Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function.

Inhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized that inhibition of C5 before reperfusion will decrease infarct size and improve ventricular function in a porcine model of myocardial infarction. In pigs (Sus scrofa), the left anterior descending coronary artery was occluded (40 min) and reperfused (240 min). Coversin or placebo was infused 20 min after occlusion and throughout reperfusion in 16 blindly randomized pigs. Coversin significantly reduced myocardial infarction in the area at risk by 39% (p = 0.03, triphenyl tetrazolium chloride staining) and by 19% (p = 0.02) using magnetic resonance imaging. The methods correlated significantly (R = 0.92, p < 0.01). Tissue Doppler echocardiography showed increased systolic displacement (31%, p < 0.01) and increased systolic velocity (29%, p = 0.01) in coversin treated pigs. Interleukin-1ß in myocardial microdialysis fluid was significantly reduced (31%, p < 0.05) and tissue E-selectin expression was significantly reduced (p = 0.01) in the non-infarcted area at risk by coversin treatment. Coversin ablated plasma C5 activation throughout the reperfusion period and decreased myocardial C5b-9 deposition, while neither plasma nor myocardial LTB4 were significantly reduced. Coversin substantially reduced the size of infarction, improved ventricular function, and attenuated interleukin-1ß and E-selectin in this porcine model by inhibiting C5. We conclude that inhibition of C5 in myocardial infarction should be reconsidered.

Effect of Perfusion Fluids on Recovery of Inflammatory Mediators in Microdialysis.

Microdialysis is an excellent tool to assess tissue inflammation in patients, but in vitro systems to evaluate recovery of inflammatory mediators have not been standardized. We aimed to develop a reference plasma preparation and evaluate different perfusion fluids with respect to recovery of metabolic and inflammatory markers. The reference preparation was produced by incubation of human blood with lipopolysaccharide and cobra venom factor to generate cytokines and activate complement, respectively. Microdialysis with 100 kDa catheters was performed using different colloid and crystalloid perfusion fluids (hydroxyethyl starch (HES) 130/0.4, HES 200/0.5, hyperosmolar HES 200/0.5, albumin 200 g/l, T1 perfusion fluid and Ringer's acetate) compared to today's recommended dextran 60 solution. Recovery of glucose, glycerol and pyruvate was not significantly different between the perfusion fluids, whereas lactate had lower recovery in HES 200/0.5 and albumin perfusion fluids. Recovery rates for the inflammatory proteins in comparison with the concentration in the reference preparation differed substantially: IL-6 = 9%, IL-1ß = 18%, TNF = 0.3%, MCP-1 = 45%, IL-8 = 48%, MIG = 48%, IP-10 = 25%, C3a = 53% and C5a = 12%. IL-10 was not detectable in microdialysis dialysate. HES 130/0.4 and HES 200/0.5 yielded a recovery not significantly different from dextran 60. Hyperosmolar HES 200/0.5 and albumin showed significantly different pattern of recovery with increased concentration of MIG, IP-10, C3a and C5a and decreased concentration of IL-1ß, TNF, MCP-1 and IL-8 in comparison with dextran 60. In conclusion, microdialysis perfusion fluid dextran 60 can be replaced by the commonly used HES 130/0.4, whereas albumin might be used if specific immunological variables are in focus. The present reference plasma preparation is suitable for in vitro evaluation of microdialysis systems.

Myocardial tissue CO2 tension detects coronary blood flow reduction after coronary artery bypass in real-time†.

BACKGROUND: Coronary stenosis after coronary artery bypass grafting (CABG) may lead to myocardial ischaemia and is clinically difficult to diagnose. In a CABG model, we aimed at defining variables that detect hypoperfusion in real-time and correlate with impaired regional ventricular function by monitoring myocardial tissue metabolism. METHODS: Off-pump CABG was performed in 10 pigs. Graft blood flow was reduced in 18 min intervals to 75, 50, and 25% of baseline flow with reperfusion between each flow reduction. Myocardial tissue Pco2 (Pt(CO2)), Po2, pH, glucose, lactate, and glycerol from the graft supplied region and a control region were obtained. Regional cardiac function was assessed as radial strain. RESULTS: In comparison with baseline, myocardial pH decreased during 75, 50, and 25% flow reduction (-0.15; -0.22; -0.37, respectively, all P<0.05) whereas Pt(CO2) increased (+4.6 kPa; +7.8 kPa; +12.9 kPa, respectively, all P<0.05). pH and Pt(CO2) returned to baseline upon reperfusion. Lactate and glycerol increased flow-dependently, while glucose decreased. Regional ventricular contractile function declined significantly. All measured variables remained normal in the control region. Pt(CO2) correlated strongly with tissue lactate, pH, and contractile function (R=0.86, R=-0.91, R=-0.70, respectively, all P<0.001). New conductometric Pt(CO2) sensors were in agreement with established fibre-optic probes. Cardiac output was not altered. CONCLUSIONS: Myocardial pH and Pt(CO2) monitoring can quantify the degree of regional tissue hypoperfusion in real-time and correlated well with cellular metabolism and contractile function, whereas cardiac output did not. New robust conductometric Pt(CO2) sensors have the potential to serve as a clinical cardiac monitoring tool during surgery and postoperatively.

Tissue gas tensions and tissue metabolites for detection of organ hypoperfusion and ischemia.

BACKGROUND: The aim of this study was to evaluate how tissue gas tensions and tissue metabolites measured in situ can detect hypoperfusion and differentiate between aerobic and anaerobic conditions during hemorrhagic shock. We hypothesized that tissue PCO(2) (PtCO(2)) would detect hypoperfusion also under aerobic conditions and detect anaerobic metabolism concomitantly with or earlier than other markers. METHODS: Prospective experimental animal study with eight anesthetized pigs subjected to a continuous blood loss ∼8% of total blood volume per hour until death. We measured cardiac index, organ blood flows, and tissue levels of PO(2), PCO(2), glucose, pyruvate, lactate, and glycerol in intestine, liver, kidney, and skeletal muscle. RESULTS: With reduction in blood flow to the organs under aerobic conditions, PtCO(2) increased ∼1-4 kPa from baseline. With the onset of tissue hypoxia there was a pronounced increase of PtCO(2), lactate, lactate-pyruvate (LP) ratio, and glycerol. Tissue pH and bicarbonate decreased significantly, indicating that metabolic acid was buffered by bicarbonate to generate CO(2). CONCLUSION: Moderate tissue hypoperfusion under aerobic conditions is associated with increased PtCO(2), in contrast to metabolic parameters of ischemia (lactate, LP ratio, and glycerol) which remain low. From the onset of ischemia there is a much more rapid and pronounced increase in PtCO(2), lactate, and LP ratio. PtCO(2) can be used as a marker of hypoperfusion under both aerobic and anaerobic conditions; it gives an earlier warning of hypoperfusion than metabolic markers and increases concomitantly with or earlier than other markers at the onset of tissue anaerobiosis.

pH-regulated anion antiport in nucleated mammalian cells.

The uptake of 36Cl- into cells was measured after preincubation in medium containing nigericin and KCl to allow control of the intracellular pH. When the pH was increased from pH 7.0 to pH 7.3 there was a 10-fold increase in the rate of 36Cl- uptake. The increase was half maximal at pH 7.15 in Vero and L-cells, whereas in phorbol 12-myristate 13-acetate-treated Vero cells the increase was half maximal at pH 6.9. Kinetic studies showed that in cells preincubated with nigericin and isotonic KCl, both at pH 7.0 and at pH 8.0, the Km for Cl- was 7 mM. In the two cases the Jmax was 1.7 X 10(8) Cl- ions X cell-1 X s-1 and 1.6 X 10(9) Cl- ions X cell-1 X s-1, respectively. Bicarbonate inhibited 36Cl- uptake with a Ki of 5-6 mM. Probably, the anion antiporter plays a role in the regulation of the intracellular pH.

Routing of internalized ricin and ricin conjugates to the Golgi complex.

Receptor-mediated endocytosis and intracellular routing of native ricin, and of ricin conjugated to colloidal gold (Ri-Au) and to horseradish peroxidase (Ri-HRP), have been studied in cultured MCF-7 and Vero cells by electron microscopical techniques including serial section analysis. Both native ricin, as demonstrated by immunoperoxidase cytochemistry, and the ricin conjugates were internalized via a common coated pit-coated vesicle pathway to reach vacuolar and tubulo-vesicular portions of the endosomal system. In addition, native ricin and a purified monovalent fraction of Ri-HRP reached distinct Golgi cisterns, whereas Ri-Au and polyvalent Ri-HRP did not. The results delineate intracellular routing of native ricin and compare it with the routing of different ricin conjugates. Moreover, our study shows that conjugates of a particular ligand (ricin) and various probes (e.g., gold and peroxidase), may be handled differently by cells. Sorting apparently takes place in the endosomal system, allowing some but not other molecules to reach Golgi elements. This sorting seems to depend on the valency of the ricin conjugate.

First Experience With Rectus Sheath Block for Postoperative Analgesia After Pancreas Transplant: A Retrospective Observational Study.

BACKGROUND: Standard of care for postoperative analgesia after pancreas transplant has been thoracic epidural analgesia (TEA). A high incidence of venous graft thrombosis necessitated a change to a more aggressive anticoagulation protocol. To minimize the risk of epidural hemorrhages, we changed from TEA to rectus sheath block (RSB) in 2017. METHODS: From June 2016 to December 2017, a total of 29 consecutive pancreas transplant recipients were included. Sixteen were treated with TEA and 13 were treated with RSB. In the TEA group, the catheter was inserted before induction of general anesthesia, and an epidural infusion was started intraoperatively. An ultrasound-guided RSB was performed bilaterally, and a bolus of local anesthetic was administered before an 18G catheter was inserted. The patients received intermittent local anesthetic boluses every 4 hours in addition to an intravenous patient-controlled analgesia with oxycodone. Both groups received oral acetaminophen and additional rescue opioids. RESULTS: The administered amount of intravenous morphine equivalents (MEQ) was not significantly different between the RSB and TEA groups. The median MEQ consumption per day during the stay at the surgical ward was 23 mg MEQ/d (interquartile range [IQR], 14-33 mg MEQ/d) in the TEA group compared with 19 mg MEQ/d (IQR, 14-32 mg MEQ/d) in the RSB group (P = .4). The duration of the pain catheters was significantly longer in the RSB group. We had no complications related to insertion, use, or removal of the RSB or the TEA catheters, and overall patient satisfaction and comfort was good. CONCLUSION: Compared with TEA, RSB was equally effective and safe for postoperative analgesia in heavily anticoagulated pancreas transplant patients.

New biomarkers in an acute model of live Escherichia coli-induced sepsis in pigs.

We developed a live Escherichia coli model of acute sepsis in pigs with emphasize on biomarkers reflecting the early inflammatory response of sepsis. Healthy pigs, 25-35 kg, were challenged intravenously (IV) (n = 12) or intrapulmonary (n = 6) with live E. coli and observed for 3 and 5 h respectively. Control pigs received culture medium (n = 6 + 3). Haemodynamic parameters and a broad panel of inflammatory mediators were measured. The dose of bacteria was carefully titrated to obtain a condition resembling the early phase of human septic shock. The IV group displayed a pro-inflammatory response [significant increase in tumour necrosis factor-alpha, interleukin (IL)-6 and IL-8] and an early anti-inflammatory response (significant increase in IL-10). For the first time, we demonstrate a significant increase in IL-12 and matrix metalloproteinase-9 (MMP) early in pig sepsis. Coagulation was activated (significant increase in thrombin-antithrombin complexes) and there was a significant decrease in the serum proteins suggesting capillary leakage. Haemodynamic parameters reflected a septic condition with significant decrease in systemic blood pressure, increases in heart rate, pulmonary artery pressure and base deficit. None of these changes was observed in the control group. Interleukin-1beta and vascular endothelial growth factor increased in both groups. Nitric oxide measurements suggested an initial pulmonary vascular endothelial inflammatory response. The intrapulmonary group, which did not resemble septic condition, showed a substantial increase in MMP-9. In this porcine model of sepsis, IL-12 and MMP-9 were detected for the first time. These biomarkers may have an impact in the understanding and future treatment of sepsis.

Ability of inhibitors of glycosylation and protein synthesis to sensitize cells to abrin, ricin, Shigella toxin, and Pseudomonas toxin.

A number of compounds that interfere with glycoprotein synthesis and transport have been tested for their ability to sensitize cells to cancerostatic protein toxins. Tunicamycin, swainsonine, cycloheximide, and puromycin sensitized Vero cells and HeLa cells to abrin and ricin, as we have found previously with monensin (K. Sandvig and S. Olsnes, J. Biol. Chem., 257: 7504-7513, 1982). Cycloheximide, but not swainsonine, sensitized Vero cells to Pseudomonas exotoxin A and Shigella toxin. The ability of ricin to intoxicate cells was much lower at 19 degrees C than at 37 degrees C and there was almost no sensitizing effect of cycloheximide and monensin at 19 degrees C. Studies by electron microscopy showed that ricin conjugated to horseradish peroxidase appeared in trans Golgi elements in Vero cells. Possibly, transport of ricin into the cytosol requires passage through the Golgi apparatus. The possibility that the sensitizing agents here described may be valuable in enhancing the action of immunotoxins is discussed.

In vivo characterization of ischemic small intestine using bioimpedance measurements.

The standard clinical method for the assessment of viability in ischemic small intestine is still visual inspection and palpation. This method is non-specific and unreliable, and requires a high level of clinical experience. Consequently, viable tissue might be removed, or irreversibly damaged tissue might be left in the body, which may both slow down patient recovery. Impedance spectroscopy has been used to measure changes in electrical parameters during ischemia in various tissues. The physical changes in the tissue at the cellular and structural levels after the onset of ischemia lead to time-variant changes in the electrical properties. We aimed to investigate the use of bioimpedance measurement to assess if the tissue is ischemic, and to assess the ischemic time duration. Measurements were performed on pigs (n = 7) using a novel two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. After induction of anaesthesia, an ischemic model with warm, full mesenteric arterial and venous occlusion on 30 cm of the jejunum was implemented. Electrodes were placed on the serosal surface of the ischemic jejunum, applying a constant voltage, and measuring the resulting electrical admittance. As a control, measurements were done on a fully perfused part of the jejunum in the same porcine model. The changes in tan δ (dielectric parameter), measured within a 6 h period of warm, full mesenteric occlusion ischemia in seven pigs, correlates with the onset and duration of ischemia. Tan δ measured in the ischemic part of the jejunum differed significantly from the control tissue, allowing us to determine if the tissue was ischemic or not (P < 0.0001, F = (1,75.13) 188.19). We also found that we could use tan δ to predict ischemic duration. This opens up the possibility of real-time monitoring and assessment of the presence and duration of small intestinal ischemia.

Inhibition of chloride/bicarbonate antiports in monkey kidney cells (Vero) by non-steroidal anti-inflammatory drugs.

Two chloride/bicarbonate antiport mechanisms are involved in the regulation of cytosolic pH (pHi) in Vero cells, namely Na+-dependent chloride/bicarbonate antiport to normalize pHi after acidification of the cytosol, and Na+-independent Cl-/HCO3- exchange to regulate pHi back to normal after alkalinization of the cytosol. We have tested the effects of the non-steroidal anti-inflammatory drugs acetylsalicylic acid (aspirin), salicylic acid, indomethacin and piroxicam on chloride/bicarbonate exchange and on chloride self exchange in Vero cells. All these drugs were found to inhibit both the Na+-independent and the Na+-linked chloride/bicarbonate antiport in a dose dependent manner. The Na+-independent chloride/bicarbonate antiport was inhibited by lower doses of the drugs than the Na+-linked antiport. The ability of the drugs to inhibit chloride self exchange did not vary much with varying external pH, indicating that the inhibitory effect is due to the anionic form of the drugs. Inhibition occurred immediately upon addition of the drugs, and it was rapidly reversible, indicating that the inhibitory effect is due to direct interaction of the drugs with chloride/bicarbonate antiport, and not to inhibition of prostaglandin synthesis. The relevance of our findings to the clinical effects of the drugs is discussed.

Minimally invasive direct coronary artery bypass grafting without cardiopulmonary bypass in combination with intraoperative percutaneous transluminal coronary angioplasty for palliative coronary revascularization in a heart transplant recipient.

The use of minimally invasive direct coronary artery bypass grafting without cardiopulmonary bypass in combination with intraoperative percutaneous transluminal coronary angioplasty for myocardial revascularization in a heart transplant recipient is reported.

Methods for detecting local intestinal ischemic anaerobic metabolic acidosis by PCO2.

Gut ischemia is often assessed by computing an imaginary tissue interstitial Ph from arterial plasma HCO3- and the PCO2 in a saline-filled balloon tonometer after equilibration with tissue PCO2 and (PtiCO2). PtiCO2 may alternatively be assumed equal to venous PCO2 (PVCO2) in that region of gut. The idea is that as blood flow decreases, gut PtiCO2 and PVCO2 will increase to the maximum aerobic value, i.e., maximum respiratory PVCO2 (PVCO2rmax). Above a "critical" anaerobic threshold, lactate (La-) generation, by titration of tissue HCO3-, should raise PtiCO2 above PVCO2rmax. During progressive selective whole intestinal flow reduction in six pentobarbital-anesthetized pigs, we used PCO2 electrodes to test the hypotheses that critical PtiCO2 is achieved earlier in mucosa than in serosa and that PVCO2rmax, computed using an in vitro model, predicts critical PtiCO2. We defined critical PtiCO2 as the inflection of PtiCO2-PVCo2 vs. O2 delivery (QO2) plots. Critical QO2 for O2 uptake was 12.55 +/- 2 ml.kg-1.min-1. Critical PtiCO2 for mucosa and serosa was achieved at similar whole intestine QO2 (13.90 +/- 5 and 13.36 +/- 5 ml.kg-1.min-1, P = NS). Critical PtiCO2 (129 +/- 24 and 96 +/- 21 Torr) exceeded PVCO2rmax (62 +/- 3 Torr). During ischemia, La- excretion into portal venous blood was matched by K+ excretion, causing PVCO2 to increase only slightly, despite PtiCO2 rising to 380 +/- 46 (mucosa) and 280 +/- 38 (serosa) Torr. These results suggest that mucosa and serosa become dysoxic simultaneously, that ischemic dysoxic gut is essentially perfused, and that in vitro predicted PVCO2rmax underestimates critical PtiCO2.

Gas supersaturation in the cecal wall of mice due to bacterial CO2 production.

PCO2 in the lumen and serosa of cecum and jejunum was measured in mice. The anesthetic used was a fentanyl-fluanisone-midazolam mixture. PCO2 was recorded in vivo and postmortem. PCO2 was 409 +/- 32 Torr (55 +/- 4 kPa) in the cecal lumen and 199 +/- 22 Torr (27 +/- 3 kPa) on the serosa in normal mice. Irrigation of the cecum resulted in serosal and luminal PCO2 levels of 65-75 Torr. Cecal PCO2 was significantly lower in germ-free mice (65 +/- 5 Torr). Cecal PCO2 increased significantly after introduction of normal bacterial flora into germ-free mice. Introduction of bacterial monocultures into germ-free mice had no effect. After the deaths of the mice, cecal PCO2 increased rapidly in normal mice. The intestinal bacteria produced the majority of the cecal PCO2, and the use of tonometry in intestinal segments with a high bacterial activity should be interpreted with caution. We propose that serosal PCO2 levels >150-190 Torr (20-25 kPa) in the cecum of mice with a normal circulation may represent a state of gas supersaturation in the cecal wall.

Mitochondrial redox state as a potential detector of liver dysoxia in vivo.

Dysoxia can be defined as ATP flux decreasing in proportion to O2 availability with preserved ATP demand. Hepatic venous beta-hydroxybutyrate-to-acetoacetate ratio (beta-OHB/AcAc) estimates liver mitochondrial NADH/NAD and may detect the onset of dysoxia. During partial dysoxia (as opposed to anoxia), however, flow may be adequate in some liver regions, diluting effluent from dysoxic regions, thereby rendering venous beta-OHB/AcAc unreliable. To address this concern, we estimated tissue ATP while gradually reducing liver blood flow of swine to zero in a nuclear magnetic resonance spectrometer. ATP flux decreasing with O2 availability was taken as O2 uptake (VO2) decreasing in proportion to O2 delivery (QO2); and preserved ATP demand was taken as increasing Pi/ATP. VO2, tissue Pi/ATP, and venous beta-OHB/AcAc were plotted against QO2 to identify critical inflection points. Tissue dysoxia required mean QO2 for the group to be critical for both VO2 and for Pi/ATP. Critical QO2 values for VO2 and Pi/ATP of 4.07 +/- 1.07 and 2.39 +/- 1.18 (SE) ml . 100 g-1 . min-1, respectively, were not statistically significantly different but not clearly the same, suggesting the possibility that dysoxia might have commenced after VO2 began decreasing, i.e., that there could have been "O2 conformity." Critical QO2 for venous beta-OHB/AcAc was 2.44 +/- 0.46 ml . 100 g-1 . min-1 (P = NS), nearly the same as that for Pi/ATP, supporting venous beta-OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector of dysoxia in liver.

Intraoperative angiography in minimally invasive direct coronary artery bypass grafting.

Intraoperative angiography in minimally invasive direct coronary artery bypass grafting without cardiopulmonary bypass and in hybrid procedures is reported. Twelve procedures were performed in a specially designed surgical-radiologic suite with a cross-disciplinary organization. In 2 patients the anastomosis was successfully revised on the basis of angiographic findings. In 4 of the 12 patients anastomosis of the left internal mammary artery to the left anterior descending coronary artery performed as a minimally invasive direct coronary artery bypass grafting procedure was combined with percutaneous transluminal coronary angioplasty of lesions in other coronary vessels in the same session. Intraoperative angiography allows a reliable diagnosis of an anastomosis or graft failure and prompt and reliable correction, and it allows the combination of minimally invasive direct coronary artery bypass grafting and angioplasty in one session.

Laparoscopic and open surgery for pheochromocytoma.

BACKGROUND: Laparoscopic adrenalectomy is a promising alternative to open surgery although concerns exist in regard to laparoscopic treatment of pheocromocytoma. This report compares the outcome of laparoscopic and conventional (open) resection for pheocromocytoma particular in regard to intraoperative hemodynamic stability and postoperative patient comfort. METHODS: Seven patients laparoscopically treated (1997-2000) and nine patients treated by open resection (1990-1996) at the National Hospital (Rikshospitalet), Oslo. Peroperative hemodynamic stability including need of vasoactive drugs was studied. Postoperative analgesic medication, complications and hospital stay were recorded. RESULTS: No laparoscopic resections were converted to open procedure. Patients laparoscopically treated had fewer hypertensive episodes (median 1 vs. 2) and less need of vasoactive drugs peroperatively than patients conventionally operated. There was no difference in operative time between the two groups (median 110 min vs. 125 min for adrenal pheochromocytoma and 235 vs. 210 min for paraganglioma). Postoperative need of analgesic medication (1 vs. 9 patients) and hospital stay (median 3 vs. 6 days) were significantly reduced in patients laparoscopically operated compared to patients treated by the open technique. CONCLUSION: Surgery for pheochromocytoma can be performed laparoscopically with a safety comparable to open resection. However, improved hemodynamic stability peroperatively and less need of postoperative analgesics favour the laparoscopic approach. In experienced hands the laparoscopic technique is concluded to be the method of choice also for pheocromocytoma.

Activation of coagulation and platelets by candidate membranes of implantable devices in a whole blood model without soluble anticoagulant.

Implantable devices are challenged with thrombus formation at their biomaterial interface. Thus the importance of identifying compatible biomaterials that will help to improve the performance of these devices are becoming increasingly paramount. The aim of this study was to evaluate the activation of coagulation and platelets by candidate membranes considered for use in implantable devices on the basis of an adapted whole blood model without soluble anticoagulants. Evaluated materials were incubated with whole blood without soluble anticoagulant in wells coated with heparin. Prothrombin fragment 1+2 (PTF 1+2), thrombin-antithrombin complex (TAT), and ß-thromboglobulin (BTG) were analyzed in plasma samples using enzyme immunoassays. The C5 inhibitor eculizumab was used to evaluate the role of complement. Incubation of two of the polyamide membranes PAR and PATF led to an increase in concentration of PTF 1+2 and TAT (p < 0.01 for PAR, ns for PATF). The BTG concentration was significantly increased for five materials [PAR, PATF, polycarbonate (PC), and two polyarylethersulphone membranes PAES-1 and PAES-2]. Complement inhibition had no effect on coagulation or platelet activation induced by PAR and PATF. In conclusion, PAR and PATF were not compatible with blood and should be avoided for use in implantable devices.