RETRACTED ARTICLE: The influence of a balanced volume replacement concept on inflammation,endothelial activation,and kidney integrity in elderly cardiac surgery patients

Purpose  A balanced fluid replacement strategy appears to be promising for correcting hypovolemia. The benefits of a balanced fluid replacement regimen were studied in elderly cardiac surgery patients. Methods  In a randomized clinical trial, 50 patients aged >75 years undergoing cardiac surgery received a balanced 6% HES 130/0.42 plus a balanced crystalloid solution (n = 25) or a non-balanced HES in saline plus saline solution (n = 25) to keep pulmonary capillary wedge pressure/central venous pressure between 12–14 mmHg. Acid-base status, inflammation, endothelial activation (soluble intercellular adhesion molecule-1, kidney integrity (kidney-specific proteins glutathione transferase-alpha; neutrophil gelatinase-associated lipocalin) were studied after induction of anesthesia, 5 h after surgery, 1 and 2 days thereafter. Serum creatinine (sCr) was measured approximately 60 days after discharge. Results  A total of 2,750 ± 640 mL of balanced and 2,820 ± 550 mL of unbalanced HES were given until the second POD. Base excess (BE) was significantly reduced in the unbalanced (from +1.21 ± 0.3 to −4.39 ± 1.0 mmol L⁻¹ 5 h after surgery; P < 0.001) and remained unchanged in the balanced group (from 1.04 ± 0.3 to −0.81 ± 0.3 mmol L⁻¹ 5 h after surgery). Evolution of the BE was significantly different. Inflammatory response and endothelial activation were significantly less pronounced in the balanced than the unbalanced group. Concentrations of kidney-specific proteins after surgery indicated less alterations of kidney integrity in the balanced than in the unbalanced group. Conclusions  A total balanced volume replacement strategy including a balanced HES and a balanced crystalloid solution resulted in moderate beneficial effects on acid-base status, inflammation, endothelial activation, and kidney integrity compared to a conventional unbalanced volume replacement regimen.     

Influence of a new hydroxyethylstarch preparation (HES 130/0.4) on coagulation in cardiac surgical patients.

OBJECTIVE: To compare volume therapy with HES 130/0.4, a new hydroxyethylstarch (HES) solution with a gelatin-based fluid replacement strategy. DESIGN: Prospective, randomized, safety study. SETTING: Urban, university-affiliated hospital (single institution). PARTICIPANTS: Forty-two patients undergoing elective cardiac surgery. INTERVENTIONS: Patients were prospectively randomized into 2 groups: In group 1 (n = 21), gelatin was given perioperatively for volume support until the 1st postoperative day to keep the central venous pressure (CVP) between 10 and 14 mmHg; in group 2 (n = 21) HES 130/0.4 was administered using the same protocol as in group 1. MEASUREMENTS AND MAIN RESULTS: Standard coagulation variables and modified thromboelastography (TEG) were used. Using different activators for extrinsic and intrinsic activation and heparin inactivation by heparinase, the onset of coagulation (coagulation time), kinetics of clot formation (clot formation time), and maximum clot firmness were measured. Measurements were performed after induction of anesthesia (T0), at the end of surgery (T1), 4 hours after surgery (T2), and on the morning of the 1st postoperative day (T3). A total of 3310 +/- 810 mL of gelatin and 3070 +/- 570 mL of HES 130/0.4 were used in the 2 groups during the study period. The 2 groups did not differ with regard to postoperative bleeding or in use of packed red blood cells or fresh frozen plasma. Standard coagulation variables were similar between the 2 groups. All TEG variables were within the normal range at baseline. Coagulation time and clot formation time data were significantly elevated after surgery and in the intensive care unit, without showing specific differences between the 2 volume replacement groups. Intrinsic TEG and heparinase TEG clot formation times remained significantly higher until the end of the study period. No differences were seen between HES-treated and gelatin-treated patients. CONCLUSIONS: Volume replacement with the new HES preparation was as safe as gelatin-based volume replacement with regard to coagulation in cardiac surgical patients. HES 130/0.4 is an alternative plasma substitute to treat volume deficits.     

Induction Of Endothelin-1 Expression By Glucose: An Effect Of Protein Kinase C Activation

Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have been associated with decreased blood flow in the retina and peripheral nerves of diabetic animals and may be related to the development of pathologies in these tissues. Hyperglycemia has been postulated to increase ET-1 secretion in endothelial cells. We have characterized the mechanism by which elevation of glucose is increasing ET-1 mRNA expression in capillary bovine retinal endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5 mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3-kinase inhibitor. By immunoblot analysis, PKC-beta 2 and -delta isoforms in BREC were significantly increased relative to other isoforms in the membranous fractions when glucose level was increased. Overexpression of PKC-beta 1 and -delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the respective cDNA enhanced in parallel PKC activities, proteins, and basal and glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition of these PKC isoforms may prevent early changes in diabetic retinopathy and neuropathy.     

PROGRESSIVE SUPRANUCLEAR PALSY PRESENTING WITH PSYCHIATRIC FEATURES

SUMMARY A patient with progressive supranuclear palsy who presented with psychiatric features is reported. His case illustrates the difficulty of early diagnosis of this condition. Associated psychiatric symptoms are common and may precede the occurrence of gaze palsy. Our patient's behavioural problems responded to fluoxetine.