Abstract
Antithrombin III (AT III) is an important inhibitor of thrombin activity, as well as of many other proteases of the coagulation system. AT III administration showed beneficial effects onseptic multiple organ dysfunction in clinical and experimental studies. This study investigates the AT III effect on leukocyte/endothelial cell interaction and microvascular perfusion. In the skin fold preparation of the hamster severe endotoxinemia was induced by repeated administration of endotoxin (LPS, 2 mg/kg, at t0= 0 h and t3= 48 h. AT III (250 U/kg) was substituted intravenously at t0, t2= 24 h, and t3 (n = 6 animals, AT III group). In control animals (n = 5, controls) LPS was given without AT III substitution. By intravital fluorescence microscopy (FITC dextrane, rhodamine 6G) venular leukocyte adherence was determined at t0, t1 = 8 h, t2, t3, t4 = 56 h, and t3 = 72 h. Functional capillary densiry (FCD) served as a measure of capillary perfusion. AT III resulted in a significant modulation of LPS-induced leukocyte adherence and in a modulation of the LPS-induced depression in FCD (P < 0.0l, MANOVA). Thus, the number of sticking leukocytes after induction of endotoxin-emia was significantly lower in the AT III group compared with control animals (AT III: t1 = 182 ± 35 cells/mm2, t2= 176 ± 21, t3= 210 ± 51, t4= 243 ± 48, t5= 144 ± 29; control: t1= 630 ± l05, t2= 465 ± 113, t3= 404 ± 50, t4 = 542 ± 93, t5= 356 ± 102; P < 0.05). AT III downregulated LPS-induced leukocyte/endothelial cell interaction and prevented the depression in FCD which served as a measure of capillary perfusion. Both mechanisms may explain beneficial AT III effects in patients with severe sepsis.
Highlights
Ill patients requiring intensive care are at risk of iatrogenic ocular damage
Intensive Care Unit (ICU) management of critically ill patients often includes the requirement for tracheostomy and feeding access, most often a pecutaneous endoscopic gastrostomy (PEG)
Percutaneous tracheostomy is performed routinely in many medical intensive care unit (ICU) settings, in high risk surgical and trauma patients who often have unstable cervical spine injury and tissue edema, direct visualization of the cervical structures and trachea is imperative during tracheostomy
Summary
Ill patients requiring intensive care are at risk of iatrogenic ocular damage. We designed an experimental situation where external cardiac pressure conditions were controlled and adjusted to physiological extremes to mimic clinically relevant situations, while cardiac performance was assessed using left ventricular pressure–volume relationships (LVPVR) which are relatively preload and afterload independent This prospective, controlled study was undertaken to evaluate the response to therapy aimed at achieving supranormal cardiac and oxygen transport values (cardiac index >4.5 l/min/m2, oxygen delivery >600 l/min/m2, and oxygen consumption >170 l/min/m2) in patients older than 60 or with previous severe cardiorespiratory illnesses, who have undergone elective extensive ablative surgery planned for carcinoma or abdominal aortic aneurism. Whilst some human studies conducted in the critically ill and in high risk surgical patients have suggested that dopexamine may cause an increase in tonometrically measured gastric intra-mucosal pH (pHi) and an improvement in clinical outcome, this has not been confirmed in other randomised trials. In the present study the association of platelet function to inflammatory markers indicating disease severity was investigated
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