Two-year follow-up after catheter-based radiotherapy to inhibit coronary restenosis.

BACKGROUND: Although early trials indicate the treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The possibility of late untoward consequences, such as aneurysm formation, perforation, and accelerated vascular disease, is of significant concern. Furthermore, it is not known whether the beneficial effects of radiation therapy will be durable or whether radiation will only delay restenosis. METHODS AND RESULTS: A double-blind, randomized trial was undertaken to compare 192Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Patients were randomly assigned to receive a 0.76-mm (0. 03-in) ribbon containing sealed sources of either 192Ir or placebo. All patients underwent repeat coronary angiography at 6 months. All living patients were contacted 24 months after their index study procedure. Patients were assessed with respect to the need for target-lesion revascularization or nontarget-lesion revascularization, occurrence of myocardial infarction, or death. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. Follow-up was obtained in 100% of living patients at a minimum of 24 months. Target-lesion revascularization was significantly lower in the 192Ir group (15.4% versus 44.8%; P<0. 01). Nontarget-lesion revascularization was similar in 192Ir and placebo patients (19.2% versus 20.7%; P=NS). There were 2 deaths in each group. The composite end point of death, myocardial infarction, or target-lesion revascularization was significantly lower in 192Ir-treated versus placebo-treated patients (23.1% versus 51.7%; P=0.03). No patient in the 192Ir group sustained a target-lesion revascularization later than 10 months. CONCLUSIONS: At 2-year clinical follow-up, treatment with 192Ir demonstrates significant clinical benefit. Although further follow-up (including late angiography) will be necessary, no clinical events have occurred to date in the 192Ir group to suggest major untoward effects of vascular radiotherapy. At the intermediate follow-up time point, vascular radiotherapy continues to be a promising new treatment for restenosis.

Three-year clinical and angiographic follow-up after intracoronary radiation : results of a randomized clinical trial.

BACKGROUND: Although several early trials indicate treatment of restenosis with radiation therapy is safe and effective, the long-term impact of this new technology has been questioned. The objective of this report is to document angiographic and clinical outcome 3 years after treatment of restenotic stented coronary arteries with catheter-based (192)Ir. METHODS AND RESULTS: A double-blind, randomized trial compared (192)Ir with placebo sources in patients with previous restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to (192)Ir and 29 to placebo. At 3-year follow-up, target-lesion revascularization was significantly lower in the (192)Ir group (15. 4% versus 48.3%; P<0.01). The dichotomous restenosis rate at 3-year follow-up was also significantly lower in (192)Ir patients (33% versus 64%; P<0.05). In a subgroup of patients with 3-year angiographic follow-up not subjected to target-lesion revascularization by the 6-month angiogram, the mean minimal luminal diameter between 6 months and 3 years decreased from 2.49+/-0.81 to 2.12+/-0.73 mm in (192)Ir patients but was unchanged in placebo patients. CONCLUSIONS: The early clinical benefits observed after treatment of coronary restenosis with (192)Ir appear durable at late follow-up. Angiographic restenosis continues to be significantly reduced in (192)Ir-treated patients, but a small amount of late loss was observed between the 6-month and 3-year follow-up time points. No events occurred in the (192)Ir group to suggest major untoward effects of vascular radiotherapy. At 3-year follow-up, vascular radiotherapy continues to be a promising new treatment for restenosis.

Clinical experience with the Palmaz-Schatz coronary stent.

Complications that occurred in 247 patients who underwent successful elective stenting to native coronary arteries with the Palmaz-Schatz balloon expandable stent included subacute thrombosis in 7 patients (2.8%), myocardial infarction in 3 (1.2%), death 3 (1.2%), urgent bypass surgery in 4 (1.6%) and major bleeding events in 24 (9.7%). Angiographic restenosis occurred in 21 (20%) of 103 patients who received a single stent. Subgroup analysis, however, revealed that restenosis of a single stent occurred in 3 (7%) of 45 patients without prior angioplasty compared with 25 (27%) of 91 patients with prior angioplasty. Patients with "suboptimal" angioplasty results (dis-section) who received a single stent seemed to have a higher thrombosis rate perioperatively (4 [4%] of 98), but no higher incidence of restenosis (7 [15%] of 46) than that of the total group of patients who received a single stent. Coronary stenting may be a valuable adjunct to coronary angioplasty in carefully selected patients. Complication rates are similar to those of routine angioplasty; however, angiographic restenosis may be reduced in certain subsets of patients.

Fate of lesion-related side branches after coronary artery stenting.

OBJECTIVES: The aim of this study was to assess the immediate and long-term patency of lesion-associated side branches after coronary artery stenting. BACKGROUND: The possible adverse effects related to implantation of coronary stents are not completely known. An important potential complication of stenting is side branch occlusion due to mechanical obstruction or thrombosis. METHODS: Serial coronary angiography was performed in 153 patients (167 lesions) at baseline, after conventional balloon angioplasty, immediately after Palmaz-Schatz stent placement and at 6 months. The patency of side branches, where present, was analyzed at each of these points. RESULTS: Of 167 lesions stented, 57 stent placements spanned 66 side branches with a diameter > or = 1 mm. Twenty-seven (41%) of these side branches had > or = 50% ostial stenosis before standard balloon angioplasty. Six side branches became occluded after standard balloon angioplasty and remained occluded after stenting. Of the 60 side branches patent after conventional angioplasty, 57 (95%) remained patent immediately after stenting. All three side branches that became occluded after stenting had > or = 50% ostial stenosis at baseline. All 60 side branches, including the 3 initially occluded after stenting, were patent at 6-month follow-up. CONCLUSIONS: These findings demonstrate that 1) acute side branch occlusion due to coronary stenting occurs infrequently; 2) when side branch occlusion occurs, it is associated with intrinsic ostial disease; and 3) the patency of side branch ostia is well maintained at long-term follow-up.

Effect of intracoronary stenting on intimal dissection after balloon angioplasty: results of quantitative and qualitative coronary analysis.

The effect of the Palmaz-Schatz stent on the angiographic appearance and residual luminal stenosis in patients with intimal dissection after balloon angioplasty was evaluated in 84 consecutive patients (90 lesions). Coronary angiography was performed before angioplasty, after conventional angioplasty and after stent implantation. The degree of intimal disruption was assessed as follows: grade 0, no dissection; grade 1, simple dissection (intraluminal linear defect or extraluminal cap extravasation); or grade 2, complex dissection (nonlinear spiral defect or luminal defect with multiple irregular borders). Quantitative coronary analysis of digitized cineangiograms was performed with use of a computerized automatic edge detection algorithm. After balloon angioplasty, 31 (34%) of 90 lesions demonstrated intimal dissection (18 simple, 13 complex). After stent implantation, intimal dissection improved by greater than or equal to 1 grade in 29 (94%) of the 31 lesions with 27 (87%) reduced to grade 0 (that is, no dissection). Dissection grade improved after stenting in 16 (89%) of 18 simple dissections and in all 13 complex dissections. Mean diameter stenosis was 77 +/- 17% before angioplasty, 47 +/- 17% after angioplasty and 14 +/- 10% after stenting (before angioplasty vs. after angioplasty and after angioplasty vs. after stenting, p less than 0.0001). In conclusion, intracoronary stenting is effective in reducing the residual luminal stenosis and in improving the angiographic appearance of intimal dissections after conventional balloon angioplasty.

Immediate results and late outcomes after stent implantation in saphenous vein graft lesions: the multicenter U.S. Palmaz-Schatz stent experience. The Palmaz-Schatz Stent Study Group.

OBJECTIVES: This study reports the multicenter registry experience evaluating the safety and efficacy of the Palmaz-Schatz stent in the treatment of saphenous vein graft disease. BACKGROUND: Saphenous vein graft angioplasty is associated with frequent periprocedural complications and a high frequency of restenosis. Stent implantation has been shown to reduce restenosis, with improved long-term outcomes in the treatment of native coronary artery disease. Preliminary experience with stent placement in the treatment of saphenous vein graft lesions has been favorable. METHODS: Twenty U.S. investigator sites enrolled a total of 589 symptomatic patients (624 lesions) for treatment of focal vein graft stenoses between January 1990 and April 1992. Follow-up angiography was performed at 6 months, and the clinical course of all study patients was prospectively collected at regular intervals for up to 12 months. RESULTS: Stent delivery was successful in 98.8% of cases, and the procedural success rate was 97.1%. The lesion diameter stenosis decreased from 82 +/- 12% (mean +/- SD) before to 6.6 +/- 10.2% after treatment. Major in-hospital complications occurred in 17 patients (2.9%); stent thrombosis was found in 8 (1.4%); and major vascular or bleeding complications were noted in 83 (14.3%). Six-month angiographic follow-up revealed an overall restenosis rate (> or = 50% diameter stenosis) of 29.7%. Multivariate logistic regression analysis indicated that 1) restenotic lesions, 2) smaller reference vessel size, 3) history of diabetes mellitus, and 4) higher percent poststent diameter stenosis were independent predictors of restenosis. The 12-month actuarial event-free survival was 76.3%. CONCLUSIONS: Stent implantation in patients with focal saphenous vein graft lesions can be achieved with a high rate of procedural success, acceptable major complications, reduced angiographic restenosis and favorable late clinical outcome compared with historical balloon angioplasty control series. The rigorous anticoagulation regimen after stent placement results in more frequent vascular and other bleeding complications. Future randomized studies comparing standard balloon angioplasty with stent implantation are warranted to properly assess the full impact of stent placement in the treatment of saphenous vein graft lesions.

Long-term angiographic and clinical outcome after implantation of a balloon-expandable stent in the native coronary circulation. Palmaz-Schatz Stent Study Group.

OBJECTIVES: The purpose of this study was to examine the long-term clinical and angiographic outcome after coronary stent implantation. BACKGROUND: Previous reports have shown a discordance between the excellent initial angiographic results and subsequent adverse clinical events after coronary artery stenting. METHODS: Single Palmaz-Schatz stents were electively implanted in the native coronary arteries of 300 consecutive patients. Angiograms were obtained at baseline, after balloon angioplasty, after stent implantation and at 6 months after implantation. Films were analyzed by a panel of angiographers utilizing an automated edge detection program. Clinical events, including death, myocardial infarction, coronary bypass surgery and repeat angioplasty, were recorded for 1 year. RESULTS: Although there were no acute in laboratory vessel closures, stent thrombosis occurred in 14 patients (4.7%) at a mean +/- SD of 5 +/- 3 days after implantation. Two hundred fifty-eight (90%) of 286 eligible patients had follow-up angiography at 6.1 +/- 2.2 months after stent implantation. Minimal lumen diameter increased from 0.80 +/- 0.39 mm at baseline to 1.65 +/- 0.51 mm after angioplasty and further increased to 2.55 +/- 0.49 mm after stent placement (p = 0.0001). At follow-up there was a 0.85-mm late loss in lumen diameter, with a final minimal lumen diameter at 6 months of 1.70 +/- 0.71 mm. Restenosis, defined as > or = 50% diameter stenosis at follow-up, occurred in 14% of patients with previously untreated lesions and in 39% of patients with previous angioplasty (p < 0.001). Clinical events after 1 year for the entire group of 300 patients included death in 0.7%, myocardial infarction in 3.7%, bypass grafting in 8% and repeat angioplasty in 13%. Freedom from any adverse clinical event was 80% for all treated patients and 87% for those with previously untreated lesions. CONCLUSIONS: Elective use of this balloon-expandable stent in the native coronary circulation is associated with a low restenosis rate by quantitative angiography in previously untreated lesions and a favorable clinical outcome with an excellent event-free survival rate at 1 year.

Efficacy of coronary stenting versus balloon angioplasty in small coronary arteries. Stent Restenosis Study (STRESS) Investigators.

OBJECTIVES: The goal of this study was to compare the efficacy of elective stent implantation and balloon angioplasty for new lesions in small coronary arteries. BACKGROUND: Palmaz-Schatz stents have been designed and approved by the Food and Drug Administration for use in coronary arteries with diameters > or = 3.0 mm. The efficacy of elective stent placement in smaller vessels has not been determined. METHODS: By quantitative coronary angiography, 331 patients in the Stent Restenosis Study (STRESS) I-II were determined to have a reference vessel < 3.0 mm in diameter. Of these, 163 patients were randomly assigned to stenting (mean diameter 2.69 +/- 0.21 mm), and 168 patients were assigned to angioplasty (mean diameter 2.64 +/- 0.24 mm). The primary end point was restenosis, defined as > or = 50% diameter stenosis at 6-month follow-up angiography. Clinical event rates at 1 year were assessed. RESULTS: Baseline clinical and angiographic characteristics were similar in the two groups. Procedural success was achieved in 100% of patients assigned to stenting and in 92% of patients assigned to angioplasty (p < 0.001). Abrupt closure within 30 days occurred in 3.6% of patients in both groups. Compared with angioplasty, stenting conferred a significantly larger postprocedural lumen diameter (2.26 vs. 1.80 mm, p < 0.001) and a larger lumen at 6 months (1.54 vs. 1.27 mm, p < 0.001). Restenosis (> or = 50% diameter stenosis at follow-up) occurred in 34% of patients assigned to stenting and in 55% of patients assigned to angioplasty (p < 0.001). At 1 year, event-free survival was achieved in 78% of the stent group and in 67% of the angioplasty group (p = 0.019). CONCLUSIONS: These findings suggest that elective stent placement provides superior angiographic and clinical outcomes than balloon angioplasty in vessels slightly smaller than 3 mm.

A subgroup analysis of the Scripps Coronary Radiation to Inhibit Proliferation Poststenting Trial.

INTRODUCTION: In the Scripps Coronary Radiation to Inhibit Proliferation Poststenting (SCRIPPS) Trial, 192Ir significantly reduced angiographic, ultrasonographic, and clinical endpoints of restenosis. The objective of this analysis was to quantitate the impact of patient, lesion and technical characteristics on late angiographic outcome. METHODS: Patients with restenotic, stented coronary lesions were randomized to receive either 192Ir or placebo sources. Late luminal loss and loss index were calculated for several patient subgroups, including patients with diabetes, in-stent restenosis, multiple previous percutaneous transluminal coronary angioplasty (PTCA) procedures, longer lesion lengths, saphenous vein grafts, small vessel diameters, and minimum dose exposures < 8.00 Gy. Two-factor analysis of variance was used to test for an interaction between patient characteristics and treatment effect. RESULTS: In the treated group, late loss was particularly low in patients with diabetes (0.19 mm), in-stent restenosis (0.17 mm), reference vessel diameters < 3.0 mm (0.07 mm), and patients who received a minimum radiation dose to the entire adventitial border of at least 8.00 Gy. The loss index in each of these subgroups was similarly low at -0.02, 0.03, -0.02, and 0.03, respectively. By 2-factor analysis of variance, a significant interaction between subgroup characteristic and treatment effect (late loss) was found in patients with in-stent restenosis (p = 0.035), and patients receiving a minimum dose of 8.00 Gy to the adventitial border (p = 0.009). CONCLUSION: In this pilot study, patient characteristics associated with a more aggressive proliferative response to injury appeared to confer an enhanced response to radiotherapy. Furthermore, a dose threshold response to 192Ir was found with an enhanced response occurring when the entire circumference of the adventitial border was exposed to at least 8.00 Gy.

Hail stentors! How the hail do I stop the warfarin?

Interest in coronary stenting has exploded since the publication of several large, randomized trials, and (due to the rapidity of patient recruitment into non-randomized trials) volumes of data are quickly abandoning "old standards" of patient selection, operative technique, and postoperative anticoagulation management. In this editorial, suggestions are offered to help clinicians take the leap from outdated Food and Drug Administration-guided regulations to off-label use and withholding of anticoagulation.

Coronary stenting for treatment of ostial stenoses of native coronary arteries or aortocoronary saphenous venous grafts.

This study examines the procedural success, complication, and restenosis rates in patients undergoing Palmaz-Schatz stenting of native coronary and saphenous vein graft ostial stenoses. All patients undergoing Palmaz-Schatz stent placement of ostial lesions (> or = 70% diameter stenosis within 3 mm from the arterial ostium) between November 1989 and February 1992 were included in this study. Patients were treated with aspirin dipyridamole, low molecular weight dextran, and heparin during the procedure and received systemic anticoagulation with warfarin for 1 month after the procedure. Angiographic measurements were obtained using electronic calipers. Coronary stents were placed in 41 ostial lesions of 41 patients. The target ostial stenosis was in a saphenous vein graft in 54% and a native coronary artery in 46% of lesions. The mean pre- and postprocedural minimal luminal diameters were 0.8 +/- 0.7 and 3.3 +/- 0.8 mm, respectively (p < 0.0001), corresponding to a mean diameter stenosis of 83.5 +/- 10.0% and 1.0 +/- 4.2%. Two patients had subacute stent thrombosis related to premature discontinuation of antithrombotic medications. Two patients died, 1 because of stent thrombosis and 1 because of progressive renal failure and sepsis. Angiographic follow-up was obtained at a mean of 5.8 +/- 1.8 months in 95% of patients with a successful stent procedure. The overall restenosis rate (> 50% diameter stenosis at follow-up) was 27.8%. Thus, stenting of ostial native coronary and vein graft stenoses can be performed with excellent angiographic and procedural success rates. Restenosis rates appear to be lower than expected using historical control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioscopic versus angiographic detection of thrombus during coronary interventional procedures.

The purpose of this study was to compare angiography and angioscopy for the detection of thrombus during coronary interventional procedures. The diagnosis of coronary thrombus has important clinical implications. Angioscopy can directly visualize the coronary luminal surface and may be more accurate than angiography in the diagnosis of thrombus. Angiography and angioscopy were sequentially performed in 75 patients undergoing a variety of interventional cardiology procedures during 117 distinct procedural time points. The angiographic presence of thrombus was defined as a noncalcified filling defect outlined on at least 3 sides by contrast media. The angioscopic presence of thrombus was defined as red material protruding into the lumen (intraluminal thrombus) or adherent to the luminal wall (mural thrombus) that persisted despite flushing. Thrombus was detected on 14 occasions (12.0%) by angiography compared with 48 (41.0%) by angioscopy (p < 0.05). In 4 of the 14 episodes (28.6%) of angiographic filling defects, angioscopy found no evidence of thrombus and provided an alternative explanation for the angiographic filling defect. When angioscopy was used as a reference standard, the sensitivity of thrombus detection by angiography was 20.8%, with a specificity of 94.2% and a predictive value of 71.4%. The sensitivity of angiography for the detection of intraluminal (protruding into the lumen) thrombus was 100% compared with only 10% for mural (adherent to the luminal wall) thrombus (p < 0.05). Angioscopy was significantly more accurate than angiography for detecting coronary thrombus and may be considered an improved reference standard for this diagnosis.

Coronary stenting with angioscopic guidance.

Coronary angioscopy can directly visualize luminal morphology and stent architecture. This new technology may provide insights into the stent mechanism of action and help guide stent procedures. Visualization of the target vessel segment with a 4.5Fr angioscope was attempted before and/or after Palmaz-Schatz coronary stent implantation in 50 patients. The target vessel segment was successfully visualized in 48 patients (96%). In 24 patients, angioscopy was performed both after balloon angioplasty and then again after stenting. In 16 of these 24 patients a dissection was documented by angioscopy after balloon angioplasty, and in each patient the dissection was absent after stenting. Angioscopy influenced the clinical management of 18 (37.5%) patients. Clinical decisions directly influenced by angioscopy included intracoronary thrombolytic therapy for thrombus visualized angioscopically, which had been unsuspected by angiography (n = 7), withholding intracoronary thrombolytic therapy for patients with suspected thrombus not confirmed by angioscopy (n = 4), repeat angioplasty in patients in whom plaque was found to be bulging into the lumen at the stent articulation site (n = 4), additional stents placed when angioscopy revealed significant proximal or distal disease (n = 4), or an unsuspected gap between 2 tandem stents (n = 1). Coronary angioscopy safely visualized stented vessel segments in most patients. Angioscopic observations provided insights into the stent mechanism of action and, in some cases, influenced clinical management.

Long-term angiographic and clinical outcome after implantation of balloon-expandable stents in aortocoronary saphenous vein grafts.

Balloon angioplasty of aortocoronary saphenous vein graft lesions is associated with high restenosis and clinical event rates. The goal of this multicenter study was to assess long-term angiographic and clinical outcome of patients electively treated with single Palmaz-Schatz stents in aortocoronary saphenous vein grafts. In 198 patients (209 lesions), elective placement of single Palmaz-Schatz stents was attempted. Angiography was performed at baseline, immediately after stent placement, and at 6-month follow-up. Stent placement was successful in 98.5% of patients. One patient (0.5%) had stent thrombosis. Restenosis occurred in 34% (45 of 133) of the restudied lesions. Restenosis was lower in de novo lesions than in restenotic lesions (22% vs 51%, p < 0.001). Ostial lesions had a higher restenosis rate than nonostial lesions (61% vs 28%, p = 0.003). Freedom from death, myocardial infarction, coronary artery bypass surgery, and repeat angioplasty was present in 70% of patients. Eighty-two percent of patients with de novo lesions remained event-free at 1 year, whereas only 55% of patients with prior angioplasty were event-free at 1 year (p < 0.001). The use of the Palmaz-Schatz stent for the treatment of focal, de novo, aortocoronary saphenous vein graft lesions is associated with a high procedural success rate, a low angiographic restenosis rate, and low clinical event rates, including the need for repeat revascularization. The results of this study need validation by a prospective randomized trial comparing stent implantation with angioplasty.

Suture-mediated closure of the femoral access site after cardiac catheterization: results of the suture to ambulate aNd discharge (STAND I and STAND II) trials.

Despite advances in other aspects of cardiac catheterization, manual or mechanical compression followed by 4 to 8 hours of bed rest remains the mainstay of postprocedural femoral access site management. Suture-mediated closure may prove to be an effective alternative, offering earlier sheath removal and ambulation, and potentially a reduction in hemorrhagic complications. The Suture To Ambulate aNd Discharge trial (STAND I) evaluated the 6Fr Techstar device in 200 patients undergoing diagnostic procedures, with successful hemostasis achieved in 99% of patients (94% with suture closure only) in a median of 13 minutes, and 1% major complications. STAND II randomized 515 patients undergoing diagnostic or interventional procedures to use of the 8Fr or 10Fr Prostar-Plus device versus traditional compression. Successful suture-mediated hemostasis was achieved in 97.6% of patients (91.2% by the device alone) compared with 98.9% of patients with compression (p = NS). Major complication rates were 2.4% and 1.1%, and met the Blackwelder's test for equivalency (p <0.05). Median time to hemostasis (19 vs 243 minutes, p <0.01) and time to ambulation (3.9 vs 14.8 hours, p <0.01) were significantly shorter for suture-mediated closure. Suture-mediated closure of the arterial puncture site thus affords reliable immediate hemostasis and shortens the time to ambulation without significantly increasing the risk of local complications.

Quantitative angiographic analysis of stent restenosis in the Scripps Coronary Radiation to Inhibit Intimal Proliferation Post Stenting (SCRIPPS) Trial.

To identify luminal dimension changes occurring within the stent alone and within the stent + margin segment, we reviewed the quantitative angiographic results obtained from the Scripps Coronary Radiation to Inhibit Proliferation Post Stenting (SCRIPPS) trial, a prospective randomized trial assessing the effect of iridium-192 (Ir-192) on the prevention of stent restenosis. Fifty-five patients were randomly assigned to receive Ir-192 or placebo sources after successful intervention. Procedural and 6-month follow-up cineangiograms were quantitatively reviewed in 52 patients to identify changes within the stent and the stent + margin segment. The percent diameter stenosis was lower within the stent than within the stent + margin segment after the procedure (6 +/- 22% vs 21+/- 15%, p <0.0001) and at follow-up (28 +/- 29% vs 42 +/- 21%, p <0.0001). As a result, a lower restenosis rate was found within the stent than within the stent + margin (25% vs 37%, p <0.0001); isolated stent margin restenosis occurred in 11.5% of lesions. Treatment with Ir-192 reduced restenosis within the stent (8% vs 39%; p = 0.010) and within the stent + margin segment (17% vs 54%; p = 0.010); the reduction in restenosis at the margin only (8.3% vs 14.3%, p = 0.503) was not significant. The lowest relative risk for restenosis resulting from Ir-192 occurred within the stent (0.21; 95% confidence interval [CI] 0.05 to 0.86) compared with the stent + margin segment (0.31; 95% CI 0.12 to 0.81) or the stent margin (0.58; 95% CI 0.12 to 2.91). In the SCRIPPS trial, 32% of restenosis occurred at the stent margins. Treatment with Ir-192 reduced restenosis primarily within the stent rather than the margin. Whether extending the treatment length to fully include the stent margins will further reduce restenosis requires further study.

Acute and long-term outcome after Palmaz-Schatz stenting: analysis from the New Approaches to Coronary Intervention (NACI) registry.

The randomized Stent Restenosis Study (STRESS) and Belgium Netherlands Stent (Benestent) trials established that elective use of Palmaz-Schatz stents (PSSs) in native coronary arteries with de novo lesions is associated with increased procedural success and reduced restenosis. However there are other clinical indications for which stents are commonly used (unplanned use, vein grafts, restenosis lesions) that are not addressed in these studies. From 1990-1992, 688 lesions in 628 patients were treated with PSSs in the New Approaches to Coronary Intervention (NACI) registry. Angiographic core laboratory readings were available for 543 patients (595 lesions, of which 106 were stented for unplanned indications, 239 were in saphenous vein bypass grafts, and 296 were previously treated). The cohort of patients in whom stents were placed for unplanned indications had more women, current smokers, and had a higher incidence of recent myocardial infarction (MI). Patients who underwent stenting of saphenous vein grafts were older, had a higher incidence of diabetes mellitus, unstable angina, prior MI, and congestive heart failure. Lesion success was similar in all cohorts (98%), but procedural success was significantly higher for planned stenting (96% vs 87%; p < 0.01). Predictors of adverse events in-hospital were presence of a significant left main stenosis and stenting for unplanned indication. The incidence of target lesion revascularization by 30 days was significantly higher for patients undergoing unplanned stenting due to a higher risk for stent thrombosis. Recent MI, stenting in native lesion, and small postprocedural minimum lumen diameter independently predicted target lesion revascularization at 30 days. Independent predictors of death, Q-wave myocardial infarction, or target lesion revascularization at 1 year included severe concomitant disease, high risk for surgery, left main disease, stenting in the left main coronary artery, and low postprocedure minimum lumen diameter.

Effect of toluene on rat synaptosomal phospholipid methylation and membrane fluidity.

This study investigated the effects of toluene (1 g/kg, 1 hr, i.p.) on rat synaptosomal phospholipid methylation (PLM), phospholipid composition, and membrane fluidity. Toluene significantly decreased basal PLM (35%) in studies using [3H]methionine [( 3H]Met) as the methyl donor; this was reflected by similar decreases in phosphatidylmonomethylethanolamine (PME) (30%). No effects were observed in either PLM reactions that used [3H]adenosylmethionine [( 3H]AdoMet) as methyl donor, or AdoMet synthetase, suggesting that toluene preferentially affects PLM reactions that derive methyl groups from [3H]Met. Also, toluene decreased synaptosomal phosphatidylethanolamine (PE) (24%), the initial substrate for PLM, and the addition of PE back to PE-depleted synaptosomes restored methyltransferase activity. Agonist-stimulated PLM using norepinephrine (NE) demonstrated that agonist-receptor coupling returned PLM to control values in synaptosomes from toluene-treated rats. NE-stimulated PLM was also blocked by propranolol (PRO), suggesting a role for toluene in receptor-mediated events. Membrane fluidity studies demonstrated that in vivo administration of toluene increased the outer synaptosomal membrane fluidity, whereas in vitro administration of toluene had no effect. Our observations support a positive relationship between increased PLM activity and increased outer, not core, membrane fluidity. These data demonstrate that specific toluene-phospholipid interactions occur in synaptosomes, resulting in altered membrane composition, function and fluidity.

Effect of chronic primidone treatment on folate-dependent one-carbon metabolism in the rat.

Rats were treated chronically with primidone (100 mg/kg/12 hr, p.o.) for up to 8 weeks. The effects of this treatment on one-carbon metabolism were determined in brain and liver. Serine hydroxymethyltransferase activity increased in both brain (44%) and liver (50%). Methylenetetrahydrofolate reductase activity increased in liver (26%) with a significant correlation to the length of treatment, but in brain it was unchanged. Methyltetrahydrofolate:homocysteine methyltransferase activity increased in brain (43%) with a significant correlation to length of treatment, but in liver no effect was observed. Methionine adenosyltransferase activity in brain was significantly lower than control at only one point after 8 weeks of chronic treatment. S-Adenosylmethionine concentration in liver increased gradually (23%) during treatment. S-Adenosylhomocysteine concentrations decreased in brain (33%) and increased in liver (23%) with chronic primidone treatment. These data support the hypothesis that chronic primidone treatment leads to folate depletion through interference with folate metabolism.

Evidence for a decrease in the efficiency of beta-receptor coupling to adenylate cyclase in liver membranes from sucrose-fed rats.

Sucrose feeding has been shown previously to alter the plasma concentration of several factors which may regulate beta-adrenergic receptors, including corticosteroids and insulin as well as altered sympathetic nervous system (SNS) tone. For this reason we initiated a study of the effects of sucrose feeding on the beta-adrenergic receptor-adenylate cyclase system in rat liver plasma membranes. Beta-Adrenergic responsiveness was monitored by measuring isoproterenol stimulation of adenylate cyclase activity, while beta-adrenergic receptor characteristics were evaluated by analyzing [125I]iodocyanopindolol [( 125I]CYP) binding. Rats fed rat chow ad lib. supplemented by drinking water containing 10% sucrose solution exhibited a 50-75% reduction in hepatic isoproterenol-sensitive adenylate cyclase activity. This effect of sucrose was also observed in adrenalectomized (ADX) and 6-hydroxydopamine-pretreated animals, ruling out a causal role for corticosteroids or the sympathetic nervous system respectively. No effect was observed on basal, glucagon-, fluoride- or GTP-stimulated adenylate cyclase. A small but significant decrease in [125I]CYP specific binding capacity was observed in liver membranes prepared from sucrose-fed ADX rats, whereas no change in [125I]CYP binding capacity was observed in in sucrose-fed normal rats. These observations suggest that beta-receptor to adenylate cyclase coupling efficiency is decreased by the sucrose diet. The activities of two membrane-associated phospholipid methyltransferases and the content of endogenous S-adenosylmethionine in liver were reduced by sucrose feeding, implying a defect in the methylation pathway for phosphatidylcholine synthesis. The possible relationship between this latter finding and the observed decrease in beta-adrenergic receptor to adenylate cyclase coupling efficiency is discussed.