A pilot study of the relationship between Doppler-estimated carotid and brachial artery flow and cardiac index.

We measured carotid and brachial artery blood flow by Doppler ultrasound in 11 human volunteers, and related these to cardiac index and to each other. The median (IQR [range]) carotid arterial blood flow was 0.334 (0.223-0.381 [0.052-0.563]) l.min(-1) on the right and 0.315 (0.223-0.369 [0.061-0.690]) l.min(-1) on the left. The brachial arterial blood flow was 0.049 (0.033-0.062 [0.015-0.204]) l.min(-1) on the right and 0.039 (0.027-0.054 [0.011-0.116]) on the left. Cardiac index was 3.2 (2.8-3.5 [1.9-5.4]) l.min(-1) .m(-2) . There was a moderate to good correlation between right-and left-sided flows (brachial: ρ = 0.45; carotid: ρ = 0.567). Brachial and carotid flow had no or a negative correlation with cardiac index (right brachial: ρ = -0.145, left brachial: ρ = -0.349; right carotid: ρ = -0.376, left carotid: ρ = -0.285). In contrast to some previous studies, we found that Doppler-estimated peripheral arterial blood flows only show a weak correlation with cardiac index and cannot be used to provide non-invasive estimates of cardiac index in man.

Hemostatic effects of antithrombin III supplementation during cardiac surgery: results of a prospective randomized investigation.

Failure to suppress thrombin generation during cardiac surgery promotes fibrin generation, fibrinolysis, and a consumptive coagulopathy. Acquired deficiencies of antithrombin III may play a contributory role. We hypothesized that antithrombin III supplementation to normal physiologic concentrations would decrease thrombin generation and potentially reduce peri-operative bleeding. Twenty patients undergoing coronary artery bypass graft surgery were randomized for this prospective, double-blind, placebo-controlled study. Ten patients received antithrombin III supplementation (50 U/kg) by intravenous infusion prior to incision, and 10 patients received a placebo. Blood samples were obtained pre-operatively, at 1 and 2 h following initiation of cardiopulmonary bypass (CPB), and at 1, 3, and 24 h after completion of CPB. Samples were analyzed for antithrombin III, thrombin-antithrombin III (TAT) complex, and D-dimer concentrations. Cumulative blood loss was recorded at 6 and 12 h after CPB. No statistically significant differences in patient demographics or total heparin dose administered were observed between groups. As expected, plasma antithrombin III concentrations were maintained near pre-operative values in the treatment group, but not in the placebo group. Despite this difference, no statistically significant alterations in generation of TAT complex, D-dimer, or blood loss occurred between groups. Antithrombin III supplementation to maintain normal physiologic concentrations during CPB did not alter significantly thrombin generation, fibrinolytic activity, or blood loss in adults undergoing elective cardiac surgery.

Use of hydroxypropyl methylcellulose acetate succinate in an enteric polymer matrix to design controlled-release tablets of amoxicillin trihydrate.

A controlled-release table of amoxicillin trihydrate was developed by use of a matrix formulation based on the enteric polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS). Sustained drug release was shown by in vitro dissolution testing; the polymer could suppress drug release in the presence of gastric pH but could enhance drug release in the presence of small intestinal pH, compared with compacts of pure drug. Grinding or physical mixing of the drug with the polymer, an alteration in normal compaction pressure, or a substitution of other enteric polymers did not markedly affect drug release from compacts. Physicochemical testing of samples confirmed that the method of mixing did not alter powder morphology. An ethanolic granulation procedure was used in the production of final tablets (21 x 10 mm) containing amoxicillin (750 mg), HPMCAS, anhydrous directly compressible lactose, and lubricants. These large tablets showed a promising sustained-release effect in vitro when a variable-pH-shift dissolution procedure was used. However, single-dose studies with a panel of fasting subjects showed that the tablets had a relative bioavailability of only 64.4%. Other pharmacokinetic parameters confirmed a lack of therapeutic advantage of these tablets over an equivalent dose of conventional capsules.