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Biomedical subjects

A B Johan Groeneveld

Publications and source records attributed to A B Johan Groeneveld.

At least 19 recordsLinked to original sources

Digital image analysis of cytoskeletal F-actin disintegration in renal microvascular endothelium following ischemia/reperfusion.

BACKGROUND: Damaged and/or dysfunctional microvascular endothelium has been implicated in the pathogenesis of ischemic acute renal failure (ARF). Rapidly occurring changes in the endothelial F-actin cytoskeleton as observed in vitro might be responsible, but have been proven difficult to measure accurately in situ. Therefore, the purpose of this study was to examine several methods of digital image analysis in order to quantify the alterations of endothelial F-actin after renal ischemia and reperfusion (I/R), and to relate these to deterioration of renal function. METHODS: Frozen sections of Sham and I/R rat kidneys were fixed in 4% formaldehyde and stained with rhodamine-phalloïdin. Microvascular structures were captured using a 3i Marianastrade mark digital imaging fluorescence microscope workstation. Images were analyzed using 3i SlideBooktrade mark software, employing several masking techniques and line-scans. RESULTS: Digital image analysis demonstrated a decrease in the mean intensity of rhodamine-phalloïdin fluorescence after I/R from 1030 +/- 187 to 735 +/- 121 a.u. (arbitrary units, mean +/- SD, n = 7). The number of F-actin fragments per pixel increased from (15.8 +/- 4.9) x 10(-5) to (20.7 +/- 3.5) x 10(-5) (n = 7), indicating cytoskeletal fragmentation. In addition, line-scan analysis demonstrated a disturbed spatial orientation of the F-actin cytoskeleton after I/R. Finally, the loss of F-actin correlated with a rise in plasma creatinine. CONCLUSIONS: The methods of digital image analysis described in the present study demonstrate that renal I/R induces profound changes in the F-actin cytoskeletal structure of microvascular endothelial cells, implicating an injured and dysfunctional microvascular endothelium, which may contribute to acute renal failure (ARF).

Actins↗

Hyperglycaemia in critically ill patients: marker or mediator of mortality?

Acute hyperglycaemia has been associated with complications, prolonged intensive care unit and hospital stay, and increased mortality. We made an inventory of the prevalence and prognostic value of hyperglycaemia, and of the effects of glucose control in different groups of critically ill patients. The prevalence of hyperglycaemia in critically ill patients, using stringent criteria, approaches 100%. An unambiguous negative correlation between hyperglycaemia and mortality has been described in various groups of critically ill patients. Although the available evidence remains inconsistent, there appears to be a favourable effect of glucose regulation. This effect on morbidity and mortality depends on patient characteristics. To be able to compare results of future studies involving glucose regulation, better definitions of hyperglycaemia (and consequently of normoglycaemia) and patient populations are needed.

Biomarkers↗

Extravascular lung water to blood volume ratios as measures of permeability in sepsis-induced ALI/ARDS.

OBJECTIVE: We studied the relationship, and the effect of fluid loading on this, between the ratio of extravascular lung water (EVLW) to intrathoracic/pulmonary blood volumes (ITBV, PBV) and the radionuclide pulmonary leak index (PLI) to protein during sepsis-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). DESIGN AND SETTING: A prospective observational study, in the intensive care unit of a university hospital. PATIENTS: Twenty-two consecutive mechanically ventilated patients with sepsis-related ALI/ARDS from pneumonia (n = 12) or extrapulmonary sources (n = 10), without elevated cardiac filling pressures. INTERVENTION: Crystalloid (1700-1800 ml) or colloid (1000-1800 ml) fluid loading until target filling pressures. MEASUREMENTS AND RESULTS: Protein permeability was assessed noninvasively over the lungs with help of 67Ga-labeled transferrin and 99mTc-labeled red blood cells (Pulmonary leak index, upper limit normal 14.1 x 10(-3)/min) and EVLW and blood volumes by the thermal-dye transpulmonary dilution technique before and after fluid loading. Prior to fluids the pulmonary leak index related to the ratio of EVLW/ITBV and EVLW/PBV (r(s) = 0.46) particularly when the pulmonary leak index was below 100 x 10(-3)/min and in extrapulmonary sepsis (PLI vs. EVLW/PBV r(s) = 0.71). Fluid loading did not alter EVLW, EVLW/ITBV, or EVLW/PBV or the relationship to PLI. CONCLUSION: The data demonstrate that EVLW/ITBV or EVLW/PBV are imperfect measures of increased protein permeability in mechanically ventilated patients with sepsis-induced ALI/ARDS particularly when the PLI is severely increased and during pneumonia, independent of fluid status.

Aged↗

Cardiac response is greater for colloid than saline fluid loading after cardiac or vascular surgery.

OBJECTIVE: To study the effects on volume expansion and myocardial function of colloids or crystalloids in the treatment of hypovolaemic hypotension after cardiac and major vascular surgery. DESIGN AND SETTING: A single-centre, single-blinded, randomized clinical trial at the intensive care unit of a university hospital. PATIENTS AND METHODS: Patients (n=67) were subjected to a 90-min filling pressure-guided fluid challenge with saline 0.9% or the colloids gelatin 4%, hydroxyethyl starch 6% or albumin 5%. Biochemical variables and haemodynamics (transpulmonary thermodilution) were measured. RESULTS: An amount of 1800 (1300-1800) ml of saline or 1600 (750-1800) ml of colloid solution (P< 0.005) was infused. Colloid osmotic pressure (COP) decreased in the saline group and increased in the colloid groups (P< 0.001). Plasma volume increased by 3.0% (-18 to 24) in the saline versus 19% (-11 to 50) in the colloid groups (P< 0.001). Cardiac index increased by median 13% (ns) in the saline group and by 22% in the colloid groups (P<0.005). The rise in left ventricular stroke work index was greater in the colloid than in the saline groups. The different colloids were equally effective. The rise in cardiac index related to the rise in plasma volume and global end-diastolic volume, confirming plasma volume and preload augmentation by the fluid loading. CONCLUSION: After cardiac or major vascular surgery, the pressure- and time-guided fluid response is dependent on the type of fluid used. Colloid fluid loading leads to a greater increase in preload-recruitable cardiac and left ventricular stroke work indices than that with saline, because of greater plasma volume expansion following an increase in plasma COP.

Adult↗

Rho kinase regulates renal blood flow by modulating eNOS activity in ischemia-reperfusion of the rat kidney.

Renal ischemia-reperfusion (I/R) results in vascular dysfunction characterized by a reduced endothelium-dependent vasodilatation and subsequently impaired blood flow. In this study, we investigated the role of Rho kinase in endothelial nitric oxide synthase (eNOS)-mediated regulation of renal blood flow and vasomotor tone in renal I/R. Male Wistar rats were subjected to 60-min bilateral clamping of the renal arteries or sham procedure. One hour before the clamping, the Rho kinase inhibitor Y27632 (1 mg/kg) was intravenously infused. After I/R, renal blood flow was measured using fluorescent microspheres. I/R resulted in a 62% decrease in renal blood flow. In contrast, the blood flow decrease in the group treated with the Rho kinase inhibitor (YI/R) was prevented. Endothelium-dependent vasodilatation of renal arcuate arteries to ACh was measured ex vivo in a pressure myograph. These experiments demonstrated that the in vivo treatment with the Rho kinase inhibitor prevented the decrease in the nitric oxide (NO)-mediated vasodilator response. In addition, after I/R renal interlobar arteries showed a decrease in phosphorylated eNOS and vasodilator-stimulated phosphoprotein, a marker for bioactive NO, which was attenuated by in vivo Rho kinase inhibition. These findings indicate that in vivo inhibition of Rho kinase in renal I/R preserves renal blood flow by improving eNOS function.

Acetylcholine↗

Cardiac output measurement by pulse dye densitometry: comparison with pulmonary artery thermodilution in post-cardiac surgery patients.

OBJECTIVE: Pulse-dye densitometry (PDD) could be a suitable, low-invasive alternative to thermodilution using a pulmonary artery catheter (PAC) for monitoring cardiac output. The aim of our study was to assess the reproducibility and validity of PDD compared to PAC-thermodilution. METHODS: In 43 post-cardiac surgery patients, the mean of triplicate readings of cardiac output was assessed using both methods. In a subgroup of 26 patients, a second set of measurements was obtained on average 2 h later. RESULTS: Reproducibility of consecutive measurements was slightly better for PAC-thermodilution than for PDD (median coefficient of variation of the triplicate measurements: 3.5% versus 5.4%, P < 0.01). Both methods correlated well (r = 0.84, p < 0.001). Using Bland and Altman analyses with PAC-thermodilution as the reference method, PDD showed a bias of -0.68 +/- 0.82 L/min, mainly due to differences in higher ranges of cardiac output (>6.5 L/min). Measured changes in cardiac output were 81% concordant (i.e. <1 L/min different) between both methods. CONCLUSION: PDD correlates well with PAC-thermodilution and thus deserves consideration as a low-invasive alternative for measurement and follow-up of cardiac output.

Aged↗

Heterogeneity and prediction of hemodynamic responses to dobutamine in patients with septic shock.

OBJECTIVE: To establish the heterogeneity of hemodynamic responses to dobutamine in patients with septic shock and to identify the predictive factors of these hemodynamic responses. DESIGN: Prospective study. SETTING AND PATIENTS: A total of 12 patients with septic shock in a tertiary medical intensive care unit. INTERVENTIONS: A 20-min dobutamine infusion at 5 microg.kg(-1).min(-1) with subsequent increments to 8, 12.6, and 20 microg.kg(-1).min(-1), on two consecutive days. Responses were dichotomized into changes in heart rate (HR) or stroke volume index (SVI) of >10% and < or =10% at the maximal dobutamine infusion. MEASUREMENTS AND MAIN RESULTS: No differences were found in survival, Acute Physiology and Chronic Health Evaluation II score, maximal dobutamine doses, or pharmacokinetics of dobutamine between HR and SVI groups. In DeltaHR > 10% vs. DeltaHR < or = 10%, baseline HR was lower, and baseline mixed venous oxygen tension and saturation were higher. During dobutamine infusion, mean arterial pressure decreased in DeltaHR > 10%. Cardiac index and the systemic oxygen delivery index increased and the systemic vascular resistance index decreased at unchanged SVI. Pressure work index increased and the ratio of the diastolic to systolic aortic pressure time indices decreased but not to <0.6. In DeltaHR < or = 10%, systemic vascular resistance index and the ratio of the diastolic to systolic aortic pressure time indices decreased (but remained >0.6) without changes in SVI or cardiac index. Baseline hemodynamic and metabolic variables did not differ between SVI groups. In DeltaSVI > 10%, cardiac index increased with dobutamine, but Pao2 and the systemic oxygen delivery index decreased. In DeltaSVI < or = 10%, HR and the systemic oxygen delivery index increased; mean arterial pressure, left ventricular stroke work index, systemic vascular resistance index, and the ratio of the diastolic to systolic aortic pressure time indices decreased. CONCLUSIONS: Patients with a positive chronotropic response to dobutamine had lower baseline HR values, and a chronotropic rather than inotropic response predicted an increase in cardiac index and systemic oxygen delivery index. Incremental dosages of dobutamine did not compromise indirectly measured myocardial oxygen balance.

Adult↗

Biomarkers of acute renal injury and renal failure.

Acute renal failure (ARF) is a frequent problem in the intensive care unit and is associated with a high mortality. Early recognition could help clinical management, but current indices lack sufficient predictive value for ARF. Therefore, there might be a need for biomarkers in detecting renal tubular injury and/or dysfunction at an early stage before a decline in glomerular filtration rate is noted by an increased serum creatinine. A MEDLINE/PubMed search was performed, including all articles about biomarkers for ARF. All publication types, human and animal studies, or subsets were searched in English language. An extraction of relevant articles was made for the purpose of this narrative review. These biomarkers include tubular enzymes (alpha- and pi-glutathione S-transferase, N-acetyl-glucosaminidase, alkaline phosphatase, gamma-glutamyl transpeptidase, Ala-(Leu-Gly)-aminopeptidase, and fructose-1,6-biphosphatase), low-molecular weight urinary proteins (alpha1- and beta2-microglobulin, retinol-binding protein, adenosine deaminase-binding protein, and cystatin C), Na+/H+ exchanger, neutrophil gelatinase-associated lipocalin, cysteine-rich protein 61, kidney injury molecule 1, urinary interleukins/adhesion molecules, and markers of glomerular filtration such as proatrial natriuretic peptide (1-98) and cystatin C. These biomarkers, detected in urine or serum shortly after tubular injury, have been suggested to contribute to prediction of ARF and need for renal replacement therapy. However, excretion of these biomarkers may also increase after reversible and mild dysfunction and may not necessarily be associated with persistent or irreversible damage. Large prospective studies in human are needed to demonstrate an improved outcome of biomarker-driven management of the patient at risk for ARF.

Acute Kidney Injury↗

Acute lung injury, overhydration or both?

Acute lung injury or acute respiratory distress syndrome (ALI/ARDS) in the course of sepsis is thought to result from increased pulmonary capillary permeability and resultant edema. However, when the edema is assessed at the bedside by measuring the extravascular thermal volume by transpulmonary dilution, some ALI/ARDS patients with sepsis may have normal extravascular lung water (EVLW). Conversely, a raised EVLW may be present even when criteria for ALI/ARDS are not met, according to GS Martin and colleagues in this issue of Critical Care. This commentary puts the findings into a broader perspective and focuses on the difficulty, at the bedside, in recognizing and separating various types of pulmonary edema. Some of these forms of edema, classically differentiated on the basis of increased permeability and cardiogenic/hydrostatic factors, may overlap, whereas the criteria for ALI/ARDS may be loose, poorly reproducible, relatively insensitive and nonspecific, and highly therapy-dependent. Overhydration is particularly difficult to recognize. Additional diagnostics may be required to improve the delineation of pulmonary edema so as to redirect or redefine treatment and improve patient morbidity and, perhaps, mortality. Monitoring EVLW by single transpulmonary thermal dilution, for instance, might have a future role in this process.

Diagnosis, Differential↗

Simple vs complex radionuclide methods of assessing capillary protein permeability for diagnosing acute respiratory distress syndrome.

PURPOSE: Using injection of gallium Ga 67 transferrin, technetium Tc 99m red cells, probes over the lungs, and blood samples, a pulmonary leak index (PLI) and pulmonary transcapillary escape rate (PTCER) for transferrin can be measured. This may help differentiating between cardiogenic pulmonary edema (CPE) and permeability (noncardiogenic) pulmonary edema of the acute respiratory distress syndrome (ARDS). The purpose of the study was to evaluate the relative importance of red cell labeling, blood sampling, and probe measurements in this assessment. MATERIALS AND METHODS: Analysis of radionuclide data obtained in consecutive patients with radiographic evidence for pulmonary edema, classified as ARDS (n = 13), CPE (n = 8), or mixed (n = 5), was performed. The latter patients met ARDS criteria except for a high pulmonary capillary wedge pressure. RESULTS: The PLI, PTCER, and the (67)Ga-lung/blood radioactivity increase (without (99m)Tc-red cell data) were specific and sensitive indices to differentiate ARDS/mixed from CPE. The blood transcapillary escape rate (TER) of (67)Ga-transferrin was about 2- to 6-fold higher in ARDS and mixed than in CPE. The TER had similar diagnostic value as the PLI, PTCER, and the (67)Ga-lung/blood radioactivity ratio increase. CONCLUSIONS: The diagnostic value of the simple blood TER of (67)Ga-transferrin is similar to that of complex methods, using (99m)Tc-red cells and probe measurements over the lungs, because the complex methods largely depend on the blood TER. Simplification of the method without red cell labeling and probes may facilitate bedside use to diagnose permeability edema of ARDS, particularly in the absence of a pulmonary artery catheter.

Adult↗

Induced nitric oxide impairs relaxation but not contraction in endotoxin-exposed rat pulmonary arteries.

BACKGROUND: Many patients with severe acute lung injury do not respond to nitric oxide (NO) inhalational therapy with alleviation of pulmonary arterial hypertension and hypoxemia, so this treatment remains controversial. MATERIALS AND METHODS.: We investigated in endotoxin-exposed Wistar rat pulmonary arteries whether endogenous NO alters contractile and relaxing responses, by electrochemical NO and isometric force measurements. RESULTS: Receptor-independent contraction was similar in control and endotoxin-exposed arteries, while thromboxane analogue (TxA)-dependent contraction was less in the latter. Neither non-selective NO synthase (NOS) inhibition by N(G)-nitro-l-arginine (l-NA) or selective inducible-NOS2 inhibition by aminoguanidine (AG) improved TxA-induced contraction in endotoxin-exposed arteries. Acetylcholine-induced relaxation was impaired in endotoxin-exposed pulmonary arteries, despite a comparable acetylcholine-induced NO release in control arteries. Additionally, NO solution-induced relaxation of endotoxin-exposed arteries was impaired, but could be improved by l-NA or AG. Application of a phosphodiesterase-insensitive cyclic guanosine monophosphate analogue induced similar relaxation in both control and endotoxin-exposed arteries. CONCLUSIONS: Endotoxin-associated NOS2-derived NO is thus associated with impaired NO-mediated relaxation, but does not underlie reduced receptor-mediated pulmonary contractile responses. An increased phosphodiesterase activity may underlie the former, so this route can be explored to replace or improve the effect of inhalational NO therapy in severe sepsis-induced acute lung injury in patients.

Acetylcholine↗

Mechanical ventilation and acute renal failure.

OBJECTIVE: To review the current literature on possible mechanisms by which mechanical ventilation may initiate or aggravate acute renal failure. DATA SOURCE: A Medline database and references from identified articles were used to perform a literature search relating to mechanical ventilation and acute renal failure. DATA SYNTHESIS: Acute renal failure may be initiated or aggravated by mechanical ventilation through three different mechanisms. First, strategies such as permissive hypercapnia or permissive hypoxemia may compromise renal blood flow. Second, through effects on cardiac output, mechanical ventilation affects systemic and renal hemodynamics. Third, mechanical ventilation may cause biotrauma-a pulmonary inflammatory reaction that may generate systemic release of inflammatory mediators. The harmful effects of mechanical ventilation may become more significant when a comorbidity is present. In these situations, it is more difficult to maintain normal gas exchange, and moderate arterial hypoxemia and hypercapnia are often accepted. Renal blood flow is compromised due to a decreased cardiac output as a consequence of high intrathoracic pressures. Furthermore, the effects of biotrauma are not limited to the lungs but may lead to a systemic inflammatory reaction. CONCLUSIONS: The development of acute renal failure during mechanical ventilation likely represents a multifactorial process that may become more important in the presence of comorbidities. Development of optimal interventional strategies requires an understanding of physiologic principles and greater insight into the precise molecular and cellular mechanisms that may also play a role.

Acute Kidney Injury↗

Sequential organ failure predicts mortality of patients with a haematological malignancy needing intensive care.

OBJECTIVES: Poor survival of patients with a haematological malignancy admitted to the intensive care unit (ICU) prompts for proper admission triage and prediction of ICU treatment failure and long-term mortality. We therefore tried to find predictors of the latter outcomes. METHODS: A retrospective analysis of charts and a prospective follow-up study were done, of haemato-oncological patients, admitted to our ICU in a 7-year period with a follow-up until 2 yr thereafter. Clinical parameters during the first four consecutive days were taken to calculate the simplified acute physiology (SAPS II) and the sequential organ failure assessment (SOFA) scores, of proven predictive value in general ICU populations. RESULTS: From a total of 58 patients (n = 47 with acute myelogenous leukaemia or non-Hodgkin lymphoma), admitted into ICU mostly because of respiratory insufficiency, sepsis, shock or combinations, 36 patients had died during their stay in the ICU. Of ICU survivors (n = 22), 20 patients died during follow-up so that the 1-year survival rate was only 12%. The SAPS II and particularly the SOFA scores were of high predictive value for ICU and long-term mortality. CONCLUSIONS: Patients with life-threatening complications of haematological malignancy admitted to ICU ran a high risk for death in the ICU and on the long-term, and the risk can be well predicted by SOFA. The latter may help us to decide on intensive care in individual cases, in order to avoid potentially futile care for patients with a SOFA score of 15 or higher.

Adult↗

Myocardial O2 consumption in porcine left ventricle is heterogeneously distributed in parallel to heterogeneous O2 delivery.

Myocardial blood flow is unevenly distributed, but the cause of this heterogeneity is unknown. Heterogeneous blood flow may reflect heterogeneity of oxygen demand. The aim of the present study was to assess the relation between oxygen consumption and blood flow in small tissue regions in porcine left ventricle. In seven male, anesthetized, open-chest pigs, local oxygen consumption was quantitated by computational model analysis of the incorporation of 13C in glutamate via the tricarboxylic acid cycle during timed infusion of [13C]acetate into the left anterior descending coronary artery. Blood flow was measured with radioactive microspheres before and during acetate infusion. High-resolution nuclear magnetic resonance 13C spectra were obtained from extracts of tissue samples (159 mg mean dry wt) taken at the end of the acetate infusion. Mean regional myocardial blood flow was stable [5.0 +/- 1.6 (SD) and 5.0 +/- 1.4 ml.min(-1).g dry wt(-1) before and after 30 min of acetate infusion, respectively]. Mean left ventricular oxygen consumption measured with the NMR method was 18.6 +/- 7.7 micromol.min(-1).g dry wt(-1) and correlated well (r = 0.85, P = 0.02, n = 7) with oxygen consumption calculated from blood flow, hemoglobin, and blood gas measurements (mean 22.8 +/- 4.7 micromol.min(-1).g dry wt(-1)). Local blood flow and oxygen consumption were significantly correlated (r = 0.63 for pooled normalized data, P < 0.0001, n = 60). We calculate that, in the heart at normal workload, the variance of left ventricular oxygen delivery at submilliliter resolution is explained for 43% by heterogeneity in oxygen demand.

Animals↗

Herpes simplex virus type 1 and normal protein permeability in the lungs of critically ill patients: a case for low pathogenicity?

INTRODUCTION: The pathogenicity of late respiratory infections with herpes simplex virus type 1 (HSV-1) in the critically ill is unclear. METHODS: In four critically ill patients with persistent pulmonary infiltrates of unknown origin and isolation of HSV-1 from tracheal aspirate or bronchoalveolar lavage fluid, at 7 (1-11) days after start of mechanical ventilatory support, a pulmonary leak index (PLI) for 67Gallium (67Ga)-transferrin (upper limit of normal 14.1 x 10(-3)/min) was measured. RESULTS: The PLI ranged between 7.5 and 14.0 x 10(-3)/min in the study patients. Two patients received a course of acyclovir and all survived. CONCLUSIONS: The normal capillary permeability observed in the lungs argues against pathogenicity of HSV-1 in the critically ill, and favors that isolation of the virus reflects reactivation in the course of serious illness and immunodepresssion, rather than primary or superimposed infection in the lungs.

Adult↗