A viable blood substitute is still of great necessity throughout the world. Perfluorocarbon-based oxygen carriers (PFCOCs) are emulsions that take advantage of the high solubility of respiratory gases in perfluorocarbons (PFCs). Despite attractive characteristics, no PFCOC is currently approved for clinical uses. Some PFCOCs have failed due to secondary effects of the surfactants employed, like Fluosol DA, whereas others to adverse cerebrovascular effects on cardiopulmonary bypass, such as Oxygent. Further in-depth, rigorous work is needed to overcome the annotated failures and to obtain a safe PFCOC approved for human use. The aim of this study is to review in detail the most-used PFCOCs, their formulation, and preclinical and clinical trials, and to reflect upon causes of failure and strategies to overcome such failures.

Despite the wide variety of tissue-engineered vascular grafts that are currently being developed, autologous vessels, such as the saphenous vein, are still the gold standard grafts for surgical treatment of vascular disease. Recently developed technologies have shown promising results in preclinical studies, but they still do not overcome the issues that native vessels present, and only a few have made the transition into clinical use. The endothelial lining is a key aspect for the success or failure of the grafts, especially on smaller diameter grafts (<5 mm). However, during the design and evaluation of the grafts, the mechanisms for the formation of this layer are not commonly examined. Therefore, a significant amount of established research might not be relevant to the clinical context, due to important differences that exist between the vascular regeneration mechanisms found in animal models and humans. This article reviews current knowledge about endothelialization mechanisms that have been so far identified: in vitro seeding, transanastomotic growth, transmural infiltration, and fallout endothelialization. Emphasis is placed on the models used for study of theses mechanisms and their effects on the development of tissue-engineering vascular conduits.

Intaglietta. Oxygen delivery and consumption in the microcirculation after extreme hemodilution with perfluorocarbons. Am J Physiol Heart Circ Physiol 287: H320 -H330, 2004; 10.1152/ajpheart.01166.2003.-The oxygen transport capacity of fluorocarbons was investigated in the hamster chamber window model microcirculation to determine the rate at which oxygen is delivered to the tissue in conditions of extreme hemodilution [hematocrit (Hct) 11%]. Hydroxyethlyl starch (HES 200; 200 kDa molecular mass) was used as a plasma expander for two isovolemic hemodilutions performed with 10% HES 200 until a Hct of 65%. A third step reduced the Hct to 75% of baseline and was performed with either HES 200 or a 60% perfluorocarbon (PFC) emulsion. Comparisons of HES 200-only-hemodiluted animals versus 4.2 g/kg PFC emulsion-hemodiluted animals were made at 21% and 100% normobaric oxygen ventilation. It was found that systemic and microvascular oxygen delivery was 25% and 400% higher in the PFC animals compared with HES 200 animals, respectively, showing that PFCs deliver oxygen to the tissue when combined with hyperoxic ventilation in the present experiments, with no evidence of vasoconstriction or impaired microvascular function. Oxygen ventilation (100%) led to a positive base excess for the PFC group (5.5 Ϯ 2.5 mmol/l) versus a negative balance (Ϫ0.8 Ϯ 1.4 mmol/l) for the HES 200 group, suggesting that microvascular findings corresponded to systemic events. hyperoxia; functional capillary density; oxygen-carrying capacity; blood substitutes; tissue oxygen delivery THE CORRECTION OF BLOOD LOSSES usually begins with the normalization of blood volume. The continued decrease of red blood cell (RBC) concentration is followed by the restoration of oxygen-carrying capacity. To date, this latter phase remains firmly within the purvey of blood transfusion medicine; however, alternative oxygen-carrying volume fluids such as modified hemoglobins (Hbs) and fluorocarbons have emerged in the past decade. Few of these materials have been objectively analyzed in terms of their transport properties at the level of the microscopic blood vessels, where the actual exchange of oxygen takes place, to determine if their properties lead to adequate transport processes at the cellular/tissue level (8).Fluorocarbons have been investigated by different approaches that extended to phase 3 clinical trials (9). These materials carry oxygen, are synthetic, and, in principle, are available in very large quantities at modest costs. This has tantalized investigators, medical practitioners, and business enterprises, because it could, in principle, lead to a convenient, largely available, and pathogen-free oxygen carrier. However, fluorocarbons only become miscible with water when emulsified with phospholipids (derived from egg yolk) and therefore are not completely synthetic. Furthermore, whereas Hb carries oxygen via a reversible chemical reaction, fluorocarbons carry oxygen as a function of their solubility; therefore, at the PO 2 s prevailing in the microcirc...

Oxygen phosphorescence quenching was used to measure tissue Po2 of lymphatic vessels of 43.6 ± 23.1 μm (mean ± SD) diameter in tissue locations of the rat mesentery classified according to anatomic location. Lymph and adipose tissue Po2 were 20.6 ± 9.1 and 34.1 ± 7.8 mmHg, respectively, with the difference being statistically significant. Rare microlymphatic vessels in connective tissue not surrounded by microvessels had a Po2 of 0.8 ± 0.2 mmHg, whereas the surrounding tissue Po2 was 3.0 ± 3.2 mmHg, with both values being significantly lower than those of adipose tissue. Lower of lymph fluid Po2 relative to the surrounding tissue was also evident in paired measurements of Po2 in the lymphatic vessels and perilymphatic adipose tissue, which was significantly lower than the Po2 in paired adipose tissue. The Po2 of the lymphatic fluid of the mesenteric microlymphatics is consistently lower than that of the surrounding adipose tissue by ∼11 mmHg; therefore, lymph fluid has the lowest Po2 of this tissue. The disparity between lymph and tissue Po2 is attributed to the microlymphatic vessel wall and lymphocyte oxygen consumption.