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Grzegorz L Kaluza

Publications and source records attributed to Grzegorz L Kaluza.

16 recordsLinked to original sources
PubMed2006

Oral rapamycin after coronary bare-metal stent implantation to prevent restenosis: the Prospective, Randomized Oral Rapamycin in Argentina (ORAR II) Study.

OBJECTIVES: The purpose of this study was to assess the role of oral rapamycin in decreased restenosis after bare metal stent implantation. BACKGROUND: Small observational studies suggest that the administration of oral rapamycin reduces angiographic restenosis after bare metal stent implantation. METHODS: Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year. RESULTS: Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively; 43% reduction, p < 0.001). At 1 year, patients in the oral rapamycin group also showed a significantly lower incidence of target vessel revascularization (8.3% vs. 38%, respectively, p < 0.001), target lesion revascularization (7.6% vs. 37.2%, respectively, p < 0.001), and major adverse cardiovascular events (20% vs. 44%, respectively, p = 0.018). CONCLUSIONS: This randomized, controlled, and unblinded study showed that the administration of oral rapamycin during 14 days after stent implantation significantly reduces angiographic and clinical parameters of restenosis.

Administration, Oral↗
PubMed2005

Single perivascular delivery of mitomycin C stimulates p21 expression and inhibits neointima formation in rat arteries.

OBJECTIVE: Mitomycin C (MMc) is an antibiotic that exerts a potent antiproliferative effect in tumor cells. Because the proliferation of vascular smooth muscle cells (VSMCs) plays a prominent role in the development of restenosis after percutaneous coronary interventions, the present study examined the effect of MMc on VSMC proliferation and on neointima formation after arterial balloon injury. METHODS AND RESULTS: Treatment of cultured rat aortic VSMCs with MMc (1 nmol to 30 micromol/L) inhibited VSMC proliferation in a concentration-dependent manner. Whereas high concentrations of MMc (1 to 30 micromol/L) induced VSMC apoptosis, as reflected by DNA laddering and caspase-3 activation, lower concentrations of MMc (1 to 300 nmol/L) directly inhibited VSMC growth by arresting cells in the G2/M phase of the cell cycle. The antiproliferative action of MMc was associated with a selective increase in the expression of the cyclin-dependent kinase inhibitor p21, and with a decrease in cyclin B1-cyclin-dependent kinase-1 complex activity. Finally, the local perivascular delivery of MMc immediately after balloon injury of rat carotid arteries induced p21 expression and markedly attenuated neointima formation. CONCLUSIONS: These studies demonstrate that MMc exerts a potent inhibitory effect on VSMC proliferation and neointima formation after arterial injury. MMc represents a potentially new therapeutic agent in treating and preventing vasculoproliferative disease.

Angioplasty, Balloon↗
PubMed2005

Effects of SolCD39, a novel inhibitor of Platelet Aggregation, on Platelet Deposition and Aggregation after PTCA in a Porcine Model.

INTRODUCTION: This study evaluated CD39 in a porcine model of balloon angioplasty and in plasma of patients undergoing percutaneous intervention. CD39 (E-NTPDase1), is the endothelial ecto-ADPase inhibiting platelet function via hydrolysis of released platelet ADP. METHODS AND RESULTS: A recombinant soluble form of CD39 (solCD39) given intravenously to pigs had an elimination half life of 5--7 days, increased the bleeding time to an extent similar to aspirin, and inhibits platelet aggregation by>90%. Platelet counts and clot retraction remained normal following solCD39 administration. In a pig model of acute coronary balloon injury, solCD39 resulted in non-statistically significant decreases in platelet (7.7+/-1.4 versus 11.7+/- 3.4) and fibrin (3.5+/- 0.4 versus 4.2+/- 0.7) deposition ratios. Adding ex vivo to human platelet rich plasma (PRP) solCD39 produced nearly 100% inhibition of ADP-induced platelet aggregation. A dose-response effect of solCD39 on platelet aggregation induced by collagen or a thrombin receptor activating peptide (TRAP(SFLLRN)) was noted in PRP obtained from volunteers and patients receiving aspirin, clopidogrel or ticlopidine. SolCD39 also provided additional and complete inhibition of TRAP-induced platelet aggregation in PRP from patients who had received abciximab, aspirin and clopidogrel. CONCLUSIONS: SolCD39, a novel inhibitor of platelet activation and recruitment with a relatively long half-life appears to be well tolerated and is a potent inhibitor of ADP-, collagen-, or TRAP-induced platelet activation. Its potential use in percutaneous coronary intervention requires further study. ABBREVIATED ABSTRACT: E-NTPDase1/CD39 is the endothelial ecto-ADPase responsible for inhibition of platelet function. A recombinant soluble form (solCD39) had an elimination half life of 5-7 days in pigs, elevated bleeding times similar to aspirin, did not affect clot retraction, and inhibited platelet aggregation by > 90%. When combined with standard heparin therapy in a pig model of acute coronary balloon injury, solCD39 resulted in a trend toward a decrease in platelet and fibrin deposition. SolCD39 added ex vivo to human platelet rich plasma yielded nearly 100% inhibition of ADP-induced platelet aggregation and provided further inhibition when combined with standard therapy.

Adenosine Diphosphate↗
PubMed2005

HIV-based vectors and angiogenesis following rabbit hindlimb ischemia.

BACKGROUND: Numerous medical and surgical options exist for the treatment of vessel ischemia, which some patients fail or cannot tolerate. These investigations were designed to determine the effects of lentiviral-delivered vascular endothelial-derived growth factor (VEGF) and angiopoietin-2 (Ang-2) on collateralization in a rabbit model of hindlimb ischemia. MATERIALS AND METHODS: Self-inactivating human immunodeficiency virus (HIV)-based vectors were constructed encoding VEGF or Ang-2, co-transfected with vesicular stomatitis virus glycoprotein (VSV G) into 293T cells, and vector supernatants (1 x 10(8) IU/ml after concentration) were harvested. New Zealand white rabbits had ligation of either the right or left external iliac artery and excision of the ipsilateral femoral artery. Ten days later, empty, VEGF, or VEGF+Ang-2 vector supernatant was injected intramuscularly (IM) into the ipsilateral thigh. Ankle systolic blood pressure (SBP) ratios were recorded and venous blood samples collected on postoperative days (POD) 10, 25, and 40. On POD 40, run-off angiography was performed to measure vessel collateralization. Capillary density was determined by thin sectioning of muscle. RESULTS: A significant increase was noted in SBP in the VEGF-treated animals over time. Capillary density was not elevated despite significantly increased large vessel collateralization in rabbits receiving VEGF, which was counteracted by Ang-2. Antibodies against vector components were detected in exposed serum. CONCLUSIONS: Arterial collateralization and SBP increased significantly following VEGF vector administration, which was reversed by the Ang-2 vector. Development of antibody against VSV G can limit repeated injections of vector. Future experiments will involve the addition of other pro-angiogenic factors, repeated vector administration, and alternative routes of vector delivery.

Angiopoietin-2↗
PubMed2004

L-arginine supplementation does not inhibit neointimal formation after coronary stenting in human beings: an intravascular ultrasound study.

BACKGROUND: In-stent restenosis results from neointimal tissue proliferation. L-arginine supplementation improves endothelial function and reduces neointimal formation after arterial injury in animals. The aim of the study was to assess the influence of L-arginine administration on neointimal proliferation after coronary stenting in human beings. METHODS: We performed a prospective, randomized, double-blinded, placebo-controlled study in 60 men without diabetes. L-arginine/placebo was administered intravenously 12 hours before percutaneous coronary intervention (200 mg/kg for 240 minutes), during the procedure (200 mg/kg for 240 minutes), and intracoronarily immediately before stent implantation (500 mg for 10 minutes), and it was followed by oral treatment for next 2 weeks (6.0 g/d). By quantitative coronary angiography, late lumen loss, and intravascular ultrasound, neointimal volume and percent neointimal volume were calculated after 7 months of follow-up to assess neointimal formation. RESULTS: There were no differences in baseline clinical or angiographic characteristics between the two groups. Intravenous infusion of L-arginine increased plasma L-arginine concentrations 6-fold compared with placebo (661 +/- 264 vs 107 +/- 71 mmol/L, P <.001). During the 2-week period of oral treatment with L-arginine there was a sustained, significant increase of plasma L-arginine level (150 +/- 50 vs 100 +/- 17, P <.001, 135 +/- 42 vs 89 +/- 27, P <.001, respectively, on days 7 and 14 in the L-arginine group vs placebo). However, at 7-month follow-up, there was no difference in neointimal formation measured both by quantitative coronary angiography and intravascular ultrasound between the study groups. CONCLUSIONS: Chronic systemic L-arginine administration has no effect on neointimal formation after coronary stenting in human beings.

Angioplasty, Balloon, Coronary↗
PubMed2004

Brachytherapy for restenosis after stenting for coronary artery disease: its role in the drug-eluting stent era.

PURPOSE OF REVIEW: Recent years have brought remarkable changes to the field of interventional cardiology. The need for repeat intervention due to restenosis, the most vexing long-term failure of percutaneous coronary intervention, has been significantly reduced owing to the introduction of two major advances, the vascular brachytherapy (VBT) and the drug-eluting stents (DES). RECENT FINDINGS: Vascular brachytherapy has demonstrated its efficacy in limiting recurrence of existing in-stent restenosis. The past 2 years have sealed its reputation, with a variety of studies demonstrating its superiority over conventional therapy in challenging patient subsets with high risk for restenosis recurrence. Moreover, the long-term follow-up confirmed durability of this therapy, and the failures of VBT were characterized as easy to treat. Conversely, DES have shown spectacular efficacy at primarily preventing the first restenosis episode following the initial stent placement. Consequently, the role of VBT may be minimized, as the overall need for repeat revascularization is diminished as a result of the wide acceptance of DES. Furthermore, if the capacity of DES to treat in-stent restenosis is confirmed in randomized trials, they may eventually supersede VBT as the therapy of choice for in-stent restenosis. SUMMARY: At present, VBT is the proven and durable therapeutic choice for patients with complex, diffuse in-stent restenosis who would otherwise have a very poor prognosis for long-term event-free survival. DES have emerged as remarkably effective in minimizing the first restenosis occurrence; they also represent a promising and competitive alternative to VBT for the treatment of in-stent restenosis.

Angioplasty, Balloon, Coronary↗
PubMed2003

The CAPTIM study.

Explore the source record for details and available documents.

Abciximab↗
PubMed2003

Drug-eluting stents for cardiovascular disorders.

Drug-eluting stents have emerged in recent years as a very promising therapy for prevention of restenosis after coronary implantation. Early randomized, clinical trials have suggested that stents eluting drugs, such as paclitaxel or sirolimus, released from polymeric and nonpolymeric coatings, are able to reduce restenosis in simple de novo lesions by more than 80% in comparison with bare metal stents. If restenosis can be indeed minimized globally by drug-eluting stents, coronary revascularization may expand to patients and lesions currently not considered for percutaneous intervention because of excessive recurrence, and may open possibilities for other stent-based endovascular treatments of atherosclerosis.

Cardiovascular Diseases↗
PubMed2003

Outcomes of patients presenting with acute coronary syndromes and negative Troponin-T.

UNLABELLED: The aim of the study was to compare need for revascularization and clinical course between troponin-positive and troponin-negative patients with unstable angina pectoris defined as class IIIB according to Braunwald classification. METHODS: The study group consisting of 104 patients was divided into troponin-positive (28 patients) and troponin-negative (76 patients) subgroups. Per study design all patients underwent coronary angiography. The subgroups were compared in regard to angiographic status and consequently the need for revascularization. Additionally, major adverse cardiac events (MACE) consisting of death, myocardial infarction, in-hospital revascularization during 30-days follow-up were assessed in subgroups. RESULTS: In 58 (76%) patients with negative troponin test, the angiographically significant coronary artery stenosis was shown. Major adverse cardiac events were similar in both groups. Regardless of the initial TnT status, in both groups revascularizations (percutaneous or surgical) were performed with high frequency (89 versus 72%, P=NS). CONCLUSION: In patients with unstable angina in class IIIB according to Braunwald classification, the negative cardiac troponin test did not exclude severe coronary artery disease, which in the majority of patients required revascularization without any additional non-invasive testing for ischemia. Therefore, we postulate that patients with clinically evident unstable angina (IIIB) should be referred to early invasive assessment despite negative troponin T screening.

Acute Disease↗
PubMed2002

Acute vasculitis after endovascular brachytherapy.

PURPOSE: Angioplasty effectively relieves coronary artery stenosis but is often followed by restenosis. Endovascular radiation (beta or gamma) at the time of angioplasty prevents restenosis in a large proportion of vessels in swine (short term) and humans (short and long term). Little information is available about the effects of this radiation exposure beyond the wall of the coronary arteries. METHODS AND MATERIALS: Samples were obtained from 76 minipigs in the course of several experiments designed to evaluate endovascular brachytherapy: 76 of 114 coronary arteries and 6 of 12 iliac arteries were exposed to endovascular radiation from 32P sources (35 Gy at 0.5 mm from the intima). Two-thirds of the vessels had angioplasty or stenting. The vessels were systematically examined either at 28 days or at 6 months after radiation. RESULTS: We found an unexpected lesion: acute necrotizing vasculitis in arterioles located < or =2.05 mm from the target artery. It was characterized by fibrinoid necrosis of the wall, often associated with lymphocytic exudates or thrombosis. Based on the review of perpendicular sections of tissue samples, the arterioles had received between 6 and 40 Gy. This arteriolar vasculitis occurred at 28 days in samples from 51% of irradiated coronary arteries and 100% of irradiated iliac arteries. By 6 months, the incidence of acute vasculitis decreased to 24% around the coronary arteries. However, at that time, healing vasculitis was evident, often with luminal narrowing, in 46% of samples. Vasculitis was not seen in any of 44 samples from unirradiated vessels (0%) and had no relation to angioplasty, stenting, or their sequelae. This radiation-associated vasculitis in the swine resembles the localized lymphocytic vasculitis that we have reported in tissues of humans exposed to external radiation. On the other hand, it is quite different from the various types of systemic vasculitis that occur in nonirradiated humans. CONCLUSION: Endoarterial brachytherapy using 32P results in vascular effects beyond the adventitia of the target vessel. This necrotizing vasculitis is causally related to radiation, but its mechanism is unclear and a dose effect is not evident. Quite possibly, local upregulation of inflammatory cytokines contributes to this radiation-associated vasculitis, which only involved some of the arterioles in each sample. It is likely that radiation-associated vasculitis also occurs around human coronary arteries and may result in foci of ischemia. To our knowledge, this lesion has not been previously recognized, either in experimental models or in human specimens examined after angioplasty/brachytherapy.

Acute Disease↗
PubMed2002

Intracoronary brachytherapy.

Patients presenting with in-stent restenosis have an increased risk of need for repeat intervention. Intracoronary brachytherapy is indicated for these patients to prevent recurrent in-stent restenosis. Three intravascular brachytherapy systems are currently FDA-approved for use in patients: one utilizing gamma-radiation (Cordis) and two using beta-radiation (Novoste and Guidant). Current evidence and labeling do not support using intracoronary brachytherapy for prevention of restenosis in de novo lesions. Brachytherapy is absolutely contraindicated in patients unable to take prolonged combination antiplatelet drugs. Aspirin and a thienopyridine should be taken for 6 months if no new stent is placed and 12 months if a new stent is placed. If possible, new stent implementation should be avoided.

Beta Particles↗
PubMed2002

Glycoprotein IIb-IIIa inhibition with abciximab and postprocedural risk assessment: lessons from the evaluation of platelet IIb/IIIa inhibitor for stenting trial and implication for ad hoc use of glycoprotein IIb-IIIa antagonists.

BACKGROUND: Angiographic features of vessels in which stents have been deployed can be used to predict the risk of postprocedural ischemic events. The purpose of this study was to compare the effects of abciximab in patients with and without high-risk postprocedure features. METHODS AND RESULTS: Protocol-mandated stent implantation was performed in 1586 patients in the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting trial, 783 of whom received abciximab, and was successful in 97% of the patients. High-risk features were defined as the presence of Thrombolysis In Myocardial Infarction (TIMI) flow <3, presence of thrombus or major dissection, or residual stenosis >10%. The primary endpoint was a composite of death, myocardial infarction, and urgent target vessel revascularization at 30 days. High-risk features were present in 21% of the patients. In patients without high-risk features after stent placement, abciximab reduced the primary endpoint from 9.0% to 3.9% (P <.001) compared with 16.2% to 8.6% (P =.046) in patients in whom high-risk features were present. There was no statistical evidence of interaction between abciximab treatment and the presence or absence of high-risk features. CONCLUSION: Glycoprotein IIb-IIIa antagonism with abciximab is equally effective in prevention of a composite of ischemic events in patients with and without high-risk features after stent placement. However, patients in whom high-risk features are present after stent placement are at increased risk of ischemic cardiac events even with abciximab treatment.

Abciximab↗
PubMed2001

The Proliferation REduction with Vascular ENergy Trial (PREVENT).

PREVENT was the first prospective, randomized placebo-controlled study of intracoronary beta radiotherapy with 32P. A total of 105 patients with de novo or restenotic lesions, treated by stenting or balloon angioplasty, received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm beyond the lumen surface. Rates of restenosis (50% diameter stenosis or more) were significantly lower in radiotherapy patients at the target site (8% compared with 39%, P = 0.012) and at the target site plus adjacent segments (22% compared with 50%, P = 0.018). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy.

Journal Article↗