate excellent properties in terms of water permeation rate and ion rejection. Using the non-equilibrium molecular dynamic simulations, the properties of promising hexagonal boron nitride (h-BN) membranes with rectangular nanopores were predicted. It has been found that not only the nanopore width but also its design (“armchair” or “zigzag”) determines the permeability and ion selectivity of the h-BN-based membrane. The results show that membranes with a zigzag-like design of nanopores of ~6.5 Å width and the armchair-like nanopores of ~7.5 Å width possess better efficiency compared with other considered geometries. Moreover, the estimated efficiency of these membranes is higher than that of any commercial membranes and many other previously studied single-layer model membranes with other designs of the nanopores.