Recombinant factor VIIa reduces transfusion requirements in liver transplant patients with high MELD scores

Patients undergoing orthotopic liver transplantation (OLT) often experience significant coagulopathy and remain at risk for excessive blood loss and massive transfusion. The ability of recombinant factor VIIa (rFVIIa) to reduce transfusion requirements during OLT has not been well established. This retrospective study investigates whether rFVIIa reduces transfusion requirements in liver transplant patients with a significantly prolonged prothrombin time (PT) and a model of end-stage liver disease (MELD) score of > 20. Eleven patients received a single dose of rFVIIa (58 +/- 18 microg kg(-1)) at the time of incision. This group was matched with a selected control group that fulfilled all of the inclusion/exclusion criteria. Patient characteristics, pre-operative PT, HCT, PLT and MELD were identical between groups. Prophylactic application of rFVIIA reduced packed red blood cells (3.9 +/- 2.6 versus 6.9 +/- 2.3 U, P = 0.01) and fresh-frozen plasma (FFP) (12.6 +/- 6 versus 19.8 +/- 7 U, P = 0.018) transfusion requirements when compared with the control group. FFP administration in the first 24 h after surgery was also significantly less in the rVIIa group when compared with the control group (388 +/- 385 versus 1225 +/- 701 mL, P = 0.003). Hospital stay following transplantation tended to be shorter in the rFVIIa group, albeit statistical significance was not achieved (11 +/- 7.3 versus 7.9 +/- 2.7, P = 0.2). All but one patient in the control group survived for 30 days after transplantation. In a selected group of patients with prolonged PT and high MELD score, the prophylactic application of rFVIIa at the start of the OLT may reduce perioperative transfusion requirements.     

Studies of the inhibition of C56-initiated lysis (reactive lysis). IV. Antagonism of the inhibitory activity c567-INH by poly-L-lysine.

The stable intermediate complex C56 can initiate the lysis (reactive lysis) of unsensitized erythrocytes (E) by the membrane attack machanism of complement. Certain serum constituents designated C567-INH inhibit reactive lysis by preventing the C567 complex, once formed, from attaching to a membrane surface. It is shown here that microgram quantities of poly-L-lysine (PLL), a synthetic polycation of molecular weight 180,000, can reverse the effests of C567-INH, and thereby potentiate formation of EC567 by erythrocytes, C56 and C7 in whole serum. Erythrocytes exposed to PLL in a preincubation step did not show either increased susceptibility to C567 or resistance to C567-INH, and reversal of C567-IHN by given amounts of PLL was not diminished as cell concentrations were greatly increased, indicating that the effect of PLL was predominantly directed against fluid phase rather than against erythrocyte membrane substrates. The effects of PLL and C567-INH were quantitatively reciprocal. Thus, PLL-induced potentiation of C56-induced lysis is a solute effect which seems to involve direct neutralization of naturally occurring serum inhibitors of the C567 trimolecular complex of complement. The use of PLL thus provides a suitable antagonist for C567-INH in reaction mixtures, and allows evaluation of the role of C567 and C567-INH in a variety of situations involving C-mediated lysis.     

No protection of the porcine kidney by ischaemic preconditioning

One or more episodes of sublethal ischaemia and reperfusion delay infarct development during subsequent, sustained ischaemia in the heart and skeletal muscle. The present study tested whether or not such ischaemic preconditioning (IP) also protects the kidney. Enflurane-anaesthetized pigs underwent 60 min of right renal vessel occlusion (RVO), followed by 8 h of reperfusion without (placebo group, n = 8) or with three preceding cycles of 10 min RVO and 10 min reperfusion (IP group, n = 8). After 8 h of reperfusion, kidneys were oliguric in both groups (placebo group: 23 +/- 21 ml x h(-1), IP group: 24 +/- 27 ml x h(-1)). A transient polyuric phase occurred in the IP group at 2 h reperfusion. The reperfused kidneys did not excrete inulin, creatinine or urea in both groups, although renal blood flow during reperfusion was similar to baseline. Morphological damage ranged in both groups from single cell necrosis to disseminated patchy necrosis; the number of pyknotic cells tended to be higher in the IP group than in the placebo group (27.0 +/- 7.1 vs. 15.6 +/- 5.6%, n.s.). In anaesthetized pigs, IP did not therefore attenuate renal dysfunction and morphological damage resulting from 60 min of renal normothermic ischaemia followed by 8 h of reperfusion.     

Ca2+-mediated suppression of the GABA-response through modulation of chloride channel gating in frog sensory neurones

A suppressant effect of intracellular free Ca2+ on the gamma-aminobutyric acid (GABA)-induced chloride inward current (ICI(GABA)) was studied in isolated frog sensory neurones under whole cell voltage clamp. Voltage-dependent Ca2+ influx elicited during the steady state of ICI(GABA)-induced a fast, slowly recovering current relaxation in the outward direction, the amplitude of which was dependent on total Ca2+ influx. This suppressant effect showed specificity for different divalent cations, suggesting action at a specific intracellular effector. Single channel recording revealed a Ca2+-dependent decrease in the duration of the open time of the GABA-gated Cl- channel without change in single channel conductance.     

Multiple roles of the messenger molecule cGMP in testicular function

The messenger molecule cyclic guanosine monophosphate (cGMP) is produced by different isoforms of the enzyme guanylate cyclase (GC). Natriuretic peptides (ANP and CNP) bind to and activate particulate GCs, whereas NO and CO activate a soluble form of GC. The specific relevance of the cGMP system for reproductive functions has been recently demonstrated by the successful use of sildenafil (Viagra), an inhibitor of cGMP-specific phosphodiesterase type 5, for the treatment of erectile dysfunction. In the testis, cGMP signal transduction pathways are involved in a variety of local functions, based on autocrine or paracrine effects. In particular, cGMP has been suggested to influence motility in spermatozoa, development of testicular germ cells, relaxation of peritubular lamina propria cells, testosterone synthesis in Leydig cells and dilatation of testicular blood vessels. The physiological significance of cGMP accumulation in Scrtoli cells is not yet clear. Taken as a whole, the evidence suggests that cGMP-mediated processes might influence both the potentia coeundi within the penis and the potentia generandi at various levels within the testis.     

Ischemic preconditioning improves energy state and transplantation survival in obese Zucker rat livers

Livers from obese donors often have fatty infiltrates and are more susceptible to ischemia-reperfusion injury and subsequent graft dysfunction. This often leads to the exclusion of organs from obese donors. We investigated whether ischemic preconditioning (IP, 10 min ischemia, 10 min reperfusion) preserves cellular metabolism in livers from obese Zucker rats during cold ischemia. Liver samples (-IP and +IP) were collected from obese and control lean rats at different time points of cold ischemia (CI) and analyzed by magnetic resonance spectroscopy (1H- and 31P-MRS) to assess whether IP improves hepatic cellular metabolism. IP significantly improved high energy metabolism in IP livers from obese rats when compared with obese controls during the first hours of CI. At 4 h of cold storage, obese IP livers were not different from control lean non-IP livers. The beneficial metabolic effect of IP on livers form obese rats, however, was absent at 8 h of reperfusion. In contrast, in livers from lean rats, IP resulted in improved high-energy metabolism during the entire observation period of 8 h. In a later part of the study, IP of liver grafts from obese rats before 4 h of cold storage improved recipient survival after graft transplantation. IP of liver grafts from obese rats before 4 h of CI increases 24-h survival of recipient animals from 25% to 88%.     

Chirurgische Ascitesbehandlung

Ohne Zusammenfassung Mit 1 Abbildung