Sternal neoangiogenesis following internal mammary artery devascularization: an experimental model.

AIM: The use of bilateral internal thoracic arteries (BIMA) for coronary artery revascularization is associated with better long-term survival and longer freedom from reoperation. Concerns of deep sternal wound infections and mediastinitis have constantly emerged with the utilization of BIMA grafts on a routine basis, especially in diabetic patients. METHODS: We performed a quantitative evaluation of sternal bone healing and angiogenesis after left (LIMA) or bilateral internal mammary artery (BIMA) ligation two and four weeks after sternotomy in normal and diabetic Sprague-Dawley rats. RESULTS: The BIMA group showed a significant increase in neoangiogenesis two weeks after surgery compared to LIMA and control groups (control: 38.3 ± 5.1 vessels/mm², LIMA: 31.4 ± 3.6 vessels/mm², BIMA: 81.6 ± 7.7 vessels/mm²; P=0.047 and P=0.04, respectively). Four weeks after the procedure, bilateral devascularization was associated with lower microvessel formation when compared to LIMA or control groups (control: 50.4 ± 5.2 vessels/mm², LIMA: 64.6 ± 4.9 vessels/mm²; BIMA: 31.5 ± 4.4 vessels/mm²; P=0.006 and P=0.02, respectively). Diabetic animals showed similar results with lower four weeks microvessel formation. However, there were no significant differences when animals with induced diabetes were compared to the normal euglycemic groups for each procedure performed. CONCLUSION: BIMA ligation promotes an early increase in neoangiogenesis. Progressive sternal consolidation is associated with a significant lower level of capillaries and arterioles in the BIMA group four weeks after ligation. Diabetes did not influence the extent of neoangiogenesis between groups with similar procedures. More important clinical determinants could explain the increase incidence of sternal infection in this specific population.

Inhibition of von Willebrand factor-mediated platelet activation and thrombosis by the anti-von Willebrand factor A1-domain aptamer ARC1779.

BACKGROUND: von Willebrand factor (VWF) has a role in both hemostasis and thrombosis. Platelets adhere to damaged arteries by interactions between the VWF A1-domain and glycoprotein Ib receptors under conditions of high shear. This initial platelet binding event stimulates platelet activation, recruitment, and activation of the clotting cascade, promoting thrombus formation. OBJECTIVE: To characterize the inhibitory activity of a VWF inhibitory aptamer. METHODS: Using in vitro selection, aptamer stabilization, and conjugation to a 20-kDa poly(ethylene glycol), we generated a nuclease-resistant aptamer, ARC1779, that binds to the VWF A1-domain with high affinity (K(D) approximately 2 nM). The aptamer was assessed for inhibition of VWF-induced platelet aggregation. In vitro inhibition of platelet adhesion was assessed on collagen-coated slides and injured pig aortic segments. In vivo activity was assessed in a cynomolgus monkey carotid electrical injury thrombosis model. RESULTS AND CONCLUSION: ARC1779 inhibited botrocetin-induced platelet aggregation (IC90 approximately 300 nM) and shear force-induced platelet aggregation (IC95 approximately 400 nM). It reduced adhesion of platelets to collagen-coated matrices and formation of platelet thrombi on denuded porcine arteries. ARC1779 also inhibited the formation of occlusive thrombi in cynomolgus monkeys. We have discovered a novel anti-VWF aptamer that could have therapeutic use as an anti-VWF agent in the setting of VWF-mediated thrombosis.

Conscious and anesthetized non-human primate safety pharmacology models: hemodynamic sensitivity comparison.

INTRODUCTION: Drug-induced cardiovascular effects identified in conscious cynomolgus monkeys equipped with tethers and prepared for radiotelemetry were compared with results from anesthetized non-human primate (cynomolgus and rhesus) models. METHODS: Remifentanil (4.0 microg/kg, bolus), esmolol (2.0 mg/kg, bolus) and dopamine (0.05 mg/kg/min, 30 min infusion) were given intravenously to all models. RESULTS: Remifentanil decreased heart rate (HR), systolic, mean and diastolic systemic arterial pressures (SAP) in anesthetized animals while conscious monkeys presented an increase in HR, systolic, mean and diastolic SAP, as seen in humans for the respective state of consciousness (conscious and anesthetized). Esmolol decreased HR, systolic, mean and diastolic SAP in anesthetized monkeys while only HR, systolic and mean SAP achieved a statistically significant decrease in the conscious model. The amplitude of SAP reduction was greater in anesthetized models, while the amplitude of HR reduction was greater in the conscious and anesthetized cynomolgus models than in the anesthetized rhesus model. Dopamine induced a significant increase in HR, systolic, mean and diastolic SAP in anesthetized models without any statistically significant effect on HR and SAP in the conscious model. DISCUSSION: The amplitude of hemodynamic and chronotropic alterations induced by positive control drugs was generally greater in anesthetized than in conscious models and statistical significance was achieved more often with the anesthetized models. These results suggest that an anesthetized model may be valuable as part of a drug screening program for cardiovascular safety evaluations in addition to a conscious model.

Antiplatelet therapy following drug-eluting stent implantation: new clinical data and recommendations.

Technological developments in percutaneous coronary interventions (PCI) allow the possibility for less invasive revascularization in an increasing number of patients with atherosclerotic coronary artery disease. Bare-metal stents (BMS) have considerably improved the efficacy of PCI in addition to greatly reducing restenosis. However, even with standard stents, restenosis has remained a significant limitation of this revascularization technique. The advent of drug-eluting stents (DES) has dramatically reduced in-stent restenosis and, as a result, the need for repeat revascularization. However, their potential thrombogenicity has raised concerns about their clinical utility and long-term safety. Indeed, there is a possible higher rate of late stent thrombosis (LST) with DES compared with BMS. Antiplatelet therapy has been shown to be efficient in preventing DES thrombosis. Nevertheless, in the future, significant improvement will occur to improve the safety and efficacy of this therapy. This article will summarize the pathophysiology and the epidemiology of stent thrombosis (ST). Definitions of definite, probable and possible ST will be described. Furthermore, clinical risk factors for ST will be clearly enumerated. Then, the various antiplatelet therapeutic strategies used to prevent ST will be taken in consideration. Finally, a summary of the major recommendations about antiplatelet therapy made by some of the most prestigious learned societies will be presented.

Diverse effects of Ace inhibitors and angiotensin II receptor antagonists on prevention of cardiac hypertrophy and collagen distribution in spontaneously hypertensive rats.

This study has compared the effects of two structurally different angiotensin converting enzyme inhibitors (ACEis) such as zofenopril (Zof, with sulfhydrylic group) and lisinopril (Lis, with carboxylic group) and an angiotensin II AT(1) receptor antagonist (losartan, Los) on the prevention of cardiac hypertrophy and collagen distribution in spontaneously hypertensive rats (SHRs). The SHRs were untreated or received: Zof (10 mg/kg/day), Lis (10 mg/kg/day) or Los (20 mg/kg/day) in drinking water starting at 4 weeks of age. At 8, 16 and 24 weeks of age, 8 rats/group were sacrificed for determination of blood pressure, cardiac hypertrophy and collagen distribution. All treatments significantly decreased blood pressure and cardiac indices, expressed as the ventricles to body weight ratio, both variables being significantly correlated. Total ventricular collagen content was similarly decreased in all treated groups. Zof significantly increased the expression of collagen type III and normalized the collagen type I/III ratio. These results suggest that the effects of these drugs on different types of collagen are independent from angiotensin II formation. Similar findings obtained with captopril seem to indicate that the antioxidant sulfhydrylic group of these ACEis can play a role in the distribution of collagen during cardiac hypertrophy.

Early quantitative coronary angiography of saphenous vein grafts for coronary artery bypass grafting harvested by means of open versus endoscopic saphenectomy: a prospective randomized trial.

OBJECTIVE: Endoscopic saphenectomy is associated with a decreased incidence of wound complications without an increase in histologic trauma or endothelial dysfunction in published reports. Concern remains about the patency of saphenous vein grafts harvested endoscopically and the development of early intimal hyperplasia. The purpose of this study was to compare early quantitative coronary analysis of saphenous vein grafts used for coronary artery bypass grafting harvested with the open versus endoscopic techniques. METHODS: Forty patients undergoing primary coronary artery bypass grafting surgery with at least 1 saphenous vein graft were randomized preoperatively to open versus endoscopic saphenectomy with bipolar cauterization of side branches. Quantitative coronary angiography was performed a mean of 3 months (range, 1-9 months) after the operation. RESULTS: There was no statistically significant difference in the patency rates of internal thoracic artery grafts between the open and endoscopic groups and no statistically significant difference in the patency rates of saphenous vein grafts between both groups (85.2% vs 84.4%, P =.991). Quantitative coronary angiography showed no difference in graft stenosis (>or=50% of the internal diameter of the graft) in the body of the saphenous vein grafts in the open versus endoscopic saphenectomy groups (3.7% vs 0%, P =.280). CONCLUSION: Angiographic appearance and patency rates of saphenous vein grafts harvested with the endoscopic technique are similar to those of saphenous vein grafts harvested with the open technique. These results support the use of endoscopic saphenectomy because of the known lower incidence of wound and infectious complications and superior functional results.

Coronary artery endothelial protection after local delivery of 17beta-estradiol during balloon angioplasty in a porcine model: a potential new pharmacologic approach to improve endothelial function.

OBJECTIVES: The goal of this research was to study the effect of locally delivered 17beta-estradiol (17beta-E) during angioplasty on endothelial function after percutaneous transluminal coronary angioplasty (PTCA) at four weeks. BACKGROUND: The endothelium plays a major role in the structural and functional integrity of coronary arteries and is damaged by PTCA. METHODS: Juvenile swine were subjected to PTCA, after which each artery was randomly-assigned to 600-microg 17beta-E delivered locally, an equal volume of vehicle (V) or PTCA alone. After four weeks, the improvement in endothelial function was assessed by angiography using intracoronary acetylcholine (Ach) infusion and by immunohistochemistry. RESULTS: At 10(-5) mol/l and 10(-4) mol/l Ach, significant vasoconstriction was noted in arteries treated with PTCA alone (p < 0.01 and p < 0.0001, respectively) and with PTCA plus V (p < 0.02 and p < 0.001, respectively). No significant vasoconstrictive response to Ach was observed in arteries treated with PTCA plus 17beta-E. Immunohistochemistry of vessels four weeks after PTCA revealed enhanced re-endothelialization (p < 0.0005) and endothelial nitric-oxide synthase (eNOS) expression (p < 0.0005) in PTCA plus 17beta-E-treated arteries compared with the other two treatment groups. Arteries treated with 17beta-E showed significantly lower neointima formation, which correlated inversely with the extent of re-endothelialization and eNOS expression. CONCLUSIONS: Locally delivered 17beta-E significantly enhances re-endothelialization and endothelial function after PTCA, possibly by improving the expression of eNOS. Since endothelial dysfunction can promote both restenosis and coronary spasm, local 17beta-E administration is a promising new approach to improve long-term results after PTCA.

Extent and distribution of in-stent intimal hyperplasia and edge effect in a non-radiation stent population.

Intimal hyperplasia within the body of the stent is the primary mechanism for in-stent restenosis; however, stent edge restenosis has been described after brachytherapy. Our current understanding about the magnitude of in vivo intimal hyperplasia and edge restenosis is limited to data obtained primarily from select, symptomatic patients requiring repeat angiography. The purpose of this study was to determine the extent and distribution of intimal hyperplasia both within the stent and along the stent edge in relatively nonselect, asymptomatic patients scheduled for 6-month intravascular ultrasound (IVUS) as part of a multicenter trial: Heparin Infusion Prior to Stenting. Planar IVUS measurements 1 mm apart were obtained throughout the stent and over a length of 10 mm proximal and distal to the stent at index and follow-up. Of the 179 patients enrolled, 140 returned for repeat angiography and IVUS at 6.4 +/- 1.9 months and had IVUS images adequate for analysis. Patients had 1.2 +/- 0.6 Palmaz-Schatz stents per vessel. There was a wide individual variation of intimal hyperplasia distribution within the stent and no mean predilection for any location. At 6 months, intimal hyperplasia occupied 29.3 +/- 16.2% of the stent volume on average. Lumen loss within 2 mm of the stent edge was due primarily to intimal proliferation. Beyond 2 mm, negative remodeling contributed more to lumen loss. Gender, age, vessel location, index plaque burden, hypercholesterolemia, diabetes, and tobacco did not predict luminal narrowing at the stent edges, but diabetes, unstable angina at presentation, and lesion length were predictive of in-stent intimal hyperplasia. In a non-radiation stent population, 29% of the stent volume is filled with intimal hyperplasia at 6 months. Lumen loss at the stent edge is due primarily to intimal proliferation.

Late (> 48 hr) myocardial infarction after PTCA: clinical and angiographic characteristics of infarction related or not to the angioplasty site.

Since late myocardial infarctions after percutaneous coronary interventions have not been well characterized, we intended to evaluate the characteristics of myocardial infarctions occurring > 48 hr after balloon angioplasty of native coronary arteries or saphenous vein grafts. The Montreal Heart Institute database (1985-1996) was interrogated for all patients readmitted with a diagnosis of MI more than 48 hr after successful percutaneous transluminal coronary angioplasty (PTCA). We compared the clinical, procedural, and angiographic variables between MIs related or not to the index PTCA site. One hundred and ninety-three patients presented with late myocardial infarction (MI) following balloon angioplasty. The median time elapsed between PTCA and MI was 55 days compared to 968 days when MI was unrelated to the PTCA site. MIs related to the PTCA site were more likely non-Q-wave (76% vs. 35%, P = 0.0001) with less marked CK-MB rise. Angiography showed less complex lesions (63% vs. 90%, P = 0.001) and better thrombolysis in myocardial infarction (TIMI) grade flow (TIMI II to III, 66% vs. 56%, P = 0.01) when the culprit lesion was at the PTCA site. Independent predictors of MI at the PTCA site were vein graft dilation, female sex, and residual stenosis post-PTCA. Myocardial infarctions occurring late after PTCA have a distinct time course and present specific characteristics according to their relationship or not to the previously dilated site.

Relationship between platelets and neutrophil adhesion and neointimal growth after repeated arterial wall injury induced by angioplasty in pigs.

Platelet and neutrophil interactions with injured vascular wall may contribute to restenosis. Their importance was mainly examined following balloon injury of intact arteries. However, dilation of diseased arteries is clinically more relevant and may elicit different responses. We investigated the relationship between platelets and neutrophil adhesion, neointima formation and P-selectin expression on damaged arteries after repeated balloon injury. In an acute single-injury model, 8 pigs were subjected to bilateral carotid angioplasty and sacrificed 1 h later. In a chronic model, 19 pigs were subjected to similar procedures and allowed to recover for 4 weeks; then 18 arteries were redilated at the same previously injured sites (double injury) while the remaining arteries were not redilated and used to investigate the extent and the adhesive properties of the neointima. After single injury, (51)Cr-platelet adhesion (x10(6)/cm(2)) increased significantly from 3.8 +/- 0.6 to 45.9 +/- 6.5 (p < 0.05) on mildly and deeply injured segments, respectively, and were statistically similar after double injury. After single injury, (111)In-neutrophil adhesion (x10(3)/cm(2)) increased from 226.6 +/- 45.5 to 512.5 +/- 70.3 (p < 0.05) on mildly and deeply injured segments, and were significantly higher (p < 0.05) after double injury (mild: 1,289.1 +/- 227.9 and deep: 2,411.8 +/- 333.9). As well, the neo-endothelium expresses P-selectin at 4 weeks and platelet and neutrophil adhesion was directly related to neointimal growth. These results, which indicate ongoing proinflammatory processes 1 month post-angioplasty, suggest that neutrophils may participate in the progression of restenosis.

Complications of cardiac catheterization in the current era: a single-center experience.

Consecutive cardiac catheterization procedures done over a 2-yr period (April 1996 to March 1998) were prospectively analyzed to determine and characterize procedure-related complications (in-hospital and 1-mo follow-up), as they occur at present. During the study period, 11,821 procedures (7,953 diagnostic and 3,868 therapeutic) were performed. The majority of procedures (> 60%) were done in high-risk patients. Stents were implanted in 33% of patients, and adjunctive abciximab was used in 6.6% of therapeutic procedures. The overall complication rate was 8% (3.6% of diagnostic procedures and 15.1% of therapeutic procedures). The procedure-related mortality rates were 0.2%, 0.1%, and 0.5% for total, diagnostic, and therapeutic procedures, respectively. Cardiac complications were seen in 3.9% (1.5% of diagnostic and 9% of therapeutic procedures). Emergency cardiac surgery was required in 0.05% of the diagnostic procedure group and 0.3% of the therapeutic procedure group (total, 0.1%). Despite marked changes in patient population and practice, the complication rates of cardiac catheterization remain very low.

Recombinant soluble p-selectin glycoprotein ligand-1-Ig reduces restenosis through inhibition of platelet-neutrophil adhesion after double angioplasty in swine.

BACKGROUND: P-selectin mediates leukocyte recruitment to activated platelets and endothelium through its high-affinity receptor P-selectin glycoprotein ligand-1 (PSGL-1). Platelet and leukocyte activation and binding have been reported after coronary angioplasty and were correlated with restenosis. We investigated the effect of a recombinant soluble PSGL-1 (rPSGL-Ig) on the adhesion of platelets and neutrophils and the development of restenosis after double arterial injury. METHODS AND RESULTS: Four weeks after angioplasty of both carotid arteries in pigs, a second angioplasty was performed at the same sites, 15 minutes after a single administration of vehicle or rPSGL-1 (1 mg/kg IV). Animals were euthanized 1 hour, 4 hours, 1 week, or 4 weeks later. Adhesion of autologous (51)Cr-platelets and (111)In-neutrophils was quantified and histological/morphometric analyses were performed. Although rPSGL-Ig did not affect adherence of these cells 1 hour after injury, it significantly reduced the adhesion of platelets (50% at 4 hours and 85% at 1 week) and neutrophils (50% at 4 hours and 78% at 1 week) to deeply injured arteries. At 4 weeks, the residual lumen was 63% larger in rPSGL-Ig-treated arteries as compared with control arteries (6.1+/-0.6 versus 3.8+/-0.1 mm(2); P:<0.002). The neointimal area was slightly reduced (0.5 in rPSGL-Ig versus 0.7 mm(2) in control). The ratio of the external elastic lamina of injured to uninjured reference segments was >1 in treated arteries and <1 in control arteries. CONCLUSIONS: P-selectin antagonism with rPSGL-Ig inhibits early platelet/leukocyte adhesion on injured arteries and reduces restenosis through a positive impact on vascular remodeling. Hence, rPSGL-Ig may have potential in the prevention of restenosis.

Local delivery of 17-beta-estradiol decreases neointimal hyperplasia after coronary angioplasty in a porcine model.

BACKGROUND: Neointimal hyperplasia is an important mechanism of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Systemically administered estrogen is known to inhibit neointimal formation after arterial injury. OBJECTIVES: We sought to assess the efficacy of locally delivered 17-beta-estradiol (BE) in inhibiting neointimal hyperplasia after PTCA. METHODS: Eighteen juvenile farm pigs were studied. Coronary angioplasty was performed in all three coronary arteries of each animal. After PTCA, each coronary artery in each pig was randomized to receive either local delivery of 600 microg BE, vehicle alone or PTCA only. Twelve animals were euthanized at 28 days for morphometric analysis, and four animals were euthanized at seven days for immunohistochemical analysis of vascular smooth muscle cell (SMC) proliferative activity. Two animals died a few days after PTCA and were excluded. RESULTS: On morphometric study, the arterial segments treated with BE demonstrated significantly less neointimal proliferation. Arteries treated with BE had reductions in several indexes of restenosis compared with arteries treated with vehicle alone or PTCA only: neointimal area (0.4+/-0.09 mm2 for BE vs. 1.14+/-0.33 mm2 for vehicle alone vs. 0.88+/-0.2 mm2 for PTCA only, p<0.05), percent neointima (12.16+/-2.57% vs. 25.46+/-4.73% vs. 23.02+/-3.97%, p<0.025), neointima/media area (0.59+/-0.14 vs. 1.75+/-0.41 vs. 1.67+/-0.43, p<0.01) and restenotic index (1.3+/-0.14 vs. 2.42+/-0.22 vs. 2.4+/-0.23, p<0.005). Immunohistochemistry showed decreased SMC proliferative activity in BE-treated arteries compared with the other two treatment groups (p<0.05). CONCLUSIONS: Local delivery of BE significantly decreases neointimal hyperplasia after PTCA in pigs, probably by the inhibition of SMC proliferation.

Management of coronary artery disease: therapeutic options in patients with diabetes.

OBJECTIVES: The aim of this review is to discuss the particularities of coronary artery disease (CAD), the effect of intensive medical management and the outcome of percutaneous and surgical revascularization in patients with diabetes mellitus (DM). BACKGROUND: CAD represents the leading cause of death in patients with DM. Numerous clinical, biological and angiographic risk factors have been shown to be associated with CAD in diabetic patients. METHODS: Metabolic abnormalities in patients with DM including insulin resistance, hyperglycemia and dyslipidemia are briefly discussed. Then the potential roles of medical management and of percutaneous and surgical coronary revascularization are more extensively reviewed. RESULTS: More vigorous control of hyperglycemia, hyperlipidemia, hypertension and other risk factors may be of crucial importance for risk reduction. Despite remarkable progress in recent years, the choice of a coronary revascularization strategy remains a challenge in these patients. Diabetic patients with CAD are predisposed to higher cardiovascular events after balloon angioplasty. Whether stenting and new antiplatelet drugs improve the results of percutaneous revascularization in this population needs further evaluation. The superiority of the surgical approach is also not definitely established. Therefore, many aspects of coronary revascularization are still unclear in these patients. CONCLUSIONS: The results of ongoing randomized trials comparing multiple coronary stents to bypass surgery will likely provide some answers to our questions and additional randomized trials evaluating intensive diabetic control with or without coronary revascularization are needed to determine the best therapeutic approach in these patients.

Heparin infusion prior to stenting (HIPS) trial: final results of a prospective, randomized, controlled trial evaluating the effects of local vascular delivery on intimal hyperplasia.

BACKGROUND: Local delivery of pharmacologic agents or genes at the site of angioplasty is a promising approach to reduce restenosis. However, there are unresolved questions concerning the safety and feasibility of local vascular delivery in clinical practice as well as the efficacy of delivered drug. To this end, the safety, feasibility, and efficacy of local delivery of heparin were evaluated in the Heparin Infusion Prior to Stenting (HIPS) trial. METHODS AND RESULTS: A total of 179 patients were enrolled in this multicenter, randomized, prospective, core laboratory-evaluated trial. Patients were randomly assigned to 5000 U heparin either administered to the coronary artery lumen or infused into the arterial wall immediately after angioplasty and before stent placement. End points included procedural events and clinical, angiographic, and intravascular ultrasound events at 6 months. Patient groups were evenly matched. There was no difference in the incidence of arterial injury, defined as an increase in arterial dissection, acute closure, or decrease in Thrombolysis In Myocardial Infarction grade blood flow in the group receiving local delivery. At follow-up there was no difference in the major adverse event rate between intraluminal (22.7%) and local groups (24.7%). There was no difference between intraluminal and local therapy in the angiographic in-stent restenosis rate (12.5%, 12.7%) or the in-stent volumetric analysis by intravascular ultrasound (IVUS) (37.19 +/- 20. 86 mm(3) vs 43.79 +/- 25.52 mm(3)). CONCLUSIONS: Local delivery of 5000 U heparin into the arterial wall before stent implantation is safe and feasible. There was not a favorable effect of locally delivered heparin on clinical, angiographic, or IVUS end points of restenosis. The use of IVUS to measure volume of intimal hyperplasia in a multicenter, core laboratory-controlled trial is feasible.

Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty.

BACKGROUND: The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina. METHODS AND RESULTS: We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction. CONCLUSIONS: Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.

Platelets and restenosis.

Restenosis is currently the major limitation of percutaneous transluminal coronary angioplasty (PTCA). Factors such as elastic recoil, migration of vascular smooth muscle cells from media to intima, neointimal proliferation and vascular remodeling underly the restenotic process. Presently there is no effective therapy available for restenosis. The role of platelets in the development of thrombosis and abrupt closure after PTCA is well recognized. However, the effects of platelets in PTCA extend well beyond the early phase. Although antiplatelet agents such as glycoprotein IIb/IIIa antagonists have been reported to reduce target vessel revascularization, major unresolved controversies still exist. This report reviews the potential role of platelets in restenosis. Various drugs, successfully tested in experimental studies and in a small number of human studies, that inhibit the effect of platelets on the restenotic process are also reviewed.

Local delivery of heparin post-PTCA: a multicenter randomized pilot study.

Bailout stenting for major dissection and threatened closure has high rates of ischemic complications. We performed a randomized trial of local heparin delivery using the infusion sleeve before bailout stenting for suboptimal angioplasty results. In phase I, 20 patients were randomized to local delivery with either 40- or 100-psi infusion pressure. In phase II, 37 patients were randomized to local delivery at 100 psi or standard therapy. Local delivery succeeded in all but one patient; overall there was no significant worsening of intimal dissection. One patient treated with 100-psi drug infusion suffered a perforation after stent placement. There were no significant differences in the composite endpoint of death, MI, CABG, urgent repeat angioplasty, and stent thrombosis at 30 days (21% vs. 0%; P = 0.18). At 6 months, the rates of myocardial infarction in phase II were 27% with local delivery vs. 10% with standard treatment (P = 0.4). Local heparin delivery in dissected vessels may be associated with increased complications and should be approached with caution.

Optimizing the percutaneous interventional outcomes for patients with diabetes mellitus: results of the EPISTENT (Evaluation of platelet IIb/IIIa inhibitor for stenting trial) diabetic substudy.

BACKGROUND: Stenting likely decreases the need for target-vessel revascularization procedures in diabetic patients compared with balloon angioplasty. However, the efficacy of stenting with platelet glycoprotein IIb/IIIa blockade has not yet been assessed in diabetics. METHODS AND RESULTS: We analyzed the outcomes of 491 diabetic patients within the multicenter Evaluation of Platelet IIb/IIIa Inhibitor for Stenting Trial (EPISTENT). Diabetic patients were a prospectively defined subset: 173 were randomized to stent-placebo, 162 to stent-abciximab, and 156 to balloon angioplasty-abciximab. The main end point for this analysis was combined 6-month death, myocardial infarction (MI), or target-vessel revascularization (TVR). The composite end point occurred in 25.2% of stent-placebo, 23.4% of balloon-abciximab, and 13.0% of stent-abciximab patients (P=0.005). Abciximab therapy, irrespective of revascularization strategy (stent or balloon angioplasty), resulted in a significant reduction in the 6-month death or MI rate: 12.7% for stent-placebo, 7.8% for balloon angioplasty-abciximab, and 6.2% for the stent-abciximab group (P=0.029). The 6-month TVR rate was 16.6% for stent-placebo, 18.4% for balloon-abciximab, and 8.1% for stent-abciximab (P=0.021). Compared with stent-placebo, stent-abciximab therapy was associated with a significant increase in angiographic net gain (0.88 versus 0.55 mm; P=0.011) and a decrease in the late loss index (0.40 versus 0.60 mm; P=0.061). The 1-year mortality rate for diabetics was 4.1% for stent-placebo and 1. 2% for stent-abciximab patients (P=0.11). CONCLUSIONS: The combination of stenting and abciximab therapy among diabetics resulted in a significant reduction in 6-month rates of death, MI, and TVR compared with stent-placebo or balloon-abciximab therapy.

Repair of left anterior descending coronary artery perforation by Magic Wallstent implantation.

Coronary rupture is a rare complication of percutaneous coronary intervention. However, it may be associated with serious hemodynamic consequences often leading to tamponade, myocardial infarction, emergency surgical intervention, or death. We report a successful percutaneous repair of a brisk left anterior descending coronary artery perforation by the implantation of a Magic Wallstent.