Inflammatory mechanisms are activated, and thrombotic complications occur during the initial months after coronary artery bypass grafting (CABG). Therefore, changes over time of platelet activation and platelet-leukocyte interactions after CABG are of interest. Whole-blood flow cytometry was performed before, and 4-6 days, one month, and three months after elective CABG in 54 men with stable coronary artery disease treated with acetylsalicylic acid (ASA). Single platelets and platelet-leukocyte aggregates (PLAs) among monocytes (P-Mon), neutrophils (P-Neu), and lymphocytes (P-Lym) were studied without and with stimulation by submaximal concentrations of ADP, thrombin, and the thromboxane analog U46619. White blood cell counts were increased during the initial postoperative course, and platelet counts were increased after one month. Platelet P-selectin expression was significantly enhanced at one month when stimulated by thrombin and U46619 and at three months with ADP and thrombin. All PLAs subtypes were increased at one month without stimulation in vitro. P-Mon and P-Neu stimulated by ADP, thrombin, or U46619 were significantly increased one month after the operation but decreased compared to baseline at three months. Agonist stimulated P-Lyms were increased at one month and remained increased at three months after ADP stimulation. There was significant platelet activation and formation of PLAs unstimulated and after agonist stimulation by ADP, thrombin, and a thromboxane analog after CABG in patients with stable coronary artery disease irrespective of ASA treatment. Changes observed up to three months after CABG support further studies of the clinical implications of protracted increases in platelet activation and platelet-leukocyte interactions.
Working towards the synthesis of 2′‐O‐[N‐(aminoethyl)carbamoyl]methyl‐modified di‐ and oligonucleotides, we have synthesised a protected 2′‐O‐[N‐(aminoethyl)carbamoyl]methyl‐modified adenosine where the modification is introduced in a convenient one‐pot three‐step procedure. The corresponding H‐phosphonate building block was also synthesised, and from this intermediate, a 2′‐O‐[N‐(aminoethyl)carbamoyl]methyl‐containing dinucleotide could be made. We also performed studies on the chemical and enzymatic stability of this dinucleotide. The dinucleotide was subjected to different ammonolysis and other basic conditions, and HPLC analysis showed that the modification was intact to most conditions, but that there was some minor hydrolysis when NH3 (concd. aq.) was used at 55 °C. Under several other sets of conditions, including saturated NH3 in methanol, and ethylenediamine, the amide remained intact. Treatment of the dinucleotide with Phosphodiesterase I from Crotalus adamanteus venom and Phosphodiesterase II from bovine spleen showed that the N‐(aminoethyl)carbamoylmethyl moiety gives the phosphodiester linkage substantial protection against enzymatic degradation; the phosphodiester was not degraded by PDE II at all after seven days.
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