Molecular modelling study of the role of cholesterol in the stimulation of the oxytocin receptor.

Cholesterol, an integral component of membranes in Eucaryota, is a modifier of membrane properties. In vivo studies have demonstrated that cholesterol can also modulate activities of some G protein-coupled receptors (GPCRs), which are integral membrane proteins. This can result either from an effect of cholesterol on the membrane fluidity or from specific interactions of the membrane cholesterol with the receptor, as recently demonstrated for the cholecystokinin type beta (CCKRbeta) or the oxytocin receptor (OTR). Using molecular modelling, we studied conformational preferences of cholesterol and several of its analogues. Subsequently, we simulated the distributions of their preferred conformations around the surface of OTR, CCKRbeta and a chimeric oxytocin/cholecystokinin receptor. Consequently, we suggest residues on the surface of OTR which are potentially significant in the OTR/cholesterol interaction.

Proliferative response of human and minipig smooth muscle cells after coronary angioplasty to growth factors and platelets.

OBJECTIVES: Platelets aggregating at the site of angioplasty, shown to be a potent proliferative stimulus for cultured smooth muscle cells (SMC), could contribute to proliferation after angioplasty. METHODS: SMC were cultivated from human aorta and restenosed coronary lesions as well as from minipig aorta and from normal and post angioplasty coronary artery segments (n = 6 per source). 3H-thymidine incorporation was used as a measure of proliferation. RESULTS: 3H-thymidine incorporation varied greatly after passage 7 in all cell lines, but was significantly higher in SMC from human coronary restenosed lesions compared to those from human aorta and minipig coronary post angioplasty segments in passage 2 (44 +/- 6.4 x 10(3) cpm/5000 SMC vs 20 +/- 3.9 and 12.1 +/- 2.1). However, all SMC exhibited a dramatic increase of 3H-incorporation after passage 7. Growth factors stimulated 3H-thymidine incorporation either dose dependently (PDGF-BB and bFGF) or only very modestly (PDGF-AA, EGF, IGF-1). The most potent stimulation was seen with PDGF-BB, 50 ng/ml, and was 17 +/- 6% (human restenosed) and 16 +/- 8% (minipig post angioplasty) of the values observed after stimulation with 10% fetal calf serum. The most effective combination of growth factors, PDGF-BB (50 ng/ml) + bFGF(20 ng/ml) + IGF-1 (50 ng/ml), produced a 3H-thymidine incorporation of 44 +/- 10% (human restenosed) and 42 +/- 11% (minipig post angioplasty) of FCS values. Stimulation by isolated platelets was dose dependent and significantly higher: 75 +/- 19% and 70 +/- 15% of FCS values for those SMC. CONCLUSIONS: 1) SMC from all sources studied exhibit significant changes of proliferation with increasing passages, excluding the comparability of data obtained with cells in different passages. 2) Data obtained with SMC from any source might not apply for SMC from human coronary restenosed lesions. 3) Currently tested growth factors do not fully account for the proliferative effect of platelets on cultured SMC.

Recoil following Wiktor stent implantation for restenotic lesions of coronary arteries.

The purpose of this study was to determine acute recoil of the vessel wall immediately after Wiktor stent implantation in native coronary arteries of 77 consecutive patients and to assess whether there was compression or "late recoil" of the stent itself at long-term follow-up. Furthermore, the relationship between recoil and a number of clinical, angiographic, and procedural variables was studied in addition to the relation between acute recoil renarrowing or restenosis was assessed. All angiograms were analyzed with the Cardiovascular Angiography Analysis System using automated edge detection. Acute recoil was defined by the difference between the mean diameter of the fully expanded balloon on which the stent was mounted and the mean diameter of the stented segment. Late recoil was calculated by comparing the mean diameter of the stent itself immediately after implantation and at follow-up without opacification of the vessel. Acute recoil amounted to 0.25 +/- 0.32 mm or 8.2%. Multivariate analysis identified sex (coefficient = -0.20, p = 0.04) and stent/artery ratio (coefficient = 0.99, p = 0.0001) as the only independent predictors of acute recoil. "Late recoil" of the stent itself was not observed. The overall difference between the mean diameter of the stent itself immediately after implantation and at follow-up was -0.15 +/- 0.33 mm, suggesting an overall increase in diameter of 5.0%. There was no relation between acute recoil and late restenosis. On the contrary, there was a trend towards a greater degree of recoil in patients without restenosis. Moreover, linear regression analysis disclosed a weak but negative correlation between acute recoil and a loss in minimal luminal diameter (coefficient: -0.55, p = 0.04). The Wiktor stent effectively scaffolds the instrumented vessel. Only a minimal amount of acute recoil was noted, which did not contribute to late luminal renarrowing or restenosis. In addition, no late compression of the stent itself was observed. These data suggest that tissue ingrowth into the lumen of the stented segment is the main cause of late luminal renarrowing after stent implantation.

Autofluorescence spectroscopy using a XeCl excimer laser system for simultaneous plaque ablation and fluorescence excitation.

Laser-induced fluorescence may be used to guide laser ablation of atherosclerotic lesions. This study was performed to evaluate arterial autofluorescence spectroscopy in vitro using a single XeCl excimer laser (308 nm) for simultaneous tissue ablation and fluorescence excitation. The laser beam was coupled to a 600-microns silica fiber transmitting 40-50 mJ/mm2 per pulse. The fluorescence radiation emanating retrogradely from the fiber was collected by a concave mirror spectroscopic analysis over a range of 321-657 nm. The arterial media (n = 26), lipid plaques (n = 26), and calcified lesions (n = 27) of aortic specimens from ten human cadavers were investigated in air, saline, and blood. Whereas the spectrum of calcified lesions changed with the surrounding optical medium, the other spectra remained constant. In air and blood, the spectra of arterial media, lipid plaques, and calcified lesions could be differentiated qualitatively and quantitatively (P < 0.0001). In saline, there was no clearcut spectroscopic difference between lipid plaques and calcified lesions. However, normal arterial media and atherosclerotic lesions (lipid plaques plus calcified lesions) could still be discriminated. Thus spectroscopy and plaque ablation can be combined using a single XeCl excimer laser. These encouraging results should stimulate further studies to determine the potential use of this approach to guide laser angioplasty in humans.

Cutting balloon coronary angioplasty--initial clinical experience.

The success of percutaneous transluminal coronary angioplasty is limited by acute occlusion and late restenosis. In 25 patients (20 men, 5 women, age range 36-81 years) coronary angioplasty was performed using a new cutting balloon into which 3-4 longitudinally orientated blades are incorporated so as to reduce the rate of severe dissections. In 12 patients stenoses were reduced from 83.9 +/- 7.8% to 28.4 +/- 10.7% (mean +/- SD) by the cutting balloon alone, using predilatation with a small conventional balloon in two cases. Thirteen other patients were additionally dilated with a conventional balloon because of a residual stenosis > 50% after cutting balloon angioplasty. Here the stenoses could be reduced from 78.1 +/- 8.7% to 29.1 +/- 11.3%. Six months follow-up angiography in 14 patients showed > 50% restenosis in two of seven patients dilated with a conventional balloon in addition to the cutting balloon, and in one of seven patients dilated with the cutting balloon alone but predilated with a small conventional balloon. These results show that coronary angioplasty by the new cutting balloon results in a stenosis reduction comparable with conventional balloons at a low complication rate. Available 6 months follow-up data show three restenoses in patients either pre- or postdilated by a conventional balloon and none in stand-alone cutting balloon cases.

Angiographic predictors of recurrence of restenosis after Wiktor stent implantation in native coronary arteries.

Intracoronary stenting has been proposed as an adjunct to balloon angioplasty to improve the immediate and long-term results. However, late luminal narrowing has been reported following the implantation of a variety of stents. One of the studies conducted with the Wiktor stent is a prospective registry designed to evaluate the feasibility, safety and efficacy of elective stent implantation in patients with documented restenosis of a native coronary artery. To identify angiographic variables predicting recurrence of restenosis, the angiograms of the first 91 patients with successful stent implantation and without clinical evidence of (sub)acute thrombotic stent occlusion were analyzed with the Computer Assisted Angiographic Analysis System using automated edge detection. The incidence of restenosis was 44% by patient and 45% by stent according to the 0.72 mm criterion, and 30% by patient and 29% by stent according to the 50% diameter stenosis criterion. The risk for restenosis for several angiographic variables was determined using an univariate analysis and is expressed as odds ratio with corresponding confidence interval. The only statistically significant predictor of restenosis was the relative gain when it exceeded 0.48 using the 0.72 mm criterion (odds ratio 2.7, 95% confidence interval 1.1-6.4). Furthermore, the relation between the relative gain (increase in minimal luminal diameter normalized to vessel size) as angiographic index of vessel wall injury and relative loss (decrease in minimal luminal diameter normalized to vessel size) as index of neointimal thickening was analyzed using a linear regression analysis. When using the categorical approach to address restenosis, there is an increased risk for recurrent restenosis when the relative gain exceeds 0.48. The continuous approach underscores this concept by indicating a weak but positive relation between the relative gain and relative loss.

[Coronary angioplasty with controlled longitudinal dissection. Initial clinical results using a new cutting balloon]. / Koronarangioplastie mit kontrollierter Längsdissektion. Erste klinische Ergebnisse mit einem neuen Schneideballon.

A recently developed cutting balloon was used for coronary angioplasty in 21 patients (4 women, 17 men; mean age 57.6 [36-81] years) with coronary heart disease (angioplasty of the right coronary artery in 4, of the circumflex branch in 4, and of the anterior interventricular branch in 13 patients). The balloon contains 3-4 longitudinally arranged metal cutters to prevent uncontrolled vessel tears. An average stenosis reduction from 84 +/- 8.6% to 30 +/- 10.6% was achieved in ten patients. In the eleven others a second dilatation with a conventional balloon was necessary because of a residual stenosis of over 50% after the first dilatation with the cutting balloon. This reduced the original stenosis from 78.6 +/- 9.4% to 30.4 +/- 9.9%. Complete occlusion at the place of previous dilatation occurred in one patient 14 hours after the procedure, due to a dissection which required a stent implantation. These preliminary results suggest that the cutting balloon can achieve a stenosis reduction similar to that with a conventional balloon.

Immune thrombocytopenia associated with hemorrhagic diathesis due to ibuprofen administration.

Acute thrombocytopenic purpura temporally related to the oral administration of ibuprofen developed in a patient with ankylosing spondylitis. Clinical manifestations, with sudden onset occurring within 12 h of drug ingestion and rapid increase of platelet counts following discontinuation of the drug, were characteristic of an antibody-mediated immune pathomechanism. Immunological studies demonstrated IgM and IgG antibodies in the patient's serum that were capable of binding to allogenic platelets in the presence of a metabolite preparation. This finding suggested that an ibuprofen metabolite, rather then the drug itself, was the antigenic agent responsible for the immune reaction. Despite its widespread therapeutic use, ibuprofen has not been described previously as causing immune-mediated thrombocytopenia.

Stent wire cutting during coronary directional atherectomy.

Directional atherectomy represents one potential approach for the treatment of restenosis in stented coronary arteries. In this case report we demonstrate an important pitfall of this angioplasty technique for stent restenosis--inadvertent entanglement of the stent wire in the device. While cutting and removal of part of the wire was achieved in the case presented, this potential adverse event limits the applicability of directional atherectomy for restenosis in coronary stents.

Fractured strut of Björk-Shiley 70 degrees convexo-concave mitral valve prosthesis found in left coronary artery. Use of a portable transcutaneous cardiopulmonary bypass system for successful valve replacement.

Strut fractures followed by disk escape of Björk-Shiley convexo-concave valve prostheses are a well-known problem. This article discusses the case of a successfully treated patient who was admitted to our institution with extreme and prolonged cardiogenic shock. The strut was dislodged into the main stem of the left coronary artery and the disk into the iuxtarenal abdominal aorta. The intent of this report is, in particular, to illustrate the management problems. Immediately after diagnosis, circulation and oxygenation were ensured by use of a portable cardiopulmonary bypass support (CPS) system whose circulation lines were introduced subcutaneously. Thus the transfer to the operating room and the surgical intervention were able to start under controlled conditions. The disk was removed by Fogarty catheter manoevre without any problems during the same operation, using a transpericardial access to the descending thoracic aorta. In our opinion, the primary insertion of the CPS and the avoidance of an additional laparotomy in disk removal help promote the survival of such critically ill patients.

Aorto-coronary artery to coronary vein fistula with the potential of coronary steal as complication of saphenous vein jump bypass graft.

We report the first documented case of an iatrogenic aorto-coronary artery to coronary vein fistula secondary to an aortocoronary saphenous vein jump bypass graft inadvertently anastomosed to a coronary vein. Angiographic and oximetric results of left and right cardiac catheterization--including direct catheterization of the anastomosed coronary vein--as well as clinical data with a four-year follow-up are presented. The role of surgery, percutaneous transcatheter embolization, and conservative treatment is discussed in this unique case with the potential of a coronary steal phenomenon.

Platelet and fibrin deposition on coronary stents in minipigs: effect of hirudin versus heparin.

OBJECTIVES: The present study was designed to test the hypothesis that the direct thrombin hirudin is more efficient than heparin in reducing thrombus formation after coronary stenting. BACKGROUND: Despite aggressive anticoagulation, subacute thrombosis of coronary stents is a major complication associated with these new devices. METHODS: In 19 minipigs indium-111-labeled thrombocytes and iodine-125-labeled fibrinogen were injected 14 to 19 h before coronary implantation of tantalum balloon-expandable stents. In group 1 (n = 6, seven stents), a bolus of heparin (100 U/kg body weight) was given before stenting. Group 2 (n = 6, 11 stents) received both dextran (500 ml) and heparin (a 100-U/kg bolus followed by a continuous infusion of 50 U/kg per h). In group 3 (n = 7, 13 stents), hirudin (recombinant desulphatohirudin HV 1 [CGP 39393] [1 mg/kg]) was given before stent implantation, followed by an infusion of 1 mg/kg per h. All animals were pretreated with aspirin (250 mg intravenously). RESULTS: Activated partial thromboplastin time was prolonged to > 1.8 times control values in groups 2 and 3. Histologic examination after perfusion fixation 12 h after stenting showed a variable extent of thrombus on all stents. Medial tear was observed in three stents in group 1, six stents in group 2 and six stents in group 3. The number of platelets on all stents averaged 116.2 (range 22 to 522) x 10(6) in group 1, 64.3 (range 11 to 169) x 10(6) in group 2 and 19.7 (range 9 to 38) x 10(6) in group 3 (p < 0.05 vs. group 1 and vs. group 2). The increase in platelet deposition, associated with medial tear in all groups, was lowest in the hirudin group. Similarly, fibrin deposition was lowest on stents in hirudin-treated animals. CONCLUSIONS: Recombinant hirudin significantly reduces platelet and fibrin deposition on coronary stents compared with the reduction achieved with combined heparin, dextran and aspirin.

[Vital recognition of complete occlusion of the left main coronary artery]. / Przyzyciowe rozpoznanie zupelnego zamkniecia pnia lewej tetnicy wiencowej.

Left main coronary artery occlusion is found in about 0.05% of all coronary arteriograms. In this case report left main occlusion was associated with a dominant right coronary artery and good collaterals to the circumflex and left anterior descending coronary arteries, which seems to be essential for survival in this lesion. Our case belongs to the minority of patients who have survived a myocardial infarction in the presence of left main occlusion.

Antiproliferative effects of a c-myc antisense oligonucleotide on human arterial smooth muscle cells.

The effects of a c-myc antisense phosphorothioate DNA oligonucleotide were assessed on the proliferation rate of human arterial smooth muscle cells (HSMCs). Compared to a control oligonucleotide the antisense oligonucleotide suppressed the proliferation of HSMCs in a concentration-dependent manner without a major cytotoxic effect. Outgrowth of HSMCs from media explants was significantly inhibited as well. Induction of c-myc expression by serum stimulation of cells was blunted by the antisense oligonucleotide, as shown by immunoblotting. These results demonstrate that c-myc expression is an essential factor for proliferation of HSMCs after growth stimulation, and they show the potential of antisense technology for modulating gene expression of HSMCs in vitro.

Low-molecular-weight heparin reduces neointimal proliferation after coronary stent implantation in hypercholesterolemic minipigs.

BACKGROUND: Intracoronary stents have been suggested as a method of reducing the restenosis rate after balloon angioplasty. Proliferation of vascular smooth muscle cells is a major contributing factor to the restenosis process. Heparin and some of its derivatives have been shown to inhibit smooth muscle cell proliferation. We investigated the effect of low-molecular-weight heparin on the proliferative response after implantation of a balloon-expandable tantalum stent in previously deendothelialized coronary artery segments of hypercholesterolemic minipigs. METHODS AND RESULTS: Minipigs were fed a diet containing 2% cholesterol, starting 1 month before balloon denudation of the endothelium in a coronary artery. One month later, a stent was implanted at this site. Animals were killed after 4 weeks (group 1, n = 6) or 3 months (group 2, n = 6). Animals in group 3 (n = 6), also followed for 4 weeks after stenting, received subcutaneous low-molecular-weight heparin at a dose of 200-300 units/kg anti-factor Xa activity per day in addition to the chronic acetylsalicylic acid (100 mg/day) also administered to groups 1 and 2. Eighteen of 22 animals survived to the end of the study. Angiography revealed patent stents in all surviving animals. In group 1, histological analysis showed extensive neointimal proliferation around stent struts. Maximal neointimal thickness seen in group 1 averaged 0.93 +/- 0.11 mm, was lower after 3 months (0.8 +/- 0.14 mm) in group 2, but was significantly reduced (0.44 +/- 0.18 mm, p less than 0.01) in group 3. CONCLUSIONS: These data show a significant reduction of the neointimal proliferative response to coronary stent implantation by low-molecular-weight heparin.

Coronary angioplasty in patients with previous coronary artery bypass grafting.

Between 1982 and 1990, in 134 patients with prior coronary artery bypass grafting and recurrent angina, repeat coronary angiography and balloon angioplasty of stenoses in grafts or native arteries were attempted. Mean age of grafts was 45.6 months, range three days to twelve years. At the time of angioplasty, 6 patients had one-vessel-disease, 33 had two-vessel-disease, and 95 had three-vessel-disease. A total of 182 lesions were dilated: 55 venous grafts, 3 internal mammary artery grafts, and 124 native vessels. Forty-nine of 55 (89%) venous grafts could be successfully dilated, and in 3 internal mammary artery grafts, a stenosis reduction greater than 50% was achieved. In 65 of 88 (74%) grafted native arteries, dilation success was achieved. Twenty-seven of 36 (75%) patients with prior bypass surgery to other arteries had successful angioplasty of nongrafted native arteries. Three patients underwent emergency bypass surgery after dissection and acute occlusion: one of them died in cardiogenic shock secondary to acute myocardial infarction. The angiographic success rate in grafts was slightly higher than in native arteries (90% vs 74%). These data indicate that percutaneous transluminal coronary angioplasty in patients after bypass surgery is possible at a low risk (3%) and constitutes an effective therapy in symptomatic patients.

Restenosis after excimer laser angioplasty of coronary stenoses and chronic total occlusions.

In an open clinical study, a xenon-chloride excimer laser was used for angioplasty of coronary stenoses (n = 48) and chronic total occlusions (n = 56) in 104 patients. Multifiber catheters (4.0F to 5.5F) transmitted 37 to 120 mjoules/mm2 of fiber surface. Excimer laser angioplasty was successful in 43 patients with a stenosis (89%), followed by percutaneous transluminal coronary angioplasty in 21 patients (49%) to reduce the stenosis to less than 50% luminal narrowing. In 39 patients (70%) with a chronic occlusion (age 1 to 14 months), recanalization by means of excimer laser angioplasty was successful, with subsequent percutaneous transluminal coronary angioplasty performed in 23 patients. Major complications included one perforation, one acute occlusion, and two severe dissections. Six-month angiographic follow-up examinations after successful angioplasty were completed in 40 patients (98%) with stenoses and 34 (94%) with occlusions. Restenosis (greater than 20% decrease in luminal diameter) occurred in 13 patients (33%) with stenoses and in 16 patients (47%) after angioplasty of a chronic occlusion. These long-term results indicate that restenosis after excimer laser angioplasty of coronary stenoses and chronic total occlusions is similar to reported results of conventional balloon angioplasty.

Wiktor stent implantation in patients with restenosis following balloon angioplasty of a native coronary artery.

Intracoronary stenting has been introduced as an adjunct to balloon angioplasty aimed at overcoming its limitations, namely acute vessel closure and late restenosis. This study reports the first experience with the Wiktor stent implanted in the first 50 consecutive patients. All patients had restenosis of a native coronary artery lesion after prior balloon angioplasty. The target coronary artery was the left anterior descending artery in 26 patients, the circumflex artery in 7 patients and the right coronary artery in 17 patients. The implantation success rate was 98% (49 of 50 patients). There were no procedural deaths. Acute or subacute thrombotic stent occlusion occurred in 5 patients (10%). All 5 patients sustained a nonfatal acute myocardial infarction. Four of these patients underwent recanalization by means of balloon angioplasty; the remaining patient was referred for bypass surgery. A major bleeding complication occurred in 11 patients (22%): groin bleeding necessitating blood transfusion in 6, gastrointestinal bleeding in 3 and hematuria in 2. Repeat angiography was performed at a mean of 5.6 +/- 1.1 months in all but 1 patient undergoing implantation. Restenosis, defined by a reduction of greater than or equal to 0.72 mm in the minimal luminal diameter or a change in diameter stenosis from less than to greater than or equal to 50%, occurred in 20 (45%) and 13 (29%) patients, respectively. In this first experience, the easiness and high technical success rate of Wiktor stent implantation are overshadowed by a high incidence of subacute stent occlusion and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS)