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1.
Circulation ; 104(8): 870-5, 2001 Aug 21.
Article in English | MEDLINE | ID: mdl-11514371

ABSTRACT

BACKGROUND: Platelet glycoprotein IIb/IIIa blockade with abciximab (ReoPro) improves the clinical outcomes of percutaneous coronary intervention. This registry was conducted to characterize the effects of repeated administration of abciximab during intervention. METHODS AND RESULTS: We recruited 500 consecutive patients at 22 centers in the United States who were receiving abciximab for at least a second time during percutaneous coronary intervention. Safety was measured as the incidence of hypersensitivity reactions, major bleeding, and thrombocytopenia. Efficacy was assessed as event-free clinical success. Human antichimeric antibody (HACA) responses were also characterized. There were no cases of hypersensitivity (95% upper confidence bound, 0.3%), major bleeding, or death. Clinical success was 94.4%. Thrombocytopenia occurred in 23 patients (4.6%; 95% CI, 2.8% to 6.4%), including 12 (2.4%; 95% CI, 1.1% to 3.7%) who developed profound thrombocytopenia (<20x10(9) cells/L). In 2 patients (0.4%), profound thrombocytopenia did not develop until after hospital discharge; in 4 (0.8%), profound thrombocytopenia recurred despite platelet transfusion. Before a first readministration, a positive HACA titer was present in 22 of 454 patients (4.8%); after a first readministration, an additional 82 of 432 (19.0%) became HACA-positive. HACA did not neutralize the in vitro inhibition of platelet aggregation by abciximab or correlate with clinical events. CONCLUSIONS: The results, including overall rates of thrombocytopenia, were consistent with randomized clinical trials of first abciximab treatment. However, there was a shift from mild to profound thrombocytopenia, and cases of delayed presentation and of recurrent thrombocytopenia were seen. These findings suggest that indications and guidelines for first-time use apply to retreatment, particularly the systematic monitoring for thrombocytopenia.


Subject(s)
Angioplasty, Balloon, Coronary , Antibodies, Monoclonal/administration & dosage , Coronary Disease/therapy , Immunoglobulin Fab Fragments/administration & dosage , Registries/statistics & numerical data , Thrombocytopenia/diagnosis , Vascular Patency/drug effects , Abciximab , Angioplasty, Balloon, Coronary/adverse effects , Antibodies/blood , Antibodies/pharmacology , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/immunology , Aspirin/administration & dosage , Coronary Disease/blood , Disease-Free Survival , Drug Administration Schedule , Hemorrhage/etiology , Heparin/administration & dosage , Humans , Immunoglobulin Fab Fragments/adverse effects , Immunoglobulin Fab Fragments/immunology , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/immunology , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Postoperative Complications/prevention & control , Thrombocytopenia/etiology , Treatment Outcome , United States
2.
Circulation ; 103(21): 2572-8, 2001 May 29.
Article in English | MEDLINE | ID: mdl-11382726

ABSTRACT

BACKGROUND: The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. METHODS AND RESULTS: Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACES: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve >/=95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P=0.006). Patients whose platelet function was <70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those >/=70% inhibited (P=0.009). By multivariate analysis, platelet function inhibition >/=95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P=0.04). CONCLUSIONS: Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.


Subject(s)
Angioplasty, Balloon, Coronary , Heart Diseases/prevention & control , Platelet Aggregation Inhibitors/therapeutic use , Tyrosine/analogs & derivatives , Abciximab , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/therapeutic use , Blood Platelets/drug effects , Blood Platelets/physiology , Cohort Studies , Eptifibatide , Female , Heart Diseases/chemically induced , Humans , Immunoglobulin Fab Fragments/adverse effects , Immunoglobulin Fab Fragments/therapeutic use , Logistic Models , Male , Multivariate Analysis , Peptides/adverse effects , Peptides/therapeutic use , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/adverse effects , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Prospective Studies , Risk Factors , Time Factors , Tirofiban , Tyrosine/adverse effects , Tyrosine/therapeutic use
3.
Catheter Cardiovasc Interv ; 52(4): 468-72, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11285599

ABSTRACT

Heparin-induced thrombocytopenia (HIT) is a well-documented complication of heparin anticoagulation therapy. Heparin's frequent use in the cardiovascular population poses a significant challenge for managing patients with HIT in need of percutaneous coronary intervention (PCI). We describe four patients with HIT who successfully underwent PCI without thrombotic or hemorrhagic complications while on lepirudin.


Subject(s)
Angioplasty, Balloon, Coronary , Anticoagulants/therapeutic use , Hirudins/analogs & derivatives , Thrombocytopenia/chemically induced , Thrombocytopenia/therapy , Aged , Heparin/therapeutic use , Hirudin Therapy , Humans , Male , Middle Aged , Recombinant Proteins/therapeutic use
4.
Catheter Cardiovasc Interv ; 51(4): 407-13, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11108670

ABSTRACT

The BARASTER registry was formed to evaluate the initial success and long-term results of rotational atherectomy in the management of in-stent restenosis. Rotational atherectomy was used in 197 cases of in-stent restenosis: 46 with stand-alone rotational atherectomy or at most 1 atmosphere of balloon inflation (Rota strategy), and 151 with rotational atherectomy and adjunctive balloon angioplasty <1 atmosphere (Combination strategy). These were compared with 107 episodes of in-stent restenosis treated with balloon angioplasty alone. In this observational study, the use of Combination therapy was associated with a slightly higher initial success rate (95% vs. 87% with the Rota strategy and 89% with Balloons, P = 0.08). There was a reduction in one year clinical outcomes (death, myocardial infarction or target lesion revascularization) in the combination group (38% vs. 60% with Rota and 52% with balloons, P = 0.02). These data support a benefit of the strategy of debulking with rotational atherectomy followed by adjunctive balloon angioplasty, in the management of in-stent restenosis.


Subject(s)
Angioplasty, Balloon, Coronary , Atherectomy, Coronary , Coronary Disease/therapy , Stents , Aged , Coronary Disease/mortality , Female , Humans , Male , Middle Aged , Registries , Retreatment , Survival Rate , Treatment Outcome
5.
Circulation ; 101(20): 2375-81, 2000 May 23.
Article in English | MEDLINE | ID: mdl-10821813

ABSTRACT

BACKGROUND: After successful percutaneous coronary arterial revascularization, 25% to 60% of subjects have restenosis, a recurrent coronary arterial narrowing at the site of the intervention. At present, restenosis is usually detected invasively with contrast coronary angiography. This study was performed to determine if phase-contrast MRI (PC-MRI) could be used to detect restenosis noninvasively in patients with recurrent chest pain after percutaneous revascularization. METHODS AND RESULTS: Seventeen patients (15 men, 2 women, age 36 to 77 years) with recurrent chest pain >3 months after successful percutaneous intervention underwent PC-MRI measurements of coronary artery flow reserve followed by assessments of stenosis severity with computer-assisted quantitative coronary angiography. The intervention was performed in the left anterior descending coronary artery in 15 patients, one of its diagonal branches in 2 patients, and the right coronary artery in 1 patient. A PC-MRI coronary flow reserve value /=70% and >/=50%, respectively. CONCLUSIONS: Assessments of coronary flow reserve with PC-MRI can be used to identify flow-limiting stenoses (luminal diameter narrowings >70%) in patients with recurrent chest pain in the months after a successful percutaneous intervention.


Subject(s)
Coronary Circulation , Coronary Disease/diagnosis , Coronary Disease/physiopathology , Coronary Vessels/physiopathology , Magnetic Resonance Imaging/methods , Adult , Aged , Blood Flow Velocity , Coronary Angiography , Diagnosis, Computer-Assisted , Female , Humans , Male , Middle Aged , Recurrence
6.
Am Heart J ; 138(1 Pt 2): S33-8, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10385789

ABSTRACT

Even with continued improvements in the technology of percutaneous coronary intervention (PCI), approximately 10% to 20% of patients undergoing PCI will require repeat procedures within 1 year. Furthermore, because of the chronic nature of coronary artery disease, many patients will require additional treatment with PCI well after an initial episode of care. Abciximab (ReoPro), a chimeric (murine/human) monoclonal antibody fragment (c7E3 Fab), has been shown to significantly improve periprocedural and long-term outcomes associated with PCI and to reduce the need for repeat target vessel revascularization. However, because the structure of abciximab is derived from an antibody, concern has been raised about subsequent repeat administration. To prospectively evaluate the safety and efficacy of abciximab readministration, we established the ReoPro Readministration Registry with the intent to determine the efficacy, human antichimeric antibody response and rates of thrombocytopenia, bleeding, intracranial hemorrhage, and anaphylaxis in at least 500 patients being retreated with abciximab. The study was conducted at 19 centers beginning in March 1997. This article details interim data that are based on the first 329 patients. Data to date indicate that readministration with abciximab is safe and efficacious and that the same indications for first-time use should apply to subsequent readministration.


Subject(s)
Angioplasty, Balloon, Coronary/adverse effects , Antibodies, Monoclonal/adverse effects , Coronary Disease/drug therapy , Immunoglobulin Fab Fragments/adverse effects , Platelet Aggregation Inhibitors/adverse effects , Platelet Glycoprotein GPIIb-IIIa Complex/antagonists & inhibitors , Registries/statistics & numerical data , Abciximab , Antibodies/immunology , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Humans , Immunoglobulin Fab Fragments/administration & dosage , Immunoglobulin Fab Fragments/immunology , Platelet Aggregation Inhibitors/administration & dosage , Platelet Aggregation Inhibitors/immunology , Prospective Studies , Recurrence , Thrombocytopenia/etiology
7.
Circ Res ; 84(11): 1268-76, 1999 Jun 11.
Article in English | MEDLINE | ID: mdl-10364564

ABSTRACT

The vitronectin receptor (alphavbeta3) mediates several biological processes that are critical to the formation of a neointima after coronary interventions. Blockade of alphavbeta3 could reduce neointima formation by inhibiting smooth muscle cell migration, decreasing transforming growth factor-beta1 expression, enhancing apoptosis, or reducing neovasculature. The effects of short-term administration of Vitaxin, a humanized monoclonal antibody to alphavbeta3, on the responses to balloon injury were tested in hyperlipidemic rabbits. Balloon angioplasty was performed on the iliac arteries of male New Zealand White rabbits that were fed an atherogenic diet for 1 week before injury and until euthanization at 4 weeks. Rabbits were given either saline (control) or 1 of 2 dosing regimens of Vitaxin (high dose, 5.0 mg/kg, and low dose, 0.5 mg/kg), which were administered intra-arterially before injury and intramuscularly on days 2 and 3. High-dose and low-dose Vitaxin were equally effective in decreasing neointima formation even in the presence of hypercholesterolemia, a stimulus to alphavbeta3 expression. Vitaxin reduced transforming growth factor-beta1 and enhanced apoptosis in injured arteries. Despite these positive effects, Vitaxin administration was associated with a reduction in artery size, indicating a negative effect on remodeling. Vitaxin has a potential role in preventing intimal hyperplasia, especially if the negative effects on remodeling can be overcome, by dose adjustment or other strategies.


Subject(s)
Angioplasty, Balloon/adverse effects , Antibodies, Monoclonal/therapeutic use , Hypercholesterolemia/therapy , Receptors, Vitronectin/immunology , Tunica Intima/injuries , Animals , Antibodies, Monoclonal, Humanized , Apoptosis/physiology , Cell Movement/physiology , Cholesterol/metabolism , Fluorescent Antibody Technique , Humans , Hyperplasia/therapy , Iliac Artery/injuries , Iliac Artery/pathology , Male , Rabbits , Transforming Growth Factor beta/metabolism , Tunica Intima/pathology
8.
Cathet Cardiovasc Diagn ; 45(3): 318-22, 1998 Nov.
Article in English | MEDLINE | ID: mdl-9829897

ABSTRACT

Heparin is considered necessary during percutaneous coronary interventions; however, heparin is contraindicated in patients with heparin-induced thrombocytopenia and/or heparin antibodies. We describe the successful use of the heparinoid Orgaran (danaparoid sodium) in addition to abciximab (ReoPro) in a patient with heparin antibodies who required rotational atherectomy.


Subject(s)
Anticoagulants/therapeutic use , Atherectomy, Coronary , Chondroitin Sulfates/therapeutic use , Dermatan Sulfate/therapeutic use , Heparin/adverse effects , Heparinoids/therapeutic use , Heparitin Sulfate/therapeutic use , Thrombocytopenia/chemically induced , Abciximab , Antibodies/analysis , Antibodies, Monoclonal/therapeutic use , Atherectomy, Coronary/methods , Blood Coagulation/drug effects , Coronary Angiography , Coronary Disease/diagnostic imaging , Coronary Disease/drug therapy , Coronary Disease/surgery , Heparin/immunology , Humans , Immunoglobulin Fab Fragments/therapeutic use , Intraoperative Period , Male , Middle Aged , Thrombocytopenia/blood , Thrombocytopenia/immunology
9.
J Am Coll Cardiol ; 30(3): 657-63, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9283522

ABSTRACT

OBJECTIVES: The purpose of this study was to evaluate the effectiveness of transluminal extraction catheter (TEC) atherectomy followed by immediate Palmaz-Schatz coronary stenting of coronary bypass vein grafts. BACKGROUND: Degeneration of saphenous vein coronary bypass grafts has become a common problem. Repeat bypass surgery is associated with greater risk and a poorer outcome than the initial operation. Moreover, percutaneous interventional procedures in vein grafts have been associated with high procedural complication rates, including distal embolization, and high restenosis rates. TEC atherectomy may reduce distal embolization, and stenting may reduce restenosis rates. METHODS: We evaluated the procedural, hospital and clinical outcomes of TEC atherectomy followed by immediate Palmaz-Schatz coronary stenting of 53 vein grafts in 49 consecutive patients. The strategy was to limit instrumentation to extraction debulking and to stabilizing the site with stent deployment before using balloon dilation for optimal gain in lumen diameter. RESULTS: Results are shown as mean value (95% confidence interval [CI]). The mean graft age was 9.2 years (95% CI 7.9 to 10.5), and 1.0 (95% CI 1 to 1) TEC cutter (2.2 mm [95% CI 2.1 to 2.3]) and 1.7 (95% CI 1.4 to 2.0) Palmaz-Schatz coronary stents/ vein graft were used. The procedural success rate was 98%, with a minimal lumen diameter at baseline of 1.3 mm (95% CI 1.1 to 1.5), increasing to 3.9 mm (95% CI 3.6 to 4.2) (p < 0.05) after the TEC-stent procedure. Procedural complications occurred infrequently: graft perforation in 1 (2%) of 53 patients and distal embolization in 1 (2%) of 53 (same patient). In-hospital complications included non-Q wave myocardial infarction in two patients and death after a successful procedure in three (6%) (n = 1 each: massive bleeding from the catheter site; sepsis; and acute myocardial infarction with asystole in the distribution of the stented vessel). The event-free survival rate to hospital discharge was 90%. Clinical follow-up (13 months [95% CI 11 to 15]) was available for all patients. There were five (11%) revascularization procedures (three bypass grafts and two percutaneous transluminal coronary interventions), four (9%) nonfatal myocardial infarctions and five (11%) deaths, for a cumulative rate of 28% for any adverse outcome occurring in 13 of 46 patients. CONCLUSIONS: TEC atherectomy followed by immediate Palmaz-Schatz coronary stenting of stenoses in old (> 9 years) saphenous vein grafts can be successfully performed, with a low incidence of procedural and hospital complications. Clinical restenosis rates are low and less than those previously reported; however, late morbid cardiac events are still frequent in this high risk group of patients. These observational findings suggest that this technique may improve percutaneous management of vein graft disease, but optimal long-term management strategies remain to be determined.


Subject(s)
Atherectomy, Coronary/methods , Coronary Artery Bypass , Coronary Disease/therapy , Saphenous Vein/transplantation , Stents , Aged , Atherectomy, Coronary/adverse effects , Coronary Angiography , Coronary Disease/diagnostic imaging , Coronary Disease/mortality , Disease-Free Survival , Female , Humans , Male , Middle Aged , Recurrence , Treatment Outcome
10.
Clin Cardiol ; 19(11): 903-5, 1996 Nov.
Article in English | MEDLINE | ID: mdl-8914786

ABSTRACT

This brief report presents a patient with isolated right heart failure and two rare underlying causes, hyperthyroidism and dysplastic tricuspid valve. Repair of the tricuspid valve and treatment of the hyperthyroidism were both essential for successful treatment of the right heart failure. Most important, recrudescence of hyperthyroidism in this patient was associated with reappearance of florid right heart failure. This report provides further information about a potential linkage of hyperthyroidism and severe right heart failure.


Subject(s)
Graves Disease/complications , Heart Failure/etiology , Antithyroid Agents/therapeutic use , Echocardiography, Doppler, Color , Echocardiography, Transesophageal , Graves Disease/drug therapy , Humans , Male , Middle Aged , Propylthiouracil/therapeutic use , Tricuspid Valve/pathology , Tricuspid Valve Insufficiency/complications , Tricuspid Valve Insufficiency/diagnostic imaging , Tricuspid Valve Insufficiency/surgery
11.
Cathet Cardiovasc Diagn ; 38(2): 202-4, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8776529

ABSTRACT

We report on a woman with severe peripheral vascular disease with unstable angina, in which access to the central circulation was not possible from a peripheral route. The translumbar approach was used for coronary angiography and a successful angioplasty of the left circumflex artery.


Subject(s)
Angina, Unstable/therapy , Angioplasty, Balloon, Coronary/instrumentation , Arterial Occlusive Diseases/physiopathology , Coronary Disease/therapy , Myocardial Infarction/therapy , Angina, Unstable/diagnostic imaging , Aorta, Abdominal , Arterial Occlusive Diseases/diagnostic imaging , Coronary Angiography , Coronary Disease/diagnostic imaging , Equipment Design , Female , Humans , Lumbosacral Region , Middle Aged , Myocardial Infarction/diagnostic imaging , Tomography, X-Ray Computed
12.
Clin Cardiol ; 18(2): 91-6, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7720296

ABSTRACT

There is evidence that the first balloon inflation during coronary angioplasty provides a preconditioning stimulus leading to decreased ischemia during subsequent balloon inflations. Endogenous adenosine release may play a role in ischemic preconditioning. Therefore, intracoronary adenosine administration prior to the first balloon inflation during percutaneous transluminal coronary angioplasty (PTCA) might modify the preconditioning response to the first balloon inflation. Forty-one patients underwent double-blind randomization to treatment with 100 mcg of intracoronary adenosine or placebo prior to coronary angioplasty. Twenty patients (11 adenosine, 9 placebo) had complete resolution of ischemia between inflations allowing comparison between the first and second inflation. An angioplasty guidewire was used to obtain an intracoronary electrocardiogram. The mean reduction in ST elevation during the second inflation compared with the first was 4.8 mm in the placebo group and -0.8 in the adenosine group (p < 0.05 placebo vs. adenosine). Seven of 9 placebo patients had a decrease in ischemia during the second inflation compared with the first, while only 2 of 11 adenosine patients showed a reduction. It was concluded that (1) the first inflation during PTCA is a preconditioning stimulus leading to a decrease in ischemia during later inflations, and (2) intracoronary adenosine administration prior to PTCA modifies the preconditioning effect of the first inflation. These data suggest that adenosine plays a role in ischemic preconditioning in humans.


Subject(s)
Adenosine/therapeutic use , Angioplasty, Balloon, Coronary , Myocardial Infarction/therapy , Adenosine/administration & dosage , Analysis of Variance , Angioplasty, Balloon, Coronary/adverse effects , Coronary Vessels , Double-Blind Method , Electrocardiography , Humans , Infusions, Intra-Arterial , Myocardial Infarction/diagnosis , Myocardial Infarction/etiology , Myocardial Infarction/prevention & control
14.
J Am Coll Cardiol ; 23(1): 40-8, 1994 Jan.
Article in English | MEDLINE | ID: mdl-8277094

ABSTRACT

OBJECTIVES: This study was designed to define and contrast the mechanisms of lumen enlargement from coronary balloon angioplasty and directional coronary atherectomy using intracoronary ultrasound imaging in vivo. BACKGROUND: The mechanisms of lumen enlargement produced by percutaneous transluminal coronary balloon angioplasty and directional coronary atherectomy are not known because the coronary artery wall has not previously been studied both before and after dilation. METHODS: We used intracoronary ultrasound to quantitate coronary lumen, vessel and plaque area both before and immediately after successful coronary angioplasty (n = 30) and directional coronary atherectomy (n = 25) at the site of most severe stenosis. RESULTS: Angioplasty increased lumen area by 2.80 +/- 0.25 mm2 (mean +/- SE, p < 0.0001). Eighty-one percent of this lumen gain resulted from an increase in vessel area and the remaining 19% from a reduction in plaque area. Lumen gain of individual lesions was separated into three groups: 67% had an increase in vessel area (vessel expansion), 13% had a decrease in plaque area and 20% had a combination of both. In contrast, vessel expansion contributed only 22% of the lumen gain with directional coronary atherectomy, with the majority (78%) of increase in lumen size coming from a reduction in plaque area. Directional coronary atherectomy increased lumen area from 2.36 +/- 0.05 to 7.00 +/- 0.28 mm2 (p < 0.0001). Plaque reduction was the sole mechanism in 60% of lesions, vessel expansion was the sole mechanism in 12% and a combination of both mechanisms occurred in 28%. Lumen enlargement of eccentric lesions treated with directional coronary atherectomy was more commonly associated with plaque reduction (p < 0.02), whereas eccentricity did not affect the mechanism of lumen enlargement with coronary angioplasty. CONCLUSIONS: This is the first study to systematically examine the coronary artery wall in vivo at the site of a severe stenosis both before and after catheter-based interventions in humans. Lumen enlargement from coronary angioplasty occurs predominantly from vessel expansion or stretching, although a reduction in plaque area contributes to the lumen gain in many patients and is the sole mechanism in a few. Lumen gain from directional coronary atherectomy is predominantly from reduction in plaque area (probably owing to tissue removal), although vessel stretching (balloon effect) occurs and is the sole mechanism in a small minority of vessels. Plaque reduction is more common in directional coronary atherectomy of eccentric lesions.


Subject(s)
Angioplasty, Balloon, Coronary , Atherectomy, Coronary , Coronary Artery Disease/pathology , Coronary Artery Disease/therapy , Coronary Vessels/pathology , Adult , Aged , Coronary Artery Disease/diagnostic imaging , Coronary Vessels/diagnostic imaging , Female , Humans , Male , Middle Aged , Ultrasonography, Interventional
15.
Circulation ; 84(2): 679-85, 1991 Aug.
Article in English | MEDLINE | ID: mdl-1860212

ABSTRACT

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) is an acute, localized stimulus to platelet and vascular function. Periprocedural cardiovascular complications are reduced by moderate-dose aspirin (ASA), presumably due to inhibition of thromboxane (TX) A2. METHODS AND RESULTS: Excretion of TXA2 and prostacyclin (PGI2) metabolites in urine increased during PTCA. Pretreatment for 3 days with either moderate- (325 mg/day) or low-dose (80 mg/day) ASA inhibited the increase in both eicosanoids. Pretreatment for 3 weeks with fish oil (10 g/day) only partially suppressed TXA2. Formation of trienoic eicosanoids and accumulation of omega-3 fatty acids in platelet membranes confirmed fish oil ingestion. Although basal PGI2 was not inhibited, the PTCA-related increment was suppressed. CONCLUSIONS: PTCA results in an acute, transient alteration of eicosanoid biosynthesis consistent with accelerated platelet-vascular interactions. Pretreatment for 3 days with moderate or low doses of ASA suppresses TXA to a similar extent during PTCA, and their effects on acute cardiovascular complications of this procedure are likely to be comparable. It is unlikely that even prolonged pretreatment with fish oil can substitute for the platelet inhibitory action of ASA during PTCA. Suppression of PGI2 may contribute to the residual acute periprocedural complication rate in patients taking ASA.


Subject(s)
Angioplasty, Balloon, Coronary , Aspirin/pharmacology , Eicosanoids/biosynthesis , Fish Oils/pharmacology , Chest Pain/blood , Chest Pain/therapy , Chest Pain/urine , Epoprostenol/metabolism , Humans , Male , Patient Compliance , Thromboxane A2/metabolism , Thromboxanes/blood
16.
Circulation ; 82(1): 178-87, 1990 Jul.
Article in English | MEDLINE | ID: mdl-2114234

ABSTRACT

To assess the platelet inhibitory effect of high doses of fish oils and relate it to alterations in eicosanoid synthesis, we used a canine model in which coronary thrombosis, the time to reperfusion induced by recombinant tissue-type plasminogen activator (rt-PA), and the rate of spontaneous reocclusion are sensitive to platelet inhibition. In the animals fed fish oil, the time to rt-PA induced thrombolysis was accelerated (mean, 63 vs. 27 minutes; p less than 0.003). The time to thrombotic occlusion and the rate of reocclusion were unaltered. The ratio of eicosapentaenoic acid (EPA) to arachidonic acid rose in platelet and endothelial cell membranes, whereas serum thromboxane (Tx) B levels fell a mean 86%, and basal excretion of 2,3-dinor-TxB2 (TxA2-M) declined. Basal prostaglandin (PG) I2 formation was unaltered, whereas biosynthesis of EPA-derived TxA3 and PGI3 increased. In control animals, TxA2 formation increased during thrombosis; there was a further, more marked rise during reperfusion. PGI2 formation also increased, probably as a response to platelet-vascular interactions. Stimulated production of both eicosanoids was strikingly suppressed in the animals fed fish oil. Fish oils significantly enhance the efficacy of rt-PA in vivo, albeit to a modest extent. Because the time to reperfusion is highly sensitive to Tx-dependent platelet activation, this effect is likely to reflect the demonstrated suppression of TxA2 biosynthesis by fish oils.


Subject(s)
Blood Platelets/drug effects , Coronary Disease/physiopathology , Coronary Thrombosis/physiopathology , Dietary Fats, Unsaturated/pharmacology , Fish Oils/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Tissue Plasminogen Activator/pharmacology , Animals , Coronary Thrombosis/metabolism , Dogs , Epoprostenol/biosynthesis , Male , Membrane Lipids/metabolism , Phospholipids/metabolism , Thromboxane A2/biosynthesis
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