Biomedical subjects

L Badimon

Publications and source records attributed to L Badimon.

At least 145 records · Page 8Linked to original sources

PubMed1986

Deep arterial injury during experimental angioplasty: relation to a positive indium-111-labeled platelet scintigram, quantitative platelet deposition and mural thrombosis.

Although it is not clear why coronary occlusion and restenosis occur after successful coronary angioplasty, factors related to the procedure may influence early and late results. The possible adverse effects of a medial tear documented histologically and produced during balloon angioplasty of the common carotid arteries were studied in 30 fully heparinized (100 U/kg body weight) normal pigs. Scanning electron microscopy showed endothelial denudation and extensive platelet deposition in all dilated arterial segments. Visible macroscopic mural thrombus was present within an hour of the procedure in 29 (91%) of the 32 arteries that had a medial tear documented by histologic study; the tear produced an indium-111-labeled platelet deposition of 116.4 +/- 26.5 X 10(6)/cm2 (mean +/- SE) and total thrombotic occlusion in 2 arteries (4%). None of the 24 arteries without a medial tear had a thrombus, and the mean platelet deposition in that group was 7.0 +/- 0.5 X 10(6)/cm2 (p less than 0.0008). In 12 pigs scanned with a gamma camera, visible thrombus was associated with platelet deposition in excess of 20 X 10(6)/cm2 in 12 arteries, 9 of which had a positive indium-111-labeled platelet scintigram. Thus, arterial angioplasty causes deep arterial injury, which appears to be a major cause of mural thrombosis, heavy platelet deposition, a positive indium-111-labeled platelet scintigram and acute arterial occlusion. A positive indium-111-labeled platelet scintigram was always associated with macroscopic thrombus of at least 20 > 10(6) platelets/cm2 and underlying deep arterial injury.

Angioplasty, Balloon↗

PubMed1986

Indium-111 platelet kinetics in normal human subjects: tropolone versus oxine methods.

The effect of labeling media on the kinetics of[111In]platelets was evaluated by performing a paired crossover study in eight normal human subjects using tropolone and oxine methods. Platelets were labeled in autologous plasma with [111In]tropolone (In-tr) and in ACD-saline with [111In]oxine (In-ox) and reinjected. Starting at 1 hr, ten blood samples were obtained over an 8-day period. The in vivo platelet recovery was higher at 1 hr and throughout the 8 days of study with In-tr and the gamma camera images showed less uptake in liver and spleen than with In-ox. When platelet life-span (PLS) was estimated using all ten samples, only linear regression showed that the platelet life-span was longer with In-tr (10.7 +/- 1.5) than with In-ox (9.5 +/- 0.8). When the PLS was estimated excluding the 1-hr sample point, the life-span of platelets was significantly longer with In-tr than with In-ox based on three out of four models of curve fitting. These results demonstrate that platelets labeled with In-tr in plasma are preserved better in circulation and have equal or longer life-span than platelets labeled with In-ox in ACD-saline.

Adult↗

PubMed1985

Intracardiac thrombi and systemic thromboembolism: detection, incidence, and treatment.

The detection of thrombus in the left atrium is discussed in this chapter, along with the problem of arterial thromboembolism in patients with valvular heart disease and prosthetic heart valves. The detection and occurrence of thrombus within the left ventricle are considered, as is the frequency of thromboembolism in acute myocardial infarction, left ventricular aneurysm, and cardiomyopathy. Treatment recommendations are given for each of these medical problems.

Anticoagulants↗

PubMed1985

Balloon angioplasty. Natural history of the pathophysiological response to injury in a pig model.

The restenosis or occlusion that frequently follows balloon angioplasty is poorly understood. Thus, the pathophysiological response to angioplasty of the common carotid artery in 38 heparinized normal pigs was investigated by quantification of the 111In-labeled platelet deposition and histological and electron microscopic examination from 1 hour to 60 days after angioplasty. At 1 hour, the following findings were noted: complete endothelial denudation in all arteries, marked platelet deposition (44.7 +/- 20.7 X 10(6)/cm2), mural thrombus in seven of 10 pigs, and a medial tear extending through the internal elastic lamina in nine of 18 arteries. All nine arteries with tears had associated mural thrombus and severe platelet deposition (76 X 10(6)/cm2); in contrast, the nine arteries without a tear had no mural thrombus and much lower platelet deposition (6 X 10(6)/cm2). Necrosis of medial smooth muscle cells was evident at 24 hours. Platelet deposition remained high at 24 hours (40.5 +/- 20.6 X 10(6)/cm2), but was markedly reduced at 4 days (4.4 +/- 1.5 X 10(6)/cm2), coincident with partial regrowth of endothelium or periluminal lining cells. No significant platelet deposition was noted at 7 days, when the endothelial cell type of regrowth was largely complete. Intimal proliferation of smooth muscle cells was mild and patchy at 7 days, significantly greater and more uniform at 14 days, and unchanged at 30 and 60 days after angioplasty. Complete thrombotic occlusion occurred in four (11%) of the 38 pigs. A significant stenosis present at 30 days after angioplasty was shown by histological examination to be due to organization of mural thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

PubMed1984

The effect of lipoproteins on the synthesis of prostacyclin, von Willebrand factor and apolipoproteins A-I and A-II in cultured human endothelial cells.

Primary cultures of confluent human endothelial cells (ECM) were grown in media containing the major lipoproteins (LP) and lipoprotein deficient serum (LDS). The release of 6-keto-PGF1 alpha, von Willebrand factor (VIII RAg) and apolipoproteins (apo) A-I and A-II were investigated by radioimmunoassay. The cell-associated VIII RAg, apo A-I and apo A-II were also confirmed by fluorescein antibodies, and the synthesis of the apolipoproteins was examined by incorporation of [3H]leucine. Apo A-I and apo A-II were located and synthesized in ECM, yet only apo A-I was released into the medium. Very low density (VLDL) and low density lipoproteins (LDL) in concentrations of 50-600 micrograms/ml stimulated release of apo A-I. Stimulation of ECM for 5 min with thrombin (T) or arachidonic acid (A) did not induce apo A-I release. VIII RAg was always released into the media from ECM. The release was not affected by the lipoproteins. VIII RAg was also localized on the cell surface (VIII RAgC) and approximately 80% was released by trypsin. LDL stimulated the occurrence of factor VIII RAg on the cell surface. 6-Keto PGF1 alpha was always released into the medium and the production was stimulated by T and AA. The main lipoproteins (50-600 micrograms/ml) and apo A-I and A-II did not affect the release of 6-keto-PGF1 alpha. This study shows that endothelial cells synthesize and release proteins important for thrombogenesis and atherosclerosis. The release of apolipoproteins A-I was stimulated by VLDL and LDL, and the concentration of cell-related factor VIII RAg was stimulated by LDL.

Apolipoprotein A-I↗

PubMed1983

New "ex vivo" radioisotopic method of quantitation of platelet deposition - studies in four animal species.

We have developed a sensitive and quantitative method of "ex vivo" evaluation of platelet deposition on collagen strips, from rabbit Achilles tendon, superfused by flowing blood and applied it to four animal species, cat, rabbit, dog and pig. Autologous platelets were labeled with indium-111-tropolone, injected to the animal 24 hr before the superfusion and the number of deposited platelets was quantitated from the tendon gamma-radiation and the blood platelet count. We detected some platelet consumption with superfusion time when blood was reinfused entering the contralateral jugular vein after collagen contact but not if blood was discarded after the contact. Therefore, in order to have a more physiological animal model we decided to discard blood after superfusion of the tendon. In all species except for the cat there was a linear relationship between increase of platelet on the tendon and time of exposure to blood superfusion. The highest number of platelets deposited on the collagen was found in cats, the lowest in dogs. Ultrastructural analysis showed the platelets were deposited as aggregates after only 5 min of superfusion.

Animals↗

PubMed1982

A sensitive new method of "ex vivo" platelet deposition.

In 1978, an "in vivo" quantitative method of platelet aggregation based on the increment of weight of a rabbit tendon when superfused with flowing blood (3 ml/min) derived from a carotid artery of a cat and reentering the contralateral jugular vein was reported. TO increase the sensitivity of the method, we labeled platelets with indium-111 and reinjected them after two hours; then, with a gamma counter, we quantitated the 111In-labeled platelets deposited on the superfused rabbit tendon. Results of the radioactivity method and of the weight method were compared. We found that the 111In-labeling of platelets was more precise and reproducible method, rendering possible the use of a small amount of blood without need for reentry into the venous system.

Animals↗

PubMedDate not supplied

Effects of progestogens on thrombosis and atherosclerosis.

In contrast with past practice, current hormone replacement usually includes a combination of oestrogens and progestogens. In this article, we review the effect of progestins on haemostasis and in the development of atherosclerosis. Second-generation progestogens produce minor haemostatic changes, and in lipid metabolism they decrease the synthesis of triglycerides and very low density lipoproteins (VLDL) and stimulate hepatic lipoprotein lipase. In combination, progestogens modify the effect of oestrogens on hepatic metabolism, endothelium and platelets. Several new progestins (known as third-generation) have less effect on lipid profiles. In vessel walls, animal studies have shown that progestogens are able dose-dependently to inhibit the beneficial effect of oestrogen without significant changes in lipid concentrations. The endothelium-dependent vasoconstrictor effect of progestogens on the arterial wall has been also evaluated. Large epidemiological studies show a two-fold increase in risk of venous thromboembolism with the use of third-generation progestins. Regarding the risk of myocardial infarction, no definite evidence is yet available with the use of third-generation progestins. The clinical consequence is therefore that second-generation progestins are the first choice in prescription for first-time users.

Animals↗

PubMedDate not supplied

Pathogenesis of the acute coronary syndromes and therapeutic implications.

Atherosclerosis is characterized by the thickening and obstruction of the arterial lumen and thrombosis associated with vulnerable disrupted plaques seems to be responsible for the accelerated process of clinical syndrome presentation. Strategies to promote plaque stabilization and reduce thrombus burden have been one of the major targets of recent times. Modification of diet and lifestyle has important benefit in reducing coronary risk. Several pharmacological strategies for reducing cardiovascular morbidity and mortality have demonstrated effectiveness. Statins and angiotensin converting enzyme, fibrinolytics, inhibitors of the intrinsic coagulation cascade and anti-platelet agents have been developed to reduce the impact of atherosclerosis and inhibit thrombogenesis.

Anticoagulants↗

PubMedDate not supplied

Thrombin in arterial thrombosis.

Thrombin plays a pivotal role in the pathogenesis of arterial thrombosis. Platelet-rich thrombosis after arterial injury is dependent on the depth and extent of injury, local rheological conditions and the persistence of residual mural thrombus. The unique effects of specific thrombin inhibitors, including thrombin action on platelets and blood coagulation, demonstrated in experimental and preliminary clinical trials, suggest that specific thrombin inhibitors may be the next major advance in antithrombotic therapy of acute coronary syndromes. The importance of thrombin lies not just in acute thrombus formation following arterial injury but thrombin also contributes to smooth muscle cell proliferation by stimulating platelet secretion of growth factors (especially platelet derived growth factor, PDGF) and directly acting on smooth muscle cells. Thus, thrombin has direct effects on cell proliferation and influences the cellular synthetic mechanisms responsible for matrix protein and collagen production. The role for thrombin as a possible mitogen for vascular cells has gained support by the identification of a cellular thrombin receptor and by the recent detection of m-RNA for this receptor in human atherosclerotic plaques. Therefore, specific thrombin inhibition may also have a potential impact on the relative proliferative response of endothelial and smooth muscle cells after arterial injury such as PTCA by preventing restenosis.

Animals↗

PubMedDate not supplied

Dynamic monitoring of platelet deposition on severely damaged vessel wall in flowing blood. Effects of different stenoses on thrombus growth.

The formation of an arterial thrombus is a dynamic process that depends upon the characteristics of blood flow, the triggering substrate, and the blood components. We have developed and characterized a sensitive and specific computer-assisted nuclear scintigraphic method to study the dynamics of platelet deposition on severely damaged vessels both in vitro and in vivo in nonstenotic and stenotic flow conditions. Heparinized pig blood with Indium-111-labeled platelets was perfused for 50 minutes. Method variability in both static and flowing conditions was evaluated by Indium-111-labeled transferrin and Indium-111-labeled platelets. Positive scintigrams were obtained mainly in the presence of severe high grade stenoses on a thrombogenic substrate. Since the method is highly sensitive, computer-assisted axial dependence analysis was performed on the scintigraphic images to locate the thrombotic accumulation with respect to the area of the stenosis and to monitor the dynamic changes in platelet accumulation over time. Both in vitro and in vivo the highest level of platelet deposition occurred at the apex of the 80% stenosis, where embolization could be usually detected after 30 minutes of perfusion. This study is the first to assess the dynamics of thrombus growth in nonparallel flow streamlines such as are encountered in stenotic vessels. This method provides a new experimental tool with which to study factors affecting thrombus formation and stability.

Analysis of Variance↗

PubMedDate not supplied

Platelet deposition at high shear rates is enhanced by high plasma cholesterol levels. In vivo study in the rabbit model.

We have studied the effects of high plasma cholesterol levels on platelet-vessel wall interactions under high shear rate conditions typical of the apex of stenotic arteries (2,600 sec-1). Hypercholesterolemia was induced by feeding rabbits a 0.5% cholesterol-rich diet for 60 days. Platelet deposition was studied by use of an annular perfusion chamber and de-endothelialized abdominal rabbit aortas as substrates. After ingestion of the atherogenic diet, the experimental group of animals developed severe hypercholesterolemia, platelets became more fluid as determined by steady-state fluorescence anisotropy (p less than 0.05), and red blood cell deformability was decreased (p less than 0.001) when compared with normal controls. The fatty acid composition of platelet membranes showed an increase in the percentage of the long-chain saturated fatty acids (palmitic, C16:0, and stearic, C18:0) that may account for the lower polyunsaturated/saturated fatty acid ratio observed in the hyperlipemic animals. Total platelet deposition was significantly increased (p less than 0.05) in the hyperlipemic group as compared with the control group at 5 minutes' perfusion time, becoming less evident at 20 minutes' perfusion time. Our results suggest that the presence of hyperlipidemia may contribute to acute thrombosis by enhancing platelet-vessel wall interaction.

Animals↗

PubMedDate not supplied

Spontaneous and diet-induced coronary atherosclerosis in normal swine and swine with von Willebrand disease.

We have observed that pigs with impaired platelet function in the form of severe von Willebrand's disease (vWd) are resistant to spontaneous and to diet-induced aortic atherosclerosis. However, it has been reported that vWd pigs are susceptible to coronary atherosclerosis produced by balloon-induced injury of coronary arteries combined with an atherogenic diet. We have evaluated the development of coronary atherosclerosis in normal control (NC) and homozygous vWd pigs in two prospective studies: 1) as a spontaneous process in five NC and vWd pigs receiving a regular diet from the age of 3 months to 4 years; and 2) in nine NC and five vWd receiving a high-fat and high-cholesterol (2%) diet from the age of 3 to 9 months. All of the coronary arteries were analyzed postmortem in 5-mm sections. None of the NC nor the vWd pigs in the spontaneous study showed coronary atherosclerosis or myocardial lesions. In the study of diet-induced atherosclerosis, only one NC and one vWd pig had discrete stenoses; the stenoses affected the three coronary arteries and were significant (50% to 80%) in the NC and mild (greater than 25%) in the vWd pigs; no pigs showed myocardial lesions. Pigs with vWd are resistant to atherosclerosis of the aorta. To assess the resistance or susceptibility to coronary disease in these pigs, a longer follow-up study would be necessary.

Animals↗

PubMedDate not supplied

Aortic atherosclerosis in pigs with heterozygous von Willebrand disease. Comparison with homozygous von Willebrand and normal pigs.

We have reported that pigs with severe homozygous von Willebrand disease (vWd) are resistant to spontaneous and high fat, high cholesterol, diet-induced atherosclerosis. In this study we report the quantitation of aortic atherosclerotic plaques in three groups of pigs fed with a high fat, high cholesterol (2%) diet from age 3 to 9 months. Nine normal pigs (normal factor VIII antigen, VIII R:AG, and ristocetin co-factor, VIII:RWF) had a mean of 21% atherosclerotic involvement of the distal aortic surface and a 4.5% mean involvement of the entire aorta. Five homozygous vWd pigs (undetected VIII R:AG and VIII:RWF) had a mean of 4.2% atherosclerotic involvement of the distal aortic surface and 1.2% involvement of the entire aorta (p less than 0.01, rank sum test). Five heterozygous vWd pigs (approximately 35% VIII R:AG and VIII:RWF) had a mean of 25% atherosclerotic involvement of the distal aortic surface and 6% involvement of the entire aorta; the results were not significantly different from those in the normal pigs. We concluded that resistance to atherosclerosis is not found in animals with moderate reduction of VIII R:AG and VIII:RWF. This may have implications for humans, since in human vWd both factors are almost always present.

Animals↗

PubMedDate not supplied

Influence of arterial damage and wall shear rate on platelet deposition. Ex vivo study in a swine model.

To study the influence of blood flow on platelet interaction with selected biological surfaces, we have developed an ex vivo perfusion chamber system. In the present experiments, deendothelialized pig aorta and collagen Type I bundles from Achilles tendon were exposed to either native or heparinized pig blood for periods of time ranging from 1 to 30 minutes, and for flow rates corresponding to wall shear rates of 106 to 3380 sec-1. On the deendothelialized vessel wall, platelet deposition increased with both exposure time and wall shear rate, reaching a maximum value between 5 and 10 minutes of perfusion. At high shear rates and long exposure time (over 10 minutes), platelet deposition decreased from maximum values, indicating that some platelets were embolized by the flow. Ultrastructure analysis of the specimens showed platelet activation, spreading, and degranulation. Collagen induced a progressive accumulation of platelets following a power type curve of aggregate growth with exposure time without reaching a saturation level, even after long perfusion times (30 minutes) and high wall shear rates (3380 sec-1). In conclusion, the reactivity of the exposed materials and the local shear rate, defined by the blood flow and the patent luminal cross section, regulate platelet deposition to injured vascular wall.

Animals↗

PubMedDate not supplied

Distribution of von Willebrand factor in porcine intima varies with blood vessel type and location.

The von Willebrand factor (vWF) has been generally accepted as a marker for endothelial cells. In a systematic immunolocalization study of porcine blood vessels that used indirect immunofluorescence with a monospecific polyclonal anti-vWF and two monoclonal anti-vWFs, we observed that vWF is not universally distributed in intact, fresh endothelia. vWF is consistently localized in veins, with the exception of the pulmonic vein. In arteries, vWF is generally absent except for areas of the distal abdominal aorta, the vaso vasorum of the thoracic aorta, and the pulmonic artery. We conclude that there are regional differences in the distribution of vWF in the various endothelial beds of pigs.

Animals↗

PubMedDate not supplied

Dehydroepiandrosterone feeding prevents aortic fatty streak formation and cholesterol accumulation in cholesterol-fed rabbit.

The concentration of dehydroepiandrosterone sulfate (DHEA-S) in human plasma is higher than any other steroid. Recent evidence has suggested an inverse relationship between plasma DHEA levels and the development of coronary atherosclerosis in humans. We used the cholesterol-fed rabbit model to investigate whether DHEA feeding would diminish aortic fatty streak formation in this model. Fifteen New Zealand White rabbits were fed rabbit chow supplemented with 0.5% cholesterol (wt/wt). Seven animals were, in addition, fed DHEA, 0.5% of diet (wt/wt). Animals were sacrificed after 2 months, and the aortic involvement with fatty streaks was evaluated by computerized planimetry of Sudan IV-stained aortas and by chemical analysis of aortic wall lipids. Compared to controls, DHEA-fed animals had similar plasma levels of total, very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol, corticoids, and estrogens. DHEA-fed animals had higher plasma levels of total, VLDL, and LDL triglycerides and lower HDL triglycerides than did controls. DHEA feeding resulted in 30% and 40%, respectively, inhibition of fatty streak formation by chemical analysis and planimetry. We conclude that DHEA feeding inhibits the development of aortic fatty streaks in cholesterol-fed rabbits, independent of changes in plasma total and LDL cholesterol levels of DHEA conversion to estrogens or corticoids.

Animals↗

PubMedDate not supplied

Functional behavior of vessels from pigs with von Willebrand disease. Values of platelet deposition are identical to those obtained on normal vessels.

Vessels from normal pigs and pigs with severe von Willebrand disease were exposed for up to 30 minutes to both nonanticoagulated and heparinized blood from normal pigs in an ex vivo perfusion system. Shear rates at the vessel surface were varied over a broad physiological range, gamma w = 212 to 3380 sec-1. The deposition of 111In-labeled platelets was determined by radiometric counting. For all shear rates and exposure times investigated, the levels of platelet deposition on de-endothelialized thoracic aorta of normal and von Willebrand disease pigs were not significantly different. Thus, the functional activity of the vessels correlated with the results obtained previously by immunofluorescence. Namely, the von Willebrand factor protein in the thoracic subendothelium of normal pigs is significantly diminished or absent and is comparable to the levels observed in von Willebrand disease pigs.

Animals↗