sepharose and Coronary-Disease

Animal models are indispensable in order to investigate the mechanism of various diseases and to explore the counter measures for those disease states. Although there are several animal models of ischemic heart diseases, surgical interventions required to create myocardial ischemia sometimes give rise to a problem in the yield of model. This study describes a new technique for inducing myocardial ischemia in rats.. A 0.014-inch guidewire was introduced via the carotid artery and selectively advanced into the coronary arteries under fluoroscopy. Transmural myocardial ischemia was confirmed by ST-segment elevation and by the appearance of left ventricular wall motion abnormalities on the echocardiogram. Reversibility of the wire-induced myocardial ischemia was demonstrated by complete resolution of both ST-segment elevation and wall motion abnormalities after removing the wire.. Wire-induced myocardial ischemia was reproducible and is less invasive than conventional ischemic models in rats. This method is a powerful and useful tool for the investigation of ischemic heart disease in small animals.

Topics: Animals; Cardiac Catheterization; Coronary Disease; Electrocardiography; Embolism; Male; Microspheres; Models, Animal; Myocardial Ischemia; Rats; Rats, Wistar; Reproducibility of Results; Sepharose; Ultrasonography

Lipoprotein(a) (Lp[a]) is associated with an increased cardiovascular risk. It is similar to low-density lipoprotein with an additional molecule of apo A covalently linked to apo B-100 by one disulfide bridge. Apo A is highly homologous to plasminogen. The kringle 4 motive of plasminogen is repeated between 10 and 40 times in apo (a). Currently, there is no drug therapy available to lower Lp(a). Since October 1993, we have carried out over 160 immunoadsorption treatments on 3 patients with elevated Lp(a) as their only risk factor and a history of myocardial infarction. Lp(a) was removed from plasma by sepharose coupled anti-Lp(a) columns. Lp(a) levels were lowered from above 170 mg/dl to below 30 mg/dl immediately after Lp(a) apheresis. To achieve this, the patient's plasma volume had to be treated 2 to 3 times. Nonspecific protein loss during column changes remained negligible. There were no serious unwanted effects during or after treatment. Minor circulatory problems (tachycardia, flush) occurred in 11% of the treatments but only with plasma flow rates above 55 ml/min. In 1 patient, coronary angiography after 2 years and in another patient after 1 year showed no progression. The third patient has not yet had repeat coronary angiography. Like the others, he reported subjective improvement after 1 year of apheresis. It is concluded that Lp(a) apheresis may retard progression of atherosclerosis in patients with selective Lp(a) elevation. Further studies to support this hypothesis are needed.

Topics: Adult; Blood Component Removal; Blood Volume; Coronary Angiography; Coronary Disease; Electrophoresis; Humans; Immunosorbents; Lipoprotein(a); Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Risk Factors; Sepharose; Treatment Outcome

Studies in vitro have suggested that inflammatory cytokines may play an important role in the pathogenesis of atherosclerosis. However, little is known about their effects in vivo. Thus, the present study was designed to determine in vivo what histological and functional changes may be induced by chronic treatment with IL-1 beta, one of the major inflammatory cytokines, and also to clarify what mechanisms are involved in those changes. Under aseptic conditions, proximal segments of the left porcine coronary arteries were gently wrapped with cotton mesh absorbing Sepharose beads either with or without recombinant human IL-1 beta. From 1 to 4 wk after the operation, coronary vasospastic responses to intracoronary serotonin or histamine were noted at the IL-1 beta-treated site but not at the control site. Histologically, intimal thickening was greater at the IL-1 beta-treated site than at the control site. Those functional and histological changes induced by the chronic treatment with IL-1 beta were significantly inhibited by the simultaneous treatment with a neutralizing antibody to either IL-1 beta or PDGF. These results indicate that chronic treatment with Il-1 beta induces coronary intimal lesions and vasospastic responses in porcine coronary arteries in vivo and also suggest that these changes are substantially mediated by PDGF.

Topics: Animals; Coronary Angiography; Coronary Disease; Coronary Vessels; Drug Administration Routes; Drug Compounding; Interleukin-1; Male; Platelet-Derived Growth Factor; Sepharose; Swine; Tunica Intima

We describe a simple method for detecting enzyme--immunoglobulin G (IgG) complexes in human serum. Protein-A Sepharose CL-4B binds IgG and therefore also the enzyme--IgG complexes, which can then be separated easily from the serum by centrifugation. We demonstrate this separation in two patients, one with a complex of IgG and creatine kinase (EC 2.7.3.2) BB isoenzyme, the other with an IgG--alkaline phosphatase (EC 3.1.3.1) complex. Both patients had unexplainably high activities of the respective enzymes in their serum. The method we propose should be a useful, simple, routine method of detection in cases where IgG--enzyme complexes are suspected.

Topics: Aged; Alkaline Phosphatase; Coronary Disease; Creatine Kinase; Electrophoresis; Female; Humans; Immunoglobulin G; Isoenzymes; Polysaccharides; Protein Binding; Sepharose; Staphylococcal Protein A

Topics: Adenosine; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Blood Pressure; Coronary Disease; Disease Models, Animal; Hypoxanthines; Hypoxia; In Vitro Techniques; Inosine; Male; Microspheres; Myocardial Contraction; Myocardium; Perfusion; Phosphocreatine; Polysaccharides; Rats; Sepharose

With appropriate electrophoretic techniques and fresh serum samples, the Lp(a) lipoprotein/pre-beta1-lipoprotein is demonstrable as a distinct zone in the area between beta-lipoprotein and ordinary pre-beta-lipoprotein, when sera which are strongly positive with respect to the Lp(a) antigen are analyzed. The Lp(a) lipoprotein is a genetically determined normal serum component. The phenotype Lp(a+) was found significantly more frequently in two series of patients with coronary heart disease (CHD) than in appropriate controls. The frequency difference between patients and controls was particularly pronounced for the Finnish samples studied, 55% of the patients having the phenotype Lp(a+), as opposed to only 31% of the healthy controls. As judged from electrophoresis strips, hibh concentrations of Lp(a) lipoprotein/pre-beta1-lipoprotein were positively correlated with coronary score as determined by angiography. This correlation was highly significant. Total serum cholesterol value was slightly higher in Lp(a+) than in Lp(a-) persons from two of the four population samples studied, but no statistically significant difference was found. Serum triglyceride levels exhibited a statistically insignificant trend towards higher values in Lp(a-) than in Lp(a+) individuals, in three of the four samples tested. The strong association between the phenotype Lp(a+) and CHD, as well as the correlation between high amounts of Lp(a) lipoprotein/pre-beta1-lipoprotein and coronary score on one hand, and the weak correlation between presence of Lp(a) lipoprotein/pre-beta1-lipoprotein and lipid values on the other, make it highly unlikely that the increased frequency of the Lp(a+) phenotype in CHD patients merely reflects an over-all increase of the intravascular pool of LDL and/or VLDL reflected in increased serum levels of cholesterol and/or triglycerides. By the same token, it is unlikely that the insignificant effect on lipid values can, on its own, explain the correlation between Lp(a) phenotype and CHD.

Topics: Adolescent; Antigens; Cholesterol; Coronary Disease; Electrophoresis; Finland; Humans; Lipids; Lipoproteins; Lipoproteins, VLDL; Male; Middle Aged; Phenotype; Sepharose; Sweden; Time Factors; Triglycerides