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Biomedical subjects

Y Ikari

Publications and source records attributed to Y Ikari.

At least 19 recordsLinked to original sources
PubMed2001

Effects of cilostazol on late lumen loss and repeat revascularization after Palmaz-Schatz coronary stent implantation.

BACKGROUND: Cilostazol is an antiplatelet agent that increases the intracellular concentration of cyclic adenosine monophosphate by inhibiting phosphodiesterase III; it has been shown to reduce neointimal hyperplasia in animal balloon injury models. METHODS: One hundred thirty patients who underwent elective stenting (Palmaz-Schatz stent) were randomly assigned to cilostazol treatment 200 mg/d (n = 65) or to ticlopidine treatment 200 mg/d (n = 65). Angiographic follow-up was performed at 6 months, and clinical follow-up was continued up to 1 year. RESULTS: One sudden death and one myocardial infarction resulting from subacute occlusion were observed in the ticlopidine group. Drug adverse effects were observed in 3 patients in the cilostazol group, as opposed to 6 patients in the ticlopidine group. In the intention-to-treat analysis, 56 patients (61 lesions) in the cilostazol group and 58 patients (58 lesions) in the ticlopidine group were assessed with quantitative coronary angiography. Late loss in the cilostazol group was smaller (0.58+/-0.52 mm vs. 1.09+/-0.65 mm, P<.0001) than in the ticlopidine group. The restenosis rate was lower in the cilostazol group than in the ticlopidine group (16% vs. 33%, P = .044). The target vessel revascularization rate at 1 year was 23% in the cilostazol group and 42% in the ticlopidine group (P =.03). CONCLUSIONS: The results of this study suggest that cilostazol may be a safe medication that is effective in preventing restenosis after stent implantation.

Cilostazol↗
PubMed2001

Short-term outcome of stent implantation in saphenous vein grafts: predictors of distal embolization and restenosis.

The present study, which aimed to determine the predictors of distal embolization and restenosis after stenting for vein graft disease, retrospectively analyzed 51 consecutive patients who underwent stent implantation for diseased saphenous vein grafts. Follow-up angiography was performed 6 months after the procedure and the clinical and angiographic variables were analyzed by multivariate logistic regression to determine the predictors of distal embolization and restenosis. Initial clinical success was achieved in 49 patients, 44 of whom underwent follow-up angiography and were enrolled in the retrospective analysis. Distal embolization occurred in 6 grafts (13.6%). Multivariate analysis showed that the lesion length and the total cholesterol level were independent predictors of distal embolization. Angiographic restenosis occurred in 13 (26.5%) of 49 lesions. The minimum luminal diameter and the percent diameter stenosis after stenting were associated with the occurrence of restenosis. Multivariate analysis of lesions located in the graft body identified graft age as an independent predictor of restenosis. Distal embolization can occur after vein graft stenting, especially in patients with hypercholesterolemia and diffuse stenosis. The post-stenting minimum luminal diameter and the percent diameter stenosis are predictors of restenosis. In particular, graft age is associated with the restenosis of graft body lesions.

Aged↗
PubMed2001

An update of the Grützbalg hypothesis: the role of thrombosis and coagulation in atherosclerotic progression.

The Grützbalg analogy has obviously held up and been greatly extended by current work implicating specific molecules in inflammation and proteolysis. Still, Virchow's explanation is only partly able to account for the chronic outcome of this disease. Many of the open questions center on fibrin. For example, we do not know why fibrin forms in Virmani's eroded lesions. If the source of tissue factor in erosion is Nemerson's "stealth" particles, we may also need to rethink the source of tissue factor in plaque rupture. At the other extreme, as we all know, atherosclerotic vascular disease is a chronic disease. While multiple episodes of plaque rupture are likely to be important in this chronic process, the critical events here--scarring, narrowing of the lumen--remain largely unexplained. The data reviewed here suggest that intramural coagulation could be a critical process underlying these chronic changes.

Animals↗
PubMed2000

alpha 1-Proteinase inhibitor, alpha 1-antichymotrypsin, and alpha 2-macroglobulin are the antiapoptotic factors of vascular smooth muscle cells.

Serum depletion induces cell death. Whereas serum contains growth factors and adhesion molecules that are important for survival, serum is also likely to have antiapoptotic factor(s). We show here that the plasma proteinase inhibitors alpha1-proteinase inhibitor, alpha1-antichymotrypsin, and alpha2-macroglobulin function as critical antiapoptotic factors for human vascular smooth muscle cells. Cell survival was assured when serum-free medium was supplemented with any one or all of the above serine proteinase inhibitors. In contrast, the cells were sensitive to apoptosis when cultured in medium containing serum from which the proteinase inhibitors were removed. The antiapoptotic effect conferred by the proteinase inhibitors was proportional to proteinase inhibitory activity. Without proteinase inhibitors, the extracellular matrix was degraded, and cells could not attach to the matrix. Cell survival was dependent on the intact extracellular matrix. In the presence of the caspase inhibitor z-VAD, the cells detached but did not die. The activity of caspases was elevated without proteinase inhibitors; in contrast, caspases were not activated when medium was supplemented with one of the proteinase inhibitors. In conclusion, the plasma proteinase inhibitors prevent degradation of extracellular matrix by proteinases derived from cells. Presumably an intact cell-matrix interaction inhibits caspase activation and supports cell survival.

Apoptosis↗
PubMed2000

Alpha(1)-proteinase inhibitor, alpha(1)-antichymotrypsin, or alpha(2)-macroglobulin is required for vascular smooth muscle cell spreading in three-dimensional fibrin gel.

It is assumed that vitronectin and other adhesion molecules induce cell spreading. We found that vascular smooth muscle cells require unidentified plasma components besides adhesion molecules to spread in fibrin gel, a likely provisional matrix at wound sites. By purification, the plasma components were found to be alpha(1)-proteinase inhibitor, alpha(1)-antichymotrypsin, and alpha(2)-macroglobulin. The chemically inactivated alpha(1)-proteinase inhibitor and alpha(2)-macroglobulin lose the spreading activity, indicating that these proteins function as proteinase inhibitors but not as adhesion molecules. Not only anti-integrin (alpha(v)beta(3) and alpha(5)beta(1)) antibodies but also anti-fibronectin antibodies inhibit the cell spreading. The spreading occurs without the addition of fibronectin and integrins, suggesting that cells produce these molecules. In the absence of the proteinase inhibitors, Western blot analysis shows that the fibronectin is degraded in fibrin gel, while it is intact in the presence of the inhibitors. Thus, the proteinase inhibitors prevent adhesion molecules such as fibronectin from being degraded by a cell-derived proteinase(s) and thus play a role in cell spreading.

Animals↗
PubMed2000

Kistrin inhibits human smooth muscle cell interaction with fibrin.

Because of the lack of function-blocking anti-integrin antibodies that react with nonprimate species, the study of the role of integrins in in vivo animal models of atherosclerosis has been limited. In contrast, peptides or small molecules have shown less species specificity and thus may be better tools to use. In an attempt to identify integrin antagonists of potential use against smooth muscle response to injury, we investigated the role of human smooth muscle cell interactions with fibrin by using a panel of integrin antagonists consisting of the snake venom disintegrin, Kistrin, as well as cyclic peptides with well-defined integrin antagonists activities. We demonstrate that Kistrin, a disintegrin that inhibits beta1, beta2, beta3, and beta5 integrin interactions, had the most potent inhibitory effect. Based on our results, Kistrin or peptides with similar pan-integrin selectivity patterns are prime candidates for use as anti-integrin antagonists in further studies of atherosclerosis and restenosis.

Aorta↗
PubMed2000

New long-tip guiding catheters designed for right transradial coronary intervention.

New long-tip catheters, one for the left and the other for the right coronary artery, were designed specifically for right transradial intervention. We utilized the overbending principle to achieve more precise control of the catheters. We also analyzed principal factors involved to determine guiding catheter support considering the anatomy of the innominate artery, ascending aorta, left and right coronary arteries. Catheter shapes were designed to exploit favorable factors to compensate for mechanically disadvantageous anatomy. The catheter for the left coronary artery has an initial loop to make use of the angle between the innominate artery and the ascending aorta to introduce the catheter to the correct position to provide strong backup support. The catheter for the right coronary artery has a unique three-dimensional curve that provides sufficient backup support and compensates for the angles between the innominate artery and the proximal portion of right coronary artery to achieve coaxial engagement. The distal portions of these catheters include long tips aiming to minimize the loss of transmitted force. The performance of these catheters was studied in 143 patients with 161 lesions. Successful engagement was achieved in 138 patients with 156 lesions (97%) and coronary intervention was successful in 136 patients with 154 lesions (99%). No major complications or coronary artery dissection occurred due to use of these catheters. This study showed the present long-tip catheters to be safe and highly effective for right transradial coronary intervention. Cathet. Cardiovasc. Intervent. 49:218-224, 2000.

Angioplasty, Balloon, Coronary↗
PubMed2000

[Gamma-interferon-induced cardiomyopathy during treatment of renal cell carcinoma: a case report].

A 78-year-old woman with renal cell carcinoma and pulmonary metastasis presented with reversible cardiomyopathy induced by gamma(gamma)-interferon. She was treated with gamma-interferon twice a week since November 1996. She presented with severe acute congestive heart failure and gamma-interferon was immediately discontinued in December 1997. Left ventricular fractional shortening was 38% before admission, 12% on admission, and improved to 31% by 40 days after discontinuation of interferon together with administration of diuretics and angiotensin converting enzyme inhibitor. We restarted the same gamma-interferon regimen because it was effective against renal cell carcinoma after 47 days. She has remained well with no significant changes of cardiac function or renal cell carcinoma for almost one year.

Aged↗
PubMed2000

Human carotid artery smooth muscle cells rarely express alpha(v)beta3 integrin at sites of recent plaque rupture.

Fibrin(ogen) is the major matrix ligand for beta3 integrins. If alpha(v)beta3 is the major receptor for fibrin(ogen) on intimal smooth muscle cells, we might expect to see this integrin associated with fibrin(ogen). Eighty-four specimens obtained from endarterectomies of 14 patients were studied. Fibrin was frequently observed in carotid intima even at the non-atherosclerotic areas. As for beta1 and beta3 integrins, beta1 was predominant in intima. The alpha(v)beta3 integrin expression was less frequent than alpha5beta1, another receptor for fibrin(ogen), in diffuse intimal thickening, fibrous cap and advanced plaques. Furthermore, alpha(v)beta3 was generally negative on smooth muscle cells in recent plaque ruptures. In conclusion, we suggest more attention should be paid on abundant fibrin matrix in intima. Histologically, the alpha5beta1 integrin rather than the alpha(v)beta3 is the major receptor for fibrin in intimal smooth muscle cells.

Adolescent↗
PubMed2000

Role of alpha5beta1 and alphavbeta3 integrins on smooth muscle cell spreading and migration in fibrin gels.

Fibrin is found at sites of vascular injury and is one of the major matrix ligands for beta3 integrins. Blocking the beta3 integrin on smooth muscle cell is hypothesized as a potential target to prevent restenosis because it could inhibit cell attachment and migration into fibrin provisional matrix. Human aortic smooth muscle cells (HNB18E6E7) spread stably in plasma gels within 24 h. Cell spreading was dramatically blocked by simultaneous use of alpha5beta1 and alphavbeta3 integrin antibodies (P <0.0001), however, blocking of either integrin alone failed to inhibit spreading. GPenGRGDSPCA, which has been considered a specific alphavbeta3 antagonist, inhibited spreading at 500 microM, suggesting that the peptide blocked both alpha5beta1 and alphavbeta3. Similarly, invasive migration into fibrin gels was blocked by simultaneous use of both alpha5beta1 and alphavbeta3 antibodies, however, blocking of either integrin alone failed to effect cell migration. Another migration assay using transwell indicated similar results. In conclusion, both alpha5beta1 and alphavbeta3 integrins are responsible for smooth muscle cell spreading and migration into fibrin gels. These data suggest that blocking beta3 integrin alone would not affect smooth muscle cell interaction with fibrin.

Cell Adhesion↗
PubMed1999

Effects of a single local administration of cilostazol on neointimal formation in balloon-injured rat carotid artery.

To elucidate if locally administered cilostazol, an inhibitor of cyclic AMP phosphodiesterase III, suppresses neointimal formation in balloon-injured carotid artery of the rat, 20 mg of cilostazol was topically applied using pluronic gel at the time of balloon injury. Rats were sacrificed 14 days after balloon injury to measure the extent of neointimal formation. Plasma and tissue concentrations of cilostazol were also measured at 1, 3, 7 and 14 days after topical application. The 5-bromo-2'-deoxyuridine (BrdU, a thymidine analogue) was given intraperitoneally to detect proliferation of smooth muscle cells in the injured media at 3 days after balloon injury. At 1 day after injury, plasma and tissue concentrations were 0.147+/-0.043 microg/ml and 1380 microg/g tissue. Although the plasma concentration of cilostazol was undetectable ( < 0.02 microg/ml), a significant amount of cilostazol (46 microg/g tissue) was still detected in the tissue at the site of application even after 2 weeks. The intimal area of the injured carotid after 2 weeks was significantly smaller in the cilostazol-treated group than in the gel-treated control group (0.06+/-0.01 vs 0.15+/-0.02 mm2, P<0.001). BrdU-positive smooth muscle cells in the injured media after 3 days were also significantly fewer in the cilostazol-treated group than in the gel-treated control group (4.3+/-0.5 vs 9.1+/-0.9% of total cells, P < 0.001). These results suggest that local administration of cilostazol using pluronic gel maintains a high concentration of the drug at the application site, has an anti-proliferative effect on smooth muscle cells, and may have potential for clinical therapeutic use for the prevention of restenosis following arterial intervention.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Neonatal intima formation in the human coronary artery.

Intimal masses develop in the human coronary arteries of all humans, becoming atherosclerotic in later life either because of focal accumulation of lipid or the resulting response to injury. We evaluated the time course of formation of the intimal mass in the proximal left anterior descending coronary artery in autopsy specimens from 91 patients between 17 weeks' gestation and 23 months of postnatal age. Intima was rarely found before 30 weeks' gestation; however, the frequency with which at least some intimal cells were observed increased to 35% between 36 weeks' gestation and birth. By 3 months after birth, all patients had an intimal mass at this coronary location. The mean intima/media ratio was 0.1 just after birth and increased continuously to the second postnatal year. Replication of medial smooth muscle cells, indicated by proliferating cell nuclear antigen staining, was high before birth and decreased between birth and 2 years of age. However, the replication index of the intima remained at 2% to 5%. Thus, coronary intimal cells appearing in the perinatal period may arise by migration after replication of medial smooth muscle, as is seen in models of carotid artery balloon injury. In conclusion, formation of the coronary artery intima is a rapid process, beginning in the peripartum or postpartum period. Given the clonality of the adult lesion and the lack of proliferation in later stages of lesion formation, it is intriguing to speculate that this event may form the basis for atherosclerosis in later life.

Aging↗
PubMed1998

Increased aggregation of human platelets produced by advanced glycation end products in vitro.

Advanced glyco-oxidation end products (AGEs) generate oxygen free radicals that potentiate the development of atherosclerosis. Thus, AGEs may potentiate the aggregation of human platelets through oxidative stress. AGE-bovine serum albumin (BSA) and AGE-poly-L-lysine were evaluated for aggregation of human platelets. Superoxide in platelet-rich plasma (PRP) was measured using lucigenin-derived chemiluminescence. The platelet aggregation induced by ADP or U46619 was potentiated by preincubation with AGE-BSA, by 40% and by 59%, P < .05, respectively, vs BSA. Aggregation was increased by AGEs in a dose-dependent manner. The production of superoxide was significantly greater in PRP incubated with AGE-BSA vs BSA. The other Maillard reaction products, such as Amadori-, pentosidine-, and carboxymethyl lysine (CML)-BSA had no effect. Superoxide dismutase or indomethacin abolished the enhancing effect of AGEs on the platelet aggregation. AGEs potentiate platelet aggregation possibly with superoxide anions and prostanoids. AGE-induced potentiation of platelet aggregation may be involved in the development of atherosclerosis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

Novel guide catheter for left coronary intervention via a right upper limb approach.

We designed a novel guide catheter specifically for interventions to the left coronary artery via a right upper limb approach. The catheter has a novel first loop design which utilizes the angle between the right subclavian and innominate arteries for support. The first loop introduces the catheter into the correct position and generates powerful and coaxial back-up power. We report successful implantation of Palmaz-Schatz stents in five cases using this 6 Fr. catheter.

Aged↗