Coronary artery deposition of factor VIII-related antigen in ischemic heart disease.

This study localized Factor VIII-related antigen (FVIIIRAg) directly in the intramural coronary arteries of patients with coronary artery disease (CAD). Assays were performed on myocardial autopsy sections from 17 patients with and 15 patients without CAD, using a monospecific FVIIIRAg antibody in the peroxidase-immunoperoxidase technic. FVIIIRAg was quantified by a FVIIIRAg index (FRI), as a numerical score based on distribution, thickness, and extension of immunostaining. The mean FRI for the CAD patients was 55 +/- 11 and that for the control patients 12 +/- 5 (P less than 0.001). The increased amounts of in situ FVIIIRAg suggest this glycoprotein may be involved in the pathogenesis of atherosclerosis.

Altered lymphocyte subsets during cardiopulmonary bypass.

Peripheral blood lymphocyte subsets were quantified by immunofluorescence in nine patients undergoing open heart surgery for coronary artery, valvular, and congenital heart disease. Compared with normal preoperative values, all patients developed an absolute lymphopenia, a reduction in T4 (helper) lymphocytes, and a statistically significant reversal of the T4/T8 ratio two hours after cardiopulmonary bypass (CPB). These changes could be caused by mechanical or immunogenic injury. A return to normal of the T4 subset and T4/T8 proportion occurred 24 hours after surgery. Whereas transient inactivation of immunoreactive lymphocyte clones may prevent unwanted immunization to blood products received during surgery, such temporary immune dysfunction could make certain patients liable to infectious sequelae. Viral-induced postperfusion syndromes, transmission of human T lymphotropic virus (HTLV) III by blood products, and reports of acquired immune deficiency syndrome after CPB foster a concern regarding postoperative infections under these circumstances.

The behavior of antithrombin III, alpha 2 macroglobulin, and alpha 1 antitrypsin during cardiopulmonary bypass.

We serially measured concentrations of three protease inhibitors, antithrombin III, alpha 2 macroglobulin, and alpha 1 antitrypsin in patients with coronary artery and valvular heart disease during extracorporeal circulation. Assays for immunoreactive antiproteases and for functional antithrombin III were performed on plasma samples obtained at selected intervals before, during, and after cardiopulmonary bypass. Significant reductions of all protease inhibitors occurred at some time during cardiopulmonary bypass, although patterns of change were dissimilar for the two patient groups. A return toward preoperative levels was observed after cardiopulmonary bypass was discontinued, but antithrombin III remained diminished in the patients with coronary artery disease. The acute serial changes in this group of alpha globulins is evidence of their participation during the dynamic stress of extracorporeal circulation. Their timely intervention as serine protease antagonists deters sustained thrombogenesis and fibrinolysis during cardiopulmonary bypass.

Interleukin-1 alpha as a factor in occlusive vascular disease.

The purpose of this study was to examine the recognized ability of interleukin-1 alpha (IL-1 alpha) to alter the functional properties of endothelial cells and to induce replication of smooth muscle and fibroblasts. Such changes could potentially link IL-1 alpha pathogenetically to the myointimal proliferation of vascular sclerosis. Using a peroxidase-immunoperoxidase immunohistochemical method, saphenous veins and internal mammary arteries were examined for the presence of IL-1 alpha before their implantation as aortocoronary bypass grafts. Occluded saphenous vein grafts requiring replacement because of recurrent angina pectoris also were similarly examined. Interleukin-1 alpha, deposited as a scarlet immunoprecipitate, was seen on the luminal surface, in the subintima, and on the spindle cells and infiltrating macrophages in the media of 13 phlebosclerotic veins before surgical insertion. The remaining 30 unchanged veins did not contain IL-1 alpha. Similarly, IL-1 alpha was not identified in any of the 43 sampled internal mammary arteries that were all considered structurally intact. All the 55 bypass grafts, which were examined by biopsy during revascularization and demonstrated diverse histopathologic abnormalities consisting of reduced luminal patency, myointimal proliferation, mononuclear cell infiltration, mural collagenization, and luminal-mural hemorrhage, also contained widely distributed IL-1 alpha. The observation that IL-1 alpha was absent in all of the internal mammary arteries concomitant with maintenance of normal microanatomic structure may help explain, in part, their recognized resistance to reduction in luminal patency and their improved clinical survival when used as coronary artery bypass grafts. Alternatively, the consistent presence of IL-1 alpha in all vessels with sclerotic histopathologic changes suggests that this cytokine may be an important in situ indicator of and a potential participant in vascular injury. Interleukin-1 alpha may be a pathogenetic factor in the complex processes leading to vascular occlusion.

Immunocytochemical features of obstructed saphenous vein coronary artery bypass grafts.

The peroxidase-immunoperoxidase immunocytochemical method was used on 27 saphenous vein coronary artery bypass grafts, which had been resected because of recurrent angina, to identify in situ cellular and humoral elements possibly associated with graft occlusion. Immunostaining was performed on paraffin wax embedded control saphenous vein and graft sections incubated directly with primary antibodies against von Willebrand antigen (vWFAg), fibronectin, fibrinogen, leucocyte common antigen (LCA), lysozyme, vimentin, desmin, platelet factor 4, and thrombospondin. Antigens were visualised by a chromogen providing an orange-red immunoprecipitate at the site of epitope localisation. The intraluminal, amorphous exudate present in most grafts was not composed simply of fibrin or fibrinogen, as previously thought, but was a multiprotein complex including wWFAg, fibronectin, thrombospondin and platelet factor 4. Along with macrophages, these components probably enter the graft after haemodynamic, physical, and chemical injury to, and disruption of, the endothelial cell. Progressive myointimal proliferation and fibrosis of these grafts may be local repetitive responses to macrophages and platelets, cells previously known to participate in vascular disease.

Hepatobiliary-lung imaging. A case report.

The use of combined hepatobiliary-lung imaging in the diagnosis and evaluation of a subphrenic process is described.

Atrial coronary angiography, tachyarrhythmias and the Ta segment.

Electrocardiograms and angiograms were reviewed to determine if atrial Ta segment displacements and atrial flutter or fibrillation indicate atrial coronary disease. Atrial circulation was assessed by angiography in 28 patients with chest pain and normal coronary arteries, 29 patients with significant stenosis of at least one major coronary vessel, and 16 with coronary artery disease and atrial flutter or fibrillation. The prevalence of Ta segment displacement was 71% without coronary disease and 79% with coronary disease. There was no relationship between Ta displacement and segmental atrial coronary insufficiency. Among an additional 28 patients with acute transmural myocardial infarction, 79% had equivalent Ta segment displacement. Half of the patients with atrial flutter/fibrillation had significant mitral regurgitation, in contrast to 3% of coronary patients in sinus rhythm (p less than 0.001), but their atrial coronary circulation was not more severely compromised. Thus, Ta segment displacement did not identify atrial coronary disease and was not more frequent during acute myocardial infarction. Abnormal atrial perfusion did not explain Ta segment displacement or atrial flutter/fibrillation.

Concentrations of factor VIII-related antigen and factor XIII during open heart surgery.

Plasma levels of factor VIII-related antigen (fVIIIRA) and factor XIII S and A subunits (fXIIIS, fXIIIA) were assayed by counterimmunoelectrophoresis before, during, and after cardiopulmonary bypass (CPB) in patients with coronary artery and valvular heart disease to define the basis for clinical and laboratory abnormalities of hemostasis occurring in this form of surgery. During CPB, concentrations of fXIIIA dropped in both patient groups but returned to preoperative levels promptly after pump removal. In contrast, fVIIIRA and fXIIIS, which are not incorporated into the clot, remained unchanged even during fluid administration. These data provide evidence of a transient consumption coagulopathy as a feature of CPB. Hemodilution probably plays a secondary role in these changes.

von Willebrand syndromes and mitral-valve prolapse; linked mesenchymal dysplasias.

We searched for mitral-valve prolapse by two-dimensional echocardiography in 15 patients with von Willebrand syndromes to test the hypothesis that this bleeding disorder is actually a mesenchymal dysplasia that resembles the heritable disorders of connective tissue. This valvular abnormality was found in nine (60 per cent) of these patients, as compared with four (13.3 per cent) of 30 sex-matched and age-matched healthy controls. This difference was statistically significant (P less than 0.01). The association between these two disorders encourages a search for mitral-valve prolapse in persons with a von Willebrand syndrome. The complex of a von Willebrand syndrome and mitral-valve prolapse may be an example of a newly recognized category of related coagulation and cardiovascular disorders.

The effect of mild alkali and alkaline borohydride on the carbohydrate and peptide moieties of fetuin.

In the light of recent reports, based on radioactive labelling studies, that substantial amounts of N-linked oligosaccharides are released from protein under the mild-alkaline borohydride degradation conditions that are usually used to release O-linked oligosaccharides, we have investigated by chemical methods the effects of alkali alone and alkaline borohydride on the carbohydrate and peptide moieties of fetuin. The chromatographic profiles on Sephadex G50 columns, of the hexose- and ninhydrin-positive components of the native and Pronase-treated glycoprotein have been compared with those obtained after treatment with mild alkali alone (0.05 M-NaOH, 50 degrees C, 16 h) or mild-alkaline borohydride (0.05 M-NaOH containing 1 M-NaBH4, 50 degrees C, 16 h). Composition and methylation analyses have been performed on carbohydrate-containing peaks and the following conclusions were drawn: mild alkali treatment alone liberated a minor hexose- and ninhydrin-positive component and mild-alkaline borohydride treatment gave a major hexose-containing peak: both of these co-chromatographed on a Sephadex G50 column with Pronase glycopeptides. The polypeptide backbone was totally broken down by the alkaline borohydride treatment. The presence of released N-linked chains after alkaline borohydride treatment was confirmed. However, from the carbohydrate composition it was calculated that no more than 10-20% of the N-linked chains were released from protein. The results of methylation analysis have raised the possibility that this release is in part due to cleavage of the chitobiosyl core.

Intravenous versus intracoronary streptokinase for acute transmural myocardial infarction.

In order to compare the thrombolytic efficacy of selective versus systemic administration of streptokinase, we gave this drug by either the intracoronary or intravenous routes to 25 patients during the first 6 hours of acute myocardial infarction. All patients had total occlusion of the infarct-related vessel, unresponsive to intracoronary nitroglycerin. Twelve patients received intravenous streptokinase and 13 received intracoronary administration of the drug. Angiograms were taken prior to and during streptokinase administration. Reopening was achieved in 11 of 13 intracoronary patients and 8 of 12 intravenous patients (P = Ns). Time to reopening was longer (54 minutes) in the intravenous patients than in the intracoronary patients (26 minutes) (P less than 0.05). In this study, intravenous streptokinase reopened infarct-related vessels nearly as often as intracoronary streptokinase, but it took longer. Given the limited access and time to prepare for intracoronary infusion and the ease of intravenous administration, further study of intravenous streptokinase is justified.

Structural analysis of the O-glycosidically linked core-region oligosaccharides of human meconium glycoproteins which express oncofoetal antigens.

Glycoproteins were extracted from meconium samples of group O neonates of secretor type by pronase digestion followed by precipitation in 67% aqueous ethanol and separated into Ii antigen enriched and depleted fractions by affinity chromatography. The latter fraction strongly expressed the oncofoetal antigens recognised by natural antibodies in mouse sera and the hybridoma antibody FC 10.2, and this activity was enhanced after mild acid hydrolysis to remove sialic acid and fucose residues. Oligosaccharides were released from the mild-acid-treated fraction by base-borohydride degradation and purified by gel permeation chromatography on Bio-Gel P4 and high performance liquid chromatography on octadecylsilyl and aminopropylsilyl columns. The major oligosaccharides were characterised by fast atom bombardment and electron impact mass spectrometry, combined gas-liquid chromatography/mass spectrometry and 500-MHz proton NMR spectroscopy. Their structures, in order of abundance, were: (Formula: see text).