Blood Pressure During Endovascular Treatment Under Conscious Sedation or Local Anesthesia.

OBJECTIVE: To evaluate the role of blood pressure (BP) as mediator of the effect of conscious sedation (CS) compared to local anesthesia (LA) on functional outcome after endovascular treatment (EVT). METHODS: Patients treated in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN) Registry centers with CS or LA as preferred anesthetic approach during EVT for ischemic stroke were analyzed. First, we evaluated the effect of CS on area under the threshold (AUT), relative difference between baseline and lowest procedural mean arterial pressure (∆LMAP), and procedural BP trend, compared to LA. Second, we assessed the association between BP and functional outcome (modified Rankin Scale [mRS]) with multivariable regression. Lastly, we evaluated whether BP explained the effect of CS on mRS. RESULTS: In 440 patients with available BP data, patients treated under CS (n = 262) had larger AUTs (median 228 vs 23 mm Hg*min), larger ∆LMAP (median 16% vs 6%), and a more negative BP trend (-0.22 vs -0.08 mm Hg/min) compared to LA (n = 178). Larger ∆LMAP and AUTs were associated with worse mRS (adjusted common odds ratio [acOR] per 10% drop 0.87, 95% confidence interval [CI] 0.78-0.97, and acOR per 300 mm Hg*min 0.89, 95% CI 0.82-0.97). Patients treated under CS had worse mRS compared to LA (acOR 0.59, 95% CI 0.40-0.87) and this association remained when adjusting for ∆LMAP and AUT (acOR 0.62, 95% CI 0.42-0.92). CONCLUSIONS: Large BP drops are associated with worse functional outcome. However, BP drops do not explain the worse outcomes in the CS group.

Programmes for the management of preoperative anaemia: audit in ten European hospitals within the PaBloE (Patient Blood Management in Europe) Working Group.

BACKGROUND AND OBJECTIVES: Preoperative anaemia is an independent risk factor for a higher morbidity and mortality, a longer hospitalization and increased perioperative transfusion rates. Managing preoperative anaemia is the first of three pillars of Patient Blood Management (PBM), a multidisciplinary concept to improve patient safety. While various studies provide medical information on (successful) anaemia treatment pathways, knowledge of organizational details of diagnosis and management of preoperative anaemia across Europe is scarce. MATERIALS AND METHODS: To gain information on various aspects of preoperative anaemia management including organization, financing, diagnostics and treatment, we conducted a survey (74 questions) in ten hospitals from seven European nations within the PaBloE (Patient Blood Management in Europe) working group covering the year 2016. RESULTS: Organization and activity in the field of preoperative anaemia management were heterogeneous in the participating hospitals. Almost all hospitals had pathways for managing preoperative anaemia in place, however, only two nations had national guidelines. In six of the ten participating hospitals, preoperative anaemia management was organized by anaesthetists. Diagnostics and treatment focused on iron deficiency anaemia which, in most hospitals, was corrected with intravenous iron. CONCLUSION: Implementation and approaches of preoperative anaemia management vary across Europe with a primary focus on treating iron deficiency anaemia. Findings of this survey motivated the hospitals involved to critically evaluate their practice and may also help other hospitals interested in PBM to develop action plans for diagnosis and management of preoperative anaemia.

Mechanisms of lidocaine's action on subtypes of spinal dorsal horn neurons subject to the diverse roles of Na(+) and K(+) channels in action potential generation.

BACKGROUND: Superficial dorsal horn neurons of the spinal cord receive sensory information from Aδ and C fibers. According to their response to sustained depolarization, these cells can be divided into 3 groups: tonic (TFN), adapting (AFN), and single spike firing (SSN) neurons. During spinal and systemic administration of lidocaine, these neurons are exposed to different concentrations of the local anesthetic lidocaine. In this study, we explored its effect on the excitability of sensory neurons. METHODS: Whole-cell patch-clamp recordings from dorsal horn neurons of Wistar rats were used to study the action of lidocaine on firing properties. To estimate the impact of a blockade of voltage-gated potassium channels by lidocaine (100 µM) on the firing properties of different neurons, the sodium and potassium channel inhibition of lidocaine was investigated in the light of the effects of tetrodotoxin (TTX, 10 nM) and tetraethylammonium (10 mM). For statistical analysis, the Wilcoxon matched-pairs signed rank test was used throughout. RESULTS: All 3 types of neurons responded to lidocaine with changes in the shape of their action potentials. The peak amplitude of the single action potentials was decreased (P = 0.031, P = 0.013, and P = 0.014 for SSN, AFN, and TFN neurons, respectively), and the duration of the action potentials was increased (P = 0.016, P = 0.032, and P = 0.031 for SSN, AFN, and TFN neurons, respectively). The maximum positive slope (P = 0.016 and P = 0.0010 for SSN and AFN, respectively) and the negative slope (P = 0.016, P = 0.0025, and P = 0.020 for SSN, AFN, and TFN neurons, respectively) decreased after application of lidocaine. In tonically firing neurons, lidocaine reduced the repetitive firing (P = 0.0016), and this effect was mimicked by a combination of TTX and tetraethylammonium. In AFN, TTX mimicked the action of lidocaine. CONCLUSIONS: Lidocaine at low concentrations suppresses tonic firing neurons by interacting with voltage-gated potassium channels. The effects on adapting firing neurons can be explained by an interaction with voltage-gated sodium channels. In contrast, the firing pattern of SSN is not affected at the administered concentrations. This different sensitivity to low concentrations of sodium and particularly of potassium channel blockers might represent a novel approach for a differentiated blockade of different spinal dorsal horn neurons.

Pyruvate: immunonutritional effects on neutrophil intracellular amino or alpha-keto acid profiles and reactive oxygen species production.

For the first time the immunonutritional role of pyruvate on neutrophils (PMN), free α-keto and amino acid profiles, important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] as well as released myeloperoxidase (MPO) acitivity has been investigated. Exogenous pyruvate significantly increased PMN pyruvate, α-ketoglutarate, asparagine, glutamine, aspartate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Moreover, increases in O(2) (-) formation, H(2)O(2)-generation and MPO acitivity in parallel with intracellular pyruvate changes have also been detected. Regarding the interesting findings presented here we believe, that pyruvate fulfils considerably the criteria for a potent immunonutritional molecule in the regulation of the PMN dynamic α-keto and amino acid pools. Moreover it also plays an important role in parallel modulation of the granulocyte-dependent innate immune regulation. Although further research is necessary to clarify pyruvate's sole therapeutical role in critically ill patients' immunonutrition, the first scientific successes seem to be very promising.

Mitochondrial complex II participates in normoxic and hypoxic regulation of α-keto acids in the murine heart.

α-Keto acids (α-KAs) are not just metabolic intermediates but are also powerful modulators of different cellular pathways. Here, we tested the hypothesis that α-KA concentrations are regulated by complex II (succinate dehydrogenase=SDH), which represents an intersection between the mitochondrial respiratory chain for which an important function in cardiopulmonary oxygen sensing has been demonstrated, and the Krebs cycle, a central element of α-KA metabolism. SDH subunit D heterozygous (SDHD(+/-)) and wild-type (WT) mice were housed at normoxia or hypoxia (10% O(2)) for 4 days or 3 weeks, and right ventricular pressure, right ventricle/(left ventricle+septum) ratio, cardiomyocyte ultrastructure, pulmonary vascular remodelling, ventricular complex II subunit expression, SDH activity and α-KA concentrations were analysed. In both strains, hypoxia induced increases in right ventricular pressure and enhanced muscularization of distal pulmonary arteries. Right ventricular hypertrophy was less severe in SDHD(+/-) mice although the cardiomyocyte ultrastructure and mitochondrial morphometric parameters were unchanged. Protein amounts of SDHA, SDHB and SDHC, and SDH activity were distinctly reduced in SDHD(+/-) mice. In normoxic SDHD(+/-) mice, α-ketoisocaproate concentration was lowered to 50% as compared to WT animals. Right/left ventricular concentration differences and the hypoxia-induced decline in individual α-KAs were less pronounced in SDHD(+/-) animals indicating that mitochondrial complex II participates in the adjustment of cardiac α-KA concentrations both under normoxic and hypoxic conditions. These characteristics are not related to the hemodynamic consequences of hypoxia-induced pulmonary vascular remodelling, since its extent and right ventricular pressure were not affected in SDHD(+/-) mice albeit right ventricular hypertrophy was attenuated.

Ketamine inhibits transcription factors activator protein 1 and nuclear factor-kappaB, interleukin-8 production, as well as CD11b and CD16 expression: studies in human leukocytes and leukocytic cell lines.

BACKGROUND: Recent data indicate that ketamine exerts antiinflammatory actions. However, little is known about the signaling mechanisms involved in ketamine-induced immune modulation. In this study, we investigated the effects of ketamine on lipopolysaccharide-induced activation of transcription factors activator protein 1 (AP-1) and nuclear factor-kappaB (NF-kappaB) in human leukocyte-like cell lines and in human blood neutrophils. METHODS: Electric mobility shift assays were used to investigate ketamine's effects on nuclear binding activity of both transcription factors in U937 cells, and a whole blood flow cytometric technique was used for AP-1 and NF-kappaB determination in leukocytes. Cell lines with different expression patterns of opioid and N-methyl-D-aspartate receptors were used for reverse transcription-polymerase chain reaction to investigate receptors involved in ketamine signaling. Ketamine's effect on interleukin-8 production was assessed in a whole blood assay. RESULTS: Ketamine inhibited both transcription factors in a concentration-dependent manner. These effects did not depend on opiate or N-methyl-D-aspartate receptors. Ketamine also reduced interleukin-8 production in whole blood and expression of CD11b and CD16 on neutrophils. CONCLUSION: The immunoinhibitory effects of ketamine are at least in part caused by inhibition of transcription factors NF-kappaB and AP-1, which regulate production of proinflammatory mediators. However, signaling mechanisms different from those present in the central nervous system are responsible for ketamine-mediated immunomodulation.

Effects of alpha-ketoglutarate on neutrophil intracellular amino and alpha-keto acid profiles and ROS production.

The aim of this study was to determine the effects of alpha-ketoglutarate on neutrophil (PMN), free alpha-keto and amino-acid profiles as well as important reactive oxygen species (ROS) produced [superoxide anion (O(2) (-)), hydrogen peroxide (H(2)O(2))] and released myeloperoxidase (MPO) activity. Exogenous alpha-ketoglutarate significantly increased PMN alpha-ketoglutarate, pyruvate, asparagine, glutamine, asparatate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Additionally, in parallel with intracellular alpha-ketoglutarate changes, increases in O(2) (-) formation, H(2)O(2)-generation and MPO activity have also been observed. We therefore believe that alpha-ketoglutarate is important for affecting PMN "susceptible free amino- and alpha-keto acid pools" although important mechanisms and backgrounds are not yet completely explored. Moreover, our results also show very clearly that changes in intragranulocytic alpha-ketoglutarate levels are relevant metabolic determinants in PMN nutrition considerably influencing and modulating the magnitude and quality of the granulocytic host defense capability as well as production of ROS.

Release of melanotroph- and corticotroph-type proopiomelanocortin derivatives into blood after administration of corticotropin-releasing hormone in patients with septic shock without adrenocortical insufficiency.

The aim of the study was to assess the adequacy of pituitary function by determining the plasma concentrations of corticotroph-type (corticotropin, beta-endorphin immunoreactive material [beta-END IRM], authentic beta-END, and beta-lipotropin IRM) as well as melanotroph-type (alpha-melanocyte-stimulating hormone [alpha-MSH] and N-acetyl-beta-END [Nac-beta-END] IRM) proopiomelanocortin (POMC) derivatives in patients under septic shock upon administration of corticotropin-releasing hormone (CRH). The objectives were to assess whether an insufficient release of corticotroph- or melanotroph-type POMC derivatives from the pituitary into the cardiovascular compartment correlates with the 28-day mortality rate. Seventeen patients with septic shock but without adrenocortical insufficiency and 16 healthy volunteers were enrolled in the study, and CRH stimulation tests were performed with an i.v. bolus injection of 100 microg human CRH. After treatment with CRH, plasma concentrations of corticotroph-type POMC derivatives increased in survivors and nonsurvivors, melanotroph-type POMC derivatives such as alpha-MSH or Nac-beta-END IRM increased only in survivors in contrast to nonsurvivors. The release of alpha-MSH and Nac-beta-END IRM was suppressed by dexamethasone in survivors but not in nonsurvivors. In patients with septic shock, the response of the pituitary to CRH stimulation in terms of alpha-MSH or Nac-beta-END IRM release was impaired in nonsurvivors compared with survivors or controls. Reduced responses of alpha-MSH or Nac-beta-END IRM to CRH and the invalid suppression by dexamethasone reflect a state of dysfunction of the melanotroph-type POMC system in nonsurvivors. Considering anticytokine and anti-inflammatory effects of alpha-MSH, this dysfunction may increase the risk of death in patients with septic shock.

Evaluation of sE-Selectin and sICAM-1 as parameters for renal function.

INTRODUCTION: In order to monitor acute renal failure, intensive care patients were examined, and routine as well as specialized parameters were compared. MATERIALS AND METHODS: Thirty-three patients at the Surgical Intensive Care Unit (ICU) were examined daily over the entire period for which they stayed in the ICU. The patients were retrospectively classified as being either with or without acute renal failure. Group 1 consisted of 22 patients who resided in the ICU for 11-15 (median 14) days without ARF. Group 2 consisted of 11 patients who developed an ARF during their stay of 13-18 (median 16) days in the ICU. In addition to the routine parameters of diuresis, serum creatinine/urea, and clearance of creatinine, specialized parameters for kidney function, including the excretion rates of alpha1-microglobulin, N-acetyl-beta-D-glucosaminidase, and total protein, were compared with the excretion rate of soluble ICAM-1 and sE-Selectin. RESULTS: Diuresis, serum creatinine, urea, and enzyme elimination were pathological among patients with ARF. Already on the day of admission, raised elimination rates of sICAM-1 were found in the urine of patients who had developed an ARF. While high values were still shown upon discharge, levels kept falling among patients without ARF. Clearly raised values were also shown for sE-Selectin compared to patients without ARF. CONCLUSIONS: sICAM-1 and sE-Selectin as supplementary parameters indicating renal function revealed early signs of kidney damage. These parameters may play a major role in the development of novel therapeutic approaches for ARF (antibodies against ICAM-1 or sE-Selectin).

Hypobaric hypoxia affects endogenous levels of alpha-keto acids in murine heart ventricles.

Alpha-keto acids have recently been identified as potent regulators of cellular adaptations to hypoxia. Their actual intracellular concentrations under such conditions are unknown. Here, we determined concentrations of alpha-ketobutyrate, alpha-ketoglutarate, alpha-ketoisocaproate, alpha-ketoisovalerate, alpha-keto-beta-methylvalerate, phenylpyruvate, and pyruvate by a recently developed ultra-sensitive fluorescence HPLC method in ventricular myocardium of mice exposed to hypobaric hypoxia for up to 3 weeks. We observed characteristic alterations of cardiac alpha-keto acid concentrations that are specific for individual alpha-keto acids, show significant side differences (right versus left ventricles), and are suited to trigger some of the cardiac metabolic and structural adaptations to chronic hypoxia.

Inhaled aerosolized iloprost in the evaluation of heart transplant candidates--experiences with 45 cases.

PURPOSE: Pulmonary hypertension represents a significant predictor of postoperative right heart insufficiency and increased mortality in patients undergoing orthotopic heart transplantation. As the use of intravenous vasodilators is limited by their systemic effects, we evaluated the pulmonary and systemic hemodynamic effects of inhaled aerosolized iloprost in heart transplant candidates with elevated pulmonary vascular resistance. METHODS: Forty-five male heart transplant candidates with dilated or ischemic cardiomyopathy were included in the study. After assessing baseline hemodynamics, 20 microg of aerosolized iloprost was administered by ultrasonic inhalation. All patients were breathing spontaneously. RESULTS: Inhalation of iloprost reduced pulmonary vascular resistance index (395 +/- 205 vs 327 +/- 222 dyne.s.cm(-5).m(-2); P < 0.05) and mean pulmonary arterial pressure (28.7 +/- 10 vs 24.3 +/- 10 mm Hg; P < 0.05). An additional improvement of ventricular performance with an increase of cardiac index (2.7 +/- 0.7 vs 3.0 +/- 0.8 L.min(-1).m(-2); P < 0.05) and a decrease of pulmonary capillary wedge pressure (16.6 +/- 7.7 vs 13.4 +/- 7.3 mm Hg; P < 0.05) was accompanied by a slight decrease of systemic vascular resistance (1280 +/- 396 vs 1172 +/- 380 dyne.s.cm(-5); P < 0.05). However, the mean arterial pressure remained uninfluenced. CONCLUSIONS: Inhaled aerosolized iloprost effectively reduces mean pulmonary arterial pressure and also induces an increase in cardiac index. Further advantages of iloprost inhalation are the lack of adverse reactions and ease of administration. Iloprost represents a useful drug to screen for vascular reactivity in cardiac transplantation patients.

Mechanisms of Chlamydophila pneumoniae-mediated GM-CSF release in human bronchial epithelial cells.

Chlamydophila pneumoniae is an important respiratory pathogen. In this study we characterized C. pneumoniae strain TW183-mediated activation of human small airway epithelial cells (SAEC) and the bronchial epithelial cell line BEAS-2B and demonstrated time-dependent secretion of granulocyte macrophage colony-stimulating factor (GM-CSF) upon stimulation. TW183 activated p38 mitogen-activated protein kinase (MAPK) in epithelial cells. Kinase inhibition by SB202190 blocked Chlamydia-mediated GM-CSF release on mRNA and protein levels. In addition, the chemical inhibitor as well as dominant-negative mutants of p38 MAPK isoforms p38alpha, beta2, and gamma inhibited C. pneumoniae-related NF-kappaB activation. In contrast, blocking of MAPK ERK, c-Jun kinase/JNK, or PI-3 Kinase showed no effect on Chlamydia-related epithelial cell GM-CSF release. Ultraviolet-inactivated pathogens as compared with viable bacteria induced a smaller GM-CSF release, suggesting that viable Chlamydiae were only partly required for a full effect. Presence of an antichlamydial outer membrane protein-A (OmpA) antibody reduced and addition of recombinant heat-shock protein 60 from C. pneumoniae (cHsp60, GroEL-1)-enhanced GM-CSF release, suggesting a role of these proteins in epithelial cell activation. Our data demonstrate that C. pneumoniae triggers an early proinflammatory signaling cascade involving p38 MAPK-dependent NF-kappaB activation, resulting in subsequent GM-CSF release. C. pneumoniae-induced epithelial cytokine liberation may contribute significantly to inflammatory airway diseases like chronic obstructive pulmonary disease (COPD) or bronchial asthma.

Preoperative concentration of beta-lipotropin immunoreactive material in cerebrospinal fluid: a predictor of postoperative pain?

Levels of beta-endorphin immunoreactive material (IRM) in cerebrospinal fluid (CSF) have been reported to correlate inversely with postoperative morphine requirement. Considering proopiomelanocortin (POMC) derivatives as predictors for sensitivity to postoperative pain, we determined authentic beta-endorphin (beta-endorphin(1-31)), beta-lipotropin IRM, N-acetyl-beta-endorphin IRM and ACTH in CSF of 17 patients undergoing hip or knee arthroplasty, before surgery (t(A)), immediately after termination of propofol infusion and still under spinal anesthesia (t(B)), under postoperative pain (t(C)) and one day after surgery (t(D)); patients rated their severity of pain on a visual analogue scale (VAS) at those four times. In all patients CSF concentrations of N-acetyl-beta-endorphin IRM and beta-lipotropin IRM were found to be increased after terminating the propofol infusion with spinal anesthesia still effective at t(B). Patients did not feel pain at times t(A), t(B) or t(D); however, they reported moderate to considerable pain at t(C). There were no correlations of postoperative pain severity at t(C) with ACTH, beta-endorphin(1-31) or N-acetyl-beta-endorphin IRM concentrations in CSF. In contrast, we observed significant inverse correlations (Spearman's rank correlation coefficients between -0.83 and -0.85, p<0.01) for postoperative pain severity with beta-lipotropin IRM concentrations in CSF at t(C), and, in addition, at t(A), t(B) and t(D); thus, postoperative pain severity appeared to be dependent on a central system controlling sensitivity to pain, linked to a POMC system releasing beta-lipotropin IRM into CSF and already active at times t(A) and t(B). We conclude that beta-lipotropin IRM in CSF might be considered to serve as a predictor of sensitivity to postoperative pain.

Corticotropin-releasing hormone reduces pressure pain sensitivity in humans without involvement of beta-endorphin(1-31), but does not reduce heat pain sensitivity.

In the present study the effects of intravenously administered corticotropin-releasing hormone (CRH) on the release of proopiomelanocortin (POMC) derivatives such as adrenocorticotropic hormone (ACTH), beta-lipotropin (beta-LPH) and beta-endorphin (beta-END) as well as direct effects of CRH on pain sensitivity were examined. In 16 healthy volunteers we studied the effects of 100 microg intravenously administered CRH in absence or presence of 12 mg naloxone on heat or pressure pain sensitivity, using a double-blind, cross-over and placebo-controlled design. To evaluate analgesic effects of CRH via release of POMC derivatives, we determined plasma concentrations of beta-END-immunoreactive material (IRM), authentic beta-END (beta-END(1-31)) and beta-LPH IRM, in parallel with heat and pressure pain tolerance thresholds before and 15 and 30 min after treatment with CRH (or placebo), and 5 min after naloxone (or placebo) administration which was administered 40 min after CRH (or placebo) injection. CRH increased levels of beta-END IRM, beta-END(1-31) and beta-LPH IRM. As compared to beta-END IRM levels measured by a commercial RIA kit, the beta-END(1-31) levels determined by a highly specific two-site RIA, proved to be remarkably small. Furthermore, CRH did not induce increases of heat pain tolerance thresholds, but of pressure pain tolerance thresholds, which, however, were not reversible by naloxone. Neither beta-END nor beta-LPH IRM nor beta-END(1-31) levels correlated with heat or pressure pain tolerance thresholds. We conclude that CRH does not modulate heat, but pressure pain; POMC derivatives like beta-END IRM, beta-END(1-31) or beta-LPH do not mediate this effect.

Quantitative determination of free intracellular alpha-keto acids in neutrophils.

For the first time, a procedure is described for the quantitative analysis of free alpha-keto acid content in human neutrophils (PMNs) relative to single cell number by reversed-phase fluorescence high-performance liquid chromatography. The procedure is minimally invasive and is unsurpassed in the quality of PMN separation, ease of sample preparation as well as sample stability. This method can satisfy the rigorous demands for an ultra-sensitive, comprehensive and rapid intracellular alpha-keto acid analysis in particularly for the surveillance of severe diseases as well as cellular or organ dysfunction.

Iloprost improves hemodynamics in patients with severe chronic cardiac failure and secondary pulmonary hypertension.

PURPOSE: Significant pulmonary hypertension is a predictor of postoperative right heart insufficiency and increased mortality in patients undergoing orthotopic heart transplantation. Since the use of iv vasodilators is limited by their systemic effects, we evaluated the pulmonary and systemic hemodynamic effects of inhaled aerosolized iloprost (IP) in heart transplant candidates with elevated pulmonary vascular resistance (PVR). METHODS: Twenty-nine male heart transplant candidates because of dilated or ischemic cardiomyopathy with elevated PVR were included in the study. After assessing baseline hemodynamics, 50 micro g aerosolized IP were administered by inhalation. RESULTS: Inhalation of iloprost reduced PVR index (PVRI; 416 +/- 180 vs 349 +/- 173 dyn x sec(-1) x m(-2) x cm(-5); P < 0.01) and mean pulmonary artery pressure (MPAP; 28.6 +/- 9 vs 24.2 +/- 9.1 mmHg; P < 0.01), but did not affect blood pressure or systemic vascular resistance. An additional improvement of ventricular performance with an increase of cardiac index (CI; 2.8 +/- 0.7 vs 2.6 +/- 0.7 L x min(-1) x m(-2); P < 0.05) and a decrease of pulmonary capillary wedge pressure (PCWP; 15.6 +/- 6.8 vs 12.8 +/- 7.1 mmHg; P < 0.01) was observed after inhalation of IP. CONCLUSIONS: Inhaled aerosolized iloprost effectively reduces MPAP and is accompanied by an increase in CI and stroke index. Further advantages of iloprost inhalation are the lack of adverse reactions and ease of administration. Iloprost may be a useful drug to screen for vascular reactivity in cardiac transplantation patients.

Hemodynamic effects of inhaled aerosolized iloprost and inhaled nitric oxide in heart transplant candidates with elevated pulmonary vascular resistance.

OBJECTIVE: An elevated pulmonary vascular resistance (PVR) is described as a predictor of postoperative right heart failure and increased mortality in patients undergoing orthotopic heart transplantation. The use of intravenous vasodilators is limited by their systemic effects. We evaluated the pulmonary and systemic hemodynamic effects of inhaled nitric oxide (NO) and inhaled aerosolized iloprost (IP) in heart transplant candidates with elevated PVR. METHODS: Fourteen male heart transplant candidates due to dilative or ischemic cardiomyopathia with elevated PVR (> or = 180 dyn s cm(-5)) were included in the study. Increasing concentrations of NO (5, 10 and 30 ppm) and 50 microg aerosolized IP were administered by inhalation. Hemodynamic measurements preceded and followed administration of each agent. RESULTS: Inhalation of IP, 10, and 30 ppm NO reduced PVR and mean pulmonary artery pressure (MPAP), but did not affect blood pressure or systemic vascular resistance. Comparing the effectiveness of 10 ppm NO and IP, we found a significant higher reduction of MPAP in patients treated with IP. An increase of cardiac index and stroke index could only be shown with IP-inhalation. CONCLUSIONS: Inhaled iloprost induces pulmonary vasodilation which is significantly greater than the effects of 10 and 30 ppm NO. The results of our study show, that inhaled iloprost induces a reliable hemodynamic response in the evaluation of heart transplant candidates. Further advantages of iloprost inhalation are the lack of adverse reactions and toxic side effects and an easier administration. Due to this facts we recommend iloprost as a routine screening drug for vascular reactivity in HTx-candidates. Based on our results it would be of great interest to investigate the role of iloprost in management of postoperative right heart insufficiency following cardiac transplantation.

Alterations of acute phase reaction and cytokine production in patients following severe burn injury.

To determine the acute immunologic reaction, mediated by cytokines, interleukines (ILs) and growth factors and the susceptibility to infections and sepsis after severe burn injury a prospective, single unit, longitudinal study of acute phase reactants and mediators who performed. After approval by the ethics committee of our hospital, we investigated the plasma concentrations of IL-2, -6, -8, -10, and -13, the soluble IL-2 receptor (sIL-2R), and the acute phase proteins procalcitonin (PCT) and C-reactive protein (CRP) at admission and every 3 days in 24 patients over a time course of 28 days after thermal injury and categorized by percent burn: < or =30% (group 1; n=12) and >30% (group 2; n=12). Shortly after burn injury we found higher concentrations of IL-2, -6, -10 and PCT in those patients >30% TBSA. During the study period, we found significant higher levels of acute phase proteins, IL-6 and -8 in patients >30% TBSA. The incidence of SIRS and MODS was three times increased in patients >30% TBSA. Our results show different patterns of cytokines and acute phase proteins in patients with different burned surface areas over a long time and continuous monitoring of a more distinct inflammatory response in these patients.

Long-term monitoring of renal function in poly-traumatized intensive care patients.

INTRODUCTION: For the long-term monitoring of kidney function, polytraumatized patients were examined and routine as well as specialized parameters were compared. MATERIALS AND METHODS: 30 patients of the Surgical Intensive Care Unit (ICU) were examined daily over the entire period they stayed in the ICU. The patients were retrospectively classified as either survivors or deceased patients. Group 1 consisted of 20 patients who resided in the ICU for 11-15 (Median 14) days before they could be transferred to a normal hospital unit. Group 2 consisted of 10 patients who had passed away after 13-18 (Median 16) days in the ICU. In addition to the routine parameters diuresis, serum creatinine and serum urea, specialized parameters for kidney function including the excretion rates of alpha1-microglobulin (alpha1-MG), N-Acetyl-beta-D-glucosaminidase (NAG), angiotensinase A (ATA) and immunoglobulin G (IgG) were determined. RESULTS: Similar biometric data were shown by all patients at admission into the ICU, but differences did exist regarding the Revised Trauma Score, Injury Severity Score and the APACHE-II-Score. In the period between the 5th and 8th day of intensive treatment almost all patients showed pathological excretion rates of tubular and glomerular parameters whereby no increased frequency of unusual events could be determined at these time-points. CONCLUSION: During treatment in the ICU, all examined patients showed at times pathological excretion rates of specialized kidney function parameters. Such transient damage was only apparent in a few of the patients when the standard parameters serum creatinine and serum urea were employed. In 90% of the surviving patients the kidney parameters had normalized until the time they were transferred, indicating that such parameters reflected the general state of health of these patients.