Biocompatibility of polymer-coated oversized metallic stents implanted in normal porcine coronary arteries.

Polymer coatings have been suggested to decrease the thrombogenicity of metallic intravascular stents. The purpose of the present study was to investigate the intimal response to two different polymers when used as coatings for stents implanted in normal porcine coronary arteries. Non-articulated stainless steel-slotted tube stents were coated with either a biodegradable poly(organo)phosphazene with amino-acid ester side groups or a biostable polyurethane prepared from an amphiphilic polyether, dephenylmethane-4,4'-diisocyanate and butane diol as chain extender. In order to induce vascular wall injury, the stents were deployed using an oversized balloon. At 6 weeks follow-up, the angiographic luminal diameter measured in four polyurethane-coated stents and in six bare metallic stents was similar and 20% less than immediately post-stenting. However, in four polyphosphazene-coated stents the difference was 65% (P = 0.01 when compared to bare metal). At post-mortem morphometry the degree of luminal area stenosis was also similar in polyurethane-coated and in bare metallic stents (32 +/- 7.6% vs. 39 +/- 14%, NS) but reached 81 +/- 19% in polyphosphazene-coated stents (P < 0.03 when compared to bare metal). Thus, poly(organo)phosphazene induced a more pronounced histiolymphocytic and fibromuscular reaction than amphiphilic polyurethane, which appeared to be promising as biocompatible stent coating and, consequently, as a potential carrier for vasoactive drugs.

Usefulness of Nisoldipine for prevention of restenosis after percutaneous transluminal coronary angioplasty (results of the NICOLE study). NIsoldipine in COronary artery disease in LEuven.

The NIsoldipine in COronary artery disease in LEuven (NICOLE) study investigates (1) whether nisoldipine, a dihydropyridine calcium antagonist, reduces the progression of minor coronary arterial lesions in the long term, and (2) whether it reduces the restenosis rate after successful percutaneous transluminal coronary angioplasty (PTCA). The NICOLE study is a single-center, randomized, double-blind trial in 826 patients, who underwent a successful PTCA. Nisoldipine 40 mg coat-core or placebo was started the morning after the procedure and continued for 3 years. All coronary arterial segments were measured on preprocedural angiogram and on the second follow-up angiogram at 3 years. On the first follow-up angiogram at 6 months only the dilated segments were measured. Although the study is still ongoing until the primary end point is reached, we report in this study the angiographic restenosis data as well as the clinical events observed at 6-month follow-up. The per-protocol population consisted of 646 patients. Restenosis, defined as a > or =50% loss of the initial gain (National Heart, Lung, and Blood Institute criterion IV) occurred in 49% and 55% of the 308 nisoldipine-treated and the 338 placebo-treated patients, respectively (p = NS). At follow-up, the rates of death and myocardial infarction were low and similar in both groups, but in the nisoldipine group, less patients required early coronary angiography (18% vs 26%, p = 0.006) and subsequent revascularization procedures (32% vs 41%, p = 0.057). Thus, nisoldipine did not significantly reduce the angiographic restenosis rate after PTCA, but reduced the number of repeat revascularization procedures, which may be due to its antianginal action.

Anti-myosin humoral immune response following cardiac injury.

A sensitive and highly specific ELISA assay was developed to determine the anti-myosin humoral immune response (AMA) in various heart diseases: acute viral myocarditis, infective endocarditis, acute myocardial infarction, and valve and coronary bypass surgery. The mean study entry AMA titer of each patient group was already significantly increased compared with age matched controls. During further follow-up (90 d) all the groups except for endocarditis showed a significant increase of AMA titer compared with their entry titer. Anti-myosin antibody titer were higher after cardiac surgery than after myocardial infarction or inflammatory heart disease. These results suggest that anti-myosin immune response is not limited to infectious processes in which the pathogen induces antibodies which cross-react with heart constituents but is merely caused by direct cardiac injury. Myosin as a major compound of heart cellular proteins turned out to be a good candidate to trigger immune response after cardiac injury.

Activation energy and lectin affinity chromatography of gamma-glutamyltransferase as a marker for enzyme heterogeneity.

Lectin affinity chromatography of gamma-glutamyl transferase (GGT,EC 2.3.2.2) is able to detect differences in the carbohydrate moiety of the enzyme. Binding of tissue GGT towards lectins is significantly different from serum GGT, showing increased galactosylation in tissue forms. Kidney GGT is less glycosylated than GGT from other tissues (liver, pancreas, prostate, vesiculae seminales). Increases in sialic acid content of GGT are associated with an increase in the activation energy of the catalyzed reaction. Differences in galactose, fucose and N-acetylhexosamine content induce much smaller effects on activation energy. In liver diseases, serum GGT is characterized by an altered affinity against lectins recognizing galactose, fucose and N-acetyglucosamine and by increased activation energy. In patients with liver disease, use of fixed temperature conversion factors can lead to erroneous calculations of serum GGT enzyme activity (errors up to 13.3%).

Enzymatic erythrocyte creatine determinations as an index for cell age.

Creatine concentration in red blood cells was determined after ammoniumsulfate precipitation on a clear hemoglobin-free filtrate with a new enzymatic assay making use of bacterial creatinase. The method described is more specific than Griffiths' method and can easily be mechanised and adapted for use in a routine laboratory using classical automated equipment. By contrast with Griffiths' method no significant interferences of amino acids and creatine-like molecules were found. Reference values for this method were 0.379 +/- 0.076 mmol/l. In patients with high turnover of erythrocytes, e.g. haemodialysis patients (0.529 +/- 0.122 mmol/l), and renal insufficiency patients (0.565 +/- 0.145 mmol/l), significantly increased creatine concentration in erythrocytes were observed. Low erythrocyte creatine concentrations were found in chronic ambulatory dialysis patients (0.311 +/- 0.042 mmol/l).

Lectin-affinity chromatography of serum gamma-glutamyltransferase in liver disease.

The variation of the carbohydrate chain of gamma-glutamyltransferase was studied in 45 liver patients by means of lectin affinity chromatography. Five lectins were used: concanavalin A, Ricinus communis I and II, Maclura pomifera and Ulex europaeus agglutinin. The binding towards Con A was shown to be independent from the binding towards the other lectins. Parallel variations of binding results against the galactose- and fucose-recognizing lectins were obtained. In liver steatosis, the binding results were comparable to those obtained in normal patients. Cirrhosis and metastasis patients showed a decreased binding towards Con A, while the binding against the various galactose- and fucose-recognizing lectins was increased. After neuraminidase treatment, an increased affinity towards all lectins was observed. However, differences in RCA I and RCA II binding between patients and controls still persisted. Besides sialic acid, also galactose and fucose residues contribute to serum gamma-glutamyltransferase heterogeneity.

Post-transcriptional modification of serum creatine kinase in infected intensive care patients.

Low creatine kinase (CK) activities in serum are associated with high fatality rates in intensive care patients. The underlying mechanisms for this phenomenon were investigated. No correlation was found with other biochemical markers of inflammation (CRP, alpha-1 acid glycoprotein, alpha-2 macroglobulin). In the patients' serum a factor is described which is capable of increasing the activation energy of normal CK-MM, indicating molecular changes in CK-structure. This factor is likely to be an enzyme which is present in liver tissue and in fibroblasts. Similar results were obtained after in vitro treatment of normal serum samples with arylsulfatase. Furthermore, bacterial strains isolated in the serum of intensive care patients were found to alter human CK structure. In the investigated patient group, changes in CK activation energy are influenced by serum factors other than carboxypeptidase N activity.

Intraarterial biocompatibility of polyethylene terephthalate self-expandable stents implanted in porcine peripheral arteries.

RATIONALE AND OBJECTIVES: We tested deployment feasibility and intraarterial biocompatibility of polyethylene terephthalate (PET) self-expandable vascular stents in a porcine peripheral artery model. METHODS: To assess the thrombogenicity and neointimal response to oversized PET self-expandable stents, we implanted 10 stents in porcine common iliac arteries, followed by a 6-mm balloon inflation to 6 atm. RESULTS: All pigs survived until the study termination 6 weeks after stent implantation. Control angiography revealed stent closure in three pigs. Minimal stent luminal diameter (MSLD) was measured using a semiautomated edge detection algorithm. The difference in MSLD after stent implantation and at control after 6 weeks was not significant (4.9 +/- 0.5 mm-->4.7 +/- 1.0 mm). Histopathologic examination showed signs of thrombotic occlusion and revascularization in occluded stents. In patient stents only a mild fibromuscular neointimal response was seen. CONCLUSION: PET self-expandable stents implanted in porcine iliac arteries are possibly thrombogenic but do not lead to a significant neointimal response.

Cutaneous periarteritis nodosa. A case report.

We studied a patient with severe ulcerations on the lower limbs due to cutaneous periarteritis nodosa. Chronic relapsing course during more than 12 years with no systemic involvement was documented.

Immediate and 6-month follow-up results of coronary angioplasty for restenosis: analysis of factors predicting recurrent clinical restenosis.

To determine the results of coronary angioplasty for a first restenosis, the clinical, anatomic, and procedural data of 400 consecutive patients were compared with the data of 507 consecutive patients undergoing a first angioplasty. After angioplasty for restenosis, emergency redilatation had to be performed in only 0.7% of the patients versus 3.1% of the control group (p = 0.02); nevertheless, the major in-hospital event (death, myocardial infarction, emergency coronary surgery, cerebrovascular accident) rate for patients was only slightly lower (3.3% vs 4.2%, p = NS). During the 6-month follow-up period, there were no cardiac deaths and only two myocardial infarctions in the study group, but recurrent ischemia was more frequent (37% vs 31%, p = 0.05) and resulted in considerably more elective coronary surgery (16% vs 2.6%, p = 0.001). In the study group, stepwise discriminant analysis revealed four variables significantly related to the occurrence of a second restenosis: time interval between first and second angioplasty, male gender, severity of angina, and complexity of the restenotic lesions. However, their individual predictive power was low. In conclusion, compared with angioplasty for primary lesions, angioplasty for restenosis was associated with fewer periprocedural complications and, after a 6-month follow-up, serious cardiac events were almost nonexistent but recurrent ischemia was more frequent.

Implantation of an endoluminal prosthesis at the distal anastomosis of a bypass graft for abrupt closure following balloon angioplasty.

A coronary Wallstent was implanted in a 10-year-old saphenous vein bypass graft following a PTCA that was complicated by abrupt closure. Anterograde flow was restored and no myocardial necrosis resulted. One week later, bypass surgery was performed due to a bleeding complication associated with the anticoagulation regimen.

Comparison of clinical complications, angiographic results, and device usage of coronary angioplasty using low- and high-compliance balloons.

We randomized 800 patients in a prospective study comparing the angiographic results, device usage and in-hospital outcome of balloon angioplasty of primary stenoses of native coronary vessels with low-compliant and highly compliant balloons. The cumulative incidence of prespecified clinical endpoints was 8.0% in both treatment groups. The primary angiographic success rates were 83.9% and 78.9% in the high- and low-compliance group, respectively (P = 0.05). For the lesions dilated with one study balloon only, the quantitative angiographic findings were virtually identical in the two treatment groups. The total number of dissections was slightly but not significantly higher in the lesions treated with a highly compliant balloon. The global usage of angioplasty balloons was similar in both treatment groups. We conclude that, in general, there is no objective reason to prefer one balloon material to another on the basis of its compliance characteristics.

Mass concentration and activity concentration of creatine kinase isoenzyme MB compared in serum after acute myocardial infarction.

We compared three current methods (immunoinhibition, "Isomune-CK" immunoprecipitation, and the Tandem-E CKMB II immunoenzymometric assay) for determination of creatine kinase (CK; EC 2.7.3.2) isoenzyme MB in serum. Although results inter-correlated well, the immunoinhibition assay gave higher activity values. Atypical CK forms did not interfere with the immunoprecipitation and immunoenzymometric methods. In acute myocardial infarction the catalytic properties of CK decreased with the enzyme's age, as reflected by a steady increase in activation energy of the catalyzed reaction. In septicemia patients with very low CK and CK-MB catalytic activity, mean CK-MB mass concentration exceeded the upper reference limit, suggesting an increased rate of loss of activity concentration in these patients' sera. Because of the assay's lesser susceptibility to conformational changes at the active site of the enzyme, we suggest that measurement of CK-MB mass concentration is better suited for infarct sizing than measurement of catalytic activity.

Humoral immune response against contractile proteins (actin and myosin) during cardiovascular disease.

Sensitive and highly specific ELISA assays were developed to determine humoral immune response against actin and myosin in 122 patients suffering from various cardiovascular diseases: acute viral myocarditis (n = 10, MYO), acute myocardial infarction (n = 28, AMI), valve surgery (n = 35, VALVE), coronary bypass surgery (n = 35, CABG), and peripheral vascular surgery (n = 14, VASC). Anti-actin and anti-myosin antibodies were determined on admission and serially during a period of 90 days. Anti-actin and anti-myosin immune response (IgG, IgM) was expressed comparing absorbance of the patients' serum with a reference serum. In the different patient groups significantly (P less than 0.01) higher anti-actin and anti-myosin antibody concentrations were found on admission compared with age-matched control groups. During follow-up, all patient groups except the vascular surgery group showed a significant immune response against actin and myosin, with an immune response ratio (peak/admission) for AMA IgG and IgM respectively of 2.12 and 2.40 in the VALVE group, 1.30 and 1.99 in the CABG group, 1.42 and 1.48 in the AMI group and 1.66 and 1.25 in the MYO group; and for AAA IgG and IgM respectively of 1.57 and 3.00 in the VALVE group, 1.54 and 1.64 in the CABG group, 1.25 and 1.07 in the AMI group, and 1.42 and 1.42 in the MYO group. A significant correlation between pre-cardiac injury and peak post-cardiac injury anti-myosin and anti-actin autoantibody levels could be demonstrated suggesting that pre-injury sensitization to these antigens plays an important role in evoking post-cardiac injury immune response.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and angiographic outcome after implantation of a home-made stent for complicated coronary angioplasty.

To defray the escalating costs of coronary stenting, we handmade a balloon-expandable, stainless steel stent, which after experimental evaluation, was implanted in 156 patients undergoing PTCA complicated by a major dissection. The procedural success rate was 98%. The in-hospital course was characterized by a 1.3% cardiopulmonary mortality and a 4.5% nonfatal myocardial infarction rate, while emergency bypass surgery and early repeat PTCA were necessary in only one patient each (0.6%). Clinical 6-mo follow-up in 150 patients revealed no deaths and no myocardial infarctions, and the event-free survival rate was 82%. Six-month control angiography was performed in 93.3% of eligible patients and revealed a restenosis rate of 20%.

Characteristics of creatine release during acute myocardial infarction, unstable angina, and cardiac surgery.

Creatine release was compared in various conditions of muscle damage: acute myocardial infarction (AMI), unstable angina, and cardiac surgery. After AMI, serum and urine creatine concentrations increased transiently. After cardiopulmonary resuscitation, serum creatine values were significantly higher because of impaired renal function, whereas urinary creatine concentrations were comparable. In 38 patients with unstable angina, no significant changes in serum and urine creatine concentrations were seen. In 37 of 92 AMI patients, secondary creatine peaks were observed 20.9 +/- 8.1 h after onset of symptoms. The magnitudes of the first and second peaks were correlated: Spearman r = 0.66. In 24 patients who underwent cardiac surgery, the changes in creatine concentration in serum during surgery were very small, despite the presence of muscle trauma.

Treatment of long dissections by use of a single long or multiple short stents: clinical and angiographic follow-up.

BACKGROUND: Recently, long (> or =20 mm) coronary stents were introduced for clinical use. They are intended as an alternative to multiple conventional stents to treat extensive dissections or suboptimal results of long lesions after balloon angioplasty. METHODS: In a total of 113 such consecutive vessels in 107 patients, the flexible Freedom stent was implanted. In 60 of these vessels, because of anatomic constraints, multiple overlapping short (16 mm) stents were implanted. The other 53 vessels were treated with a single long (> or =20 mm) stent. RESULTS: In the single stent group there were four implantation failures (8%) successfully managed by crossover to multiple overlapping short stents. During early follow-up, in-stent thrombosis was not observed, but three patients with a single long stent and two patients with multiple overlapping stents suffered myocardial infarction as a result of long lasting myocardial ischemia during a difficult angioplasty procedure. At 6-month follow-up, > or =50% restenosis was measured in 29% and 35% of the patients with a single long stent and in those with multiple overlapping stents, respectively (not significant). CONCLUSIONS: Compared with the alternative treatment modality (i.e., implantation of multiple short stents), no difference between in-hospital and 6-month outcome was observed. However, implantation of a single long stent, when technically feasible, reduces catheterization time, dye volume for the patient, and radiation exposure for both patient and operator during these embarrassing angioplasty procedures.

Long term effects of nisoldipine on the progression of coronary atherosclerosis and the occurrence of clinical events: the NICOLE study.

BACKGROUND: Earlier angiographic studies have suggested that calcium antagonists may prevent the formation of new coronary lesions and the progression of minimal lesions. Conversely, a meta-analysis suggested that these drugs may increase cardiovascular mortality and morbidity in patients with coronary heart disease. OBJECTIVE: To investigate whether nisoldipine retards the progression of coronary atherosclerosis or reduces the occurrence of clinical events. DESIGN AND SETTING: The NICOLE study (NIsoldipine in COronary artery disease in LEuven) is a single centre, randomised, double blind, placebo controlled trial with coronary angiography at baseline, six months, and three years of follow up. PATIENTS: 826 patients who had undergone successful coronary angioplasty were randomised to nisoldipine 40 mg once daily or placebo. The intention to treat and per protocol population consisted of 819 and 578 patients, respectively. RESULTS: In the per protocol population, 625 of the nisoldipine treated and 655 of the placebo treated patients (NS) showed angiographic progression in at least one coronary arterial segment, defined as an increase in diameter stenosis of > or = 13%. The average minimum luminal diameter of the non-dilated lesions decreased by 0.163 mm and 0.167 mm in the nisoldipine and placebo groups, respectively (NS). The respective numbers of new lesions detected were 7 and 13 (NS). In the intention to treat population, the rates of death, stroke, and acute myocardial infarction were similar in both treatment groups. However, nisoldipine use was associated with fewer revascularisation procedures and thus the percentage of patients with any clinical event was lower (44.6% v 52.6%, p = 0.02). CONCLUSIONS: Nisoldipine has no demonstrable effect on the angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but its use is associated with fewer revascularisation procedures.