Estimation of Blood Flow in Transcutaneous PO2 Measurements

A method for estimation of the cutaneous blood flow in transcutaneous Po₂ measurements is presented. Recordings of electrode and skin temperature make it possible to compute the effect dissipated to the circulating blood. Eighteen measurements were performed on three healthy volunteers at electrode temperature settings from 37.0°C to 45.0°C. The blood-flow estimates ranged from 0.07 to 0.19 ml·cm^-2·min^-1. At an electrode temperature of 45.0°C the investigations showed a tc-Po₂ value as low as 7 mmHg (0.9 kPa) which, however, corresponded well to the lowest blood-flow estimate determined. The temperature-corrected (37°C) a-Po₂-tc-Po₂ gradient ranged from 50 mmHg to 95 mmHg (6.7–12.6 kPa). The investigations confirm the importance of simultaneous determinations of cutaneous blood flow, capillary temperature and cutaneous oxygen consumption in order to describe the connection between arterial and cutaneous oxygen tension. The cutaneous blood How seems in this connection to be the most important parameter.     

Minimum Cerebral Blood Flow and Metabolism During Craniotomy. Effect of Thiopental Loading

Cerebral blood flow and metabolism were measured repeatedly during surgery for cerebral tumours by a modification of the classical Kety & Schmidt method using ¹³³Xe infusion intravenously. Our standard procedure for neuroanaesthesia (pentobarbitone-fentanyl induction, halothane-nitrous oxide maintenance) reduced blood flow from 47.1 to 24.2 ml.100 g . ml^-1 and metabolism from 3.30 to 1.83 ml O₂ . 100 g^-1 . ml^-1. PacO₂ was reduced by hyperventilation from 5.3 to 3.6 kPa. Additional thiopental loading and maintenance using 4 + 4 mg.kg^-1 (n=5) or 8 + 8 mgkg^-1 (n = 5) reduced cerebral metabolism by an additional 15% ( P <0.0) and blood flow by 16.5% ( P <0.01), while mean arterial blood pressure fell from 11.0 to 9.9 kPa ( P <0.05). Paco₂ remained unchanged. This additional reduction in cerebral metabolism and blood flow is small, but we nevertheless conclude that it may well be of clinical interest to the problem of protecting the brain in case of episodes of focal cerebral ischaemia which may arise peroperatively during intracramal surgery.     

Subcutaneous blood flow in man during sleep with continuous epidural anaesthesia

Background: Subcutaneous blood flow increases during sleep and we evaluated if this increase is affected by epidural anaesthesia.
Methods: Lower leg subcutaneous blood flow was determined by ¹³³Xenon clearance in ten subjects during continuous epidural anaesthesia at L₂-L₃ including eight hours of sleep, while the upper abdominal subcutaneous blood flow served as control.
Results: Epidural anaesthesia to the level of the umbilicus was followed by an increase in the lower leg subcutaneous blood flow from 3.4 (1.8-6.3) to 7.8 (3.6–16.9) ml min^-1 100 g^-1 (median and range; P <0.001) and returned to 3.5 (2.4–7.6) ml min^-1 100 g^-1 after 88 (45–123) min. In contrast, until the period of sleep the upper abdominal region blood flow remained at 5.2 (3.2–6.4) ml min^-1 100 g^-1. During sleep, lower leg subcutaneous blood flow did not change significantly, but the upper abdominal flow increased to 6.2 (5.2–7.2) ml min^-1 100 g^-1 after 34 (29–70) min ( P <0.01), and it remained elevated for 125 (100–164) min.
Conclusions: The results indicate that although epidural anaesthesia induced only a temporary increase in lower leg subcutaneous blood flow, it hindered the rise in subcutaneous blood flow normally manifest during early sleep.     

Changes in venous hemodynamics after renal transplantation

Abstract To explain an occasionally observed transient swelling of the ipsilateral leg in renal transplant recipients in the absence of deep vein thrombosis, we took serial measurements of venous outflow resistance and duplex examinations of both legs. Fourteen recipients of a living related donor kidney graft were submitted to strain gauge plethysmography and duplex examination before transplantation and 1 and 6 weeks thereafter. Venous outflow resistance and venous flow were measured and the veins were assessed for thrombosis. Strain gauge plethysmography showed a significant increase in venous outflow resistance in the leg on the side of the renal transplant 1 week after transplantation [0.28 ± 0.13 vs 0.40 ± 0.15 mmHg.s (ml/100 ml)^-1; P < 0.05]. Six weeks later, the venous outflow resistance had returned to preoperative values [0.30 ± 0.11 mmHg.s (ml/100 ml)^-1; P = NS]. On the contralateral side, no significant differences were found. Duplex examinations showed no signs of thrombosis. Venous flow measurements in the common femoral vein showed no significant differences. We conclude that the additional blood supply to the iliac veins results in an increase in venous outflow resistance in the ipsilateral leg, which can explain the observed swelling of this leg and may have implications for the preferred method of diagnosis of venous thrombosis after renal transplantation.     

Pentoxifylline in Regional Cerebral Ischemia in Cats

The effect of pentoxifylline on regional cerebral ischemia was evaluated in 22 cats. In one group of 10 cats the middle cerebral artery (MCA) was occluded by a transorbital approach, and the cats were maintained on an intensive care protocol for 48 h. Pentoxifylline 10 mg · kg^-1 initiated intravenously 30 niin post-occlusion and followed by 6.3 mg · kg^-1 · h^-1 for 48 h failed to improve the neurologic outcome or infarct size when compared to controls. In another group of 12 cats with the same ischemic lesion, regional cerebral blood flow in the anterior (ischemic) area and an ipsilateral parieto-occipital region was measured by ¹³³Xe wash-out after intra-arterial injection. MCA occlusion reduced the anterior flow by 50% from a mean control value of 62.7 ml · 100 g^-1 · min^-1 to 31.9 ml · 100 g^-1 · min^-1. The parieto-occipital flow was reduced by 20–30%, probably due to diaschisis. Pentoxifylline produced only a brief, although approximately 50%, increase in flow detected over both brain regions and failed to improve the cerebral energy stores as measured 150 min following MCA occlusion. From the neurologic, blood flow and metabolic data, it is concluded that pentoxifylline failed to affect cerebral ischemia favorably in cats.     

Intrathoracic and pulmonary blood volume during CO2-pneumoperitoneum in humans

Background : Induction of CO₂-pneumoperitoneum may have significant effects on systemic and pulmonary haemodynamics. We hypothesized, that intrathoracic (ITBV) and pulmonary blood volume (PBV) are affected during intra-abdominal CO₂-insufflation, which may be pronounced by positional changes of the patient.
Methods : Sixteen anaesthetized patients were studied before, during and after CO₂-pneumoperitoneum for laparoscopic cholecystectomy. A dye indicator technique was used to assess ITBV and PBV. In addition, gas exchange and haemodynamics were recorded.
Results : In the supine position, induction of CO₂-pneumoperitoneum had no effects on ITBV, PBV and cardiac output. Mean systemic arterial pressure increased from 10.9±1.5 kPa (82±11 mmHg) to 12.7±1.5 kPa (95±11 mmHg, P<0.01). In the reverse Trendelenburg position ITBV decreased from 19.8±5.1 ml . kg^-1 to 16.7±3.7 ml . kg¹ ( P <0.05) during CO₂-insufflation, but increased to control values after 20 min. PBV decreased from 4.2±1.2 ml . kg^-1 to 3.4±1.1 ml . kg^-1 (P<0.05) and remained decreased during CO₂-pneumoperitoneum. Calculated venous admixture was unchanged throughout the study. Deflation of CO₂-pneumoperitoneum increased ITBV (22.4±5.2 ml . kg^-1, P<0.05) and cardiac output above control values.
Conclusions : In anaesthetized-paralyzed patients in the reverse Trendelenburg position intra-abdominal CO₂-insufflation is associated with significant alterations of ITBV and PBV. The release of CO₂-pneumoperitoneum is associated with a re-distribution of blood into the thorax.     

Skeletal Muscle Oxygen Pressure Fields in Artificially Ventilated, Critically 111 Patients

The MDO (Mehrdraht Dortmund Oberfläche) oxygen electrode was used in a study of skeletal muscle oxygen pressure fields. presented as histograms, in critically ill patients artificially ventilated with gas mixtures of different oxygen concentrations. The histograms were compared with forearm blood flow measurements performed with strain gauge plethysmography. Local blood flow and permeability-surface area product (PS) were also studied by the simultaneous clearances of ¹³³xenon and ⁵¹ Cr-EDTA. The histogram distribution type was normal, i.e. approximately Gaussian, at arterial oxygen pressure levels between 10 and 18 kPa. At arterial oxygen pressures outside this range the histogram distribution types were abnormal, i.e. they showed a nonsymmetrical distribution of oxygen pressure values, but their mean was approximately the same as in the normal histogram. However, there were significantly higher tissue oxygen pressure mean values in the patients (3.43 kPa) than in a group of healthy human volunteers (2.25 kPa). Mean forearm blood flow and the clearances of ¹³³ xenon and ⁵¹ Cr-EDTA showed marked variations during the measurements both intraindividually and interindividually. Mean forearm blood now and mean clearances of¹³³ xenon showed opposite trends compared with arterial oxygen pressures. Mean clearances of ⁵¹ Cr-EDTA and mean PS showed only minor variations at the different arterial oxygen pressure levels.     

Efficiency of an External Support to Reduce Lipid Infiltration into Venous Grafts: In Vitro Evaluation

Abstract: Excessive distension of venous grafts due to arterial pressure enhances the convective water transport (filtration flow) through the vessel wall, and thus might affect the infiltration of macromolecules such as lipoproteins. In this paired experimental study, filtration velocities were measured at 100 mm Hg for canine jugular veins with or without external supports of expanded poly-tetrafluoroethylene (ePTFE) arterial prostheses. In addition, to assess the effect of filtration velocity on lipid infiltration or uptake, canine jugular veins were wrapped over half of their lengths with ePTFE arterial prostheses and perfused with dog serum containing ³H-cholesterol at a pressure of 100 mm Hg. At 100 mm Hg, the average filtration velocity of the wrapped jugular veins was 7.9 ± 1.3 ± 10^-6 cm/s whereas the average filtration velocity of the unwrapped veins was 27.3 ± 2.7 ± 10^-6 cm/s (p < 0.005). Moreover, the unwrapped veins had a significantly higher uptake rate of labeled cholesterol than the wrapped veins (10.9 ± 7.3 ± 10^-4 cm/h and 5.0 ± 1.6 ± 10^-4 cm/h, respectively, p < 0.005). In conclusion, under arterial pressure, veins experience excessive distention, which leads to significant increases in both filtration flow and cholesterol uptake. An external wrap or support of ePTFE material protects veins from excessive distension and thus may prevent atherosclerosis in venous grafts by reducing cholesterol uptake.     

Validation of plasma clearance of 51Cr-EDTA in adult renal transplant recipients: comparison with inulin renal clearance

Plasma clearance of ⁵¹Cr-EDTA (⁵¹Cr-EDTA-Cl) is an alternative method to evaluate glomerular filtration rate (GFR). This study aimed to investigate the concordance between ⁵¹Cr-EDTA-Cl and renal inulin clearance (In-Cl) in renal transplant recipients as well to determine the repeatability of ⁵¹Cr-EDTA-Cl in kidney donors. Forty four kidney recipients and 22 kidney donors were enrolled. Simultaneous measurements of ⁵¹Cr-EDTA-Cl and In-Cl were performed. A single dose of 3.7MBq of ⁵¹Cr-EDTA was injected and the plasma disappearance curve was created by taking blood samples at 2, 4, 6 and 8 h after injection. Bland and Altman statistical approach was used to quantify the agreement between In-Cl and ⁵¹Cr-EDTA-Cl and to determine the better concordance between all possibilities of measure for the ⁵¹Cr-EDTA-Cl. The mean of In-Cl was 44.5 ± 17.9 ml/min/1.73 m². There was a positive correlation between In-Cl and all possible measurements of ⁵¹Cr-EDTA-Cl. ⁵¹Cr-EDTA-Cl with two samples taken at 4 and 8 h or at 4 and 6 h presenting the narrow limits of agreement and a difference (bias) of 2.8 and 2.7 ml/min, respectively. Two plasma sampling for ⁵¹Cr-EDTA-Cl was a reliable method to measure GFR compared with In-Cl and comprises a suitable method to be used in kidney transplanted patients.     

Dermal Heat Transport Analysis for Transcutaneous O2 Measurement

Heat from a transcutaneous oxygen electrode is transmitted locally to the blood beneath it causing a shift in the HbO₂ dissociation curve. This increases the local PO₂, and allows a measurable PO₂, at the skin surface. The temperature effect on the HbO₂, curve must be accounted for in in vivo calibration of Ptco₂, data. To do this, the capillary blood temperature beneath the electrode must be known. A heat balance is written around the capillary blood with heat being conducted in from the electrode and carried out by two means: conduction to deep tissue; and transport away by the flowing capillary blood. The following equation is the steady state solution of the heat transport problem:
T₈ = ±
where Z = ± = 0.17
T₈, = capillary blood temperature
T₁ = electrode temperature
T_o = body temperature
ρ = blood density
P = cutaneous perfusion
δ = dermal capillary depth
k = thermal conductivity of skin
C± = heat capacity of blood
This solution shows the capillary blood temperature may be calculated if the T₁ and T_o are measured and the physiologic constants in 2 are known. 2 is a dimensionless heat transport number which represents the relative importance of perfusion to conduction effects on the deterring T₈, and may be used as a data correlating parameter. Z = 0.17 is obtained using literature values for the physiological constants. This analysis used in conjunction with a mass transport analysis for oxygen will produce a theoretically based correlation scheme for in vivo calibration of heated transcutaneous oxygen electrodes.     

Oxygen tension and consumption measured by a tc-Po2 electrode on heated skin before and after epidermal stripping

Oxygen tensions, cutaneous blood flow rate, and skin oxygen consumption rate were determined by tc-PO2 measurements at an electrode temperature of 45 degrees C. The epidermal surface was stripped by 50 applications of adhesive plaster to the surface. Ten healthy, normotensive adults were examined. Cutaneous blood flow rate was 41.2 +/- 8.6 ml X (100 g)-1 X min-1 before and 42.8 +/- 5.9 ml X (100 g)-1 X min-1 after epidermal stripping. Oxygen consumption before stripping was 0.327 +/- 0.065 ml O2 X (100 g)-1 X min-1, and after stripping it was determined at two different saturation levels to be 0.208 +/- 0.072 ml O2 X (100 g)-1 X min-1 and 0.251 +/- 0.096 ml O2 X (100 g)-1 X min-1. Capillary temperature was estimated to be approximately 43 degrees C before and after stripping. At this temperature mean arterial PO2 was estimated to be 18.1 kPa (136 mmHg), which would be reduced by the computed local metabolism to a mean capillary PO2 of 14.4 kPa (108 mmHg) before stripping and 15.2 kPa (114 mmHg) after. Stripping increased mean skin PO2 from 10.9 +/- 0.6 kPa (82.3 +/- 4.7 mmHg) to 14.6 +/- 1.0 kPa (109.4 +/- 7.7 mmHg). Thus, stripping eliminated 82% of the gradient between the capillaries and electrode while reducing the computed oxygen consumption by 23-36%. It is concluded that the epidermal membrane is a significant barrier to oxygen diffusion and that the transcutaneous oxygen electrode has a significant effect on skin PO2 owing to its own even low oxygen consumption. This will reduce the observed skin PO2 significantly.     

Blood Density Monitoring During Dialysis

Abstract Continuous monitoring of blood density (BD) was preformed in 4 stable dialysis patients in 20 sessions using a density meter based on a mechanical oscillator technique. Mean predialysis and postdialysis BDs were 1.0427 ± 0.0031 g/cm³ and 1.0502 ± 0.0055 g/cm respectively. For similar predialysis to postdialysis total body water reduction, significant difference in the mean BD increase was found between hypotensive and nonhy-potensive groups (1.29 ± 0.07%, 0.47 ± 0.12%, respectively; p < 0.001). Eight hypotensive episodes occurred during 6 sessions. The mean value of the blood density changes slope (dBD/dt) during the 5 min preceding a hypotensive episode increased about 2.5 times more than did the mean of the predialysis to postdialysis blood density slope (27.6 ± 2.2 g/cm³ min 10^-5, 10.5 ± 0.4 g/cm³ min 10^-5 respectively; p < 0.001) under the condition of a constant ultrafiltration rate of 18.9 ± 0.6 ml/min. Continuous monitoring of blood density allows abrupt change in plasma volume to be identified and seems to have a potential utility to the prevention of symptomatic hypotension episodes in patients receiving hemodialysis.     

New Insights into Mechanisms of Spontaneous Liver Transplant Tolerance: The Role of Foxp3-Expressing CD25+CD4+ Regulatory T Cells

Liver allografts in mice are accepted across MHC barriers without requirement for immunosuppressive therapy. The mechanisms underlying this phenomenon remain largely undefined. In this study, we investigated the role of Foxp3-expressing CD25⁺CD4⁺ regulatory T cells (Treg) in the induction of murine liver transplant tolerance. Foxp3⁺CD25⁺CD4⁺ T cells were increased in liver grafts and recipient spleens from day 5 to day 100 posttransplantation, associated with enhanced CTLA4 and TGF-β expression and IL-4 production. Depletion of recipient CD25⁺CD4⁺ T cells using anti-CD25 mAb (250 μg/day) induced acute liver allograft rejection. This was associated with a decreased ratio of Foxp3⁺ Treg: T effector cells, decreased IL-4 and elevated IL-10 and IL-2 production by graft-infiltrating T cells, and reduced apoptotic activity of graft-infiltrating CD4⁺ and CD8⁺ T cells in anti-CD25-mAb-treated recipients. Thus, the data suggest that Foxp3⁺CD25⁺CD4⁺Treg are involved in spontaneous acceptance of liver allografts in mice. The ratio of Treg to T effector cells appears to determine liver transplant outcome. CTLA4, IL-4, TGF-β and apoptosis of graft-infiltrating T cells are also associated with liver transplant tolerance and may contribute, at least in part, to the mechanisms of Treg-mediated immune regulation in this model.     

CD4+CD25+FOXP3+ Regulatory T Cells Increase De Novo in Kidney Transplant Patients After Immunodepletion with Campath-1H

Campath-1H (Alemtuzumab) is an effective immunodepletion agent used in renal transplantation. To evaluate its influence on T lymphocytes during repletion, we analyzed peripheral blood from Campath-1H-treated renal allograft recipients for the presence of FOXP3⁺ regulatory T (Treg) cells. Flow cytometry demonstrated that CD4⁺CD25⁺FOXP3⁺ lymphocytes increased significantly within the CD4⁺ T-cell population, skewing Treg/Teff (T effector) ratios for up to several years. In contrast, Treg levels in patients treated with anti-CD25 (Basiliximab) and maintained on CsA demonstrated a sustained decrease. The increase in Tregs in Campath-1H treated patients developed independent of maintenance immunosuppression. Importantly, the increase in Tregs was not fully explained by their homeostatic proliferation, increased thymic output, or Treg sparing, suggesting de novo generation/expansion. Consistent with this, in vitro stimulation of PBMCs with Campath-1H, with or without anti-CD3, activation led to an increase in CD4⁺CD25⁺FOXP3⁺ cells that had suppressive capabilities. Together, these data suggest that Campath-1H promotes an increase in peripheral Tregs and may act as an intrinsic generator of Tregs in vivo .     

Homeostatic Repopulation by CD28−CD8+ T Cells in Alemtuzumab-Depleted Kidney Transplant Recipients Treated With Reduced Immunosuppression

Alemtuzumab (CAMPATH-1H) is a depleting agent introduced recently in transplantation and often used with reduced maintenance immunosuppression. In the current study we investigated the immune response of 13 kidney allograft recipients treated with alemtuzumab followed by weaned immunosuppression with reduced dose of mycophenolate mofetil (MMF) and tacrolimus. Tacrolimus was switched to sirolimus at 6 months and MMF withdrawn at 12 months after transplantation.
We found that after alemtuzumab induction the recovery of CD8⁺ T cells was much faster than that of CD4⁺ T cells. It was complete 6 months posttransplant while CD4⁺ T cells did not fully recover even 15 months posttransplant. Repopulating CD8⁺ T cells were mainly of immunosenescent CD28⁻CD8⁺ phenotype. In a series of in vitro experiments we showed that CD28⁻CD8⁺ T cells might suppress proliferation of CD4⁺ T cells. There were three successfully treated acute rejections during the study (first at +70 day, two others +12 months) that occurred in patients with the lowest level of CD28⁻CD8⁺ T cells.
We hypothesize that expanded CD28⁻CD8⁺ T cells might compete for 'immune space' with CD4⁺ T cells suppressing their proliferation and therefore delaying CD4⁺ T-cells recovery. This delay might be associated with the clinical outcome as CD4⁺ T cells, notably CD4⁺ T effector memory cells, were shown to be associated with rejection.     

Influence of Blood Flow on Adsorption of β2-Microglobulin onto AN69 Membrane

Abstract: Adsorption onto the dialyzer membrane is a contributing factor to the elimination of β₂-microglobulin (β₂M) from the sera of uremic patients. The purpose of this prospective study was to ascertain the influence of the blood flow rate on adsorption of β₂M onto the polyacrylonitrile (AN69) hollow-fiber dialyzer membrane in 8 pa tients during regular hemodialysis (HD). Blood first passed through a low-flux polysulfone dialyzer and then through an AN69 dialyzer, which was not in contact with the dialysis fluid. During the investigation period (first hour of the HD session), the blood flow rate was 100 ml/min (first part of the study), 200 mumin (second part of the study), and 300 ml/min (third part of the study). Ultrafiltration was not performed during the investigation period. At the start of the HD sessions, the serum concentration of β₂M in the afferent blood line did not differ significantly among the 3 parts of the study. Serum β₂M was measured in samples taken from the afferent and efferent blood lines of the AN69 dialyzer at 5,10, 15, 30, 45, and 60 min. The serum β₂M concentration decreased significantly in blood that had passed through the AN69 dialyzer. This decrease, indicating membrane adsorption, was maximal during the first part and minimal during the third part of study. The decrease in the contact time between the blood and the AN69 could be the underlying cause. The calculated quantities of β₂M adsorbed onto the AN69 membrane (44.2 ± 10.2, 43.2 ± 12.1, and 42.6 ± 17.3 mg) did not differ significantly among the 3 parts of the study. These results suggest that an increase in blood flow rate from 100 to 300 ml/min did not significantly affect the quantity of β₂M adsorbed onto the AN69 membrane.     

Erythrocyte counts in the cerebrospinal fluid associated with continuous spinal anaesthesia

Continuous spinal anaesthesia technique can be associated with peridural haemorrhage due to blood vessel damage caused by the needle or the catheter. We studied whether thrombosis prophylaxis or anticoaguladon medications increase the risk of subarachnoid haemorrhage when continuous spinal anaesthesia is used. Twenty arthroplasty patients received low-molecular-weight heparin preoperatively and twenty-two vascular surgery patients received heparin (100 IU kg^-1) peroperatively; eight of the latter patients were on regular preoperative antiplatelet medication. Twenty-four prostate surgery patients, not exposed to heparin or other drugs affecting coagulation, served as controls. A 22-gauge spinal catheter was used and bupivacaine was injected through the catheter. Within the following 24 hours, 4—5 cerebrospinal fluid samples were collected for erythrocyte counts. In the arthroplasty and the vascular group there were five patients each and in the control group seven patients with more than 100 × 10⁶ 1^-1 erythrocytes in at least one of the samples. The highest erythrocyte count was 23900 × 10⁶ 1^-1 in a control patient, The 24-hour sample was blood-tinged (erythrocytes >1000X10⁶ 1^-1) in two patients in the arthroplasty group, in one patient in the vascular group and in four patients in the control group. In spite of the haemorrhages detected in this study, no related neurological symptoms or other serious consequences were observed. The risk of subarachnoid haemorrhage was not increased by drugs affecting coagulation.     

The effect of thiopental on cerebral blood flow, and its relation to plasma concentration, during simulated induction of anaesthesia in a porcine model

The reversible effect of an induction dose of thiopental on the cerebral blood flow (CBF) was characterized by repeated ¹³³Xe washout measurements during stable physiological conditions in anaesthetized pigs. A thiopental effect corresponding to induction of light and transient anaesthesia was confirmed by electroencephalography (EEG). The concentration (arterial plasma) – effect (– % CBF) relationship of thiopental was estimated using a sigmoidal E_max model. The injection caused a rapid 36 4.5% (means.d.) drop in CBF, with return to baseline by 80 min. According to the pharmacodynamic model, the maximal effect of thiopental (E_max) in this experimental set–up was a 58% lowering of the CBF and the concentration at half–maximal effect (EC₅₀) was 25 μg–ml^-1. This study provides a complete characterization of the effect of thiopental on the CBF, including the time–course and concentration–effect relationship. A comparison to limited data in the literature suggests that the findings in the pigs constitute a fair approximation of the action of thiopental during the clinical induction of anaesthesia.     

Type I Interferons Are Not Critical for Skin Allograft Rejection or the Generation of Donor-Specific CD8+ Memory T Cells

Type I interferons (IFN-I) link innate to adaptive immunity in microbial infection, autoimmune disease and tumor immunity. It is not known whether IFN-I have an equally central role in alloimmunity. Here we tested this possibility by studying skin allograft survival and donor-specific CD8⁺ T-cell responses in mice that lack the IFN-I receptor (IFN-IR^−/−). We found that IFN-IR^−/− mice reject fully allogeneic wild-type skin grafts at the same rate as wild-type recipients. Similarly, allograft rejection was not delayed if IFN-IR^−/− male skin was transplanted to syngeneic IFN-IR^−/− female mice. Quantitation of the male (H-Y)-specific CD8⁺ T-cell response in these mice revealed normal generation of donor-specific CD8⁺ effector T cells but fourfold reduction in CD8⁺ memory T cells. Memory CD8⁺ T cells generated in the absence of IFN-IR had normal phenotype and recall function, assessed by ex vivo cytokine production and the ability of IFN-IR^−/− mice to mount second set rejection. Finally, these memory T cells were maintained at a constant number despite their inability to respond to IFN-1. Our findings indicate that IFN-I cytokines are not critical for acute allograft rejection or for the expansion and differentiation of donor-specific CD8⁺ T cells into long-lived, functional memory T cells.