Critical O2 Delivery Research Articles

Abstract 188: Arterial Oxygen Saturation May Be the Limiting Factor for O 2 Delivery During Compression-Only CPR

Background Previous studies show that there is no difference in outcomes between bystander conventional and chest-compression-only (CCO) CPR. However, several points need to be addressed: 1) the equivalent, but low, survival rate indicates that there is much room for improvement. The question is whether effective ventilation can be achieved during CPR regardless of approach. 2) the subgroup of patients whose cardiac arrest was not of cardiac origin did not sustain any benefit from ventilation. This finding would imply that adequate ventilation was not achieved. Because cardiac output (CO) generated by chest-compression is low, O 2 delivery (DO 2 ) is mainly dependent on arterial O 2 content. We hypothesize that DO 2 is the rate limiting factor and improvement in DO 2 is mainly determined by O 2 content of arterial blood, since CO is at best only 1/3 of the normal value. Methods We modeled DO 2 in a range of 0 to critical DO 2 (8.2 ml/kg/min) at variable CO and O 2 contents of arterial blood. We assumed a 70kg patient with a hemoglobin level (Hb) of 15g/dl. Arterial O 2 Content (ml/L) = Hb × Arterial O 2 Saturation × 1.34 ×10. DO 2 (ml/min) = Arterial O 2 Content (ml/L) × CO (L/min). Result The half-critical DO 2 at arterial blood O 2 saturation of 80% can be achieved with CO of 1.8L/min. While to achieve the same level of DO 2 at O 2 saturation 40%, require CO of 3.6 L/min. Critical O 2 delivery and half-critical DO 2 are represented with horizontal yellow and red lines respectively. The vertical mahogany and blue lines represent the CO where half-critical delivery at O 2 saturations of 80% and 40%, respectively. Conclusion Since the CO obtained with chest compression is at best 1/3 of the normal value; to reach half-critical O 2 delivery requires an O 2 saturation of 80%. CCO seems unlikely to produce O 2 saturation greater than 80%. Therefore, effective ventilation during CPR is essential. Further study is needed to demonstrate whether confirmed adequate ventilation improves outcome during CPR.

Dexmedetomidine constant rate infusion for 24 hours during and after propofol or isoflurane anaesthesia in dogs

ObjectiveTo evaluate cardiovascular and respiratory effects and pharmacokinetics of a 24-hour intravenous constant rate infusion (CRI) of dexmedetomidine (DMED) during and after propofol (PRO) or isoflurane (ISO) anaesthesia in dogs. Study designProspective, randomized, cross-over study. AnimalsTen healthy adult Beagles. MethodsInstrumented dogs received a DMED-loading bolus (25 μg m−2) at time 0 followed by a 24-hour CRI (25 μg m−2 hour−1), with PRO or ISO induction/maintenance of anaesthesia during the first 2 hours (PRO and ISO treatment groups, respectively). Cardiovascular, respiratory, blood gas, airway gas, serum chemistry variables and DMED plasma concentration data were collected at -15, 5, 15, 30, 45, 60, 90 and 120 minutes. A number of cardiorespiratory and tissue oxygenation variables were calculated from the above data. After the 2-hours of anaesthesia, heart and respiratory rates and electrocardiograms were recorded and DMED plasma concentrations were determined for up to 26 hours. ResultsVasopressor effects and the decrease in heart rate (HR) and cardiac index induced by DMED were greater for PRO than ISO, but were within clinically acceptable ranges. Adequate oxygenation was maintained above the critical O2 delivery level. The overall incidence of unfavourable arrhythmias was low and tended to vary inversely with HR. Mean DMED plasma concentration ranged from 0.23 to 0.47 ng mL−1 for both groups during the 24-hour CRI with a mean elimination half-life of approximately 0.46 hour.Conclusion and/clinical relevance DMED CRI resulted in typical α2-agonist induced haemodynamic changes with minimal respiratory effects, and appeared to be an efficacious adjunct during and after PRO or ISO anaesthesia in healthy dogs.

Experimental analysis of critical oxygen delivery

Systemic variables were evaluated with respect to O(2) delivery to test the hypothesis that critical O(2) delivery and critical Hb can be estimated by multiple variables collected simultaneously. Rats were subjected to transfusion with either fresh or stored blood and then subjected to stepwise isovolemic hemodilution. Critical levels were measured by the dual-regression method from plots of systemic variables against O(2) delivery and Hb. Delivery was calculated from cardiac index and arterial O(2) content. We found that 1) after hemodilution, O(2) delivery changed in a nonlinear relationship with Hb; 2) critical delivery calculated using 30 different systemic variables was not statistically different from each other; 3) critical delivery and critical Hb were correlated but were not different between animals receiving fresh or stored blood; and 4) similar critical levels were found using a single variable from several animals and using several variables from the same subject. The best variables to estimate critical delivery were lactate, bicarbonate, base excess, O(2) extraction ratio, expired CO(2), pulse pressure, cardiac index, and systolic pressure. The data suggest that a multivariable analysis of critical delivery may help determine the physiological oxygenation boundary at the whole body level. This may assist in finding therapeutic triggers on an individual basis using systemic markers of the transition from aerobic to anaerobic metabolism.

Hepato-splanchnic Blood Flow and Oxygen Extraction Capabilities during Experimental Tamponade: Effects of Endotoxin

We studied the hepato-splanchnic vascular response and changes in O2extraction capabilities to a reduction in blood flow following endotoxemia. Fourteen anesthetized and mechanically ventilated dogs were divided into two groups of seven each. Group 1 received 2 mg/kg ofE. coliendotoxin, and group 2 served as a control. After initial fluid resuscitation following endotoxic shock, regional blood flow estimated by an ultrasonic technique increased similarly in the hepatic artery, portal vein, and mesenteric artery, but microvascular blood flow estimated by a laser Doppler technique was lower in the liver than in the intestinal mucosa. When blood flow was reduced by cardiac tamponade, endotoxin-treated animals had greater whole body and regional critical O2delivery (DO2crit) and lower whole body, liver, and intestinal critical O2extraction ratios (O2ERcrit). DO2critwas higher in the liver than in intestine but O2ERcritwas similar in the two organs. Whole bodyDO2critat the onset of organ O2supply dependency was similar under control (9.4 ± 1.9 mL/kg · min for whole body, 10.3 ± 4.7 mL/kg · min for liver, and 10.0 ± 2.6 mL/kg · min for intestine) and endotoxic conditions (13.6 ± 3.2 mL/kg · min for whole body, 15.6 ± 2.7 mL/kg · min for liver, and 15.4 ± 8.7 mL/kg · min for intestine). We conclude that fluid-resuscitated endotoxic shock in dogs is characterized by blood flow redistribution within the liver and intestine. Microvascular depression may be more severe in the liver than in the intestinal mucosa, although the whole body, the liver, and the intestine became O2supply-dependent simultaneously.

Effects of nitric oxide on blood flow distribution and O2 extraction capabilities during endotoxic shock.

The effects of the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) and the NO donor 3-morpholinosydnonimine (SIN-1) were tested in 18 endotoxic dogs. L-NMMA infusion (10 mg . kg-1 . h-1) increased arterial and pulmonary artery pressures and systemic and pulmonary vascular resistances but decreased cardiac index, left ventricular stroke work index, and blood flow to the hepatic, portal, mesenteric, and renal beds. SIN-1 infusion (2 microg . kg-1 . min-1) increased cardiac index; left ventricular stroke work index; and hepatic, portal, and mesenteric blood flow. It did not significantly influence arterial and pulmonary artery pressures but decreased renal blood flow. The critical O2 delivery was similar in the L-NMMA group and in the control group (13.3 +/- 1.6 vs. 12.8 +/- 3.3 ml . kg-1 . min-1) but lower in the SIN-1 group (9.1 +/- 1.8 ml . kg-1 . min-1, both P < 0.05). The critical O2 extraction ratio was also higher in the SIN-1 group than in the other groups (58.7 +/- 10.6 vs. 42.2 +/- 7.6% in controls, P < 0.05; 43.0 +/- 15.5% in L-NMMA group, P = not significant). We conclude that NO is not implicated in the alterations in O2 extraction capabilities observed early after endotoxin administration.

Pathological O2 supply dependence of diaphragmatic and systemic O2 uptake during endotoxemia.

Our aim was to assess whether endotoxemia impairs the ability of the diaphragm to extract O2 and whether this defect leads to a greater dependence of O2 uptake on O2 delivery. In two groups of anesthetized mechanically ventilated dogs, the left hemidiaphragm was vascularly isolated. Diaphragmatic blood flow and cardiac output (CO) were measured simultaneously in all animals. Saline (S group) or Escherichia coli endotoxin (100 mg; E group) was infused intravenously over 60 min. In both groups, CO was reduced in stages by controlled hemorrhage, and systemic and diaphragmatic O2 deliveries and consumptions were measured at each stage to construct the O2 delivery-O2 consumption relationships. In the S group, the average systemic O2 delivery below which O2 uptake became supply dependent was 7.2 ml.kg-1.min-1. At this O2 delivery, systemic O2 extraction ratio (ER) averaged 67.9%, whereas the maximum O2 ER was 91.3%. Critical diaphragmatic O2 delivery and critical and maximum diaphragmatic O2 ER, by comparison, averaged 9.0 ml.kg-1.min-1, 65%, and 81.9%, respectively. Endotoxin infusion raised critical systemic O2 delivery to 16.7 ml.kg-1.min-1 (P < 0.05) and reduced critical and maximum systemic O2 ER to 55.5 and 77% (P < 0.05), respectively. Similarly, critical diaphragmatic O2 delivery in the E group increased to 14.8 ml.kg-1.min-1 (P < 0.05), whereas critical and maximum O2 ER declined to 51.8 and 72.8%, respectively (P < 0.05). Thus, endotoxemia impairs diaphragmatic O2 extraction. This, in turn, leads to a greater dependence of diaphragmatic O2 uptake on O2 delivery.

Systemic and diaphragmatic oxygen delivery-consumption relationships during hemorrhage.

When tissue O2 delivery falls below a critical threshold, tissue O2 uptake (VO2) becomes limited. We compared critical O2 delivery and critical and maximum O2 extraction ratios of the resting and contracting left hemidiaphragm with those of nondiaphragmatic tissues in seven dogs. The left hemidiaphragm was perfused through the left inferior phrenic artery with blood from the left femoral artery. Phrenic venous blood was sampled through a catheter in the inferior phrenic vein. Systemic O2 delivery was reduced in stages by controlled hemorrhage. Left diaphragmatic VO2 during rest and during 3 min of continuous stimulation (3 Hz) of the left phrenic nerve and VO2 of the remaining nonleft hemidiaphragmatic tissues were measured at each stage. Critical diaphragmatic O2 delivery for the resting diaphragm averaged 0.8 +/- 0.16 ml.min-1.100 g-1 with a critical O2 extraction ratio of 65.5 +/- 6%. In the contracting diaphragm, they averaged 5.1 +/- 0.9 ml.min-1.100 g-1 and 81 +/- 5%, respectively. Whole body O2 delivery at which resting diaphragmatic VO2 became supply limited was similar to that for nondiaphragmatic tissues. By comparison, supply limitation of VO2 occurred at a higher systemic O2 delivery in the contracting diaphragm than in the rest of the body despite the increase in critical diaphragmatic extraction ratio. Thus, oxygenation of the isolated diaphragm does not appear to be preferentially preserved during generalized reductions in O2 delivery. These results suggest that, in diseases associated with increased work of breathing and decreased O2 delivery, the diaphragm may become metabolically impaired before limitation of VO2 is observed systemically.

Critical O2 delivery in rat brain.

As O2 delivery (DO2) of whole body,1,2 intestine,3,4 liver,5 or skeletal muscle6 is progressively decreased in anesthetized animals, O2 consumption (VO2) is initially maintained constant via increased O2 extraction by the tissues (O2 supply independence). However, below a critical threshold DO2 value (DO2c), VO2 of these organs decreases in proportion to DO2 (O2 supply dependence). More importantly, dysoxia (i.e. O2 demand that exceeds O2 supply)7 appears to commence at the onset of liver O2 supply dependence, as reflected by the simultaneous decrease in VO2 and increase in hepatic mitochondrial reduction.5 Accordingly, it tentatively appears that dysoxia may be identified, in liver at least, by the DO2c inflection of a biphasic VO2- DO2 relation.KeywordsCerebral Blood FlowMean Arterial PressureExtraction RatioSuperior Sagittal SinusImmobilization StressThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Identification of the Critical Oxygen Delivery for Anaerobic Metabolism in Critically III Septic and Nonseptic Humans

To determine the critical oxygen delivery threshold for anaerobic metabolism and to compare its value between septic and nonseptic critically ill patients. Cohort analytic study, consecutive sample. Two tertiary care medical and surgical intensive care units in university hospitals. Nine septic and nine nonseptic critically ill humans. A diagnosis of sepsis was established by the presence of sepsis syndrome, positive cultures obtained within 48 hours of study, and autopsy evidence of a source of infection. The O2 consumption (determined by indirect calorimetry), O2 delivery (calculated from the Fick equation), and concentration of arterial plasma lactate were simultaneously determined at 5- to 20-minute intervals while life support was discontinued. Critical O2 delivery, critical O2 extraction ratio, and maximal O2 extraction ratio. In all septic and eight nonseptic patients, O2 delivery and O2 consumption displayed a biphasic relationship over the range of O2 delivery studied. There were no differences in critical O2 delivery threshold (3.8 +/- 1.5 vs 4.5 +/- 1.3 mL.min-1 x kg-1; P > .28), critical O2 extraction ratio (0.61 +/- 0.05 vs 0.59 +/- 0.16; P > .64), and maximal O2 extraction ratio (0.74 +/- 0.08 vs 0.80 +/- 0.11; P > .29) between septic and nonseptic patients. These data have greater than 90% power to detect a difference of 2 mL.min-1 x kg-1 in the critical O2 delivery and 0.1 in the critical and maximal O2 extraction ratios between the septic and nonseptic groups. The critical O2 delivery for anaerobic metabolism was identified from the biphasic relationship between O2 delivery and O2 consumption in individual humans. The critical O2 delivery is considerably lower than previously reported in humans with the use of pooled group data. Sepsis does not alter the critical O2 delivery for anaerobic metabolism or tissue O2 extraction ability. Interventions to increase O2 delivery to supranormal levels in critically ill humans in the hope of increasing O2 consumption may be inappropriate.

Low-dose dopamine hastens onset of gut ischemia in a porcine model of hemorrhagic shock.

Gut metabolism may become anaerobic before the whole body during progressive phlebotomy in dogs. Because dopamine has selective mesenteric vasodilator effects, we asked whether dopamine could delay onset of bowel ischemia during hemorrhagic shock. We studied whole body and gut O2 consumption (VO2) and O2 delivery (QO2) using progressive phlebotomy in anesthetized pigs. Nine pigs received a dopamine infusion of 2 micrograms.kg-1.min-1, whereas a control group of seven pigs received equivalent saline infusion. Onset of ischemia in whole body and gut was determined as critical O2 delivery (QO2c), the intersection point of biphasic regression on plots of VO2-QO2 relationships. Blood flow and O2 extraction were measured as mechanisms of gut ischemia for entire in situ small and large gut using a superior mesenteric venous fistula. Dopamine hastened onset of gut ischemia relative to onset of whole body ischemia (gut critical point in terms of whole body QO2 9.9 +/- 2.1 ml O2.kg-1.min-1, whole body QO2c 7.8 +/- 0.7 ml O2.kg-1.min-1, P less than 0.01). In contrast, onset of gut ischemia in control animals occurred at same time as onset of whole body ischemia (gut critical point in terms of whole body QO2 7.4 +/- 2.3 ml O2.kg-1.min-1, whole body QO2c 7.1 +/- 2.7 ml O2.kg-1.min-1, P = not significant). Hastening of onset of gut ischemia in dopamine-treated animals was associated with decreased ability of gut to extract O2. Low-dose dopamine was not protective against gut ischemia during shock but rather caused earlier onset of gut ischemia during hemorrhagic shock.

Effects of anesthetic agents on systemic critical O2 delivery

The present study tested the hypothesis that anesthetic agents can alter tissue O2 extraction capabilities in a dog model of progressive hemorrhage. After administration of pentobarbital sodium (25 mg/kg iv) and endotracheal intubation, the dogs were paralyzed with pancuronium bromide, ventilated with room air, and splenectomized. A total of 60 dogs were randomized in 10 groups of 6 dogs each. The first group served as control (C). A second group (P) received a continuous infusion of pentobarbital (4 mg.kg-2.h-2), which was started immediately after the bolus dose. Three groups received enflurane (E), halothane (HL), or isoflurane (I) at the end-tidal concentration of 0.7 minimum alveolar concentration (MAC). The sixth group received halothane at the end-tidal concentration of 1 MAC (HH). Two groups received intravenous alfentanil at relatively low dose (AL) or high dose (AH). The last two groups received intravenous ketamine at either relatively low dose (KL) or high dose (KH). In each group, O2 delivery (Do2) was progressively reduced by hemorrhage. At each step, systemic Do2 and O2 consumption (VO2) were measured separately and the critical point was determined from a plot of Vo2 vs. Do2. The critical O2 extraction ratio (OER) in the control group was 65.0 +/- 7.8%. OER was lower in all anesthetized groups (P, 44.3 +/- 11.8%; E, 47.0 +/- 7.7%; HL, 45.7 +/- 11.2%; I, 44.3 +/- 7.1%; HH, 33.7 +/- 6.0%; AL, 56.5 +/- 9.6%; AH, 43.5 +/- 5.9%; KH, 57.7 +/- 7.1%), except in the KL group (78.3 +/- 10.0%). The effects of halothane and alfentanil on critical OER were dose dependent (P less than 0.05), whereas critical OER was significantly lower in the KH than in the KL group. Moreover, the effects of anesthetic agents on critical Do2 appeared related to their effects on systemic vascular resistance. Anesthetic agents therefore alter O2 extraction by their peripheral vascular effects. However, ketamine, with its unique sympathetic stimulant properties, had a lesser effect on OER than the other anesthetic agents. It could therefore be the anesthetic agent of choice in clinical situations when O2 availability is reduced.

Hepatic oxygen and lactate extraction during stagnant hypoxia

As O2 delivery falls, tissues must extract increasing amounts of O2 from blood to maintain a normal O2 consumption. Below a critical delivery threshold, increases in O2 extraction cannot compensate for the falling delivery, and O2 uptake falls in a supply-dependent fashion. Numerous studies have identified a critical delivery in whole animals, but the regional contributions to the critical O2 delivery are less fully understood. In the present study, we explored the limits of O2 extraction in the isolated liver, seeking to determine 1) the normal relationship between O2 consumption and delivery in the liver and 2) the relationship of hepatic lactate extraction to the drop in hepatic O2 consumption at low O2 deliveries. To answer these questions, using support dogs as a source for oxygenated metabolically stable blood, we studied eight pump-perfused canine livers. By lowering the blood flow in a model of stagnant hypoxia, we explored the relationship between O2 consumption and delivery over the entire physiological range of O2 delivery. The critical O2 delivery was 28 +/- 5 (SD) ml.kg-1.min-1; the livers extracted 68 +/- 9% of the delivered O2 before reaching supply dependence. This suggests that the liver has an O2 extraction capacity quite similar to the body as a whole and not different from other tissues that have been isolated. At high blood flows, the livers extracted approximately 10% of the lactate delivered by the blood, but the arteriovenous lactate differences were small. At low blood flows, however, the livers changed from lactate consumption to production. The O2 delivery coinciding with the dropoff in lactate extraction did not differ significantly from the critical O2 delivery. We conclude that reductions in lactate uptake by the liver do not precede the transition to O2 supply dependence.

Oxygen Consumption in Resting Dog Gracilis Muscle Perfused at Varying Oxygen Delivery.

The different response of O2 uptake (VO2) of resting skeletal muscle to the changes in blood flow has been thought to reflect a species difference. To scrutinize this notion, we investigated the relation between O2 delivery (arterial O2 content multiplied by blood flow) and VO2 in isolated dog gracilis muscle perfused solely with normal hematocrit (Ht) blood (n = 9), or alternately with normal and low Ht blood (n = 6), or alternately with normal and high Ht blood (n = 3) at varying perfusion rates. Eleven out of the 18 preparations showed an autoregulation of blood flow, and the others did not. But, in all preparations, the VO2 was delivery-independent above a critical O2 delivery (0.45 ml/(min.100 g muscle)) and showed the constant VO2 of 0.30 ml/(min.100 g), while below the critical level it turned out to be delivery-dependent. The maximal extraction ratio was 0.67. The same relationship was found with the low and high Ht perfusion. The pattern observed in dog gracilis muscle was essentially the same as that in rat gracilis muscle (KOLAR and JANSKY, 1984).

Flow redistribution during progressive hemorrhage is a determinant of critical O2 delivery

O2 consumption (VO2) of anesthetized whole mammals is independent of O2 delivery (DO2) until DO2 declines to a critical value (DO2c). Below this value, VO2 becomes O2 supply dependent. We assessed the influence of whole body DO2 redistribution among organs with respect to the commencement of O2 supply dependency. We measured DO2, VO2, and DO2c of whole body, liver, intestine, kidney, and remaining carcass in eight mongrel dogs during graded progressive hemorrhage. Whole body DO2 was redistributed such that the organ-to-whole body DO2 ratio declined for liver and kidney and increased for carcass. We then created a mathematical model wherein each organ-to-whole body DO2 ratio remained approximately constant at all values of whole body DO2 and assigned organ VO2 to predicted organ DO2 by interpolation and extrapolation of observed VO2-DO2 plots. The model predicted that O2 supply dependency without redistribution would have commenced at a higher value of whole body DO2 for whole body (8.11 +/- 0.89 vs. 6.98 +/- 1.16 ml.kg-1.min-1, P less than 0.05) and carcass (6.83 +/- 1.16 vs. 5.06 +/- 1.15 ml.kg-1.min-1, P less than 0.01) and at a lower value of whole body DO2 for liver (6.33 +/- 1.86 vs. 7.59 +/- 1.95, ml.kg-1.min-1, P less than 0.02) and kidney (1.25 +/- 0.64 vs. 4.54 +/- 1.29 ml.kg-1.min-1, P less than 0.01). We conclude that redistribution of whole body DO2 among organs facilitates whole body O2 regulation.

Halothane Alters the Oxygen Consumption-Oxygen Delivery Relationship Compared with Conscious State

The authors' objectives were as follows: 1) to characterize for the first time the relationship between whole body O2 delivery (DO2) and O2 consumption (VO2) in adult conscious dogs; and 2) to asses the effects of the inhalational anesthetic, halothane, on that relationship. DO2 was varied over a wide range in chronically instrumented dogs by gradual inflation and deflation of a hydraulic occluder implanted around the thoracic inferior vena cava to alter venous return and cardiac output. VO2 was measured at different values of DO2 in dogs in the fully conscious state and again during halothane anesthesia. A "binning" technique indicated that halothane decreased VO2 (P less than 0.01) at any given value of DO2 over a broad range of VO2. A two-line piecewise linear regression analysis technique indicated that halothane decreased (P less than 0.01) the critical O2 delivery (COD) from 20 +/- 3 to 10 +/- 1 ml.kg-1.min-1 and increased (P less than 0.01) O2 extraction at COD from 31 +/- 3 to 40 +/- 2%. However, the DO2-VO2 plots measured in both conscious and halothane-anesthetized dogs did not exhibit a discrete discontinuity but rather were closely fit (correlation coefficient = 0.98) by an exponential equation of the following form: O2 extraction = B1.(1 - exp (-DO2/B2))/DO2, where B1 is the delivery-independent estimate of VO2 and B2 is the "delivery constant," i.e., the DO2 associated with a VO2 equal to 63% of B1. Halothane decreased B1 (P less than 0.01) from 5.3 +/- 0.1 to 3.9 +/- 0.1 ml.kg-1.min-1 and decreased B2 (P less than 0.01) from 5.6 +/- 0.3 to 3.6 +/- 0.3 ml.kg-1.min-1 compared with that measured in conscious dogs. Thus, compared with the conscious state, halothane anesthesia alters the fundamental relationship between DO2 and VO2 and may have a beneficial effect on tissue oxygenation at low values of DO2.

Critical O2 delivery to skeletal muscle at high and low PO2 in endotoxemic dogs.

An ischemic canine limb model was used to determine whether endotoxin reduces the ability of resting skeletal muscle to extract O2 and whether increasing the arterial PO2 would increase its O2 extraction. Isolated limbs were pump perfused via an extracorporeal circuit with membrane oxygenator at three progressively lower flows and PO2 of both 60 and 200 Torr, whereas the rest of the body remained normoxic and normotensive. Six anesthetized, paralyzed dogs were injected with endotoxin (4 mg/kg, ENDO), and another six were controls (CONT). Limb critical O2 delivery was higher (P less than 0.05) in ENDO than CONT (8.3 vs. 6.1 ml.kg-1.min-1). Critical venous PO2 was also higher (P less than 0.05) in ENDO than CONT (38 vs. 30 Torr). Critical O2 extraction ratio was lower (P less than 0.05) in ENDO than CONT (0.60 vs. 0.73). There were no differences in these variables between low and high arterial PO2. We concluded that 1) endotoxin can cause a small but significant O2 extraction defect in skeletal muscle, 2) increasing arterial PO2 did not correct such a defect, nor did it improve O2 uptake in ischemic, but otherwise healthy, muscle, and 3) skeletal muscle may contribute to the peripheral O2 extraction defect in adult respiratory distress syndrome insofar as endotoxin effects model those found in adult respiratory distress syndrome.

Pathological supply dependence of O2 uptake during bacteremia in dogs.

When systemic delivery of O2 [QO2 = cardiac output X arterial O2 content (CaO2)] is reduced, the systemic O2 extraction ratio [(CaO2-concentration of O2 in venous blood/CaO2] increases until a critical limit is reached below which O2 uptake (VO2) becomes limited by delivery. Many patients with adult respiratory distress syndrome exhibit supply dependence of VO2 even at high levels of QO2, which suggests that a peripheral O2 extraction defect may be present. Since many of these patients also suffer from serious bacterial infection, we tested the hypothesis that bacteremia might produce a similar defect in the ability of tissues to maintain VO2 independent of QO2, as QO2 reduced. The critical O2 delivery (QO2crit) and critical extraction ratio (ERcrit) were compared in a control group of dogs and a group receiving a continuous infusion of Pseudomonas aeruginosa (5 x 10(7) organisms/min). Dogs were anesthetized, paralyzed, and ventilated with room air. Systemic QO2 was reduced in stages by hemorrhage as hematocrit was maintained. At each stage, systemic VO2 and QO2 were measured, and the critical point was determined from a plot of VO2 vs. QO2. The mean QO2crit and ERcrit of the bacteremic group (11.4 +/- 2.2 ml.min-1.kg-1 and 0.51 +/- 0.09) were significantly different from control (7.4 +/- 1.2 and 0.71 +/- 0.10) (P less than 0.05). These results suggest that bacterial infection can reduce the ability of peripheral tissues to extract O2 from a limited supply, causing VO2 to become limited by O2 delivery at a stage when a smaller fraction of the delivered O2 has been extracted.(ABSTRACT TRUNCATED AT 250 WORDS)

Systemic and intestinal limits of O2 extraction in the dog.

When systemic delivery of O2 (QO2 = QT X CaO2, where QT is cardiac output and CaO2 is arterial O2 content) is reduced by bleeding, the systemic O2 extraction ratio [ER = (CaO2 - CVO2)/CaO2, where CVO2 is venous O2 content] increases until a critical limit is reached below which O2 uptake (VO2) becomes limited by O2 delivery. During hypovolemia, reflex increases in mesenteric arterial tone may preferentially reduce gut blood flow so that the onset of O2 supply dependence occurs in the gut before other regions. We compared the critical O2 delivery (QO2c) and critical extraction ratio (ERc) of whole body and an isolated segment (30-50 g) of small bowel in seven anesthetized paralyzed dogs ventilated with room air. Systemic QO2 was reduced in stages by controlled hemorrhage as arterial O2 content was maintained, and systemic and gut VO2 and QO2 were measured at each stage. Body QO2c was 7.9 +/- 1.9 ml X kg-1 X min-1 (ERc = 0.69 +/- 0.12), whereas gut O2 supply dependency occurred when gut QO2 was 34.3 +/- 11.3 ml X min-1 X kg gut wt-1 (ERc = 0.63 +/- 0.09). O2 supply dependency in the gut occurred at a higher systemic QO2 (9.7 +/- 2.7) than whole-body QO2c (P less than 0.05). The extraction ratio at the final stage (maximal ER) was less in the gut (0.80 +/- 0.05) than whole body (0.87 +/- 0.06). Thus during reductions in systemic QO2, gut VO2 was maintained by increases in gut extraction of O2.(ABSTRACT TRUNCATED AT 250 WORDS)