The formation of an anti-restenotic/anti-thrombotic surface by immobilization of nitric oxide synthase on a metallic carrier.

Coronary stenosis due to atherosclerosis, the primary cause of coronary artery disease, is generally treated by balloon dilatation and stent implantation, which can result in damage to the endothelial lining of blood vessels. This leads to the restenosis of the lumen as a consequence of migration and proliferation of smooth muscle cells (SMCs). Nitric oxide (NO), which is produced and secreted by vascular endothelial cells (ECs), is a central anti-inflammatory and anti-atherogenic player in the vasculature. The goal of the present study was to develop an enzymatically active surface capable of converting the prodrug l-arginine, to the active drug, NO, thus providing a targeted drug delivery interface. NO synthase (NOS) was chemically immobilized on the surface of a stainless steel carrier with preservation of its activity. The ability of this functionalized NO-producing surface to prevent or delay processes involved in restenosis and thrombus formation was tested. This surface was found to significantly promote EC adhesion and proliferation while inhibiting that of SMCs. Furthermore, platelet adherence to this surface was markedly inhibited. Beyond the application considered here, this approach can be implemented for the local conversion of any systemically administered prodrug to the active drug, using catalysts attached to the surface of the implant.

Preliminary marked increase in the national organ donation rate in Israel following implementation of a new organ transplantation law.

Israel's organ donation rate has always been among the lowest in Western countries. In 2008 two new laws relevant to organ transplantation were introduced. The Brain-Respiratory Death Law defines the precise circumstances and mechanisms to determine brain death. The Organ Transplantation Law bans reimbursing transplant tourism involving organ trade, grants prioritization in organ allocation to candidates who are registered donors and removes disincentives for living donation by providing modest insurance reimbursement and social supportive services. The preliminary impact of the gradual introduction and implementation of these laws has been witnessed in 2011. Compared to previous years, in 2011 there was a significant increase in the number of deceased organ donors directly related to an increase in organ donation rate (from 7.8 to 11.4 donors per million population), in parallel to a significant increase in the number of new registered donors. In addition the number of kidney transplantations from living donors significantly increased in parallel to a significant decrease in the number of kidney transplantations performed abroad (from 155 in 2006 to 35 in 2011). The new laws have significantly increased both deceased and living organ donation while sharply decreasing transplant tourism.

Embolic potential and ultrasonic characteristics of plaques in patients with severe unilateral carotid restenosis more than one year after surgery.

PURPOSE: The purpose of the study is to investigate the embolic potential as well as ultrasonic characteristics of plaques in patients presenting with severe unilateral restenosis at least 1 year after carotid endarterectomy (CEA), compared with patients with severe unilateral primary carotid stenosis. METHODS: We used transcranial Doppler (TCD) to monitor microembolic signals (MES) and Doppler ultrasound to classify types and density of plaques in 27 patients with restenosis after CEA and in 97 patients with primary stenosis. RESULTS: Mean period between surgery and examination in patients with restenosis was 36.7+/-30.5 months (range 12-96). The groups were similar in distribution of main vascular risk factors. There were 36 (37.1%) patients with MES on TCD in primary stenosis versus 11 (40.7%) in restenosis group (NS). An average number of MES in primary stenosis group was 2.9+/-3.5/30 min and in restenosis group -3.4+/-2.9 (NS). There was no difference in distribution of plaques by echogenicity as well as by density. After adjustment by age, sex, and main risk factors, no influence was found for the effect of stenosis or restenosis on either the presence or the amount of emboli, as well as on the ultrasonic character of plaques. CONCLUSION: Carotid plaques in patients with severe unilateral carotid restenosis at least 1 year after surgery and in patients with primary lesions are similar in their embolic potential and ultrasonic characteristics.

Determinants of micro-embolic signals in patients with atherosclerotic plaques of the internal carotid artery.

BACKGROUND AND PURPOSE: This study aimed to investigate the embolic potential of carotid plaques, employing both the presence and the rate of micro-embolic signals (MESs), based on the presence and timing (current or past) of symptoms, degree of stenosis and ultrasonic characteristics of plaques. METHODS: We used the transcranial Doppler (TCD) to monitor MES and the Doppler ultrasound to classify carotid plaques in newly symptomatic (acute stroke or transient ischaemic attack (TIA)), formerly symptomatic (relevant stroke or TIA per anamnesis) and asymptomatic patients with internal carotid artery (ICA) stenosis. RESULTS: Stroke-related arteries evidenced a significantly greater presence of MES than the TIA-related and asymptomatic arteries (p=0.04), with no significant difference found between the latter two groups (stroke: 42/90, 46.7%; TIA: 15/49, 30.6%; asymptomatic: 40/130, 30.8%). Adjustment for anti-platelet treatment did not change this finding. The degree of stenosis, ultrasonic characteristics of texture and the density of plaques were not found to be associated with the presence or quantity of MES. CONCLUSION: MESs are present significantly more often in stenosed, stroke-related carotid arteries as compared with TIA-related or asymptomatic arteries. Neither the ultrasonic characteristics nor the degree of stenosis were found to influence the presence or rate of MES.

Multicenter evaluation of a self-expanding carotid stent system with distal protection in the treatment of carotid stenosis.

PURPOSE: Carotid artery stent placement may be limited by the embolization of atheromatous material. We evaluated the safety and feasibility of the Medtronic Self-Expanding Carotid Stent (Exponent) in combination with the Medtronic Interceptor Carotid Filter System for the treatment of carotid stenosis among patients at high risk for carotid endarterectomy. METHODS: Patients at high risk for carotid endarterectomy but amenable to percutaneous treatment with stent placement were enrolled. Clinical follow-up was performed at 30 days and 6 and 12 months postprocedure. The National Institutes of Health Stroke Scale was assessed before and within 3 days postprocedure and at 30 days and 6 months postprocedure. Angiography was performed pre- and postprocedure, and carotid duplex scans were performed at baseline and at 30 days and 6 months. RESULTS: Fifty-two carotid procedures were performed in 51 patients (mean age, 69 years; 84% of patients were men). The major adverse event (MAE) rate (death, stroke, and myocardial infarction [MI]) at 30 days was 5.9%: 2 strokes and a single death from periprocedural MI. MAE rates after 6 and 12 months were 5.9% and 11.8%, respectively. The delivery success rate was 94.2% (49/52) for the Interceptor Filter System and 95.9% (47/49) for the Exponent Stent. The mean diameter stenosis of the target lesion was reduced from 62.4% preprocedure to 21.2% postprocedure. CONCLUSION: High delivery success rates were achieved with a low rate of MAE (death, stroke, or MI) in a high-risk population. Treatment of carotid artery disease with the Exponent Carotid Stent combined with distal protection from the Interceptor Filter System is effective and safe.

Severe hypoxemia in a patient with acute myocardial infarction.

A case report of a patient with acute myocardial infarction and severe hypoxemia due to acute right to left interatrial shunt (RLIAS) is presented. Diagnostic and therapeutic procedures are discussed.

Chronic total occlusion due to diffuse in-stent restenosis: is brachytherapy the solution?

Percutaneous coronary intervention of chronic total occlusions (CTO) is associated with a significantly higher incidence of reocclusion and restenosis compared with non-total occlusions. Randomized and observational trials have demonstrated the effectiveness of intracoronary brachytherapy (ICBT) for the prevention of recurrent in-stent restenosis. However, limited data are available on the effectiveness of ICBT in patients with totally occluded in-stent restenosis. The authors assessed the long-term outcome of patients treated with intracoronary gamma radiation for totally occluded in-stent restenotic lesions. Percutaneous coronary intervention and subsequent catheter-based irradiation with iridium-192 was performed in 100 patients (103 vessels) with diffuse in-stent restenosis. At baseline, CTO of the target vessel at the site of the stent was present in 15 vessels (14.5%). Follow-up data were collected during follow-up visits and from telephone interviews. Repeat coronary angiography was performed in symptomatic patients with clinical restenosis. Clinical and angiographic characteristics were similar between the two groups, although there was a trend towards more unstable angina at the index procedure in CTO patients (66.7% versus 41.4%; p = 0.12) compared with patients without non-total occlusions. A higher percentage of patients (53.3%) with CTO required longer radiation sources (14 seeds, covering a length of 55 mm), compared with 23.9% of patients with non-total occlusion (p = 0.04). With a mean follow-up period of 47.5 +/- 24.0 months, major adverse cardiac events (MACE) were observed in 10 of 15 patients (66.7%) with CTO compared with 25 out of 88 patients (28.4%) without CTO (p = 0.009). According to multivariate analysis, total occlusion of the target vessel at baseline was the single independent predictor of MACE at one-year follow-up (relative risk 16.2, 95% confidence interval 4.2-62.9; p < 0.0001). This study shows that the use of gamma radiation for the prevention of recurrence of in-stent restenosis in patients with CTO does not seem to be as effective as in patients with non-total occlusions. Furthermore, CTO was an independent predictor of worse outcome at long-term follow-up in this study.

Bypass surgery versus stenting for the treatment of multivessel disease in patients with unstable angina compared with stable angina.

BACKGROUND: Earlier reports have shown that the outcome of balloon angioplasty or bypass surgery in unstable angina is less favorable than in stable angina. Recent improvements in percutaneous treatment (stent implantation) and bypass surgery (arterial grafts) warrant reevaluation of the relative merits of either technique in treatment of unstable angina. Methods and Results- Seven hundred fifty-five patients with stable angina were randomly assigned to coronary stenting (374) or bypass surgery (381), and 450 patients with unstable angina were randomly assigned to coronary stenting (226) or bypass surgery (224). All patients had multivessel disease considered to be equally treatable by either technique. Freedom from major adverse events, including death, myocardial infarction, and cerebrovascular events, at 1 year was not different in unstable patients (91.2% versus 88.9%) and stable patients (90.4% versus 92.6%) treated, respectively, with coronary stenting or bypass surgery. Freedom from repeat revascularization at 1 year was similar in unstable and stable angina treated with stenting (79.2% versus 78.9%) or bypass surgery (96.3% versus 96%) but was significantly higher in both unstable and stable patients treated with stenting (16.8% versus 16.9%) compared with bypass surgery (3.6% versus 3.5%). Neither the difference in costs between stented or bypassed stable or unstable angina ($2594 versus $3627) nor the cost-effectiveness was significantly different at 1 year. CONCLUSIONS: There was no difference in rates of death, myocardial infarction, and cerebrovascular event at 1 year in patients with unstable angina and multivessel disease treated with either stented angioplasty or bypass surgery compared with patients with stable angina. The rate of repeat revascularization of both unstable and stable angina was significantly higher in patients with stents.

A novel technique for measurement of pericardial pressure.

To determine whether pericardial liquid pressure accurately measures pericardial constraint, we developed a technique in which a catheter was positioned perpendicular to the epicardial surface. This device, which occupies little or no pericardial space, couples the thin film of liquid to a transducer. In six open-chest dogs, we also measured left ventricular (LV) end-diastolic pressure (LVEDP) and anteroposterior and septum-to-free wall diameters. LVEDP was raised incrementally to approximately 25 mmHg by saline infusion. With the use of the product of the two diameters as an index of area (A(LV)), LVEDP-A(LV) relationships were obtained with the pericardium closed and again after the pericardium had been widely opened to obtain the isovolumic difference in LVEDP (DeltaLVEDP). In all dogs, the technique yielded values of pericardial pressure equal to DeltaLVEDP as well as equal to that measured using a previously placed balloon transducer in the same location and at the same A(LV). We conclude that, when the pressure of the pericardial liquid is appropriately measured, it (in addition to the balloon-measured contact stress) defines the diastolic constraining effect of the pericardium. Furthermore, we suggest that earlier measurements of pericardial "liquid pressure" were low, due to an artifact of measurement.

Haptoglobin phenotype as a predictor of restenosis after percutaneous transluminal coronary angioplasty.

We have demonstrated that a genetic polymorphism in the antioxidant protein haptoglobin is important in determining which patients develop restenosis after percutaneous transluminal coronary angioplasty. Knowledge of the haptoglobin phenotype may be useful in the assessment and utilization of new therapies to reduce restenosis, particularly in patients who are homozygous for the haptoglobin 2 allele.

Stents in total occlusion for restenosis prevention. The multicentre randomized STOP study. The Israeli Working Group for Interventional Cardiology.

AIMS: This multicentre randomized study set out to evaluate whether coronary stenting improves the results of successful balloon angioplasty for chronic total occlusion. Balloon angioplasty for chronic total occlusion has a high restenosis rate. Several reports have suggested that coronary stenting may decrease the likelihood of restenosis and reocclusion. METHODS AND RESULTS: Patients with total coronary artery occlusions who had an optimal PTCA result were randomized either to no further treatment or additional stent implantation. The AVE microstent was used and all patients were scheduled for a 1-, 3-, and 6-month clinical follow-up. Repeat coronary angiography to assess the rate and pattern of restenosis was performed at 6 months or earlier if clinically indicated. Ninety-six patients were enrolled in this study. The mean age was 59. 3+/-10.3 years and 15 were females. Forty-eight patients were randomized to the stent arm, receiving 52 stents (lengths 18-39 mm). Stent implantation was successful in all and there were no major procedure-related complications. Sixty-nine patients (72%) were restudied after 6 months. The binary restenosis rates (50%), in the PTCA arm were 70.9% with a minimal lumen diameter of 1.01+/-0.79 mm compared to 42.1% in the stent arm with a minimal lumen diameter of 1.63+/-1.02 mm (P=0.034). Reocclusion occurred in 7.9% in the stent group compared to 16.1% in the PTCA group. Restenosis in the PTCA group was focal in 88% of patients and occurred at the point of total obstruction (within 5 mm), compared to diffuse instent restenosis, which occurred in 54% of the patients in the stent group. CONCLUSION: Coronary stenting can significantly decrease the rate of restenosis and reocclusion of total occlusions. As restenosis in the stent group was more diffuse, care should be taken to implant short stents at the site of occlusion.

Three-dimensional automatic quantitative analysis of intravascular ultrasound images.

Intravascular ultrasound (IVUS) has established itself as a useful tool for coronary assessment. The vast amount of data obtained by a single IVUS study renders manual analysis impractical for clinical use. A computerized method is needed to accelerate the process and eliminate user-dependency. In this study, a new algorithm is used to identify the lumen border and the media-adventitia border (the external elastic membrane). Setting an initial surface on the IVUS catheter perimeter and using active contour principles, the surface inflates until virtual force equilibrium defined by the surface geometry and image features is reached. The method extracts these features in three dimensions (3-D). Eight IVUS procedures were performed using an automatic pullback device. Using the ECG signal for synchronization, sets of images covering the entire studied region and corresponding to the same cardiac phase were sampled. Lumen and media-adventitia border contours were traced manually and compared to the automatic results obtained by the suggested method. Linear regression results for vessel area enclosed by the lumen and media-adventitia border indicate high correlation between manual vs. automatic tracings (y = 1.07 x -0.38; r = 0.98; SD = 0.112 mm(2); n = 88). These results indicate that the suggested algorithm may potentially provide a clinical tool for accurate lumen and plaque assessment.