Search

Introduction: The correction of hypovolemia with acellular fluids results in acute normovolemic anemia. Whether the choice of the infusion fluid has an impact on the maintenance of oxygen (O₂) supply during acute normovolemic anemia has not been investigated so far., Methods: Thirty-six anesthetized and mechanically ventilated pigs were hemodiluted to their physiological limit of anemia tolerance, reflected by the individual critical hemoglobin concentration (Hbcrit). Hbcrit was defined as the Hb-concentration corresponding with the onset of supply-dependency of total body O₂-consumption (VO₂). The hemodilution protocol was randomly performed with either tetrastarch (6% HES 130/0.4, TS-group, n = 9), gelatin (3.5% urea-crosslinked polygeline, GEL-group, n = 9), hetastarch (6% HES 450/0.7, HS-group, n = 9) or Ringer's solution (RS-group, n = 9). The primary endpoint was the dimension of Hbcrit, secondary endpoints were parameters of central hemodynamics, O₂ transport and tissue oxygenation., Results: In each animal, normovolemia was maintained throughout the protocol. Hbcrit was met at 3.7 ± 0.6 g/dl (RS), 3.0 ± 0.6 g/dl (HS P < 0.05 vs. RS), 2.7 ± 0.6 g/dl (GEL, P < 0.05 vs. RS) and 2.1 ± 0.4 g/dl (TS, P < 0.05 vs. GEL, HS and RS). Hemodilution with RS resulted in a significant increase of extravascular lung water index (EVLWI) and a decrease of arterial oxygen partial pressure (paO₂), and O₂ extraction ratio was increased, when animals of the TS-, GEL- and HS-groups met their individual Hbcrit., Conclusions: The choice of the intravenous fluid has an impact on the tolerance of acute normovolemic anemia induced by acellular volume replacement. Third-generation tetrastarch preparations (e.g., HES 130/0.4) appear most advantageous regarding maintenance of tissue oxygenation during progressive anemia. The underlying mechanism includes a lower degree of extravasation and favourable effects on microcirculatory function.

Objective: To investigate the impact of prophylactic hyperoxic ventilation with Fio2 0.6 on the physiologic limit of acute normovolemic anemia., Design: Prospective, controlled, randomized experimental study., Setting: Experimental animal laboratory of a university hospital., Subjects: Fourteen anesthetized domestic pigs., Interventions: Animals were randomly ventilated with either Fio2 0.21 (group 0.21, n = 7) or Fio2 0.6 (group 0.6, n = 7), and acute anemia was induced by isovolemic blood-for-hydroxy-ethylstarch (HES) exchange using a 6% HES solution (130/0.4)., Measurements and Main Results: The blood-for-HES-exchange was continued until a sudden decrease of total body oxygen consumption indicated the onset of oxygen supply dependency (primary end point); the corresponding hemoglobin (Hb) concentration was defined as "critical" (Hb(crit)). Secondary end points were changes in myocardial function, central hemodynamics, oxygen transport, and tissue oxygenation. Compared with room air ventilation (Fio2 0.21), hyperoxic ventilation with Fio2 0.6 enabled a larger blood-for-HES-exchange (139%, 124/156) of circulating blood volume vs. 87% (68/94, p < .05), until Hb(crit) was reached (1.5 g/dL [1.4/2.1] vs. 2.4 g/dL [2.0/2.8], p < .05). At Hb 2.4 g/dL (i.e., Hb(crit) in group 0.21), animals of group 0.6 still presented with superior oxygen transport, tissue oxygenation, and hemodynamic stability. However, hemodynamic and oxygen transport variables were found deteriorated more severely at Hb 1.5 g/dL (i.e., Hb(crit) of group 0.6) compared with group 0.21 at Hb 2.4 g/dL., Conclusion: During cell-free volume replacement, hyperoxic ventilation with Fio2 0.6 generates a readily usable plasmatic oxygen reserve and thereby increases the tolerance toward acute normovolemic anemia.

Background: When initiated in anemic hypoxia, hyperoxic ventilation (ventilation with pure O2, FiO2 1.0, HV) reverses hypoxia-induced ECG-changes and enables survival for several hours. The quantification of the HV-induced gain in anemia tolerance and particularly the Hb-equivalent of HV in this situation are unknown., Methods: Nine anaesthetized pigs were hemodiluted under normoxia (FiO2 0.21) by exchange of whole blood for hydroxyethyl starch (HES) until predefined, ischemia associated ECG-changes occurred (timepoint Hb(crit)). From that time on all animals were ventilated with 100% O2 (FiO2 1.0). In the case of disappearance of the ECG changes with onset of HV, the animals were further hemodiluted until ECG changes reoccurred., Results: HV initiated in anemic hypoxia (Hb 2.3 +/- 0.2 g/dl) improved ECG-readings of all animals, and allowed for a further exchange of 14 +/- 11 ml/kg blood until ECG-changes reoccurred at Hb 1.2 +/- 0.4 g/dl., Conclusion: HV initiated in anemic hypoxia creates a margin of safety for myocardial tissue oxygenation and thus further increases anemia tolerance. The Hb equivalent of HV in this situation amounts to approximately 1g/dl.

Background: Ventilation with pure oxygen (hyperoxic ventilation, HV) increases arterial oxygen content (CaO(2)). However HV induces arteriolar constriction and thus potentially affects O(2) supply. We therefore investigated the effects of HV on regional blood flow (RBF) and O(2) supply of different vital organs during moderate normovolaemic anaemia., Methods: Twenty-two anaesthetized dogs were haemodiluted under normoxia (i.e. FiO(2) = 0.21) to a target haemoglobin concentration (Hb) of 7 g dl(-1) and were subsequently ventilated with pure O(2). 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 (RBF(relative)), the variation coefficient of RBF (VC) and regional O(2) supply (rDO(2)) 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 RBF(relative) 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 O(2) supply. Cardiac, pancreatic and muscular O(2) supply decreased, however without any critical restriction of organ function.

The aim of the present study was to demonstrate the practicality and efficacy of acute normovolemic hemodilution (ANH) to reduce allogeneic red blood cell (RBC) transfusion in patients undergoing elective surgery with anticipated high intraoperative blood loss (BL). 124 patients (age 48 +/- 18 years, ASA classes I-III) underwent major maxillofacial surgery in a university hospital (68% tumor surgery, 32% dysgnathia correction). After induction of general anesthesia, ANH was performed by standardized withdrawal of 900 ml (2 units) of whole blood and simultaneous infusion of 500 ml of hydroxyethyl starch solution (6% HES 130,000/0.4) and 1500 ml of crystalloidal solution. Intraoperative BL was fluid-compensated until physiologic parameters indicated the need for RBC transfusion. First, autologous ANH-blood was retransfused followed by, if necessary, allogeneic RBC. Total BL was referred to the patient's calculated blood volume (BV): fractional blood volume loss, BL(fract) = BL/BV. ANH took 16 +/- 2 min and was void of any adverse event. The costs for ANH was 24 per patient. 55 patients had a mean BL(fract) of 44 +/- 28% and required an intraoperative transfusion; 49/55 patients with an average BL(fract) of 37 +/- 14% were transfused with only autologous ANH-blood; 6/55 patients with a mean BL(fract) of 100 +/- 47% underwent additional transfusion with allogeneic RBC. Standardized, 2 unit, ANH is a practicable, safe and economic blood conservation technique that allowed for the complete avoidance of allogeneic RBC transfusion in 89% of patients undergoing maxillofacial surgery that required an intraoperative RBC transfusion.

Objective: During normovolaemic haemodilution arterial O(2)-content decreases exponentially. Nevertheless, tissue oxygenation is first maintained initially by increased organ perfusion and O(2)-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% O(2)., 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 O(2) delivery and consumption, local tissue O(2) partial pressure (tpO(2)) (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%), tpO(2) was reduced from 23+/-3 to 10+/-2 Torr with 50% of all values in the hypoxic range (<10 Torr, all P<0.05). During hyperoxic ventilation, contribution of physically dissolved O(2) to the O(2) delivery and O(2) consumption increased by 400 and 563% (P<0.05) and instantly restored tpO(2) to 18+/-2 Torr, (hypoxic values 25%, P<0.05)., Conclusion: Hyperoxic ventilation reversed tissue hypoxia at the critical Hct due to preferential utilization of plasma O(2) and allowed temporary preservation of tissue oxygenation. During haemodilution, hyperoxic ventilation might offer an effective bridge until red cells are ready for transfusion.

Background: The blood volume that has to be exchanged for crystalloids and/or colloids during acute normovolemic hemodilution (ANH) in order to reach a preset target hemoglobin concentration (hb) is usually predicted by the Bourke and Smith formula developed in 1974. This formula systematically overestimates the 'true' exchangeable blood volume (EBV), a fact that may potentially endanger patients because the target hb will be missed and the normovolemic anemia might turn out to be more severe than a priori intended. Our objective was to develop a more accurate mathematical model of hemodilution kinetics and to validate this new model in animals and in patients undergoing ANH., Methods: Twenty-two anesthetized beagle dogs and 18 patients under balanced anesthesia underwent isovolemic hemodilution with hydroxyethyl starch (HAES 6%, 200 000) to a target hb of 7 g dl-1 or 9 g dl-1, respectively. Exchangeable blood volume predicted by use of the different mathematical models was compared with the blood volume actually exchanged to meet the preset target hb., Results: Calculation of EBV by the Bourke and Smith formula (EBVB + S) systematically overestimated the volume actually exchanged (overestimation: dogs 15%, patients 20%), whereas our new iterative model predicted EBV (EBViterative) more reliably (overestimation: dogs 1%, patients 8%). In both cases EBVB + S differed significantly from the EBViterative., Conclusion: Exchangeable blood volume is predicted more accurately by the new iterative model than by the Bourke and Smith formula. The iterative model leads to an improvement in patient safety and provides a physiologically adequate basis for future studies investigating the efficacy of ANH in reducing allogenic blood transfusions.

Intraoperative surgical blood loss is initially replaced by infusion of red cell-free, cristalloidal or colloidal solutions. When normovolemia is maintained the ensuing dilutional anemia is compensated by an increase of cardiac output and of arterial oxygen extraction. In the ideal case, a surgical blood loss can entirely be 'bridged' without transfusion by intraoperative normovolemic hemodilution. However major blood loss results in extreme hemodilution and the transfusion of red blood cells may finally become necessary to increase arterial oxygen content and to preserve tissue oxygenation. When transfusion has to be started before surgical control of bleeding has been achieved, parts of the red blood cells transfused will get lost, thereby increasing intraoperative transfusion needs. Beside red blood cell transfusion, arterial oxygen content can be rapidly increased by ventilating the patient with 100% oxygen (hyperoxic ventilation), thus enhancing the amount of physically dissolved oxygen in plasma (hyperoxia). In experimental and clinical studies hyperoxic ventilation has emerged as a simple, safe and effective intervention to enlarge the margin of safety for hemodynamic compensation and tissue oxygenation in hemodiluted subjects experiencing major bleeding. The hyperoxia-associated microcirculatory dysregulation and impaired tissue oxygenation known to take place in the presence of a physiologic hemoglobin concentration are not encountered in hemodiluted subjects. Hyperoxic hemodilution i.e. the combination of intraoperative extreme hemodilution and hyperoxic ventilation may therefore be considered a cost-effective, safe and efficient supplement to reduce allogeneic transfusion during surgical interventions associated with high blood losses. The vast majority of the experimental and clinical investigations this new concept is based on was initiated and performed under the guidance of Prof. Konrad Messmer., (Copyright 2002 S. Karger AG, Basel)

Background: Normovolemic hemodilution is an effective strategy to limit perioperative homologous blood transfusions. The reduction of hematocrit related to hemodilution results in reduced arterial oxygen content, which initially is compensated for by an increase in cardiac output and oxygen extraction ratio. To increase the efficacy of hemodilution, a low hematocrit should be aimed for; however, this implies the risk of myocardial ischemia and tissue hypoxia., Objective: To assess whether hemodilution can be extended to lower hematocrit values by the use of a hemoglobin-based artificial oxygen carrier solution., Design: Prospective, randomized, controlled., Setting: Animal laboratory of a university hospital., Subjects: Twelve anesthetized, mechanically ventilated pigs., Interventions: Isovolemic hemodilution was performed with either 10% diaspirin crosslinked hemoglobin (DCLHb Baxter Healthcare, Boulder, CO; n = 6) or 8% human albumin solution (HSA, oncotically matched to DCLHb, Baxter Healthcare; n = 6) to a hematocrit of 15%, 8%, 4%, 2%, and 1%., Measurements and Main Results: In both groups, measurements were performed at baseline at the previously mentioned preset hematocrit values and at the onset of myocardial ischemia characterized by critical hematocrit (significant ST-segment depression >0.1 mV and/or arrhythmia). To determine peripheral tissue oxygenation and myocardial perfusion and function, the following variables were evaluated: total body oxygen transport variables, tissue oxygen partial pressure (tPo2, MDO-Electrode, Eschweiler Kiel, Germany) on the surface of the skeletal muscle, coronary perfusion pressure, left ventricular (LV) end-diastolic pressure, global and regional myocardial contractility (maximal change in pressure over time, LV segmental shortening, microsonometry method), LV myocardial blood flow (fluorescent microsphere technique), LV oxygen delivery, and the ratio between LV subendocardial and subepicardial myocardial perfusion. In the HSA group, critical hematocrit was found at 6.1 (1.8)% (hemoglobin, 2 g x dL(-1)), whereas all DCLHb-treated animals survived hemodilution until hematocrit 1.2 (0.2)% (hemoglobin, 4.7 g x dL(-1)) was achieved without signs of hemodynamic instability. Although arterial oxygen content was higher in the DCLHb group at 1.2% hematocrit than in the HSA group at critical hematocrit (i.e., hematocrit, 6.1%; hemoglobin, 2 g.dL-1) neither oxygen delivery and oxygen uptake nor median tPo2 and hypoxic tPo2 values on the skeletal muscle were different between groups. In contrast, subendocardial ischemia was absent in DCLHb-diluted animals until 1.2% hematocrit was achieved. This was attributable to a higher coronary perfusion pressure (65 (22) mm Hg vs. 19 (8) mm Hg; p <.05), higher subendocardial perfusion (4.1 (2.6) mL.min-1.g-1 vs. 1.2 (0.4) mL x min(-1) x g(-1)), and subendocardial oxygen delivery (5.7 (2) mL x min(-1) x g(-1), p <.05) in DCLHb-diluted animals, resulting in superior myocardial contractility reflected by maximal change in pressure over time (3829 (1914) vs. 1678 (730); p <.05) and higher regional myocardial contractility (11 (8)% vs. 6 (2)%; p <.05). An increased LV end-diastolic pressure reflected LV myocardial pump failure in HSA-diluted animals but was unchanged in DCLHb-diluted animals. In the DCLHb group, systemic vascular resistance index remained at baseline values throughout the protocol, whereas coronary vascular resistance decreased. In contrast, both variables decreased in HSA-diluted animals., Conclusion: DCLHb as a diluent allowed for hemodilution beyond the hematocrit value, determined "critical" after hemodilution with HSA (6.1% (1.8)%). Even at 1.2% hematocrit (hemoglobin, 4.7 g x dL(-1)) myocardial perfusion and function were maintained, although at the expense of peripheral tissue oxygenation. This discrepancy in regional oxygenation might be caused by a redistribution of blood flow favoring the heart, which is related to a disproportionate decrease of coronary vascular resistance index during hemodilution with DCLHb.

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.

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.

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.

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.

Background: In subjects who have undergone acute preoperative normovolemic hemodilution (ANH), intraoperative hemorrhage is generally treated by immediate return of autologous blood collected during ANH. Simply increasing blood oxygen content by hyperoxic ventilation (HV, inspiratory fraction [FIO2] 1.0) might compensate for the acute anemia, allow further ANH, and delay onset of autologous blood return., Study Design and Methods: This study 1) evaluated the effects of HV (FIO2 1.0) upon ANH to a hemoglobin (Hb) concentration of 7 g per dL in anesthetized dogs ventilated with room air and 2) compared the effects of subsequent profound ANH (Hb, 3 g/dL) with and without an intravenous perfluorocarbon emulsion (perflubron 60% wt/vol) versus those of autologous red cell transfusion. The results of the entire study are presented in two parts. Organ tissue oxygenation was assessed in skeletal muscle and liver, and systemic oxygenation status was evaluated. Myocardial contractility was deduced from left ventricular pressure-volume relationship. Seven of 22 dogs underwent further hemodilution while breathing 100-percent O2, for a determination of the Hb concentration at which HV-induced effects were abolished., Results: HV completely reversed the ANH-induced increase in cardiac index (4.6 +/- 0.7 vs. 3.8 +/- 0.9 L/min/m2 before and during HV; p < 0.05) and partially reversed the decrease in systemic vascular resistance (1784 +/- 329 vs. 2087 +/- 524 dyn x cm-5 x sec x m-2; p < 0.05). Despite unchanged global O2 delivery, organ tissue oxygenation improved during HV (mixed venous partial pressure of O2: 40 +/- 3 vs. 59 +/- 7 torr; coronary venous pressure of O2: 30 +/- 4 vs. 43 +/- 6 torr; p < 0.05; liver surface: 31 +/- 11 vs. 39 +/- 13 torr; skeletal muscle surface: 30 +/- 14 vs. 41 +/- 22 torr; p < 0.05). This improvement was due to an increased contribution of physically dissolved O2 in plasma to O2 delivery (3.2 +/- 0.2% before HV vs. 14.6 +/- 1% during HV; p < 0.05) and O2 consumption (whole body: 6 +/- 1% vs. 47 +/- 8%, p < 0.05; myocardium: 4.3 +/- 0.9% vs. 31 +/- 6%, p < 0.05). The beneficial effects of HV were lost after an additional volume-compensated exchange of 19 percent of blood volume (Hb, 5.6 g/dL)., Conclusion: In anesthetized dogs ventilated with room air and hemodiluted to a Hb of 7 g per dL, simple oxygen therapy by HV (FIO2 1.0) rapidly improves tissue oxygenation and permits extended hemodilution to Hb of 5.8 g per dL until the HV-induced effects are lost.

Background: Intravenously administered perfluorocarbon (PFC) emulsions increase oxygen solubility in plasma. PFC might therefore temporarily replace red cells (RBCs) lost during intraoperative hemorrhage. In patients who have undergone hemodilution, the return of autologous blood may be delayed by the administration of PFC, and autologous RBCs may be saved for transfusion after surgical bleeding is stopped and PFC is cleared by the reticuloendothelial system., Study Design and Methods: In 22 anesthetized, hemodiluted dogs (hemoglobin [Hb] 7 g/dL) breathing 100-percent O2, an intraoperative volume-compensated blood loss was simulated. The efficacy of three therapeutic regimens in maintaining tissue oxygenation was compared: 1) RBC group (n = 7): maintenance of a Hb > 7 g per dL by transfusion of autologous RBCs; 2) PFC group (n = 7): bolus application of a second-generation PFC emulsion (60% wt/vol perflubron) and further acute normovolemic hemodilution (ANH) to a Hb of 3 g per dL; and 3) control group (n = 7): further ANH alone to a Hb of 3 g per dL. Systemic and myocardial oxygenation status and tissue oxygenation were assessed., Results: Autologous RBCs transfused to maintain a Hb of 7 g per dL preserved hemodynamics and tissue oxygenation during blood loss. In the PFC and control groups, heart rate and cardiac index increased significantly in response to further ANH. Tissue oxygenation was not different in the PFC and the RBC groups. Direct comparison of the PFC and control groups revealed better tissue oxygenation in the PFC group, as reflected by significantly higher mixed venous, coronary venous, and local tissue pO2 on liver and skeletal muscle., Conclusion: Bolus intravenous administration of 60-percent (wt/vol) perflubron emulsion and further hemodilution from a Hb of 7 g per dL to one of 3 g per dL were as effective as autologous RBC transfusion in maintaining tissue oxygenation during volume-compensated blood loss designed to mimic surgical bleeding.

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 (rho) of rPBF in the whole lung was 0.6 +/- 0.08. D is a resolution-independent measure for global rPBF distribution, and rho is the averaged flow relationship of directly neighboring lung samples. With regard to the entire lung, neither ANH nor hyperoxia changed D or rho. 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, rho 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.

Hepatorenal perfusion and function were assxssed in 22 dogs undergoing acute normovolemic hemodilution (ANH) to a hematocrit (Hct) of 20% using 6% hydroxyethyl starch (200.000/0.5) as the diluent. Organ perfusion was determined with the radioactive microspheres method. Renal function was assessed by urinary output, creatinine clearance and fractional sodium excretion. Blood volume as well as hepatic function were derived from indocyanine green (ICG) dilution kinetics. Hepatocellular integrity was determined by serum enzymatic activity of glutamate-oxalacetate-transaminase (GOT) and glutamate-pyruvate- transaminase (GPT). ANH to Hct 20% did not change blood volume and mean aortic pressure, while heart rate was slightly elevated (p<0.05) by 5 beats per minute and cardiac output increased by 29% (p<0.05). In contrast to the liver, where arterial and portal venous blood flow increased (86% and 28%, respectively; p<0.05), total renal blood flow as well as intraorgan distribution of renal blood flow remained unchanged post-ANH. While creatinine clearance remained unchanged following ANH, urinary output and fractional urinary excretion increased (p<0.05). In response to enhanced hepatic blood flow after ANH, intravascular half-life of ICG was reduced (p<0.05) and ICG clearance increased (p<0.05). Serum enzymatic activity of GPT decreased upon ANH (p<0.05), while GOT activity remained unchanged. ANH to a Hct 20% does not impair hepatorenal function. Increased urinary output points out the necessity for proper adjustment of crystalloid infusion to maintain normal intravascular volume and avoid hypovolemia and the associated risk of tissue hypoxia.

Perfusion of intestinal organs increases in response to acute normovolemic hemodilution (ANH). However, detailed studies on distribution of regional splanchnic organ perfusion during ANH are lacking. We therefore carried out this study to test the hypothesis that ANH does not cause disturbance of physiologic patterns of regional splanchnic organ blood flow. After governmental permission, 22 anesthetized dogs were instrumented to allow invasive hemodynamic measurements and intracardial injection of radioactive microspheres (diameter 15 micro m) for determination of regional organ perfusion. Measurements were made at baseline (hematocrit 37 +/- 3%) and after ANH with 6% hydroxyethyl starch (mol. wt. 200000 / 0.5) to hct 20 +/- 1%. After completion of the protocol, splanchnic organs were removed and dissected into small samples according to anatomical and functional principles. Regional perfusion was determined based on the microsphere content of each sample. Hepatic, intestinal, and pancreatic blood flow increased with ANH. Hepatic arterial blood flow rose by 86%, whereas portal venous perfusion increased by 28%. Small intestine mucosal perfusion was augmented by 68% while the non-mucosal tissue compartment of the gut wall received 32% more blood flow after ANH which is in proportion to the increase in cardiac index after ANH. This redistribution of intestinal flow might be the basis for the preservation of tissue oxygenation during moderate isovolemic anemia.

Unlabelled: 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.

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: During acellular replacement of an acute blood loss, hyperoxic ventilation (HV) increases the amount of O2 physically dissolved in the plasma and thereby improves O2 supply to the tissues. While this effect could be demonstrated for HV with inspiratory O2 fraction (FiO2) 0.6, it was unclear whether HV with pure oxygen (FiO2 1.0) would have an additional effect on the physiological limit of acute normovolemic anemia. Methods: Seven anesthetized domestic pigs were ventilated with FiO2 1.0 and subjected to an isovolemic hemodilution protocol. Blood was drawn and replaced by a 6% hydroxyethyl starch (HES) solution (130/0.4) until a sudden decrease of total body O2 consumption (VO2) indicated the onset of O2 supply dependency (primary endpoint). The corresponding hemoglobin (Hb) concentration was defined as 'critical Hb' (Hbcrit). Secondary endpoints were parameters of myocardial function, central hemodynamics, O2 transport and tissue oxygenation. Results: HV with FiO2 1.0 enabled a large blood-for-HES exchange (156 ± 28% of the circulating blood volume) until Hbcrit was met at 1.3 ± 0.3 g/dl. After termination of the hemodilution protocol, the contribution of O2 physically dissolved in the plasma to O2 delivery and VO2 had significantly increased from 11.7 ± 2 to 44.2 ± 9.7% and from 29.1 ± 4.2 to 66.2 ± 11.7%, respectively. However, at Hbcrit, cardiovascular performance was found to have severely deteriorated. Conclusion: HV with FiO2 1.0 maintains O2 supply to tissues during extensive blood-for-HES exchange. In acute situations, where profound anemia must be tolerated (e.g. bridging an acute blood loss until red blood cells become available for transfusion), O2 physically dissolved in the plasma becomes an essential source of oxygen. However, compromised cardiovascular performance might require additional treatment. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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. 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). 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 < 0.05). Hyperoxic ventilation produced increased coronary vascular resistance secondary to vasoconstriction, and reduced myocardial blood flow [426 (404;464), ml min−1100 g−1; P < 0.05]. Myocardial oxygenation was found to be maintained by increased O2-content [4.4 (4.2;4.8), ml dl−1; P < 0.05], the contribution of dissolved O2 to subendocardial O2-delivery increased (32 vs. 8%; P < 0.05), which preserved myocardial function. Hyperoxic ventilation at Hctcrit is followed by coronary vasoconstriction and reduction of coronary blood flow. However, myocardial oxygenation and function is maintained, as increased O2-content (in particular dissolved O2) preserves myocardial oxygenation. [ABSTRACT FROM AUTHOR]