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Background Increased vascular permeability is a characteristic feature of sepsis which, in the past, has been ascribed exclusively to a malfunction of endothelial cells. However, recently it has become evident that the endothelial glycocalyx is of considerable importance concerning various aspects of vascular physiology, e.g. the vascular barrier and inflammation. Heparan sulfate, one of its essential components is characteristically traceable in blood, in case the endothelial glycocalyx is damaged or destroyed. Methods In 15 pigs we investigated whether the administration of endotoxin from gram-negative bacteria (Escherichia coli) results in increased serum levels of heparan sulfate, signalizing a shedding of the glycocalyx. In addition, markers of inflammation (white blood cell count, platelet count, tumour necrosis factor-α and interleukin-6) were evaluated over an observation period of 6 hours. Results Serum heparan sulfate concentrations significantly increased over time in the endotoxin group and were significantly elevated in comparison to the control group 6 hours after administration of endotoxin (p < 0.001). In the endotoxin group all markers of inflammation significantly changed during the time course. Conclusions The administration of bacterial endotoxin induced a significant rise in degradation products of the endothelial glycocalyx.

The aim was, to identify an estimate of left ventricular contractility derived from the aortic pressure wave without load changing manoeuvres. For this purpose, left ventricular contractility was assessed with several aortic pressure wave form derived parameters and was compared to standard parameters of left ventricular contractility (conductance technique) in an experimental study. Measurements were taken during baseline, after beta-stimulation and after injection of a beta-antagonist. The initial and the secondary tangent, the area under the aortic pressure, and the stroke volume were correlated with the endsystolic elastance, a mainly load independent measure of left ventricular contractility: The initial tangent of the aortic pressure increase correlated significantly with the endsystolic elastance (r = 0.54, P0.05). The initial tangent of the aortic pressure increase was significantly increased from baseline at beta-stimulation (from 20.2 +/- 4.7 to 36.4 +/- 6.8 mmHg s(-1), P0.05) and decreased after injection of a beta-antagonist (from 20.2 +/- 4.7 to 12.3 +/- 2.0, P0.05). Thus, we conclude that the initial tangent of the aortic pressure increase is a valid estimate of left ventricular contractility in piglets.

Background Acute normovolemic hemodilution reduces the circulating erythrocyte mass and, thus, the hemoglobin concentration. After extreme acute normovolemic hemodilution to the critical hemoglobin concentration (Hbcrit), oxygen demand of the tissues is no longer met by oxygen supply, and death occurs with increasing oxygen debt. The aim of the current study was to investigate whether ventilation with 100% oxygen (fraction of inspired oxygen [FiO2] = 1.0; hyperoxic ventilation) initiated at Hbcrit could restore adequate tissue oxygenation and prevent death. Methods Fourteen anesthetized pigs ventilated with room air (FiO2 = 0.21) were hemodiluted by exchange of whole blood for 6% hydroxyethyl starch (200,000:0.5) until the individual Hbcrit was reached. Hbcrit was defined as the onset of oxygen supply dependency of oxygen consumption and was identified with indirect calorimetry. For the next 6 h, animals were either ventilated with an FiO2 of 0.21 (n = 7) or an FiO2 of 1.0 (n = 7). Results All animals in the 0.21 FiO2 group died within the first 3 h at Hbcrit (i.e., 6-h mortality 100%). Death was preceded by an increase of serum concentrations of lactate and catecholamines. In contrast to that, six of the seven animals of the 1.0 FiO2 group survived the complete 6-h observation period without lactacidosis and increased serum catecholamines (i.e., 6-h mortality 14%; FiO2 0.21 vs. FiO2 1.0, P < or = 0.05). After 6 h at Hbcrit, the FiO2 was reduced from 1.0 to 0.21, and five of the six animals died within the next 3 h. Conclusion In anesthetized pigs submitted to lethal anemia, hyperoxic ventilation enabled survival for 6 h without signs of circulatory failure.

Although inhaled nitric oxide (NO i ) is considered to act selectively on pulmonary vessels, EEG abnormalities and even occasional neurotoxic effects of NO i have been proposed. Here, we investigated cerebrovascular effects of increasing concentrations of 5, 10 and 50 ppm NO i in seven anesthetized pigs. Cerebral hemodynamics were assessed non-invasively by use of near-infared spectroscopy and indicator dilution techniques. NO i increased cerebral blood volume significantly and reversibly. This effect was not attributable to changes of macrohemodynamic parameters or arterial blood gases. Simultaneously, cerebral transit time increased while cerebral blood flow remained unchanged. These data demonstrate a vasodilatory action of NO i in the cerebral vasculature, which may occur preferentially in the venous compartment.

Objective: During normovolaemic haemodilution arterial O2-content decreases exponentially. Nevertheless, tissue oxygenation is first maintained initially by increased organ perfusion and O2-extraction. As soon as these compensatory mechanisms are exhausted, myocardial ischaemia and tissue hypoxia occur at an individual ‘critical’ haematocrit (Hct) value. This study was conducted in order to assess whether tissue hypoxia at the critical Hct is reversed by hyperoxic ventilation with 100% O2. Method: Eighteen anaesthetized pigs were ventilated with room air and were hemodiluted by 1:1 exchange of blood with 6% pentastarch to their individual critical Hct (onset of myocardial ischaemia; significant ECG changes). At the critical Hct, hyperoxic ventilation was initiated. In nine complete datasets, global O2 delivery and consumption, local tissue O2 partial pressure (tpO2) (MDO-Electrode, Eschweiler, Kiel, Germany) and organ blood flow (microsphere method) in skeletal muscle were analyzed at baseline, after haemodilution to the critical Hct and after 15 min of hyperoxic ventilation. Results: At the critical Hct (7.2±1.2%), tpO2 was reduced from 23±3 to 10±2 Torr with 50% of all values in the hypoxic range (

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.

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.

Objective: Inhalation of high concentrations of nitric oxide (NO) has been shown to improve gas exchange and to reduce pulmonary vascular resistance in individuals with ischemia-reperfusion injury following orthotopic lung transplantation. We assessed the cardiopulmonary effects of low doses of NO in early allograft dysfunction following lung transplantion. Design: Prospective clinical dose- response study. Setting: Anesthesiological intensive care unit of a university hospital. Patients and participants: 8 patients following a single or double lung transplantation who had a mean pulmonary arterial pressure (PAP) in excess of 4.7 kPa (35 mmHg) or an arterial oxygen tension/fractional inspired oxygen ratio (PaO2/FIO2) of less than 13.3 kPa (100 mmHg). Interventions: Gaseous NO was inhaled in increasing concentrations (1, 4 and 8 parts per million, each for 15 min) via a Siemens Servo 300 ventilator. Measurements and results: Cardiorespiratory parameters were assessed at baseline, after each concentration of NO, and 15 min after withdrawal of the agent [statistics: median (25th/75th percentiles: Q1/Q3), rANOVA, Dunnett's test, p < 0.05]. Inhaled NO resulted in a significant, reversible, dose-dependent, selective reduction in PAP from 5.5(5.2/6.0) kPa at control to 5.1(4.7/5.6) kPa at 1 ppm, 4.9(4.3/5.3) kPa at 4 ppm, and to 4.7(4.1/5.1) kPa at 8 ppm. PaO2 increased from 12.7(10.4/17.1) to 19.2(12.4/26.0) kPa at 1 ppm NO, to 23.9(4.67/26.7) kPa at 4 ppm NO and to 24.5(11.9/28.7) kPa at 8 ppm NO. All patients responded to NO inhalation (either with PAP or PaO2), all were subject to long-term inhalation (1–19 days). All were successfully weaned from NO and were discharged from the intensive care unit. Conclusion: The present study demonstrates that low-dose inhaled NO may be an effective drug for symptomatic treatment of hypoxemia and/or pulmonary hypertension due to allograft dysfunction subsequent to lung transplantation.

The influence of severe acute normovolemic hemodilution (ANH) on myocardial contractility (MC) was investigated in 14 splenectomized, anesthetized dogs. MC was assessed by the maximum rate of left ventricular pressure increase (LVdp/dt(max)), end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) (conductance catheter, left ventricular pressure-volume relationship). Measurements of myocardial perfusion and oxygenation (radioactive microsphere technique) assured comparability of the model to previously performed studies. Global and regional myocardial blood flow increased significantly upon hemodilution with preference to midmyocardium and subendocardium. This resulted in preservation of both myocardial oxygen delivery and consumption after ANH. Myocardial oxygen extraction as well as coronary venous Po2 were unaffected by ANH, while coronary venous lactate concentration decreased, indicating that myocardial oxygen need was met. LVdp/dt(max) decreased significantly after hemodilution (2278 +/- 577 vs 1884 +/- 381 mm Hg/s, P < 0.01), whereas Ees and PRSW increased significantly (1.76 +/- 0.54 vs 2.15 +/- 0.75 mm Hg/mL, P < 0.05, for Ees and 33 +/- 14 vs 45 +/- 14 mm Hg.mL, P < 0.05, for PRSW). While the decrease of LVdp/dt(max) most likely reflects ANH-induced changes of ventricular pre- and afterload, the increase of Ees and PRSW indicates a true increase of myocardial contractility during ANH in anesthetized dogs.

Background Inhaled perfluorohexan vapor has been shown to improve gas exchange and pulmonary mechanics in oleic acid- and ventilator-induced lung injury. However, in the clinical setting, lung injury frequently occurs in the context of systemic inflammation and consecutive lung injury, which may be induced experimentally by intravenous administration of endotoxin. The authors studied whether vaporized perfluorohexan is efficacious during endotoxin-induced lung injury in domestic pigs. Methods Twenty-two pigs (29 [23, 31] kg body weight [first, third interquartile]; tracheostomy) were anesthetized and mechanically ventilated. In the endotoxin (n = 8) and perfluorohexan groups (n = 7), we administered endotoxin of Escherichia coli 111:B4, 1 mg.kg . h for 1 h and 10 microg.kg.h for 5 h in consecutive order. In the perfluorohexan group, inhalation of the test drug was started 2 h 30 min after the start of the intravenous endotoxin and terminated after 30 min. In a control group (n=7), animals were instrumented and observed over time without further intervention. Oxygenation function was assessed from oxygen partial pressures (Po2, blood gases) and calculated shunt fraction. Respiratory compliance was calculated from airway pressure and tidal volume. Measurements were performed before and every hour during endotoxin infusion. Results After 6 h of endotoxin, gas exchange and pulmonary compliance were deteriorated in the endotoxin group (Pao2: 184 [114, 289] vs. 638 [615, 658] mmHg, pulmonary shunt fraction: 30 [23, 38] vs. 4 [3, 6]%, respiratory compliance: 12 [11, 14] vs. 22 [19, 23] ml/mbar; P < 0.05, endotoxin vs. control). Inhalation of vaporized perfluorohexan did not improve Pao 2 (107 [60, 221] mmHg), pulmonary shunt fraction (32 [26, 58]%), or respiratory compliance (14 [10, 17] ml/mbar) when compared with intravenous endotoxin (not significant, perfluorohexan vs. endotoxin). Conclusions Inhalation of vaporized perfluorohexan does not improve pulmonary gas exchange or respiratory compliance in endotoxin-induced porcine lung injury.

Summary Background: Ventilation with pure oxygen (hyperoxic ventilation, HV) increases arterial oxygen content (CaO2). However HV induces arteriolar constriction and thus potentially affects O2 supply. We therefore investigated the effects of HV on regional blood flow (RBF) and O2 supply of different vital organs during moderate normovolaemic anaemia. Methods: Twenty-two anaesthetized dogs were haemodiluted under normoxia (i.e. FiO2 = 0·21) to a target haemoglobin concentration (Hb) of 7 g dl−1 and were subsequently ventilated with pure O2. RBF was determined by use of the radioactive microspheres method in the myocardium, kidney, skeletal muscle, liver, intestine, stomach, and pancreas at Hb = 7 g dl−1 and after subsequent initiation of HV. RBF in proportion to cardiac output (RBFrelative), the variation coefficient of RBF (VC) and regional O2 supply (rDO2) were calculated. Results: Initiation of HV at Hb = 7·0 ± 0·3 g dl−1 reduced cardiac index (−17%) as well as RBF within the myocardium (−21%), pancreas (−25%), and skeletal muscle (−25%), whereas renal, hepatic, and intestinal RBF remained unchanged. Consequently RBFrelative of the latter organs increased. Heterogeneity of RBF was marginally affected by HV. Conclusion: The initiation of HV during moderate normovolaemic anaemia (Hb =7 g dl−1) was accompanied by RBF redistribution with preference for renal, hepatic and intestinal O2 supply. Cardiac, pancreatic and muscular O2 supply decreased, however without any critical restriction of organ function.

Background: Fluid resuscitation from hemorrhagic shock is intended to abolish microcirculatory disorders and to restore adequate tissue oxygenation. Diaspirin cross-linked hemoglobin (DCLHb) is a hemoglobin-based oxygen carrier (HBOC) with vasoconstrictive properties. Therefore, fluid resuscitation from severe hemorrhagic shock using DCLHb was expected to improve perfusion pressure and tissue perfusion of kidneys and pancreas. Methods: In 20 anesthetized domestic pigs with an experimentally induced coronary stenosis, shock (mean arterial pressure 45 mmHg) was induced by controlled withdrawal of blood and maintained for 60 min. Fluid resuscitation (replacement of the plasma volume withdrawn during hemorrhage) was performed with either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). Completion of resuscitation was followed by a 60-min observation period. Regional blood flow to the kidneys and the pancreas was measured by use of the radioactive microspheres method at baseline, after shock and 60 min after fluid resuscitation. Results: All animals (10/10) resuscitated with DCLHb survived the 60-min observation period, while 5/10 control animals died within 20 min due to persisting subendocardial ischemia. In contrast to HSA survivors, pancreas and kidneys of DCLHb-treated animals revealed lower total and regional organ perfusion and regional oxygen delivery. Renal and pancreatic blood flow heterogeneity was higher in the DCLHb group. Conclusion: DCLHb-induced vasoconstriction afforded superior myocardial perfusion, but impaired regional perfusion of the kidneys and the pancreas.

The prostaglandin I2 analogues epoprostenol and iloprost increase left ventricular contractility. Therefore, we hypothesize that the prostaglandin I2 analogues epoprostenol and iloprost improve also left ventricular diastolic function. To test this hypothesis, the effects of epoprostenol and iloprost on left ventricular diastolic function were assessed in vivo and compared to two vasodilators sodium nitroprusside and adenosine, not formerly associated with changes of left ventricular contractility. Eleven pigs (25.9+/-2.8 kg, balanced anaesthesia) were exposed to the short-acting intravenous vasodilators sodium nitroprusside, adenosine and epoprostenol in a randomized cross over design. The long-acting iloprost was administered at the end of the protocol. The drugs are titrated to achieve a 25% reduction of diastolic aortic pressure. Active isovolumic relaxation properties of the left ventricle were assessed by the maximum velocity of left ventricular pressure drop. Passive phase of relaxation and filling was assessed by the determination of end diastolic compliance during a preload reduction manoeuvre. The maximum velocity of left ventricular pressure drop worsened during the infusion of sodium nitroprusside (baseline: -1950; sodium nitroprusside: -1293 mm Hg/s, p0.05, Wilcoxon signed rank test versus vs. baseline) and adenosine (baseline: -2015; adenosine: -1345 mm Hg/s, p0.05), but remained stable during the infusion of the prostaglandins (baseline: -1943; epoprostenol: -1785 mm Hg/s; baseline: -2042; iloprost: -1923 mm Hg/s). End diastolic compliance was not altered significantly by any vasodilator. Interstitial myocardial cAMP increased during the infusion of epoprostenol (7.60 to 13.87 fmol/ml, p0.05) and tended to increase during the infusion of iloprost (7.56 to 11.66 fmol/ml, p=0.21). The prostaglandin I(2) analogues epoprostenol and iloprost preserved the early phase of active isovolumic relaxation, presumably mediated by myocardial cAMP, whereas sodium nitroprusside and adenosine impaired early active isovolumic relaxation. Passive relaxation and filling properties remained stable during the infusion of each applied vasodilator in the intact left ventricle in vivo.

Background: Hemodilution reduces hematocrit (Hct) and blood oxygen content. Tissue oxygenation is mainly preserved by increased cardiac output. As myocardial O2-demands increase, coronary vasodilatation becomes necessary to increase myocardial blood flow. Myocardial ischemia occurs at a critical Hct-value (Hctcrit), with accompanying exhaustion of coronary reserve. Hyperoxic ventilation is known to both reverse peripheral tissue hypoxia at Hctcrit and also to induce coronary vasoconstriction. This study aimed to determine whether hyperoxic ventilation at Hctcrit further exacerbates myocardial ischemia and dysfunction. Methods: Nine anesthetized pigs ventilated on room air were hemodiluted by 1 : 1 exchange of blood with pentastarch (6%HES) to Hctcrit , defined as onset of myocardial ischemia (ECG changes). At Hctcrit , hyperoxic ventilation was started. Measurements were performed at baseline, at Hctcrit, and after 15 min of hyperoxic ventilation. We determined myocardial blood flow (microsphere method), arterial O2-content, subendocardial O2-delivery and myocardial function (left ventricular pressure increase). Results: At Hctcrit 7 (6;8)%, O2-content was reduced [3.7 (3.1;3.9) ml dl−1]. Despite a compensatory increase of myocardial blood flow [531 (449;573), ml min−1100 g−1], all pigs displayed myocardial ischemia and compromised myocardial function (P

Ventilation with 100% oxygen (Fio(2) 1.0; hyperoxic ventilation; HV) as an alternative to red blood cell transfusion enables survival in otherwise lethal normovolemic anemia. The aim of the present study was to investigate whether HV as a supplement to fluid infusion therapy could also restore adequate tissue oxygenation and prevent death in otherwise lethal hemorrhagic shock. In 14 anesthetized pigs ventilated on room air (Fio(2) 0.21), hemorrhagic shock was induced by controlled withdrawal of blood (target mean arterial pressure 35-40 mmHg) and maintained for 1 h. Subsequently, the animals were partially fluid-resuscitated (i.e., replacement of lost plasma volume) either with hydroxyethyl starch (6% HES, 200/0.5) alone (G 0.21) or with HES supplemented by HV (G 1.0). After completion of partial fluid resuscitation, all animals were followed up for the next 6 h. Five of seven animals of G 0.21 died within the 6-h observation period (i.e., 6-h mortality 71%). Death was preceded by a continuous increase of the serum concentrations of arterial lactate and persistent tissue hypoxia. In contrast to that, all animals of G 1.0 survived the 6-h observation period without lactic acidosis and with improved tissue oxygenation (i.e., 6-h mortality 0%; G 0.21 versus G 1.0 P < 0.05). In anesthetized pigs submitted to lethal hemorrhagic shock, the supplementation of partial fluid resuscitation with HV improved tissue oxygenation and enabled survival for 6 h.

Reperfusion triggers the expression of inflammatory cytokines and adhesion molecules that increase the rate of apoptosis in the reperfused tissues after ischaemia, thus worsening the outcome of the grafts. Polyclonal anti-thymocyte globulins (pATGs) are able to reduce the number of lymphocytes as well as block adhesion molecules and induce apoptosis in T-lymphocytes through Fas-ligand. The aims of this study were to investigate the influence of pATGs on the prevention of apoptosis of reperfused tissues after ischaemia and to monitor their capability to enhance lymphocyte apoptosis thus decreasing the deleterious effects of ischaemia/reperfusion injury (IRI). Extremities of cynomolgus monkeys ( n=8) were flushed via either the femoral or the brachial artery. After 60 min of ischaemia the limbs were reperfused with human blood. ATG was added to the blood in a therapeutic dose 20 min prior to reperfusion of the extremities. Surgically available limbs ( n=20) were assigned to the following groups: ATG group ( n=10) and control group (without ATG; n=10). DNA fragmentation analysis was performed in situ to detect apoptosis at the single-cell level. Our study shows an increased rate of muscle and connective tissue apoptosis in the control group compared with the ATG-treated group. Cells found in the vascular areas present different rates of apoptosis, with enhanced cellular death of endothelium and connective perivascular areas being observed in the control group. The group treated with ATG shows an increased rate of white blood cell (WBC) apoptosis in vascular and perivascular areas. Previous studies have shown that pATGs are able to induce apoptosis as well as complement-mediated cell death in peripheral T-lymphocytes in vitro. Our results confirm that pATGs not only increase the rate of apoptosis of WBCs in vivo but also have a protective effect on the reperfused tissue. This may alleviate the damage after reperfusion of solid-organ transplantation.

In severe hemorrhagic shock, left ventricular (LV) diastolic dysfunction is an early sign of cardiac failure due to compromised myocardial oxygenation. Immediate fluid replacement or, in particular, administration of a hemoglobin-based oxygen carrier (diaspirin cross-linked hemoglobin; DCLHb) improves myocardial oxygenation; therefore, positive effects on LV diastolic function could be expected. The effects of fluid resuscitation from severe hemorrhagic shock with DCLHb were investigated in 20 anesthetized domestic pigs. After generation of a critical left anterior descending coronary artery stenosis (narrowing of the artery until disappearance of reactive hyperemia after a 10-second complete vessel occlusion), hemorrhagic shock (mean arterial blood pressure 45 mm Hg) was induced within 15 min by controlled blood withdrawal and maintained for 60 min. Fluid resuscitation consisted of replacement of the plasma volume withdrawn during hemorrhage by infusion of either 10% DCLHb (DCLHb group, n = 10) or 8% human serum albumin (HSA) oncotically matched to DCLHb (HSA group, n = 10). After completion of resuscitation, an observation period of 60 min elapsed. Measurements of central hemodynamics, myocardial oxygenation, and LV diastolic function were performed at baseline, after induction of critical coronary artery stenosis, after 60 min of hemorrhagic shock, immediately after resuscitation, and 60 min later. While 5 out of 10 animals treated with HSA died within the first 20 min after fluid resuscitation from acute LV pump failure, all DCLHb-treated animals survived until the end of the protocol (p < 0.05). Despite superior myocardial oxygenation due to augmentation of the arterial O2 content as well as of coronary perfusion pressure, no beneficial effects on LV diastolic function were observed after infusion of DCLHb. Peak velocity of LV pressure decrease (dp/dtmin) did not reveal significant differences between the two groups. Immediately after completion of fluid resuscitation with DCLHb, the time constant of LV diastolic relaxation (τ) was prolonged when compared with HSA-treated animals (p < 0.05), indicating retardation of early LV diastolic relaxation. Our data suggest that DCLHb fails to improve LV diastolic function after fluid resuscitation from severe hemorrhagic shock. However, positive effects on myocardial perfusion and oxygenation result in a significant reduction of the mortality of severe hemorrhagic shock.

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

In seven anesthetized dogs, the effects of acute normovolemic hemodilution (ANH) to a hematocrit of 20 and 8% and the effects of hyperoxic ventilation (100% oxygen) on distribution of regional pulmonary blood flow (rPBF; radioactive microspheres) were investigated. Normovolemia was monitored with blood volume measurements (indocyanine green dilution kinetics). Before ANH, fractal dimension ( D) of rPBF in the whole lung was 1.19 ± 0.09 (mean ± SD). Spatial correlation (ρ) of rPBF in the whole lung was 0.6 ± 0.08. D is a resolution-independent measure for global rPBF distribution, and ρ is the averaged flow relationship of directly neighboring lung samples. With regard to the entire lung, neither ANH nor hyperoxia changed D or ρ. With regard to horizontal, isogravitational planes, ANH induced opposite changes of rPBF heterogeneity depending on the vertical location of the plane and the parameter used. In ventral planes, a change in relative dispersion (SD/mean) indicated decreased homogeneity. However, ρ suggested more homogeneous perfusion. Hyperoxia restored baseline rPBF distribution. Our data suggest that ANH causes different alterations of heterogeneity of rPBF depending on location within the lung.

Acute normovolemic hemodilution (ANH) has been shown to be a cost-effective method of reducing allogenic blood transfusion during elective surgery. ANH has been implicated with impaired oxygenation in isolated canine gastric flaps. The present study was designed to investigate the effects of ANH on gastric mucosal oxygenation using a model closely imitating the clinical situation. Sixteen splenectomized anesthetized beagles were isovolemically hemodiluted to a hematocrit of 20 +/- 1% (6% hydroxyethyl starch; mol wt 200,000; substitution ratio 0.45-0.55). Blood volume (indocyanine green), cardiorespiratory parameters, gastric intramucosal pH (pHi), and gastric regional blood flow (radioactive microspheres; 15 microns) were measured before and after ANH. Results: blood volume was unchanged (87 +/- 8 ml/kg before and 88 +/- 7 ml/kg after ANH). Median total gastric mucosal blood flow at baseline was 0.51 +/- 0.35 ml.min-1.g-1 and did not change significantly upon ANH. The mean pHi was 7.29 +/- 0.05 before and 7.28 +/- 0.05 after hemodilution. There was a homogenization of blood flow distribution in gastric mucosa. Severe hemodilution to a hematocrit of 20% does not impair gastric mucosal oxygenation and poses no risk to gastric mucosal integrity.

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 [Formula: see text] 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.