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Published ahead of print on December 12, 2002, doi:10.1164/rccm.200205-490OC
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American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 868-872, (2003)
© 2003 American Thoracic Society

Original Article

Critical Oxygen Delivery in Conscious Septic Rats under Stagnant or Anemic Hypoxia

Yoshihisa Morita, Ian Chin-Yee, Pei Yu, William J. Sibbald and Claudio M. Martin

AC Burton Vascular Biology Laboratory, London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada

Correspondence and requests for reprints should be addressed to Claudio Martin, M.Sc., M.D., London Health Sciences Centre, 375 South Street, London, ON, Canada N6A 4G5. E-mail: cmartin1{at}uwo.ca


   ABSTRACT
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 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Although evidence shows that critical O2 delivery (QO2crit), the point at which oxygen consumption becomes limited by O2 delivery (QO2), is not affected by the method used to decrease QO2 in healthy subjects, microcirculatory injury caused by sepsis may modify QO2crit in a unique manner. We therefore designed this study to compare QO2crit in anemic and stagnant hypoxia in conscious septic rats. Rats were randomized to control or sepsis induced by cecal ligation and perforation; 24 hours later, oxygen consumption was measured using expired gas analysis, whereas QO2 was calculated from standard formula. Rats were further randomized to anemic hypoxia by isovolemic hemodilution or stagnant hypoxia by stepwise inflation of a balloon-tip catheter in the right atrium. QO2crit and critical hemoglobin concentration were calculated by dual linear regression analysis. We found that (1) QO2crit was not different between anemic and stagnant hypoxia in sepsis and that (2) the critical hemoglobin concentration in anemic hypoxia was similar between sepsis and control, indicating that tolerance to acute anemia is not altered by sepsis. Further studies are needed before the clinical relevance of these conclusions can be fully understood.

Key Words: oxygen consumption • cardiac output • anemic hypoxia • sepsis

In health, O2 consumption (O2) is independent of O2 delivery (QO2) at normal levels of O2 supply, but at levels less than a critical point (QO2crit), O2 becomes limited by delivery in a supply-dependent manner. To date, this biphasic relationship of QO2 and O2 has been verified in a variety of animal models in both normal and septic conditions (1–6). Among several compensatory mechanisms to maintain O2, capillary recruitment is crucial in response to any type of local hypoxia, as this reduces intercapillary space, thus allowing tissues to extract O2 efficiently to lower end capillary levels of PO2 (7). Specifically, the reduction in hemoglobin level (anemic hypoxia) is compensated by an increase in cardiac output and O2 extraction, whereas the reduction in cardiac output (stagnant hypoxia) is solely compensated by an increase in O2 extraction. Despite such differences in compensatory mechanisms, QO2crit is similar among different types of hypoxia in normal subjects (1–3), indicating that the absolute level of whole-body QO2 (convective QO2) is of greater importance than the individual determinants (hemoglobin, oxygen saturation, flow) of QO2 in preventing delivery dependence.

In sepsis, however, it remains to be elucidated whether such mechanisms are able to work, as the circulation is impaired at microregional, regional, and central levels even at the early stage of sepsis (8–10). For example, rheologic changes in both red and white blood cells due to altered deformability lead to capillary plugging, especially in low flow states (11, 12). Increased transvascular permeability, another characteristic of sepsis, causes tissue edema, which in turn expands intercapillary distance, augments shunts, and results in diffusion limitation. Furthermore, abnormal redistribution of blood flow between and within organs (13, 14) and a loss of the ability to modulate QO2 to react against changes in O2 demand in sepsis (15) can also create heterogeneous blood flow, subsequently augmenting the mismatch of the O2 supply and demand. Collectively, these profiles lead to an impaired O2 extraction capacity in sepsis that results in higher QO2crit (4, 16). Differences in microvascular flow between anemic and stagnant hypoxia may produce differences in the ability to increase oxygen extraction, and because compensation in stagnant hypoxia occurs only through increased oxygen extraction, these changes may have an exaggerated effect. Therefore, we tested the hypothesis that QO2crit in sepsis will be higher when hypoxia is caused by stagnant flow as compared with anemia. We used rats made septic by cecal ligation and perforation (CLP), the model that mimics the early stage of hyperdynamic sepsis that is defined by increased cardiac output with normotension. If the hypothesis were true, septic patients with limited myocardial function to increase cardiac output would be more susceptible to O2 debt with similar QO2 compared with anemic hypoxia. Some of the results of this study have been previously presented in the form of an abstract (17).


   METHODS
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 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
The experimental protocol was approved by the Council on Animal Care of the University of Western Ontario. Using a 2 x 2 factorial design, male Sprague-Dawley rats (300–400 g), cannulated as previously described (18), were first randomly allocated into control or septic groups. For the latter group (n = 12), CLP was performed, and they were fluid resuscitated at 3 ml/hour of normal saline with fentanyl analgesia as previously described (19). Because the laparotomy per se causes septic responses in rats (20), the former group (n = 12) in this experiment did not receive open laparotomy. At 24 hours after surgery, rats were placed in a tubular restrainer in a metabolic box for measurement of O2 (Oxymax; Columbus Instruments, Columbus, OH), and the analgesic infusion was stopped. After stabilization for 30 minutes, baseline parameters were obtained as follows: body temperature by the thermocouple; mean arterial pressure and central venous pressure by disposable transducers (Baxter, Deerfield, MI) and a display monitor (Hewlett Packard, Wertheim, MA); heart rate from a recording of the arterial pressure trace; hemoglobin, arterial O2 saturation, and mixed venous O2 saturation by an OSM2 Hemoximeter (Radiometer, Copenhagen, Denmark); lactate by a YSI 2300 STAT Plus (Yellow Spring Instrument Co., Inc., Yellow Springs, OH); white blood cells by Coulter STKS (Coulter Inc., Miami, FL). Cardiac index (CI) was measured by thermodilution method as previously described (18). The volume of blood withdrawn was replaced with three times the amount of 0.9% saline. Rats were kept at ± 0.5°C from the baseline temperature using a heat pad and lamp.

In the anemic hypoxia group, isovolemic hemodilution was performed with rat plasma. Blood was withdrawn from the femoral arterial line, whereas plasma was infused into the left jugular line at the rate of 8 ml/hour using an infusion pump (Harvard Apparatus, Boston, MA). A standard 40-µ filter was used to prevent transfusion of aggregates or cell debris. In the stagnant hypoxia group, the balloon-tip catheter was inflated with distilled water in a stepwise manner using a micrometer syringe (Stoeling, Chicago, IL) as previously described (18). After each balloon inflation, a 15- to 30-minute equilibration period was allowed before measuring CI and collecting blood samples. O2 was directly measured by an analysis of inhaled and exhaled gases using the Oxymax system, whereas QO2 was calculated from CI and CaO2 according to the standard formula. In both groups, the protocol was continued until the rats were clearly well into supply dependency as judged by at least a 25% decrease in the continuously monitored O2 and subsequently confirmed by an increase in arterial lactate concentration. Rats were then euthanized with pentobarbital overdose.

All data are presented as mean ± SD. QO2crit, critical hemoglobin (Hbcrit), and critical CI for stagnant hypoxia were calculated by dual linear regression analysis (21). Two best fit lines were obtained, and the intersection was defined as the critical point as shown in Figure 1 . Critical CI for the anemic hypoxia was estimated from the graph plotted with CI and O2. A full factorial design was applied for all subsequent analysis using a statistical software package (SPSS version 7.5; Chicago, IL). In the absence of interactions, this allows for the main factors to be assessed individually. Based on a SD for QO2crit of 0.6 ml/minute/100 g and significance level of 0.01 (to allow for post hoc comparisons in a factorial design), a sample size of six rats per group is sufficient to detect a difference of 1.2 ml/minute/100 g with 80% power. This difference is smaller than the sepsis effect of 1.7 ml/minute/100 g seen previously (22).



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  		Figure 1. Representative QO2–O2 relationships in the control and CLP groups during stagnant or anemic hypoxia. Each figure is obtained from one animal, and each point represents one measurement. The lines are the best fit determined by dual-line regression. The intersection of the two lines denotes the QO2crit.

 

   RESULTS
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 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
All CLP rats showed piloerection and crusty eyes, with panperitonitis at 24 hours after surgery. Proper positioning of all lines was confirmed at autopsy. Because no significant interaction was found between the presence of sepsis and the mechanism of hypoxia, the results are presented as the combined groups to take advantage of the full factorial design (that is, control versus CLP group or stagnant versus anemic hypoxia group).

Baseline measurements at 24 hours after the surgery, but before induction of hypoxia, are summarized in Table 1 . The CLP group showed significantly lower body temperature, hemoglobin, white blood cell count, and arterial O2 saturation, and a simultaneously higher heart rate, CI, and lactate level compared with the control group. There were no significant differences between stagnant and anemic hypoxia groups.


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  		TABLE 1. Baseline measurements 24 hours after preparatory surgery

 
Values of baseline O2, QO2, and O2 extraction (O2ER) are summarized in Table 2 . These data show that at baseline, before induction of hypoxia, there was no significant effect of CLP on O2 or O2ER. Also, baseline QO2 was not significantly different between CLP and control groups despite the increased cardiac output in the CLP group, because hemoglobin concentration and arterial O2 saturation were lower in CLP animals. There were no significant differences between stagnant and anemic hypoxia groups in any of these parameters.


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  		TABLE 2. Baseline oxygen kinetics 24 hours after preparatory surgery

 
In response to hemodilution in the anemic hypoxia group, CI increased in both control and CLP groups. The maximum increase of CI from the baseline was 39.5 ± 30.1% in control and 42.7 ± 26.7% in CLP rats (p = NS) with absolute values of 70.4 ± 13.8 and 107.0 ± 14.8 mL/min/100 g (p < 0.05), respectively. The increase in CI was maintained similarly in both groups until the late phase of supply dependency.

Representative QO2–O2 relationships for each group are depicted in Figure 1. All of the rats showed a biphasic relationship. The QO2crit, critical O2 extraction ratio (O2ERcrit), critical CI, and Hbcrit are summarized in Figure 2 . As described previously here, there was no interaction between the method to decrease QO2 and CLP (p = 0.275) with respective QO2crit values of 3.99 ± 0.59 ml/minute/100 g for control stagnant, 4.00 ± 0.78 ml/minute/100 g for control anemic, 6.09 ± 0.53 ml/minute/100 g for CLP stagnant, and 6.67 ± 0.52 ml/minute/100 g for CLP anemic. Using the combined results, the QO2crit was not different between anemic and stagnant hypoxia groups, whereas CLP rats showed significantly higher QO2crit compared with control rats (6.38 ± 0.58 and 4.00 ± 0.66 ml/minute/100 g, respectively; p < 0.05). Simultaneously, the O2ERcrit was not different between anemic and stagnant hypoxia but was significantly lower in CLP rats compared with control rats (0.29 ± 0.04 and 0.47 ± 0.07, respectively; p < 0.05). The O2 at the critical point was not significantly different in all groups (control 1.83 ± 0.10, CLP 1.81 ± 0.18, stagnant 1.79 ± 0.07, anemic 1.85 ± 0.18 ml/minute/100 g, respectively). The Hbcrit was similar with control and CLP rats but was significantly lower with anemic hypoxia compared with stagnant hypoxia (stagnant 10.4 ± 1.4, anemic 5.2 ± 1.4 g/dl, respectively; p < 0.05). The critical CI was significantly higher in CLP rats compared with control rats and also with anemic hypoxia compared with stagnant hypoxia (control 47.5 ± 19.9, CLP 72.1 ± 29.8 ml/minute/100 g, p < 0.05, stagnant 38.7 ± 10.7, anemic 80.9 ± 23.1 ml/minute/100 g, p < 0.05).



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  		Figure 2. QO2, O2ER, CI, and hemoglobin concentration at the critical point are shown (n = 12 in each group). The error bar indicates SD. Symbol: *p < 0.05 control versus CLP; **p < 0.05 anemic versus stagnant.

 

   DISCUSSION
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
This is the first study to examine the QO2crit in conscious control and septic animals under anemic and stagnant hypoxia. In this experiment, we demonstrated that (1) QO2crit, as shown previously in normal animals (1–3), in septic rats was the same under anemic and stagnant hypoxia, (2) the QO2crit was increased in conscious septic rats compared with control rats, and (3) despite known myocardial dysfunction (9, 10), this septic model, considered relevant to the early stage of sepsis, was able to increase CI in anemic hypoxia greater than control rats in absolute values, thus suggesting a similar tolerance of anemia (Hbcrit). Although there are several limitations to extrapolate to the clinical situation from our study design, these data are consistent with a recent clinical trial indicating that a restrictive transfusion strategy was well tolerated, and perhaps beneficial, to critically ill patients (23).

Compared with some previous animal studies examining QO2crit, this study is characterized by several important features. We undertook studies with awake animals because anesthetic agents independently modify vascular reactivity (24) or whole-body O2. The similar QO2crit observed in both anemic and stagnant hypoxia in conscious control animals is consistent with previous studies performed under anesthesia (1–5). In this study using conscious rats, however, average QO2crit of the control group was 4 ml/100 g/minute, which was higher than previously reported values of 2.3 mL/100 g/minute in anesthetized and ventilated rats (25). Because mechanical ventilation is unlikely to modulate the QO2–O2 relationship (26), anesthesia per se affects this relationship by reducing O2, QO2crit, or O2ERcrit (24). In addition, it should be noted that this model of sepsis represents the early, but not late, stage of hyperdynamic sepsis without severe tissue hypoxia. In this experiment, the CLP group had an approximately 37% higher CI and slightly, but significantly, elevated lactate compared with the control group without hypotension (Table 1). Because hypotension is another confounding factor that modifies the QO2 at regional and microregional levels of the circulation, we resuscitated the animals with continuous fluid infusion for 24 hours.

Despite apparent dysfunction at several level of the circulation in sepsis (8–10), we found no difference in QO2crit or O2ERcrit between anemic and stagnant hypoxia in whole body. Stagnant hypoxia may produce longer transit time that allows greater oxygen extraction, whereas anemic hypoxia may recruit more capillaries as a result of reduced viscosity and an increase in cardiac output. Thus, different individual mechanisms could have resulted in similar values for QO2crit. Although indices of myocardial function may appear to be normal or even elevated in sepsis under resting or nonstressed conditions, it is known that the functional reserve is decreased when an additional stress is imposed on the myocardium (10). However, in this experiment, we found that the septic rats were able to increase CI sufficiently to compensate for a reduction of hemoglobin concentration to a greater degree than control rats until the relatively late phase of supply dependency. Such a response to acute anemia is commonly observed in normal dogs (27) and humans (28) but has not been demonstrated in septic animals. This finding indicates that cardiac function did not limit the O2 in addition to the tolerance against acute anemia in sepsis. In addition, mitochondrial dysfunction (cytopathic hypoxia) may limit O2 regardless of the methods to decrease QO2 as previously reported (29). Although this study is unable to clarify the mechanisms further, alterations at the level of microcirculation within individual organs are likely to play a role under these conditions. Crouser and colleagues showed LPS-induced mitochondrial injury despite unchanged relative oxyhemoglobin content and blood flow in feline ileum (30). However, Ellis and colleagues demonstrated maldistribution of microcirculatory blood flow in the skeletal muscle of septic rats (31). Thus, individual organs may have different regulatory mechanisms that may be elucidated by further studies.

There are several limitations to interpretation of the data. Foremost is the significance of the QO2crit, which is a useful parameter but most evidence indicates that supply dependency does not occur frequently in patients. Also, it is possible that whole-body measures may not represent the status of all tissues. Second, some may argue that clinical relevance of this study design is uncertain because stagnant hypoxia to this extent is unlikely to occur. In view of these limitations and the fact that results from a small animal model may differ from humans, further studies are necessary before our results can be applied in the clinical situation. Finally, because our hypothesis was disproven, we need to consider whether the study was powered sufficiently. However, the 95% confidence intervals for the septic anemic and stagnant hypoxia groups have a range of approximately 1.1 ml/minute/100 g, which is less than the difference we had specified and represents between 18 to 28% relative difference in QO2crit. Therefore, it is unlikely that an important and detectable difference was missed with this sample size.

In conclusion, QO2crit and O2ERcrit did not differ between anemic and stagnant hypoxia in both control and septic rats. Septic rats were similarly tolerant to anemic hypoxia as control rats in our model at the expense of increased cardiac output. Further investigations are necessary to clarify the circulatory and cytopathic mechanisms that limit O2 and the long-term effect of anemia on septic cardiac function.

Received in original form May 30, 2002; accepted in final form December 10, 2002


   REFERENCES
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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Cain SM. Oxygen delivery and uptake in dogs during anemic and hypoxic hypoxia. J Appl Physiol 1997;42:228–234.
  2. Schwartz S, Frantz RA, Shoemaker WC. Sequential hemodynamic and oxygen transport responses in hypovolemia, anemia, and hypoxia. Am J Physiol 1981;241:H864–H871.
  3. Heusser F, Fahey JT, Lister G. Effect of hemoglobin concentration on critical cardiac output and oxygen transport. Am J Physiol 1989;256:H527–H532.[Abstract/Free Full Text]
  4. Nelson DP, Samsel RW, Wood LDH, Schumacker PT. Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia. J Appl Physiol 1988;64:2410–2419.[Abstract/Free Full Text]
  5. Rock P, Beattie C, Kimball AW, Nyhan DP, Chen BB, Fehr DM, Derrer SA, Parker SD, Murray PA. Halothane alters the oxygen consumption–oxygen delivery relationship compared with conscious state. Anesthesiology 1990;73:1186–1197.[Medline]
  6. Schumacker PT, Samsel RW. Analysis of oxygen delivery and uptake relationships in the Krogh tissue model. J Appl Physiol 1989;67:1234–1244.[Abstract/Free Full Text]
  7. Tenny SM. A theoretical analysis of the relationship between venous blood and mean tissue oxygen pressures. Respir Physiol 1974;20:283–296.[CrossRef][Medline]
  8. Lam C, Tyml K, Martin C, Sibbald W. Microvascular perfusion is impaired in a rat model of normotensive sepsis. J Clin Invest 1994;94:2077–2083.
  9. Bersten AD, Sibbald WJ. Circulatory disturbances in multiple systems organ failure. Crit Care Clin 1989;5:233–254.[Medline]
  10. McDonough KH, Lang CH, Spitzer JJ. Depressed function of isolated hearts from hyperdynamic septic rats. Circ Shock 1984;12:241–251.[Medline]
  11. Hinshaw LB. Sepsis/septic shock: participation of the microcirculation. Crit Care Med 1996;24:1072–1078.[CrossRef][Medline]
  12. Kirschenbaum LA, Aziz M, Astiz ME, Saha DC, Rackow EC. Influence of rheologic changes and platelet-neutrophil interactions on cell filtration in sepsis. Am J Respir Crit Care Med 2000;161:1602–1605.[Abstract/Free Full Text]
  13. Morisaki H, Sibbald WJ, Martin CM, Doig G, Inman K. Hyperdynamic sepsis depresses circulatory compensation to normovolemic anemia in conscious rats. J Appl Physiol 1996;80:656–664.[Abstract/Free Full Text]
  14. Piiper J, Haab P. Oxygen supply and uptake in tissue models with unequal distribution of blood flow and shunt. Respir Physiol 1991;84:261–271.[CrossRef][Medline]
  15. Chittock DR, Russel JA. Oxygen delivery and consumption during sepsis. Clin Chest Med 1996;17:263–278.[CrossRef][Medline]
  16. D'Orio V, Mendes P, Carlier P, Fatemi M, Marcelle R. Lung fluid dynamics and supply dependency of oxygen uptake during experimental endotoxic shock and volume resuscitation. Crit Care Med 1991;19:955–962.[Medline]
  17. Morita Y, Martin CM, Chin-Yee I, Sibbald WJ. Critical oxygen delivery in control and septic rats with anemic or stagnant hypoxia [abstract]. Am J Respir Crit Care Med 2000;161:A884.
  18. Morita Y, Yu P, Martin CM. An alternative thermodilution method to measure cardiac output in a rat model of stagnant hypoxia. Shock 2000;14:550–554.[Medline]
  19. Martin CM, Yaghi A, Sibbald WJ, McCormack D, Patterson NAM. Differential impairment of vascular reactivity of small pulmonary and systemic arteries in a rat model of hyperdynamic sepsis. Am Rev Respir Dis 1993;148:164–172.[Medline]
  20. Yaghi A, Paterson NA, McCormack DG. Vascular reactivity in sepsis: importance of controls and role of nitric oxide. Am J Respir Crit Care Med 1995;151:706–712.[Abstract]
  21. Samsel RW, Schumacker PT. Determinations of the critical O2 delivery from experimental data: sensitivity to error. J Appl Physiol 1988;64:2074–2082.[Abstract/Free Full Text]
  22. Sielenkamper AW, Yu P, Eichelbronner O, MacDonald T, Martin CM, Chin-Yee IH, Sibbald WJ. Diaspirin cross-linked Hb and norepinephrine prevent the sepsis-induced increase in critical O2 delivery. Am J Physiol Heart Circ Physiol 2000;279:H1922–H1930.[Abstract/Free Full Text]
  23. Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care: transfusion requirements in critical care investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340:409–417.[Abstract/Free Full Text]
  24. Gelman S, Fowler KC, Smith LR. Regional blood flow during isoflurane and halothane anesthesia. Anesth Analg 1984;63:557–565.[Abstract/Free Full Text]
  25. Adams RP, Dieleman LA, Cain SM. A critical value for O2 transport in the rat. J Appl Physiol 1982;53:660–664.[Abstract/Free Full Text]
  26. Griffel MI, Astiz ME, Rackow EC, Weil MH. Effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis during early septic shock in rats. Crit Care Med 1990;18:72–76.[Medline]
  27. von Restorff W, Hofling B, Holtz J, Bassenge E. Effects of increased blood fluidity through hemodilution on general circulation at rest and during exercise in dogs. Pflugers Arch 1975;357:25–34.[CrossRef][Medline]
  28. Weiskopf RB, Viele MK, Feiner J, Kelly S, Lieberman J, Noorani M, Leung JM, Fisher DM, Murray WR, Toy P, et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 1998;279:217–221.[Abstract/Free Full Text]
  29. Fink MP. Cytopathic hypoxia: mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis. Crit Care Clin 2001;17:219–237.[CrossRef][Medline]
  30. Crouser ED, Julian MW, Dorinsky PM. Ileal O2–DO2 alterations induced by endotoxin correlate with severity of mitochondrial injury. Am J Respir Crit Care Med 1999;160:1347–1353.[Abstract/Free Full Text]
  31. Ellis CG, Bateman RM, Sharpe MD, Sibbald WJ, Gill R. Effect of a maldistribution of microvascular blood flow on capillary O2 extraction in sepsis. Am J Physiol 2002;282:H156–H164.[Abstract/Free Full Text]



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