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Biomedical subjects

V Fuster

Publications and source records attributed to V Fuster.

At least 289 records · Page 16Linked to original sources

Coronary laser thermal angioplasty in the swine: reduced complications with shorter laser delivery time.

Although laser thermal angioplasty (LTA) with a laser heated metal probe has been tolerated in diseased human coronary arteries, definition of a safety threshold is lacking. Determination of safer operation parameters for coronary LTA using a new "over the wire" 1.3-mm laser probe catheter was attempted in seven normal pigs in which platelets were labeled with indium-111. Argon laser power of 10 watts was used for 1, 2, 3, and 5 seconds. Macroscopic findings, platelet deposition and histologic changes were compared between the laser treated coronary segments and controls, the nonheated laser probe, and the wire alone segments. After 1-second LTA, there was no vessel perforation or occlusive thrombi and only infrequent nonocclusive thrombi; platelet deposition was minimal; and histologic alterations rare and superficial. These findings were comparable to controls, the nonheated laser probe, and the wire alone segments. In contrast, vessels treated for 2, 3, and 5 seconds had more frequent perforation, and occlusive and nonocclusive thrombi that was accompanied by platelet deposition significantly greater than vessels treated with LTA for 1 second. A deep histologic injury was present in most of these segments. Additionally, the safety of laser delivery of 1 second repeated for five times was tested in two additional pigs. On macroscopic and histologic analysis the incidence of vessel perforation, occlusive and nonocclusive thrombi appeared slightly less when compared to the 2-, 3-, and 5-second LTA groups, and more than the 1-second LTA group.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Laser↗

Antithrombotic therapy for deep arterial injury by angioplasty. Efficacy of common platelet inhibition compared with thrombin inhibition in pigs.

BACKGROUND: Platelet-thrombus formation is a complication of arterial wall deep injury by balloon angioplasty that may lead to acute arterial occlusion and may contribute to restenosis. METHODS AND RESULTS: Because common platelet-inhibitor drugs with a heparin bolus (100 units/kg) may be effective in inhibiting platelet-thrombus formation after arterial angioplasty, these were compared with a bolus of heparin alone (control), the specific thrombin inhibitor hirudin (1.0 mg/kg), and saline (hirudin control) in normal pigs after angioplasty of the common carotid arteries. In the presence of deep arterial wall injury (injury exposing the media), indium-111-labeled platelet deposition (x 10(6)/cm2) was 68.8 +/- 12.3 and 48.1 +/- 16.9 in the control animals. This was significantly reduced by pretreatment with low-dose aspirin (1 mg/kg/day), by high-dose aspirin (20 mg/kg/day) plus dipyridamole, and especially by thrombin inhibition with hirudin. Treatment regimens with aspirin alone (20 mg/kg/day), dipyridamole alone, or sulfinpyrazone were ineffective. Likewise, the incidence of mural thrombosis was 75% and 80% in deeply injured arteries of controls and was significantly reduced to 46% with aspirin plus dipyridamole, 25% with low-dose aspirin, and 0% with hirudin. The incidence of mural thrombosis was unchanged with high-dose aspirin (69%), dipyridamole (90%), or sulfinpyrazone (92%). This mural thrombosis could not be identified by angiography. In the presence of mild injury (deendothelialization), platelet deposition was low (less than 10 x 10(6)/cm2, a single layer) and was not changed by any therapy, including hirudin. CONCLUSIONS: These therapies do not affect platelet adhesion to deeply or mildly injured artery. These data suggest a greater role for thrombin inhibition than with thromboxane or cyclooxygenase inhibition in the pathogenesis of platelet-rich mural thrombosis after deep injury during angioplasty. Antithrombotic therapy for arterial thrombosis by thrombin inhibition appears promising.

Angioplasty, Balloon↗

Vessel wall-related risk factors in acute vascular events.

Angiography in patients with unstable angina or myocardial infarction with subtotal coronary occlusion often reveals eccentric stenoses with irregular borders, suggesting ruptured atherosclerotic plaques and thrombosis, as documented by angioscopy and at autopsy. We have studied these processes in an ex vivo perfusion chamber, an in vivo swine model, and in human subjects. Our results, and those of other investigators, suggest that specific local risk factors at the time of plaque disruption influence the degree of thrombogenicity and, therefore, the various clinical syndromes. These risk factors can be divided into 2 groups: local vessel wall-related factors, and local (focal action) systemic factors. These risk factors include the following: 1) Rheological factors. It has been demonstrated that the more severe the stenotic lesion after plaque rupture, the higher the local shear rate with enhanced platelet deposition and thrombus formation; platelet deposition and thrombosis are particularly likely if the rupture includes the apex of the stenotic plaque, because of the high shear rate induced. 2) Degree of plaque damage. Plaque rupture produces a rough surface and stimulates an occlusive thrombus, which is enhanced depending on the degree of damage or amount of collagen type I and macrophage-dependent tissue factor exposed. 3) Residual thrombus. After spontaneous or pharmacological reperfusion, the surface of the residual thrombus is very thrombogenic and may contribute to reocclusion; this is partially due to thrombin bound to fibrin in the original thrombus. 4) Systemic factors. There is clinical and experimental evidence to suggest that 3 systemic factors at the time of plaque rupture may enhance thrombogenicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina, Unstable↗

Importance of experimental models for the development of clinical trials on thromboatherosclerosis.

Experimental models of vascular injury have enhanced our understanding of the pathophysiological process leading to vascular obstruction in both spontaneous and accelerated atherosclerosis. Based on experimental findings, we present and discuss a pathological classification of vascular injury or damage and its role in the pathogenesis of various vascular diseases. In addition, these animal models have provided insights into the roles of platelets and lipid metabolism in the evolution and progression of atherosclerosis and have suggested potential therapeutic applications. Thus, based on studies in the pig models, antiplatelet agents have been shown for the first time to have a beneficial effect in preventing the formation and progression of coronary atherosclerotic lesions in humans. Similarly, our findings in high density lipoprotein plasma fractions regarding inhibition and even reversal of the process of atherosclerosis in a hypercholesterolemic rabbit model have added new insights to an explosive field of lipoprotein research and provided new avenues of therapeutic strategies. our in vivo and ex vivo pig models of an extracorporeal perfusion chamber mimicking the various coronary conditions have aided in the understanding of the pathophysiology of the acute coronary syndromes and intensified our search for the ideal antithrombotic regimen in these high-risk patients. Finally, a carotid pig model of balloon angioplasty, a dog model of saphenous vein grafting, and a pig model of heart transplantation not only have provided insights into the pathophysiological process of accelerated atherosclerosis but also are allowing development of new antithrombotic and antiproliferative approaches for the prevention of these accelerated vascular diseases. In summary, we are entering an exciting era in vascular research. Significant advances in our understanding of vascular injury or damage as well as the interactions of blood cells and lipids with the vascular wall have allowed us to formulate new experimental strategies with subsequent clinical application in the prevention and progression of these vascular diseases.

Animals↗

Usefulness of antithrombotic therapy in resting angina pectoris or non-Q-wave myocardial infarction in preventing death and myocardial infarction (a pilot study from the Antithrombotic Therapy in Acute Coronary Syndromes Study Group).

In a prospective pilot trial of antithrombotic therapy in the acute coronary syndromes (ATACS) of resting and unstable angina pectoris or non-Q-wave myocardial infarction, 3 different antithrombotic regimens in the prevention of recurrent ischemic events were compared for efficacy. Ninety-three patients were randomized to receive aspirin (325 mg/day), or full-dose heparin followed by warfarin, or the combination of aspirin (80 mg/day) plus heparin and then warfarin. Trial antithrombotic therapy was added to standardized antianginal medication and continued for 3 months or until an end point was reached. Analysis, by intention-to-treat, of the 3-month end points, revealed the following: recurrent ischemia occurred in 7 patients (22%) after aspirin, in 6 patients (25%) after heparin and warfarin, and in 16 patients (43%) after aspirin combined with heparin and then warfarin; coronary revascularization occurred in 12 patients (38%) after aspirin, in 12 patients (50%) after heparin and warfarin, and in 22 patients (60%) after aspirin combined with heparin and then warfarin; myocardial infarction occurred in 1 patient (3%) after aspirin, in 3 patients (13%) after heparin and warfarin, and in no patient after aspirin combined with heparin and then warfarin; no deaths occurred after aspirin or after aspirin combined with heparin and then warfarin, but 1 patient (4%) died after warfarin alone; major bleeding occurred in 3 patients (9%) after aspirin, in 2 patients (8%) after heparin and warfarin, and in 3 patients (8%) after aspirin combined with heparin and then warfarin. Recurrent myocardial ischemia occurred at 3 +/- 3 days after randomization.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

New approaches to treatment of myocardial infarction.

Survival of patients with acute transmural infarction is largely related to the size of the myocardial infarction. The goal of thrombolytic therapy in acute myocardial infarction is maximal salvage of myocardium by reestablishment of flow in the occluded infarct-related artery and the establishment and maintenance of a patent infarct-related artery. Results of randomized trials show a significant reduction in mortality in patients who have undergone thrombolysis. A patent infarct-related artery, even in the absence of a change in left ventricular function, is associated with reduced mortality. The Thrombolysis in Myocardial Infarction Trial and the European Cooperative Trial showed that recombinant tissue-type plasminogen activator is superior to streptokinase in reestablishing flow in a totally occluded artery. Experimental and clinical evidence suggests that thrombolysis and thrombosis occur simultaneously, and that lysis appears to increase both thrombin and platelet activity. Effective reduction of thrombosis accelerates thrombolysis. Rethrombosis after thrombolysis is due to anchored residual thrombus, which alters the hemorrheology of blood flow and produces a highly thrombogenic substrate that is largely due to residual fibrin-bound thrombin. Platelet deposition is directly related to severity of residual stenosis and shear rate. Thrombin appears to be the most potent of the 5 potential stimulators of platelet activation during arterial thrombosis. Proper anticoagulation can play an important role in reducing thrombosis. Experimental evidence strongly supports the use of heparin during and after thrombolysis. A recently reported study shows continued reduction of residual stenosis after 1 month of vigorous anticoagulation with intravenous heparin and subsequent oral anticoagulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin↗

Antithrombotic therapy in cardiac disease: an approach based on pathogenesis and risk stratification.

An approach to the management of thrombosis and embolism in various cardiovascular disorders is discussed. This approach is based on current knowledge of pathogenesis and risk of thromboembolism. Rational therapeutic guidelines are formulated along the lines of anatomic location (arterial circulation, cardiac chambers or prosthetic valves), pathophysiology (activation of platelets or the coagulation system, or both), and degree of thromboembolic risk. With clear understanding of these factors, it may be possible to determine the most suitable platelet inhibitor or anticoagulant regimen for the individual patient, and whether these agents should be given singly or in combination.

Anticoagulants↗

Angiographic patterns of balloon inflation during percutaneous transluminal coronary angioplasty: role of pressure-diameter curves in studying distensibility and elasticity of the stenotic lesion and the mechanism of dilation.

There are few in vivo data concerning the mechanisms of balloon inflation during coronary angioplasty. To characterize how lesions dilate, videodensitometry was used to measure the diameter of the inflated balloon across 29 coronary lesions in 27 patients. Pressure-diameter curves for each lesion were derived with use of a standardized incremental inflation protocol in which pressures between 2 and 6 atm in 3 mm low profile balloons approximated normal vessel diameter. The diameter of coronary stenosis before and after angioplasty was also measured. Pressure-diameter curves showed that the most improvement in luminal caliber occurred at low inflation pressure. A distensibility factor was defined as the ratio of the amount of balloon inflation at 2 atm compared with the balloon diameter at 6 atm. Eccentric irregular lesions (n = 11) had a greater distensibility factor (0.49 +/- 0.17) than did lesions (n = 18) without this configuration (0.33 +/- 0.14) (p less than 0.02). The former were soft, presumably because of thrombus in these lesions. In addition, there were no differences in patterns of balloon inflation for lesions requiring additional inflation or for dilations resulting in an intimal crack or dissection after angioplasty. There was often a loss of luminal caliber when balloon diameter at 6 atm was compared with the diameter after angioplasty. This was defined as elasticity or recoil. There was a significant direct correlation between the amount of elasticity and the extent of balloon inflation at 6 atm (that is, lesions more fully dilated at 6 atm showed more elasticity).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗

Coronary excimer laser angioplasty: reduced complications and indium-111 platelet accumulation compared with thermal laser angioplasty.

The relative safety and thrombogenicity of pulsed excimer and thermal laser angioplasty systems were compared in 20 normal coronary artery segments in a total of seven pigs. Using similar over the wire catheter systems and laser delivery periods of 3 to 5 s, thermal laser angioplasty was achieved with a 1.3 mm metal probe heated with 10 W of continuous argon laser energy and excimer laser angioplasty was performed with a 4.5F excimer laser catheter consisting of 13 concentrically arranged 200 microns fiber optics delivering 35 to 40 mJ/mm2 of xenon chloride (308 nm) excimer laser irradiation at a repetition rate of 25 to 30 Hz and a pulse duration of 120 ns. On angiography, the incidence of vessel perforation (1 in 10 versus 3 in 10) and abrupt vessel closure (0 in 10 versus 2 in 10) was less with excimer compared with thermal laser angioplasty. Macroscopically, there was a greater incidence of mural and occlusive thrombus formation after thermal laser than after pulsed excimer laser angioplasty. Histologic examination confirmed that this thrombogenicity was associated with greater charring and coagulation necrosis of the media. Quantitative indium-111-labeled platelet deposition was significantly increased after thermal laser angioplasty (median 87.2 x 10(6)/cm length) compared with excimer-treated (0.4 x 10(6)/cm length) or control (1.2 x 10(6)cm length) segments (p less than 0.001). Thus, excimer laser angioplasty was found to result in fewer complications and, as a consequence, less thrombosis and platelet accumulation than did thermal laser angioplasty.

Angioplasty, Balloon, Coronary↗

Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation.

Vascular injury represents a critical initiating event in the pathogenesis of various vascular diseases, including atherosclerosis. This review discusses 1) the current understanding and a new pathologic classification of vascular injury; 2) the resultant cellular pathophysiologic responses, specifically, lipid accumulation, platelet aggregation, thrombus formation and smooth muscle cell proliferation; 3) the role of vascular injury in the pathogenesis of spontaneous and accelerated atherosclerosis; and 4) emerging therapeutic approaches in preventing these vascular diseases. The process of type I vascular injury (nondenuding functional injury) followed by lipid accumulation, monocyte and platelet adhesion, smooth muscle cell proliferation and resultant plaque formation represents the prevalent view of the early stages of spontaneous atherogenesis. The syndromes of accelerated atherosclerosis (namely, heart transplant atherosclerosis, coronary vein graft disease and restenosis after percutaneous transluminal coronary angioplasty) appear to share etiologic mechanisms with spontaneous atherosclerosis by means of the "response to injury" hypothesis. However, type II and type III vascular injury (denuding endothelial and intimal injury with or without medial damage) followed by thrombus and its organization by smooth muscle cell proliferation and subsequent fibrosis appear to be responsible for the vascular process. This accelerated and premature occlusive process accounts for significant morbidity and mortality in patients with these conditions. Better understanding of the nature of vascular injury and its pathophysiologic responses in these clinical situations may aid in developing therapeutic strategies for preventing these vascular diseases.

Animals↗