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S J Warner

Publications and source records attributed to S J Warner.

22 records · Page 2Linked to original sources
PubMedDate not supplied

Sotalol and infarct size after coronary ligation in the baboon.

We investigated the hemodynamic effects and myocardial salvage actions of sotalol during experimental myocardial infarction in the baboon. Ten baboons received placebo and six were given sotalol. In anesthetized open-chest baboons base-line determinations included heart rate (HR), rate-pressure product (RPP), left ventricular dP/dt, aortic pressures, serum creatine kinase MB isoenzyme (CK-MB) activity, and a 16-point epicardial ST segment map. The left anterior descending coronary artery was then ligated and the measurements were repeated at 15-min and at 2-h intervals up to 12 h after occlusion. At 12 h, coronary blood flow and myocardial CK activity were also measured. Twenty minutes after ligation, either sotalol (3 mumol . kg-1 followed by 2 nmol . kg-1 . min-1) or placebo (saline) was administered intravenously. Sotalol reduced HR but not dP/dt or the degree of afterload. The reduction in HR resulted in a significant decrease in RPP (myocardial O2 consumption). Sotalol administration also resulted in a decrease in coronary blood flow (myocardial O2 supply). There were no significant differences between the two groups in serum CK-MB activity or in the extent of myocardial damage, as predicted by the 15-min ST-segment deviations and myocardial CK activity at 12 h. The reduction in myocardial oxygen demand caused by sotalol was accompanied by a decrease in oxygen supply. As a consequence, no significant reduction in myocardial ischemic damage was found in the group given sotalol.

Animals↗
PubMedDate not supplied

Regulation of major histocompatibility gene expression in human vascular smooth muscle cells.

Human atheromata, but not normal blood vessels, contain numerous smooth muscle cells (SMC) that bear class II major histocompatibility (MHC) antigens. These lesions also contain leukocytes that can secrete cytokines, which may modulate SMC functions. Because of morphologic evidence for immune-activated (class II+) SMC in vascular lesions, we studied the regulation by cytokines of MHC gene expression in SMC cultured from human vessels. Under basal conditions, these SMC contained mRNA for class I MHC (detected by Northern blotting with a cDNA probe for HLA-B7) and expressed surface class I MHC product determined by enzyme-linked immunoassay with monoclonal antibody (MAb) W6/32. Unstimulated SMC contained little or no class II MHC mRNA (probed with HLA-DR alpha cDNA) or surface antigen (examined using MAb I2). Secretory products of activated human leukocytes (the cell-free supernatant of a mixed leukocyte reaction) induced class II MHC antigen expression by SMC after 3 days. Treatment of SMC with interferon (IFN)-alpha or -beta (1000 U/ml for 72 hours) increased class I MHC mRNA content and surface antigen but did not alter class II expression. Immune IFN (IFN-gamma), a leukocyte product known to induce class II MHC expression in classical antigen presenting cells as well as epithelial and endothelial cells, not only increased class I MHC expression by SMC but also induced substantial levels of class II MHC mRNA and surface antigen. IFN-gamma (ED50 approximately 10 U/ml) increased class II MHC mRNA maximally after 2 to 3 days and surface expression linearly from 1 to 4 days. Immunohistochemical study demonstrated few class II+ SMC in cultured human SMC under basal conditions but homogeneous expression of high levels of DR antigen after exposure to IFN-gamma for 3 days. Neither interleukin-1 (IL-1 alpha or beta), tumor necrosis factor alpha (TNF), nor endotoxin altered class II expression by SMC. Local secretion of IFN-gamma by activated leukocytes may account for the presence of HLA-DR+ SMC in the human atheroma. Immune activation of SMC might participate in the pathogenesis of vasculitis and arteriosclerosis, particularly in the form found in the coronary arteries of transplanted hearts.

Antigens, Surface↗