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Background: Donor treatment with dopamine (DA) is an effective modality to improve organ quality by reduction of hypothermic, ischemic and reperfusion (I/R) injury. It is unknown by which mechanism DA reduces oedema formation and inflammation. Therefore we tested the first time in an isolated rat lung model if dopaminergic or adrenergic receptors are involved., Material/methods: Rats were treated for 1 hr with NaCl, DA or simultaneously with DA alpha- beta- D1- or D2-receptor blockers. Thereafter lungs were explanted, flushed with Perfadex-solution and stored at 4°C. Peak inspiratory pressure (PIP), pulmonary arterial pressure (PAP) and lung weight were measured during reperfusion of 3 hrs. Inflammatory mediators and the expression of adhesion molecules were measured after perfusion., Results: Up to 6 hours of hypothermia did not influence oedema formation or PIP and PAP during reperfusion time. However, hypothermia after 8 hrs significantly increased PIP, PAP and pulmonary oedema in NaCl, alpha- and beta-blocker treated lungs, but significantly not in DA, D1- or D2-blocker treated lungs. Perfusion and ventilation alone induced a strong upregulation of cytokine-induced neutrophil chemoattractant-1 and adhesion molecules in untreated, alpha- and beta-blocker treated lungs, while in DA, D1- and D2-blocker treated lungs significant lower levels were found., Conclusions: Our study suggests that dopamine mediated protective effects on I/R damage and inflammation in donor lungs are most likely mediated via adrenergic receptors. These findings are highly relevant because new strategies for organ preservation are necessary in terms of long donation waiting lists.

Interindividual differences of endothelial cells in response to endotoxins might contribute to the diversity in clinical outcome among septic patients. The present study was conducted to test the hypothesis that endothelial cells (EC) with high and low proinflammatory potential exist and to dissect the molecular basis underlying this phenomenon. Thirty human umbilical vein endothelial cell (HUVEC) lines were stimulated for 24 h with lipopolysaccharide (LPS) and screened for interleukin (IL)-8 production. Based on IL-8 production five low and five high producers, tentatively called types I and II responders, respectively, were selected for genome-wide gene expression profiling. From the 74 genes that were modulated by LPS in all type II responders, 33 genes were not influenced in type I responders. Among the 41 genes that were increased in both responders, 17 were expressed significantly stronger in type II responders. Apart from IL-8, significant differences in the expression of proinflammatory related genes between types I and II responders were found for adhesion molecules [intercellular adhesion molecule (ICAM-1), E-selectin)], chemokines [monocyte chemoattractant protein (MCP-1), granulocyte chemotactic protein (GCP-2)], cytokines (IL-6) and the transcription factor CCAAT/enhancer binding protein-delta (C/EBP-delta). Type I responders also displayed a low response towards tumour necrosis factor (TNF)-alpha. In general, maximal activation of nuclear factor (NF)-kappaB was achieved in type I responders at higher concentrations of LPS compared to type II responders. In the present study we demonstrate that LPS-mediated gene expression differs quantitatively and qualitatively in types I and II responders. Our results suggest a pivotal role for common transcription factors as a low inflammatory response was also observed after TNF-alpha stimulation. Further studies are required to elucidate the relevance of these findings in terms of clinical outcome in septic patients.

Large quantitaties of inflammatory mediators are released during the course of endotoxaemia. These mediators in turn can stimulate the sympathetic nervous system (SNS) to release catecholamines, which ultimately regulate inflammation-associated impairment in tissue perfusion, myocardial impairment and vasodilatation. Treatment of sepsis is based on surgical and/or antibiotic therapy, appropriate fluid management and application of vasoactive catecholamines. With respect to the latter, discussions on the vasopressor of choice are still ongoing. Over the past decade dopamine has been considered the 'first line' vasopressor and is frequently used to improve organ perfusion and blood pressure. However, there is a growing body of evidence that dopamine has deleterious side effects; therefore, its clinical relevance seems to be more and more questionable. Nevertheless, it has not been convincingly demonstrated that other catecholamines are superior to dopamine in this respect. Apart from its haemodynamic action, dopamine can modulate immune responses by influencing the cytokine network. This leads to inhibition of expression of adhesion molecules, inhibition of cytokine and chemokine production, inhibition of neutrophil chemotaxis and disturbed T-cell proliferation. In the present review we summarize our knowledge of the immunomodulatory effects of dopamine, with an emphasis on the mechanisms by which these effects are mediated.

Background: Laboratory tests can be an important source of blood loss in hospitals, especially for newborns and patients in intensive care. The aim of this study was to quantify blood loss for laboratory diagnostic tests in a large number of patients in a teaching hospital., Methods: We estimated blood loss by multiplying the number and volumes of sampling tubes collected from 2654 adult inpatients. We compared the number of tests per patient for all inpatients and intensive care unit patients during the first period and again in the same time period 1 year later when cumulative blood-loss volumes were being reported to physicians and educational information had been given to decrease blood loss from laboratory tests., Results: For 95% of the patients, blood loss during hospitalization was <196 mL. The largest proportion of the blood samples was used for clinical chemical tests (median, 45%), followed by hematologic (median, 26%) and coagulation (median, 17%) tests. In the surgical and cardiovascular surgical intensive care units, however, blood gas analyses accounted for 19-34% (medians) of the use. For 5% of the patients, all undergoing intensive care, blood loss was >200 mL and for 0.7% was >600 mL during their hospital stay. Such high blood losses were observed in patients with long-term ventilation, coagulation disorders, and repeated surgery. The largest median blood loss was in patients undergoing cardiovascular surgery (median, 201 mL). The mean number of tests was 44 per inpatient before cumulative blood loss was being reported and 46 when it was being reported., Conclusions: Blood loss from laboratory diagnostic testing is not likely to pose a problem for most hospitalized patients. Blood loss is greater in intensive care patients and after cardiovascular surgical procedures. Reporting of the cumulative individual blood loss did not decrease blood loss for laboratory testing.

Unlabelled: In some patients, cardiopulmonary resuscitation (CPR) can revive spontaneous circulation (ROSC). However, neurological outcome often remains poor. Hypertonic-hyperoncotic solutions (HHS) have been shown to improve microvascular conductivity after regional and global ischemia. We investigated the effect of infusion of HHS in a porcine CPR model. Cardiac arrest was induced by ventricular fibrillation. Advanced cardiac life support was begun after 4 min of nonintervention and 1 min of basic life support. Upon ROSC, the animals randomly received 125 mL of either normal saline (placebo, n = 8) or 7.2% NaCl and 10% hydroxyethyl starch 200,000/0.5 (HHS, n = 7). Myocardial and cerebral damage were assessed by serum concentrations of cardiac troponin I and astroglial protein S-100, respectively, up to 240 min after ROSC. In all animals, the levels of cardiac troponin I and S-100 increased after ROSC (P < 0.01). This increase was significantly blunted in animals that received HHS instead of placebo. The use of HHS in the setting of CPR may provide a new option in reducing cell damage in postischemic myocardial and cerebral tissues., Implications: Infusion of hypertonic-hyperoncotic solutions (HHS) after successful cardiopulmonary resuscitation in pigs significantly reduced the release of cardiac troponin I and cerebral protein S-100, which are sensitive and specific markers of cell damage. Treatment with HHS may provide a new option to improve the outcome of cardiopulmonary resuscitation.

1. In acute respiratory distress syndrome (ARDS) induced by endotoxins, a high production of inflammatory mediators by microvascular lung endothelial cells (LMVEC) can be observed. Activation of cells by endotoxins may result in elevated secretion of phospholipase A(2) (sPLA(2)) which is thought to contribute to tissue damage. The present study was undertaken to investigate the role of sPLA(2) in chemokine production in human lung microvascular endothelial cells (LMVEC) stimulated with the endotoxins lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In particular, we investigated the effects of sPLA(2) inhibitors, specifically, the extracellular PLA(2) inhibitors (ExPLIs), composed of N-derivatized phosphatidyl-ethanolamine linked to polymeric carriers, and LY311727, a specific inhibitor of non-pancreatic sPLA(2). 2. ExPLIs markedly inhibited LPS and LTA induced production and mRNA expression of the neutrophile attracting chemokines IL-8, Gro-alpha and ENA-78, as well as of the adhesion molecules ICAM-1 and E-selectin. Concomitantly, ExPLIs inhibited the LPS-induced activation of NF-kappaB by LPS but not its activation by TNF-alpha or IL-1. 3. Endotoxin mediated chemokine production in LMVEC seems not to involve PLA(2) activity, since LPS stimulation was not associated with activation of intracellular or secreted PLA(2). It therefore seems that the inhibitory effect of the ExPLIs was not due to their PLA(2) inhibiting capacity. This was supported by the finding that the LPS-induced chemokine production was not affected by the selective sPLA(2) inhibitor LY311727. 4. It is proposed that the ExPLIs may be considered a prototype of potent suppressors of specific endotoxin-induced inflammatory responses, with potential implications for the therapy of subsequent severe inflammation.

Serum concentrations of catecholamines are high in patients with sepsis or acute respiratory distress syndrome (ARDS). Because chemokines mediate the recruitment of neutrophils into inflammatory sites, we addressed the question of whether dopamine (DA) is able to influence chemokine production in endothelial cells under basal and proinflammatory conditions. To this end, lung microvascular endothelial cells (LMVEC) were stimulated or not for 24 h with the bacterial toxins lipopolysaccharide (LPS) (1 microg/ml) or lipoteichonic acid (LTA) (10 microg/ml) in the presence or absence of various concentrations of DA (1-100 microg/ml). Whereas under basal and stimulatory conditions, the addition of DA to endothelial cells dose-dependently increased IL-8 production, the production of ENA-78 and Gro-alpha was significantly inhibited (P < 0.01). This effect could still be demonstrated when the cells were stimulated for up to 3 h with LPS before DA administration. Similar findings were detected for the mRNA expression of these chemokines. The influence of DA on chemokine production was not receptor mediated and could be prevented by antioxidants or radical scavengers. Moreover, addition of H(2)O(2) to endothelial cells gave results similar to those observed with DA stimulation, suggesting a pivotal role for reactive oxygen species in DA-mediated modulation of chemokine production in endothelial cells. Our data thus demonstrate that DA administration results in the induction of oxidative stress, with profound effects on endothelial chemokine production.

We addressed the question to which extent cerebral blood flow (CBF) is maintained when, in addition to a high blood viscosity (Bvis) arterial oxygen content (CaO2) is gradually decreased. CaO2) was decreased by hemodilution to hematocrits (Hct) of 30, 22, 19, and 15% in two groups. One group received blood replacement (BR) only and served as the control. The second group received an additional high viscosity solution of polyvinylpyrrolidone (BR/PVP). Bvis was reduced in the BR group and was doubled in the BR/PVP. Despite different Bvis, CBF did not differ between BR and BR/PVP rats at Hct values of 30 and 22%, indicating a complete vascular compensation of the increased Bvis at decreased CaO2. At an Hct of 19%, local cerebral blood flow (LCBF) in some brain structures was lower in BR/PVP rats than in BR rats. At the lowest Hct of 15%, LCBF of 15 brain structures and mean CBF were reduced in BR/PVP. The resulting decrease in cerebral oxygen delivery in the BR/PVP group indicates a global loss of vascular compensation. We concluded that vasodilating mechanisms compensated for Bvis increases thereby maintaining constant cerebral oxygen delivery. Compensatory mechanisms were exhausted at a Hct of 19% and lower as indicated by the reduction of CBF and cerebral oxygen delivery.

Background: Tourniquets are often used as part of orthopedic surgery but may cause local and remote organ injury. The authors hypothesized that the procedures used to induce ischemia (circulatory occlusion or exsanguination) may have differential effects on the metabolic state of the muscle that should be reflected in the interstitial levels of metabolites., Methods: Microdialysis probes were implanted in both quadriceps femoris muscles of 18 patients. Interstitial fluid was obtained during tourniquet-induced ischemia and reperfusion and was analyzed for glucose, lactate, choline, and purines by high-performance liquid chromatography., Results: At a flow rate of 2 microl/min, the average baseline concentrations in the dialysate were 2.5 mM for glucose, 1.7 mM for lactate, 5.2 microM for choline, and 14.3 microM for hypoxanthine. Circulatory occlusion by tourniquet caused a 40% decrease of the extracellular glucose concentration within 30 min. Concomitantly, the interstitial levels of lactate and hypoxanthine increased in a linear fashion to 206% (lactate) and 241% (hypoxanthine) of basal values. The extracellular concentration of choline was also significantly elevated. After exsanguination, the glucose levels were significantly more reduced (by 65%), and the levels of lactate (to 268%) and hypoxanthine (to 286%) were more increased than after circulatory occlusion alone., Conclusion: Our microdialysis results demonstrate that the interstitial concentrations of glucose, lactate, and hypoxanthine, which are indicators of tissue ischemia, change more prominently after exsanguination than after circulatory occlusion alone.

Background: It is not known whether the effects of desflurane on local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) are different from those of other volatile anesthetics., Methods: Using the autoradiographic iodoantipyrine and deoxyglucose methods, LCGU, LCBF, and their overall means were measured in 60 Sprague-Dawley rats (10 groups, n = 6 each) during desflurane and isoflurane anesthesia and in conscious controls., Results: During anesthesia, mean cerebral glucose utilization was decreased compared with conscious controls: 1 minimum alveolar concentration (MAC) desflurane: -52%; 1 MAC isoflurane: -44%; 2 MAC desflurane: -62%; and 2 MAC isoflurane: -60%. Local analysis showed a reduction of LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased: 1 MAC desflurane: +40%; 1 MAC isoflurane: +43%; 2 MAC desflurane and 2 MAC isoflurane: +70%. LCBF was increased in all brain structures investigated except in the auditory cortex. No significant differences (P < 0.05) could be observed between both anesthetics for mean values of cerebral glucose use and blood flow. Correlation coefficients obtained for the relation between LCGU and LCBF were as follows: controls: 0.95; 1 MAC desflurane: 0.89; 2 MAC desflurane: 0.60; 1 MAC isoflurane: 0.87; and 2 MAC isoflurane: 0.68., Conclusion: Differences in the physicochemical properties of desflurane compared with isoflurane are not associated with major differences in the effects of both volatile anesthetics on cerebral glucose utilization, blood flow, and the coupling between LCBF and LCGU.

In the present study, the sensitivity of LMVEC and human umbilical vein endothelial cells (HUVEC) to lipopolysaccharide (LPS) and the proinflammatory cytokines IL-1, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) was compared. To this end, the production of the CC- (MCP-1), CXC- (IL-8, ENA-78, Groalpha, NAP-2, GCP-2) and CX3C (fractalkine) chemokines was studied. A low basal production of these chemokines was observed in both cell types. TNF-alpha, IL-1 and LPS up-regulated all chemokines tested. IFN-gamma however was only able to up-regulate MCP-1 production. LMVEC were more sensitive to IL-1 and LPS compared with HUVEC, since LMVEC produced significantly more MCP-1, ENA-78 and Groalpha (P < 0. 01) under these conditions. Maximal production of MCP-1 in LMVEC was achieved with TNF-alpha (28.4 ng/ml, P < 0.01), whereas IL-1 was the most potent stimulator of ENA-78 (2.78 ng/ml, P < 0.001) and Groalpha (29.2 ng/ml, P < 0.001). IL-8 production in LMVEC cells was maximal after LPS stimulation (28.4 ng/ml), but lower than on HUVEC (P < 0.01). LPS, TNF-alpha and IL-1 stimulation strongly up-regulated all chemokine mRNA. No quantitative differences in mRNA expression between LMVEC and HUVEC were detected for MCP-1 and Groalpha after LPS stimulation. mRNA expression of ENA-78, GCP-2, CX3C and NAP-2 was however higher in LMVEC under LPS stimulation. In contrast, IL-8 mRNA was slightly more expressed in HUVEC under these conditions. These results further support the hypothesis that the microvascular lung endothelium plays an active role in the induction and perpetuation of acute lung injury.

The aim of the study was to investigate the distribution of 2 subtypes of endothelin-receptors, mediating the effects of endothelin-1 (ET-1) in the pulmonary circulation. Until now, it is still unclear, whether ET(A) receptors or ET(B) receptors or even both are localized in pulmonary vessels. The experiments were performed on 72 isolated and ventilated rabbit lungs that were perfused with a cell- and plasma-free buffer solution. The arterial pressure and the lung weight gain were continuously registered. Intermittently perfusate samples were taken for determination of thromboxane A2 (TXA2) and prostacyclin (PGI2). The injection of ET-1 (10(-8) M, n = 6) resulted in a biphasic increase in pulmonary arterial pressure (PAP) that was accompanied by the generation of TXA2 and PGI2. Pretreatment with the ET(A)-receptor antagonist LU135252 (10(-6) M, n = 6) suppressed the pressure response after ET-1 application (P < 0.01 at 120 min) and reduced the generation of TXA2 (P < 0.05 at 120 min) and PGI2 (P < 0.05 at 120 min). Pretreatment with the cyclooxygenase inhibitor diclofenac (10 microg/mL; n = 6) also reduced the PAP increase after ET-1 injection. In contrast to this, the pulmonary vascular pressure reaction after ET-1 application was elevated, when ET(B)-receptor antagonist BQ788 (10(-6) M; n = 6) was given. Furthermore, the PGI2 to TXA2 ratio was shifted from 2.3 to 0.9, reflecting a predominance of vasoconstrictive TXA2. The simultaneous application of LU135252 and BQ788 significantly reduced the PAP increase after ET-1 application, but no beneficial effects were observed compared with the application of LU135252 solely. The injection of the ET(B)-receptor agonist sarafotoxin S6c (S6c; 10(-8) M, n = 6) also induced an increase in PAP that was not attenuated by pretreatment with the ET(B)-receptor antagonist BQ788 (10(-6) M, n = 6). LU135252 (n = 6) as well as the application of LU135252 in combination with BQ788 (n = 6) failed to suppress the pressure response after S6c, whereas the cyclooxygenase inhibitor diclofenac (10 microg/mL, n = 6) alone and in combination with LU135252 and BQ788 (n = 6) was able to prevent the PAP increase after S6c injection (P < 0.001). The results demonstrate that the ET-1-induced increase in pulmonary vascular resistance is mainly mediated via ET(A) receptors, whereas ET(B) receptors seem to mediate vasodilation, which was shown by an imbalance of TXA2 and PGI2 generation. On the other hand, the ET(B)-receptor agonist S6c induced vasoconstriction, which was only attenuated by the cyclooxygenase inhibitor diclofenac. From the current results we conclude that, apart from vasoconstrictor ET(A) receptors, at least 2 ET(B)-receptor subtypes are expressed in the pulmonary circulation, one mediating vasoconstriction, which was not blocked by BQ788, and one mediating vasodilation, which was influenced by BQ788.

Background: Compared to isoflurane, knowledge of local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) during sevoflurane anesthesia is limited., Methods: LCGU, LCBF, and their overall means were measured in Sprague-Dawley rats (8 groups, n=6 each) during sevoflurane and isoflurane anesthesia, 1 and 2 MAC, and in conscious control animals (2 groups, n=6 each) using the autoradiographic 2-[14C]deoxy-D-glucose and 4-iodo-N-methyl-[14C]antipyrine methods., Results: During anesthesia, mean cerebral glucose utilization was decreased: control, 56+/-5 micronmol x 100 g(-1) x min(-1); 1 MAC isoflurane, 32+/-4 micromol x 100 g(-1) x min(-1) (-43%); 1 MAC sevoflurane, 37+/-5 micromol x 100 g(-1) x min(-1) (-34%); 2 MAC isoflurane, 23+/-3 micromol x 100 g(-1) x min(-1) (-58%); 2 MAC sevoflurane, 23+/-5 micromol x 100 g(-1) x min(-1) (-59%). Local analysis showed a reduction in LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased as follows: control 93+/-8 ml x 100 g(-1) x min(-1); 1 MAC isofurane, 119+/-19 ml x 100 g(-1) x min(-1) (+28%); 1 MAC sevoflurane, 104+/-15 ml x 100 g(-1) x min(-1) (+12%); 2 MAC isoflurane, 149+/-17 ml x 100 g(-1) x min(-1) (+60%); 2 MAC sevoflurane, 118+/-21 ml x 100 g(-1) min(-1) (+27%). LCBF was increased in most brain structures investigated. Correlation coefficients obtained for the relationship between LCGU and LCBF were as follows: control 0.93; 1 MAC isoflurane, 0.89; 2 MAC isoflurane, 0.71; 1 MAC sevoflurane, 0.83; 2 MAC sevoflurane, 0.59)., Conclusion: Mean and local cerebral blood flows were lower during sevoflurane than during isoflurane anesthesia. This difference cannot be explained by differing changes in glucose utilization because glucose utilization was decreased to the same extent in both groups.

The average in vivo chest computed tomographic (CT) attenuation number (air = -1,000, soft tissue = 0, perflubron = +2,300 Hounsfield units [HU]) of 10 ventrodorsal-oriented lung segments was calculated to assess the distribution of gas and perflubron in 14 oleic acid lung-injured adult sheep during partial liquid ventilation (PLV, n = 7) or gas ventilation (GV, n = 7). Partial liquid ventilation was associated with a significant decrease in shunt fraction (PLV = 40 +/- 12%, GV = 76 +/- 12%, p = 0.004). Computed tomographic attenuation data during expiration (HUexp) demonstrated minimal gas aeration in GV animals in the dependent (segments 6-10) lung zones (HUexp = -562 +/- 108 for segments 1-5, HUexp = -165 +/- 104 for segments 6-10, p = 0.015). During PLV, perflubron was predominantly distributed to the dependent lung regions (HUexp = 579 +/- 338 for segments 1-5, HUexp = 790 +/- 149 for segments 6-10, p = 0.04). The ratio of the inspiratory to expiratory HU (HUinsp/exp) was greater in dependent than nondependent regions (mean HUinsp/exp segments 1-5 = 0.56, segments 6-10 = 0.81, p = 0.01), indicating that during inspiration relatively more gas than perflubron was distributed to the nondependent lung regions. We conclude that during PLV in this lung injury model, (1) gas exchange is improved when compared with gas ventilation, (2) perflubron is distributed predominantly to the dependent regions of the lung, and (3) although gas is distributed throughout the lung with each inspiration, more gas than perflubron goes to the nondependent lung regions.

Background: Anesthesia may represent a considerable bias in experimental medicine, particularly in conditions of stress (such as hemorrhage). Sodium pentobarbital (PB), widely used for cardiovascular investigations, may impair oxygen delivery by hemodynamic and respiratory depression. The critical issue, however, is whether the microcirculation can still maintain tissue oxygenation during anesthesia. To answer this question, the authors studied the effect of PB anesthesia on subcutaneous microvascular oxygen delivery and interstitial oxygenation in Syrian golden hamsters., Methods: Sodium pentobarbital anesthesia was induced by intravenous injection (30 mg/kg body weight) and maintained by a 15-min infusion (2 mg.kg-1.min-1), with animals breathing spontaneously (PB-S) or ventilated with air (PB-V). Systemic parameters evaluated were mean arterial pressure (MAP), heart rate, cardiac index (CI), arterial oxygen tension (PaO2), arterial carbon dioxide tension (PaCO2), base excess, and pH. Microvascular and interstitial oxygen tension (PO2), vessel diameter, red blood cell velocity (vRBC), and blood flow (Qb) were measured in a dorsal skinfold preparation. Microcirculatory PO2 values were determined by phosphorescence decay., Results: Sodium pentobarbital anesthesia significantly decreased CI, MAP, vRBC, and Qb. During PB infusion, PaO2 values were 56 +/- 12.8 mmHg (PB-S) and 115.9 +/- 14.6 mmHg (PB-V) compared with 69.4 +/- 18.2 mmHg and 61.4 +/- 12.6 mmHg at baseline. However, microvascular PO2 was reduced by 25-55% in both groups, resulting in an interstitial PO2 decrease from 23.9 +/- 5.6 mmHg (control) to 13.1 +/- 9.1 mmHg (PB-S) and 15.2 +/- 7 mmHg (PB-V). Microcirculatory PO2 values were restored 30 min after PB infusion, even though hemodynamic depression and a light anesthetic plane were maintained., Conclusions: Sodium pentobarbital anesthesia caused impairment of microvascular oxygen delivery and interstitial oxygenation, effects that were not prevented by mechanical ventilation. Although these effects were restricted to deep anesthetic planes, prolonged hemodynamic depression suggests that caution is warranted when using PB as an anesthetic in cardiovascular investigations.

The aim of this study was to investigate the influence of the activation of the complement and coagulation systems on bacterial clearance and killing capacity of the reticuloendothelial system in rabbits. To enable quantification of the clearance process, defined numbers of exogenous Escherichia coli (1.3 x 10(8) colony-forming units) were injected intravenously, after complement activation with inulin-activated rabbit serum (n = 6), after complete defibrination with the snake toxin ancrod (n = 6), and in sham-operated animals (controls, n = 6). During the following 180 min observation period, parameters monitored were arterial pressure, fibrinogen, blood gases, and bacterial counts in blood and tissue samples of liver, kidney, spleen, and lung. Defibrination produced a significant delay in blood clearance (p < .05) compared with controls, coupled with up to four times higher bacterial counts in organ homogenates. Complement activation did not affect bacterial elimination kinetics, but was associated with accumulation of E. coli in lung and kidney (up to 100-fold of control values, p < .001). The impaired bacterial clearance associated with increased organ colonization after activation of the complement and coagulation systems reflect reticuloendothelial system dysfunction, thus pointing toward a weaker resistance against bacterial infection.

The effects of small volume hypertonic/hyperoncotic fluid resuscitation from hemorrhage on brain metabolism and blood flow were evaluated by autoradiographic techniques with high spatial resolution. The data were compared to fluid resuscitation with a volume equal to shed blood of isotonic 6% hydroxyethyl starch solution (HES) and a control group without hemorrhage and fluid resuscitation (n = 6 in each group). In conscious rats, volume-controlled hemorrhage for 30 min (30 mL/kg body weight, resulting in a blood loss of approximately 50% of the circulating blood volume) was followed by intravenous infusion of a hypertonic/hyperoncotic saline hydroxyethyl starch solution (HTHO; 7.5% saline/10% hydroxyethyl starch, 4.0 mL/kg body weight). Local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) were measured in 34 brain structures 2 h after fluid resuscitation by means of the quantitative autoradiographic iodo [14C]antipyrine and 2-[14C]-deoxy-D-glucose methods. Compared to the untreated control group, LCBF increased significantly in all brain regions analyzed after fluid resuscitation with HTHO (mean, +63%) or HES (mean, +56%). The increases in LCBF after fluid resuscitation were sufficient to restore cerebral oxygen delivery to the level calculated for the untreated control group. LCGU was unchanged after fluid resuscitation. The close relationship between LCGU and LCBF observed in the control group (r = 0.95) was preserved after hemorrhage and fluid resuscitation with HTHO (r = 0.97) and HES (r = 0.96), although the LCBF-to-LCGU ratio was reset to a higher level (1.5 mL/mumol in the control group and 2.7 mL/mumol after fluid resuscitation with HTHO and HES, P < 0.05). We conclude that the increase in LCBF compensates for the reduction of arterial oxygen content to maintain cerebral oxygen delivery. Therefore, "small volume resuscitation" appears to be as effective as resuscitation with large volumes of isotonic HES in meeting the circulatory and metabolic demands of the brain tissue within the first 2 h after fluid resuscitation from hemorrhage.

Regional cerebral blood flow and metabolism were investigated after addition of a small volume of perfluorocarbon (PFC) emulsion to the resuscitation fluid after hemorrhage. Severe volume-controlled hemorrhage (40 mL/kg body weight (bw) withdrawn over 30 min followed by hypovolemia of 30 min duration) was induced in conscious rats. While breathing 100% oxygen, the intravascular volume was repleted by the infusion of either 6% hydroxyethyl starch (mean mol wt 200,000/0.5; HES) or 6% hydroxyethyl starch plus perflubron (90% wt/vol emulsion of perfluoroctylbromide, 3 mL/kg bw; HES-PFOB). Two hours after fluid resuscitation either iodo[14C]antipyrine or 2[14C]deoxy-D-glucose were infused. Local cerebral blood flow (LCBF) or local cerebral glucose utilization (LCGU) were determined in 34 brain structures using quantitative autoradiography. Local cerebral metabolism was not disturbed in the HES and the HES-PFOB groups after fluid resuscitation, although slight reductions (mean -14%) were measured (HES-PFOB vs HES; P < 0.05). The HES-PFOB group showed LCBF values that were higher in the different brain structures than those of the HES group (mean +30%). A close correlation was found between LCGU and LCBF of the 34 brain structures in both groups (HES: r = 0.96, P < 0.01; HES-PFOB: r = 0.98, P < 0.01), whereas the LCBF-to-LCGU ratio was reset from 2.2 mL/mumol in the HES group to 3.4 mL/mumol in the HES-PFOB group (P < 0.05). The higher blood flows in the HES-PFOB group were sufficient to restore cerebral oxygen delivery to normal levels at a reduced arterial oxygen content.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of resuscitation fluids on the brain have been investigated in previous studies by global measurements of cerebral blood flow and metabolism. In this study we have examined the effects of a novel haemoglobin-based oxygen carrier on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU) after resuscitation from a volume-controlled haemorrhage of 30 min (3.0 ml/100 g body weight) with ultrapurified, polymerized, bovine haemoglobin (UPBHB). LCBF and LCGU were measured in 34 brain structures of conscious rats 2 h after resuscitation using quantitative iodo(14C)antipyrine and 2-(14C)-deoxy-D-glucose methods. The data were compared with a control group without haemorrhage and fluid resuscitation. In the haemorrhage group, LCBF increased after resuscitation by 12-56% in the different brain structures (mean 36%). LCGU changed less (0 to +18%, mean +9%). In the control group there was a close relationship between LCGU and LCBF (r = 0.95). After fluid resuscitation the relationship was preserved (r = 0.95), although it was reset at a higher ratio of LCBF to LCGU (P < 0.05). We conclude that fluid resuscitation of a 30 min volume-controlled haemorrhage using the haemoglobin-based oxygen carrier, UPBHB, induced a moderate degree of heterogeneity in the resulting changes of LCGU and LCBF. Local disturbances of cerebral blood flow or metabolism were not observed.