[Perioperative anemia--tolerance or therapy?].
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Anemia↗
Biomedical subjects
O Habler
Publications and source records attributed to O Habler.
[Combination of beta blockers with dobutamine].
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Adrenergic beta-Agonists↗
Three-dimensional visualization of lung blood flow heterogeneity based on fluorescent microsphere technique and fractal dimension: The Blood Flow Analysis System - BFA System.
The heterogeneity of regional pulmonary blood flow (RPBF) can be assessed by fractal analysis. The fractal dimension (FD) is a scale-independent measure of spatial heterogeneity of blood flow. The relative dispersion (RD) is often used to obtain the heterogeneity of RPBF but it is influenced by the resolution of measurement. The Blood Flow Analysis (BFA) System was developed in Delphi to represent the three-dimensional structure of lung blood flow and calculates statistics of FD, RD, spatial correlation of neighbored tissue samples and shows histograms of blood flows at diverse time points during different experiments. The BFA System reads a text file with flows, measured with fluorescent microsphere technique, and constructs the lung anatomy with volumetric pixels showing the flows with a color schema. It is possible to rotate the lungs into two axis (XY) and the statistics are shown with 3D graphics. The System maintains a database with data from various studies at same time. The BFA System was validated with four data sets from previous experiments. The BFA System has shown consistency and it is a new tool to help researchers during lung perfusion studies.
Animals↗
Augmented acute normovolemic hemodilution (A-ANH(tm)) in cardiac and non-cardiac patients.
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Blood Volume↗
[Acute normovolemic hemodilutin (ANH). Effects of ANH on the diastolic function of the left ventricle].
Ischemia-induced changes of diastolic leftventricular (LV) properties commonly precede corresponding ECG-changes. In the present experimental study the consequences of acute normovolemic hemodilution (ANH) induced dilutional anemia (hematocrit, hct 20%) for LV diastolic function were investigated. A total of 22 anaesthetized, splenectomized beagle dogs breathing room air were hemodiluted with isooncotic hydroxyethylstarch solution (6% HAES 200,000/0.5) until a hct value of 20% was reached. Before and after ANH intravascular blood volume (indocyaningreen dilution technique), global and regional myocardial blood flow (radioactive microspheres technique) and the following parameters reflecting LV diastolic properties were ascertained: 1) the maximum rate of LV pressure decrease (LVdp/dtmin), 2) slope and intercept of the enddiastolic pressure-volume relationship (EDPVR, conductance technique) and 3) the time-constant of isovolumic LV pressure decline "tau". After ANH to hct 20% diastolic LV function was found unchanged. Particularly the load-independent parameters (EDPVR-slope and tau) remained constant. The decrease of LV dp/dtmin (-2724 +/- 479 vs. -2388 +/- 408 mmHg.sek-1; p < 0.05) reflects ANH induced changes of LV pre- and afterload. Signs of subendocardial perfusion mismatch were not encountered. Presumed that the coronary vascular system is intact ANH to hct 20% does not provoque changes of LV diastolic function. Moreover neither myocardial perfusion and oxygenation nor myocardial function are endangered by this degree of dilutional anemia.
Animals↗
Diaspirin-crosslinked hemoglobin reduces mortality of severe hemorrhagic shock in pigs with critical coronary stenosis.
OBJECTIVE: To evaluate the effects of resuscitation with a 10% diaspirin-crosslinked hemoglobin (DCLHb) solution on global hemodynamic variables, systemic and myocardial oxygen transport and tissue oxygenation, and contractile function of the left ventricle in an experimental model of severe hemorrhagic shock and critical stenosis of the left anterior descending coronary artery (LAD). DESIGN: Prospective, placebo-controlled, randomized study. SETTING: Experimental animal laboratory. SUBJECTS: A total of 20 anesthetized pigs. INTERVENTIONS: After implementation of a permanent critical LAD stenosis (ie, maintenance of basal blood flow but absence of reactive hyperemia after a 10-sec complete vessel occlusion), hemorrhagic shock (target mean aortic pressure, 45 mm Hg) was induced within 15 mins by programmed withdrawal of blood and maintained for 60 mins. Subsequently, the volume of plasma lost during hemorrhage was replaced by either a balanced electrolyte solution containing 10 g/dL DCLHb (DCLHb group; n = 10) or an 8 g/dL human albumin solution (HSA) oncotically matched to DCLHb (HSA group; n = 10). Data were collected immediately after the infusion of the different solutions and again after 60 mins had elapsed. MEASUREMENTS AND MAIN RESULTS: Although five of ten HSA-treated animals died of acute left ventricular failure within the first 20 mins after complete fluid resuscitation, all of the DCLHb-treated animals survived the 60-min observation period after resuscitation (p < .05). This significant difference in mortality is explained by higher coronary perfusion pressure in DCLHb-treated animals (75 +/- 17 vs. 27 +/- 17 torr DCLHb vs. HSA group; p < .05) and persistence of subendocardial ischemia and hypoxia (radioactive microspheres method) in HSA-treated animals on resuscitation particularly affecting the LAD-supported myocardium (subendocardial oxygen delivery: 20 +/- 11 vs. 3 +/- 1 mL oxygen x g(-1) x min(-1), DCLHb vs. HSA group; p < .05). Except for enhanced myocardial contractility immediately on infusion of DCLHb (maximal left ventricular pressure increase: 2373 +/- 782 vs. 1730 +/- 543 torr x sec(-1) DCLHb vs. HSA group; p < .05), no differences were detected between groups concerning the variables of systemic oxygen transport, tissue oxygenation, and regional contractile function of the myocardium (determined with microsonometry). CONCLUSIONS: Fluid resuscitation with 10% DCLHb solution completely reverses hemorrhagic shock-induced subendocardial ischemia and hypoxia in the presence of compromised coronary circulation and thereby prevents early death after resuscitation.
Animals↗
Effects of primary resuscitation from shock on distribution of myocardial blood flow.
Hemorrhagic shock alters heterogeneity of regional myocardial perfusion (RMP) in the presence of critical coronary stenosis in pigs. Conventional resuscitation has failed to reverse these effects. We hypothesized that improvement of the resuscitation regime would lead to restoration of RMP heterogeneity. Diaspirin-cross-linked hemoglobin (10 g/dl; DCLHb) and human serum albumin (8.0 g/dl; HSA) were used. After baseline, a branch of the left coronary artery was stenosed; thereafter, hemorrhagic shock was induced. Resuscitation was performed with either DCLHb or HSA. At baseline, the fractcal dimension (D) of subendocardial myocardium was 1.31 +/- 0.083 (HSA) and 1.35 +/- 0.106 (DCLHb) (mean +/- SD). Coronary stenosis increased subendocardial D slightly but consistently only in the DCLHb group (1.39 +/- 0.104; P < 0.05). Shock reduced subendocardial D: 1.21 +/- 0.093 (HSA; P = 0.10), 1.25 +/- 0.092 (DCLHb; P < 0.05). Administration of DCLHb increased subendocardial D in 7 of 10 animals (1.31 +/- 0.097; P = 0.066). HSA was ineffective in this respect. DCLHb infusion restored arterial pressure and increased cardiac index (CI) to 80% of baseline values. Administration of HSA left animals hypotensive (69 mmHg) and increased CI to 122% of the average baseline value. Shock-induced disturbances of the distribution of RMP were improved by administration of DCLHb but not by HSA.
Animals↗
Response to inhaled nitric oxide (NO) is not associated with changes of plasma cGMP levels in patients with acute lung injury.
BACKGROUND: A clinically relevant increase of PaO subset2 or decrease of pulmonary vascular resistance (PVR) upon inhalation of NO (iNO) does occur in only 60 to 80% of patients with acute lung injury. The mechanisms for divergent responses of different patients have not yet been fully elucidated. Since NO mediates its pulmonary effects by stimulating soluble guanylate cyclase, thereby increasing levels of cyclic guanosinemonophosphate (cGMP), we hypothesized that pulmonary cGMP production upon iNO might be suppressed in patients not responding to iNO treatment. METHODS: After approval by the local ethical committee and after informed consent had been obtained, both arterial and mixed-venous cGMP levels were analyzed in 13 patients in whom iNO was administered to treat pulmonary hypertension and/or hypoxemia due to acute respiratory distress syndrome (n = 11) or reperfusion injury following lung transplantation (n = 2). Both cardiorespiratory variables and cGMP concentrations were documented simultaneously at baseline, 15 min after inhalation of 8 ppm of NO, and 15 min after withdrawal of NO, respectively. RESULTS: Inhaled NO resulted in a significant increase in PaO(2)/FiO(2) and a decrease in PVR. Arterial and mixed venous concentration of cGMP (median) also increased significantly upon iNO from 2.5 to 6.5 nM (p <0.05) and from 3.0 to 5.7 nM (p <0.05), respectively. Theses effects were fully reversible after withdrawal of iNO. No gradients between arterial and mixed venous cGMP concentrations were detected (p = 0.12). Regression analysis showed no relationship between baseline arterial cGMP concentrations and changes of either PaO(2)/FiO(2) (p = 0. 62) or PVR (p = 0.91). Similarly, no relationship was found between the rise of arterial cGMP concentration subsequent to iNO and corresponding changes of PaO(2) (p = 0.40) or PVR (p = 0.74), respectively. CONCLUSION: Inhalation of NO significantly stimulates soluble guanylate cyclase within the lungs in patients with acute lung injury. However, neither baseline cGMP nor its rise during treatment with inhaled NO can predict the clinical efficacy of iNO in humans. Furthermore, the fact that increased cGMP concentrations were detected during administration of iNO in mixed venous blood (i.e. pulmonary inflow) strongly suggest that the pharmacological effects of iNO are not fully selective for the lungs, but may also affect extrapulmonary organs.
Acute Disease↗
Effect of acute normovolemic hemodilution on distribution of blood flow and tissue oxygenation in dog skeletal muscle.
Acute normovolemic hemodilution (ANH) is efficient in reducing allogenic blood transfusion needs during elective surgery. Tissue oxygenation is maintained by increased cardiac output and oxygen extraction and, presumably, a more homogeneous tissue perfusion. The aim of this study was to investigate blood flow distribution and oxygenation of skeletal muscle. ANH from hematocrit of 36 +/- 3 to 20 +/- 1% was performed in 22 splenectomized, anesthetized beagles (17 analyzed) ventilated with room air. Normovolemia was confirmed by measurement of blood volume. Distribution of perfusion within skeletal muscle was determined by using radioactive microspheres. Tissue oxygen partial pressure was assessed with a polarographic platinum surface electrode. Cardiac index (3.69 +/- 0.79 vs. 4.79 +/- 0.73 l. min-1. m-2) and muscle perfusion (4.07 +/- 0.44 vs. 5.18 +/- 0.36 ml. 100 g-1. min-1) were increased at hematocrit of 20%. Oxygen delivery to skeletal muscle was reduced to 74% of baseline values (0.64 +/- 0.06 vs. 0.48 +/- 0.03 ml O2. 100 g-1. min-1). Nevertheless, tissue PO2 was preserved (27.4 +/- 1.3 vs. 29.9 +/- 1. 4 Torr). Heterogeneity of muscle perfusion (relative dispersion) was reduced after ANH (20.0 +/- 2.2 vs. 13.9 +/- 1.5%). We conclude that a more homogeneous distribution of perfusion is one mechanism for the preservation of tissue oxygenation after moderate ANH, despite reduced oxygen delivery.
Animals↗
[Artificial oxygen carriers. Alternatives to homologous blood transfusion?].
The expected explosion of costs in transfusion medicine due to the shortfall of healthy donors and the more frequent treatment of transfusion-associated complications (chronic hepatitis, cirrhosis, wound infection, tumor recurrence) increases the socio-economic importance of the development of safe and effective synthetic oxygen carriers as an alternative to the transfusion of homologous red blood cells. Currently two types of artificial oxygen carriers are experimentally and clinically investigated for their capacity to ensure adequate tissue oxygenation in the case of severe anemia. In addition to their oxygen transport capacity solutions based on free human or bovine hemoglobin provide vasoconstrictor properties. Their hyperoncotic properties make them particularly attractive for the treatment of severe hemorrhagic shock. Perfluorocarbon (PFC) emulsions allow an increase of the physically dissolved portion of arterial oxygen content. Due to their particulate nature (emulsion droplets) PFC may only be infused in low doses. Otherwise there is risk of overload and malfunction of phagocytic cells of the reticulo-endothelial system. In the case of an intraoperative blood-loss in preoperatively hemodiluted patients, bolus infusion of PFC represents an effective means to avoid immediate retransfusion of autologous blood and allows for further, extreme hemodilution without risking tissue hypoxia.
Animals↗
Recombinant human interleukin-10 attenuates TNFalpha production by porcine monocytes.
BACKGROUND: Human recombinant interleukin-10 (rhIL-10) has been found to inhibit endotoxin-induced production of several proinflammatory cytokines including tumor necrosis factor alpha (TNFalpha) from human monocytes. The exogenous therapeutic administration of rhIL-10 in acute and chronic hyperinflammatory conditions has been discussed. For none of the large animal species that have been used to study the role and effects of various mediators during septicemia, crossreactivity of rhIL-10 has been shown so far. Therefore, the aim of the present investigation was to evaluate the crossreactivity of rhIL-10 in a porcine model. METHODS: To determine the effects of rhIL-10 on endotoxin-challenged porcine monocytes, we incubated porcine peripheral blood monocytes from five donors with three different concentrations of rhIL-10 (500 ng/ml, 1000 ng/ml and 2000 ng/ml, respectively) either simultaneously with, or two hours prior to lipopolysaccharide (LPS) administration. RESULTS: As compared to incubation with LPS (1 microg/ml) alone, coincubation with LPS and rhIL-10 (500 ng/ml, 1000 ng/ml and 2000 ng/ml) (n = 5) for four hours resulted in a marked and uniform reduction of immunoreactive TNFalpha. For preincubation (n = 5), only the addition of 500 ng/ml rhIL-10 led to a homogeneous decrease of TNFalpha levels in each sample. There was no consistent reduction in TNFalpha after preincubation with 1000 and 2000 ng/ml rhIL-10. Our results indicate crossreactivity of recombinant human interleukin-10 in porcine peripheral blood monocytes. Further investigations on the potential therapeutical role of exogenously administered rhIL-10 are thus possible in porcine models.
Adjuvants, Immunologic↗
IV perflubron emulsion versus autologous transfusion in severe normovolemic anemia: effects on left ventricular perfusion and function.
Intact cardiac compensatory mechanisms are necessary to maintain adequate tissue oxygenation during acute normovolemic hemodilution (ANH). Left ventricular (LV) perfusion, oxygenation and function were analyzed in an experimental whole-body model of profound ANH (Hct 9%) and effectiveness of a perfluorocarbon-based oxygen carrier in maintaining myocardial oxygenation and function was evaluated. A total of 22 anesthetized dogs were hemodiluted to Hct 20% followed by a simulated, controlled blood-loss phase in which dogs were randomized to either: (1) 1:1 exchange of lost blood with autologous red blood cells (RBC-group), (2) 1:1 exchange with a colloid (control-group) and (3) 1:1 exchange with a colloid after a single dose of 1.8 g/kg BW perflubron i.v. (PFC-group). Myocardial oxygen delivery and consumption as well as endocardial perfusion were determined using radioactive microspheres. LV myocardial contractility (LV MC) was assessed from: (1) the relationship between maximum rate of LV pressure increase (LVdp/dtmax) and LV enddiastolic volume (LVEDV) and (2) analysis of the LV endsystolic pressure volume relationship (ESPVR). LV diastolic properties were reflected by (1) minimum rate of LV pressure increase (LVdp/dtmin), (2) slope and intercept of the enddiastolic pressure-volume relationship (EDPVR) and (3) the time-constant of isovolumic LV pressure decline "tau 1/2". Full sets of LV MC data were obtained from 18 dogs (n = 6 per group). LV MC (LVdp/dtmax-LVEDV relation) increased after perflubron administration. At the lowest Hct level, all parameters reflecting LV MC as well as LVdp/dtmin were significantly higher in the PFC-group than in the control-group. After profound normovolemic hemodilution (Hct 9%) superiority of LV MC and LV diastolic properties was found, when myocardial oxygenation was supported by i.v. perflubron emulsion, a temporary O2 carrier.
Anemia↗
Programs for assessment of spatial heterogeneity of regional organ blood flow.
Regional organ blood flow (RBF) is spatially heterogeneous. Relative dispersion (standard deviation S.D./mean) is often used to assess heterogeneity of RBF. Relative dispersion is a global measure of heterogeneity and is strongly influenced by the tissue sample size making comparisons between research groups inappropriate. Spatial correlation (s.c.) of blood flow is, on the other hand, averaged local self similarity. Both parameters change oppositely secondary to interventions. Fractal dimension (D) is a scale-independent measure of spatial heterogeneity and thus facilitates comparison of data. Programs for calculation of s.c. and D have not been published. We present two portable computer programs written in C+2 for calculating s.c. and D. The programs were validated with six computer generated data sets of known heterogeneity. The results were in agreement with data from the literature: we conclude that the programs accurately calculate spatial correlation and fractal dimension of 1-, 2-, or 3-dimensional perfusion matrices.
Humans↗
Normovolaemic haemodilution and hyperoxia have no effect on fractal dimension of regional myocardial perfusion in dogs.
Hypervolaemic haemodilution makes myocardial perfusion more homogenous as reflected by reduced fractal dimension of regional myocardial perfusion. The clinically more commonly performed acute normovolaemic haemodilution, however, has not yet been studied in this respect. Hyperoxic ventilation with 100% oxygen is used in conjunction with haemodilution to compensate for low oxygen content by increasing physically dissolved oxygen in plasma. Since hyperoxia is known to cause disturbance in microcirculatory regulation we studied the effects of acute normovolaemic haemodilution to haematocrit (hct) 20 +/- 1% and hyperoxia on regional myocardial perfusion heterogeneity in 22 anaesthetized dogs using fractal and correlation analysis. Regional myocardial perfusion was assessed with radioactive microspheres. The results of the study were that heart rate, blood volume and arterial pressure were unchanged during haemodilution. Cardiac index was 3.6 +/- 0.7 L min-1 m-2 before and 4.6 +/- 0.7 L min-1 m-2 after haemodilution (P < 0.05). Fractal dimension (D) of regional myocardial perfusion was 1.17 +/- 0.10 at baseline. Neither haemodilution (D = 1.19 +/- 0.10) nor hyperoxia (D = 1.17 +/- 0.10) altered fractal properties of regional myocardial perfusion. Spatial correlation of blood flow to adjacent tissue samples before haemodilution was 0.58 +/- 0.15. Haemodilution and hyperoxia did not significantly influence spatial correlation (0.57 +/- 0.12 vs. 0.60 +/- 0.09; ns). We conclude that neither acute normovolaemic haemodilution nor haemodilution in combination with hyperoxic ventilation alter physiological myocardial perfusion heterogeneity.
Animals↗
Efficacy of inhaled prostanoids in experimental pulmonary hypertension.
OBJECTIVES: To evaluate the effects of inhaled prostacyclin (PGI2) and inhaled as well as intravenous prostaglandin E1 (PGE1) on thromboxane A2 mimetic-induced pulmonary vasoconstriction. Active pulmonary vasoconstriction was to be distinguished from passive resistance to blood flow. DESIGN: Prospective, randomized, crossover study. SETTING: Experimental animal laboratory. SUBJECTS: Eight anesthetized and paralyzed sheep. INTERVENTIONS: The stable thromboxane A2 mimetic, U46619, was infused in increasing dosage to obtain a stable pulmonary hypertension of approximately 30 mm Hg. Subsequently, PGE1 aerosol (0.6, 6, 58, 259 ng/kg/min), intravenous PGE, (0.5 microg/kg/min), or PGI2 aerosol (27 ng/kg/min) were administered in randomized order. MEASUREMENTS AND MAIN RESULTS: Active pulmonary vasoconstriction was assessed by determining the pulmonary pressure-flow relationship (PPFR). For measurement of pulmonary artery flow, an ultrasound flow probe was placed around the pulmonary artery after a sternotomy. Pulmonary arterial pressure was measured with a pulmonary artery flotation catheter. Flow was varied by partial occlusion of the inferior vena cava or incremental opening of an arterio-venous fistula between the large neck vessels. The primary end points were the slope of the resulting linear pressure-flow relationship, and pulmonary vascular resistance (PVR). Infusion of U46619 increased the slope of the PPFR (2.9+/-0.7 vs. 4.2+/-1.2 mm Hg/L/min [median+/-semi-interquartile range]; p < or = .05), and PVR (221+/-20 vs. 424+/-57 dyne x sec/cm5) (p < .05). Neither dose of PGE1 aerosol induced changes of the slope of PPFR or PVR. In contrast, intravenous administration of the same drug reduced the slope of the PPFR (4.0+/-1.0 vs. 3.1+/-0.4) (p < .05) but left PVR unchanged. Inhalation of PGI2 reduced both the slope of the PPFR, slightly but significantly, and PVR (424+/-98 vs. 323+/-26 dyne x sec/cm5) (p < .05). CONCLUSIONS: This study is the first to show reduction of active pulmonary vasoconstriction by PGI2 aerosol. Neither inhalation nor intravenous administration of PGE1 reduced PVR but the latter reduced the slope of PPFR. We conclude that PGE1 has potential for pulmonary vasodilation, but that it is ineffective as an aerosol, even in high doses, in sheep. PVR may fail to reflect drug-induced pulmonary vasodilation.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Noninvasive measurement of regional cerebral blood flow by near-infrared spectroscopy and indocyanine green.
Clinicians lack a practical method for measuring CBF rapidly, repeatedly, and noninvasively at the bedside. A new noninvasive technique for estimation of cerebral hemodynamics by use of near-infrared spectroscopy (NIRS) and an intravenously infused tracer dye is proposed. Kinetics of the infrared tracer indocyanine green were monitored on the intact skull in pigs. According to an algorithm derived from fluorescein flowmetry, a relative blood flow index (BFI) was calculated. Data obtained were compared with cerebral and galeal blood flow values assessed by radioactive microspheres under baseline conditions and during hemorrhagic shock and resuscitation. Blood flow index correlated significantly (rs = 0.814, P < 0.001) with cortical blood flow but not with galeal blood flow (rs = 0.258). However, limits of agreement between BFI and CBF are rather wide (+/- 38.2 +/- 6.4 mL 100 g-1 min-1) and require further studies. Data presented demonstrate that detection of tracer kinetics in the cerebrovasculature by NIRS may serve as valuable tool for the noninvasive estimation of regional CBF. Indocyanine green dilution curves monitored noninvasively on the intact skull by NIRS reflect dye passage through the cerebral, not extracerebral, circulation.
Algorithms↗