No abstract

Esterification of cholesterol with [l-14 C]palmityl-CoA by an atherosclerotic cell-free homogenate was approximately 16-50-fold greater than that by a normal cell-free homogenate for a given amount of protein in the homogenate. This difference was due to hyperactivity of the cholesterol-esterifying system in the atherosclerotic cell-free homogenate rather than to depletion of radioactive palmityl-CoA in the reaction mixture containing normal homogenate. Neither an activator of cholesterol esterification in the soluble fraction of the atherosclerotic aortic homogenate nor an inhibitor in the soluble fraction of the normal aortic homogenate could be demonstrated. The pH optimum within the pH range covered for esterification and the apparent K m values were approximately the same in normal and atherosclerotic microsomes, suggesting that the enzymes were probably the same. The results suggested a higher concentration or a higher activity of the enzyme in or on atherosclerotic microsomes. An alternative possibility is that high concentrations of free cholesterol in the atherosclerotic microsomes were responsible for the augmented cholesterol esterification. This possibility seems unlikely, because the observed 2.3-fold increase in the free cholesterol concentration should not produce a 25-fold increase in cholesterol esterification. The rate of cholesterol esterification by atherosclerotic microsomes varied with the substrate: oleyl-CoA ] > palmitylCoA > linoleyl-CoA. KEY WORDS pH optimum microsomes acyl-CoA cholesterol concentration atherosclerosis cholesterol esterification cell-free homogenate K• Cholesteryl ester of atherosclerotic aortas is derived in part from plasma and in part from in situ synthesis. The latter has been shown by the incorporation of radioactivity into cholesteryl ester using acetate (l) and fatty acids (2) as substrates. This process contributes at least 13% and perhaps much more to the total cholesteryl ester in atherosclerotic aortas of rabbits (3). Two pathways for cholesterol esterification in atherosclerotic arterial tissues have been reported: one involves direct esterification of cholesterol with acyl-CoA (4) and the other transesterification of cholesterol 176 with the /3-fatty acid of lecithin (5). The rate of direct esterification is enhanced 28-40-fold in atherosclerotic tissue (6), suggesting that this pathway is probably responsible for the accumulation of cholesteryl ester in the atheroma. The present paper describes additional studies comparing the cholesterol-esterifying activity of normal and atherosclerotic aortic homogenates. We attempted to demonstrate the existence of an activator in atherosclerotic homogenates or an inhibitor in normal homogenates. Moreover, we investigated the effects of pH and palmityl-CoA concentration, the relation of free cholesterol concentration of microsomes to cholesterol-esterifying activity, and the relative utilization of CoA esters of palmitic, stearic, oleic, and linoleic acids in cholesterol esterification. MethodsMale New Zealand rabbits (...

The use of this preoperative regimen resulted in decreased LOS, maximum pain, and nausea ratings. Patients in the intervention group required less postoperative anti-emetics.

Adequate autogenous vein is often the limiting factor in achieving a successful infrainguinal bypass. Attempts have been made to find alternative conduits; however, these alternatives have demonstrated inferior patency rates. We attempt to show that a split-thickness skin graft conduit provides a feasible autogenous arterial conduit. Neoconduits were prepared with an autogenous split-thickness skin graft (STSG) tubularized for a length of 5-6 centimeters with an appropriate caliber match to native artery. The deep dermal side of the graft was randomized to form either the external surface or the luminal surface. The neoconduit was placed as an interposition graft in the left common carotid artery. Grafts were studied in vivo with duplex ultrasonography and ex vivo by histopathology and immunohistochemistry. Feasibility study involved 4 animals with grafts harvested for study at 24 hours (n = 2) and 7 days (n = 2). Two subsequent groups were studied to evaluate 3-month (n = 8) and 6-month (n = 5) patency. All grafts (n = 4) in the feasibility phase of the study were patent at the time of harvest without evidence of aneurysmal degeneration. In the subsequent 8 goats, grafts with the deep dermal side forming the extraluminal surface (n = 4) had a propensity to ulcerate and rupture or to become aneurysmal (75%). The patency rate of these grafts at 6 weeks was 25%. In contrast, grafts with the deep dermal side forming the intraluminal surface (n = 4) demonstrated 75% patency at 6 weeks. Because of these results the remaining goats underwent placement of neoconduits with the deep dermal side forming the luminal surface. These grafts maintained a patency rate of 80% at 6 months. Neoconduits implanted with a diameter greater than 1.5 times the native arterial diameter became aneurysmal. Histopathology demonstrated neointimal formation in all grafts patent for longer than 7 days. Immunohistochemical staining for Factor VIII/von Willebrand's factor (vWF) was reactive in the endoluminal cells of these grafts. Immunohistochemical staining for a-smooth muscle actin demonstrated reactivity in conduits patent for greater than 1 month. Split-thickness skin may provide a feasible source for autogenous conduit in arterial reconstructions and warrants further study. Technical factors affecting patency include orientation of the deep dermal surface of the STSG and the diameter of the neoconduit at the time of implantation.