Cellular effects of beta-particle delivery on vascular smooth muscle cells and endothelial cells: a dose-response study.
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BACKGROUND: Although endovascular radiotherapy inhibits neointimal hyperplasia, the exact cellular alterations induced by beta irradiation remain to be elucidated. METHODS AND RESULTS: We investigated in vitro the ability of 32P-labeled oligonucleotides to alter (1) proliferation of human and porcine vascular smooth muscle cells (VSMCs) and human coronary artery endothelial cells (ECs), (2) cell cycle progression, (3) cell viability and apoptosis, (4) cell migration, and (5) cell phenotype and morphological features. beta radiation significantly reduced proliferation of VSMCs (ED50 1.10 Gy) and ECs (ED50 2.15 Gy) in a dose-dependent manner. Exposure to beta emission interfered with cell cycle progression, with induction of G0/G1 arrest in VSMCs, without evidence of cell viability alteration, apoptosis, or ultrastructural changes. This strategy also proved to efficiently inhibit VSMC migration by 80% and induce contractile phenotype appearance, as shown by the predominance of alpha-actin immunostaining in beta-irradiated cells compared with control cells. CONCLUSIONS: 32P-labeled oligonucleotide was highly effective in inhibiting proliferation of both VSMCs and ECs in a dose-dependent fashion, with ECs showing a higher resistance to these effects. beta irradiation-induced G1 arrest was not associated with cytotoxicity and apoptosis, thus demonstrating a potent cytostatic effect of beta-based therapy. This effect, coupled to that on VSMC migration inhibition and the appearance of a contractile phenotype, reinforced the potential of ionizing radiation to prevent neointima formation after angioplasty. (+info)
Lipoprotein(a) and coronary thrombosis and restenosis after stent placement.
(18/6088)
OBJECTIVES: The objective of this prospective study was to evaluate the relation between high lipoprotein(a) levels and thrombotic and restenotic events after coronary stent implantation. BACKGROUND: Lipoprotein(a) may promote atherogenesis, coronary thrombosis and restenosis after balloon angioplasty, but the clinical significance remains unclear. METHODS: The study included 2,223 consecutive patients with successful coronary stent placement. According to the serum level of lipoprotein(a), patients were divided in two groups: 457 patients of the highest quintile formed the high lipoprotein(a) group, and 1,766 patients of the lower four quintiles formed the low lipoprotein(a) group. Primary end points were the incidence of angiographic restenosis at six months and the event-free survival at one year. Secondary end point was the incidence of angiographic stent occlusion. RESULTS: Early stent occlusion occurred in four of the 457 patients (0.9%) with high and 37 of the 1,766 patients (2.1%) with low lipoprotein(a) levels, odds ratio of 0.41 (95% confidence interval, 0.15 to 1.16). Angiographic restenosis occurred in 173 of the 523 lesions (33.2%) in the high lipoprotein(a) group and 636 of the 1,943 lesions (32.7%) in the low lipoprotein(a) group, odds ratio of 1.02 (0.83 to 1.25). The probability of event-free survival was 73.0% in the high lipoprotein(a) group and 74.8% in the low lipoprotein(a) group (p = 0.45). On the basis of the findings in the low lipoprotein(a) group, the power of this study to detect a 25% increase in the incidence of restenosis and adverse events in the group with elevated lipoprotein(a) was 90% and 75%, respectively. CONCLUSIONS: Elevated lipoprotein(a) levels did not influence the one-year clinical and angiographic outcome after stent placement. Thrombotic events and measures of restenosis were not adversely affected by the presence of high lipoprotein(a) levels. (+info)
Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?
(19/6088)
OBJECTIVES: The purpose of this study in patients with quantitatively determined, poorly developed coronary collaterals was to assess the contribution of ischemic as well as adenosine-induced preconditioning and of collateral recruitment to the development of tolerance against repetitive myocardial ischemia. BACKGROUND: The development of myocardial tolerance to repeated ischemia is nowadays interpreted to be due to biochemical adaptation (i.e., ischemic preconditioning). METHODS: In 30 patients undergoing percutaneous transluminal coronary angioplasty, myocardial adaptation to ischemia was measured using intracoronary (i.c.) electrocardiographic (ECG) ST segment elevation changes obtained from a 0.014-in. (0.036 cm) pressure guidewire positioned distal to the stenosis during three subsequent 2-min balloon occlusions. Simultaneously, an i.c. pressure-derived collateral flow index (CFI, no unit) was determined as the ratio between distal occlusive minus central venous pressure divided by the mean aortic minus central venous pressure. The study patients were divided into two groups according to the pretreatment with i.c. adenosine (2.4 mg/min for 10 min starting 20 min before the first occlusion, n = 15) or with normal saline (control group, n = 15). RESULTS: Collateral flow index at the first occlusion was not different between the groups (0.15 +/- 0.10 in the adenosine group and 0.13 +/- 0.11 in the control group, p = NS), and it increased significantly and similarly to 0.20 +/- 0.14 and to 0.19 +/- 0.10, respectively (p < 0.01) during the third occlusion. The i.c. ECG ST elevation (normalized for the QRS amplitude) was not different between the two groups at the first occlusion (0.25 +/- 0.13 in the adenosine group, 0.25 +/- 0.19 in the control group). It decreased significantly during subsequent coronary occlusions to 0.20 +/- 0.15 and to 0.17 +/- 0.13, respectively. There was a correlation between the change in CFI (first to third occlusion; deltaCFI) and the respective ST elevation shift (deltaST): deltaST = -0.02 to 0.78 x deltaCFI; r = 0.54, p = 0.02. CONCLUSIONS: Even in patients with few coronary collaterals, the myocardial adaptation to repetitive ischemia is closely related to collateral recruitment. Pharmacologic preconditioning using a treatment with i.c. adenosine before angioplasty does not occur. The variable responses of ECG signs of ischemic adaptation to collateral channel opening suggest that ischemic preconditioning is a relevant factor in the development of ischemic tolerance. (+info)
Coronary artery stenting in unstable angina pectoris: a comparison with stable angina pectoris.
(20/6088)
OBJECTIVE: To compare early complication rates in unselected cases of coronary artery stenting in patients with stable v unstable angina. SETTING: Tertiary referral centre. PATIENTS: 390 patients with stable angina pectoris (SAP) and 306 with unstable angina (UAP). Patients treated for acute myocardial infarction (primary angioplasty) or cardiogenic shock were excluded. INTERVENTIONS: 268 coronary stents were attempted in 211 patients (30.3%). Stents used included AVE (63%), Freedom (14%), NIR (7%), Palmaz-Schatz (5%), JO (5%), and Multilink (4%). Intravascular ultrasound was not used in any of the cases. All stented patients were treated with ticlopidine and aspirin together with periprocedural unfractionated heparin. RESULTS: 123 stents were successfully deployed in 99 SAP patients v 132 stents in 103 UAP patients. Failed deployment occurred with nine stents in SAP patients, v four in UAP patients (NS). Stent thrombosis occurred in four SAP patients and 11 UAP patients. Multivariate analysis showed no relation between stent thrombosis and clinical presentation (SAP v UAP), age, sex, target vessel, stent length, or make of stent. Stent thrombosis was associated with small vessel size (p < 0.001) and bailout stenting (p = 0.01) compared with elective stenting and stenting for suboptimal PTCA, with strong trends toward smaller stent diameter (p = 0.052) and number of stents deployed (p = 0.06). Most stent thromboses occurred in vessels < 3 mm diameter. CONCLUSIONS: Coronary artery stenting in unstable angina is safe in vessels >/= 3 mm diameter, with comparable initial success and stent thrombosis rates to stenting in stable angina. (+info)
Platelet IIb/IIIa antagonists followed by delayed stent implantation. A new treatment for vein graft lesions containing massive thrombus.
(21/6088)
The percutaneous treatment of saphenous vein graft lesions containing angiographically massive thrombus is associated with a high risk of distal embolisation and no-reflow. The optimal management for these lesions remains unclear and a challenge to the interventional cardiologist. Five cases are described in whom the risks of percutaneous angioplasty were felt to be excessive owing to a high thrombus load. Each case was treated with a bolus and infusion of abciximab (ReoPro; Eli Lilly-a platelet glycoprotein IIb/IIIa receptor antagonist) at least 24 hours before further angiography. Repeat angiography of the culprit vein graft, following treatment with abciximab alone, demonstrated a major reduction in the thrombus score and the presence of TIMI 3 flow in each case. Immediately following repeat angiography, angioplasty with stent insertion was performed successfully with no distal embolisation or no-reflow phenomenon. This staged approach, with abciximab used alone to reduce thrombus load, is a new treatment for vein graft lesions containing massive thrombus. (+info)
Clinical and angiographic follow-Up after primary stenting in acute myocardial infarction: the Primary Angioplasty in Myocardial Infarction (PAMI) stent pilot trial.
(22/6088)
BACKGROUND: Restenosis has been reported in as many as 50% of patients within 6 months after PTCA in acute myocardial infarction (AMI), which necessitates repeat target-vessel revascularization (TVR) in approximately 20% of patients during this time period. Routine (primary) stent implantation after PTCA has the potential to further improve late outcomes. METHODS AND RESULTS: Primary stenting was performed as part of a prospective study in 236 consecutive patients without contraindications who presented with AMI of <12 hours' duration at 9 international centers. A mean of 1.4+/-0.7 stents were implanted per patient (97% Palmaz-Schatz) at 17.3+/-2.4 atm. During a clinical follow-up period of 7.4+/-2.6 months, death occurred in 4 patients (1.7%), reinfarction occurred in 5 patients (2.1%), and TVR was required in 26 patients (11.1%). By Cox regression analysis, small reference-vessel diameter and the number of stents implanted were the strongest determinants of TVR. Angiographic restenosis occurred in 27.5% of lesions. By multiple logistic regression analysis, the number of stents implanted and the absence of thrombus on the baseline angiogram were independent determinants of binary restenosis. CONCLUSIONS: A strategy of routine stent implantation during mechanical reperfusion of AMI is safe and is associated with favorable event-free survival and low rates of restenosis compared with primary PTCA alone. (+info)
Predictors for waiting time for coronary angioplasty in a high risk population.
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Objective--To describe the clinical and non-clinical factors which influence the waiting time from initial angiography to angioplasty. Design--Follow up of a random sample of 106 patients undergoing their first coronary angiography for whom a decision to revascularise by percutaneous transluminal angioplasty was made in 1991. The period between the date of angiography and the date of angioplasty and various clinical characteristics of patients were retrieved from medical notes in mid 1993. Patients were sampled from those investigated in the two Northern Ireland catheterisation laboratories in Belfast, which provide services for the whole of the province (population 1.5 million). Main measures--The dependent variable was the period between initial angiography and angioplasty, and the independent variables included age, sex, distance from cardiac catheterisation centre, referral source, characteristics of the clinical history, severity of angina, and anatomical extent of disease. Cox's proportional hazards analysis was used to derive a relative hazard, expressing the relative chances of revascularisation occurring at any time during follow up. Results--Of the 106 patients studied, 93 had had percutaneous transluminal angioplasty at follow up. The most important predictors of waiting time were the presence of severe angina (relative hazards 3.1(95 % confidence interval (95% CI) 1.4-6.8) and 2.7(1.2-6.2) for Canadian Cardiovascular grades III and IV v angina grade I angina), a recent history of myocardial infarction (relative hazard, 2.5(1.3-4.8), and whether or not the patient was economically active (relative hazard 0.6(0.4-1.0) for economically inactive v active patients). Although there was also an association with the relative deprivation of the area of residence of the patient it had no clear linear trend. Conclusions--Although waiting time for percutaneous transluminal angioplasty was predictably related to the patient's clinical presentation, demographic factors may also be important in determining access to intervention. These factors clearly merit further study; ultimately, the evaluation of equity in a waiting time distribution may more properly be a societal rather than a clinical judgment. (+info)
Economic winners and losers after introduction of an effective new therapy depend on the type of payment system.
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An effective therapy for a costly illness has economic consequences. There may also be differences between provider costs and payer costs and initial versus long-term costs; costs may also vary with the reimbursement scheme. Consider the case of an effective therapy to prevent restenosis after coronary angioplasty. Assume that the initial provider cost of angioplasty is $12,000 and that restenosis within 6 months results in repeat angioplasty in 20% of cases, with a follow-up cost of $2,400, or $14,400 total. Assume that a therapy costs $1,000 per angioplasty and decreases restenosis by 50%, resulting in repeat angioplasty in 10% of cases. This will result in an initial cost of $13,000 and a follow-up cost of $1,300, or $14,300 total. The total societal costs will be -$100, a slight savings. Thus, the $1,100 cost of therapy is offset by reduced costs associated with restenosis, and the societal costs are almost neutral. Assume that under fee for service providers charge costs plus 10% and that without the new therapy either a package price or a capitated system is revenue neutral. Changes in costs resulting from therapy to prevent restenosis are as follows (plus sign indicates cost or loss; minus sign indicates savings or profit): [table: see text] Under fee for service, the payer takes the risks, and the economic consequences to providers are minimal. The situation is reversed under capitation. For whoever takes the risk, there is an initial loss to pay for the therapy, but a long-term gain due to less restenosis. Under package pricing, the providers lose because of the cost of therapy and fewer procedures, while the payers gain. A new therapy, even if it is revenue neutral to society overall, may have considerable economic consequences, which vary with time and with the different perspectives of providers and payers. (+info)