Hepatic and splanchnic oxygen consumption during acute hypoxemic hypoxia in anesthetized pigs

OBJECTIVE: To compare the hepatosplanchnic oxygen consumption (VO2) with the hepatic and splanchnic VO2 and to calculate the critical oxygen delivery (DO2crit) below which VO2 decreases in the hepatic, splanchnic, and hepatosplanchnic regions in a model of hypoxemic hypoxia. DESIGN: Prospective animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized and ventilated pigs (n = 7). INTERVENTIONS: The right carotid artery was cannulated to measure mean arterial pressure. A pulmonary artery catheter was inserted to measure mean pulmonary arterial pressure and cardiac output. After a midline abdominal incision, two flow probes were positioned around the portal vein and the hepatic artery to measure portal vein blood flow and hepatic artery blood flow. Oxygen and lactate contents in the carotid artery, the portal vein, and the hepatic vein were measured in blood samples obtained from the appropriate catheters. MEASUREMENTS AND MAIN RESULTS: After a 2-hr stabilization period, hemodynamic and biological variables were recorded during acute hypoxemic hypoxia (FIO2 = 0.5, 0.4, 0.3, 0.21, 0.15, 0.10, and 0.07). VO2, DO2, and DO2crit were determined in the hepatic, splanchnic, and hepatosplanchnic regions. The hepatosplanchnic VO2 was 48 +/- 5 mL/min at high FIO2 (40% for the liver and 60% for the splanchnic organs) and decreased below FIO2 of 0.15. Lactate uptake in the whole hepatosplanchnic region remained steady at FIO2 values of 0.5 to 0.15 and then switched to a lactate release at low FIO2. However, the splanchnic region released lactate, whereas lactate was taken up by the liver. DO2crit in the hepatic, splanchnic, and hepatosplanchnic regions was 24 +/- 3, 38 +/- 2, and 49 +/- 4 mL/min, but the systemic DO2crit, below which regional VO2 became oxygen supply dependent, did not differ in the liver, splanchnic, and hepatosplanchnic regions. CONCLUSIONS: The variables of oxygenation and lactate flux measured in the hepatosplanchnic region summarize the metabolic changes of various organs that may vary in different ways during hypoxemic hypoxia.     

Blood transfusion and oxygen consumption in surgical sepsis

OBJECTIVE: To evaluate the use of serum lactic acid values to predict flow-dependent increases in oxygen consumption (VO2) in response to increasing oxygen delivery (DO2) after blood transfusion in surgical sepsis. DESIGN: Prospective study. SETTING: Tertiary care, trauma center. PATIENTS: Twenty-one patients, postsurgical or posttrauma, judged septic by defined criteria. INTERVENTIONS: Serum lactic acid concentrations, DO2, and VO2 were measured before and after transfusion therapy. MEASUREMENTS AND MAIN RESULTS: Overall, the DO2 increased from 532 +/- 146 to 634 +/- 225 (SD) mL/min.m2 (p less than .001), and the VO2 increased from 145 +/- 39 to 160 +/- 56 mL/min.m2 (p = .02). These changes occurred with an Hgb increase from 9.3 +/- 1.1 to 10.7 +/- 1.5 g/dL (p less than .001). The patients were grouped by their pretransfusion serum lactic acid values. In those patients with normal (less than 1.6 mmol/dL) serum lactic acid (n = 10), DO2 increased from 560 +/- 113 to 676 +/- 178 mL/min.m2 (p less than .02), and VO2 increased from 150 +/- 25 to 183 +/- 46 mL/min.m2 (p less than .02). However, in the increased serum lactic acid group (n = 17), VO2 was not significantly changed after transfusion (143 +/- 46 to 146 +/- 58 mL/min.m2) despite increased DO2 (515 +/- 163 to 609 +/- 251 mL/min.m2, p less than .01). CONCLUSIONS: Blood transfusion can be used to augment DO2 and VO2 in septic surgical patients. Increased serum lactic acid values do not predict patients who will respond. The absence of lactic acidosis should not be used in this patient population to justify withholding blood transfusions to improve flow-dependent VO2. Patients who have increased lactate concentrations may have a peripheral oxygen utilization defect that prevents improvement in VO2 with increasing DO2.     

Dopamine does not correct oxygen consumption/oxygen delivery relation abnormality during vasomotor shock induced by interleukin-1beta

We previously showed that interleukin 1beta (IL-1beta) induces vasomotor shock and impairs the oxygen consumption (VO2)/oxygen delivery (DO2) relation by increasing the slope of the supply-independent line in rabbits. In the present study, we investigated the inotropic effect of dopamine on the VO2/DO2 abnormality induced by IL-1beta. Twelve rabbits were divided into two groups (n = 6, each) and were given 10 microg/kg of IL-1beta or saline (control) intravenously. After baseline measurements were obtained, dopamine was infused continuously at a rate of 20 microg/kg/min throughout the study in both groups. All rabbits were subjected to stepwise cardiac tamponade to reduce the DO2 to <5 mL/min/kg by inflation of a handmade balloon placed into the pericardial sac. The VO2/DO2 relation was then analyzed by the dual-line method. Dopamine failed to correct the IL-1beta-induced decrease in mean arterial pressure to the baseline level. Dopamine significantly increased cardiac index in both groups, resulting in significant increases in DO2 (IL-1beta, 28.5 +/- 6.0 mL/min/kg from baseline 24.1 +/- 3.5 mL/min/kg; control, 27.7 +/- 2.9 mL/min/kg from baseline 22.9 +/- 2.9 mL/min/kg), but did not affect VO2 (IL-1beta, 10.0 +/- 0.5 mL/min/kg from baseline 9.9 +/- 0.7 mL/min/kg; control, 10.2 +/- 0.4 mL/min/kg from baseline 10.2 +/- 0.2 mL/min/kg). The IL-1beta group showed a significantly greater supply-independent line slope than that of controls (IL-1beta, y = 0.14x + 6.3; control, y = 0.06x + 8.6) during stepwise decreases in DO2. These results indicate that continuous infusion of dopamine at 20 microg/kg/min increases DO2 but does not correct the vasomotor disturbance or VO2/DO2 abnormality caused by IL-1beta.     

Effect of blood transfusion on oxygen consumption in pediatric septic shock

Treatment plans for pediatric septic shock advocate increasing oxygen consumption (VO2). Recent studies in septic shock indicate that improving oxygen delivery (DO2) by increasing blood flow will increase VO2. We prospectively examined the effect on VO2 of improving DO2 by increasing oxygen content (CO2) with blood transfusion in eight hemodynamically stable septic shock patients. Transfusion consisted of 8 to 10 ml/kg of packed RBC over 1 to 2 h. Hemodynamic and oxygen transport measurements were obtained before and after blood transfusion. Transfusion significantly (p less than .05) increased Hgb and Hct from 10.2 +/- 0.8 g/dl and 30 +/- 2% to 13.2 +/- 1.4 g/dl and 39 +/- 4%, respectively (mean +/- SD). DO2 significantly (p less than .05) increased after transfusion (599 +/- 65 to 818 +/- 189 ml/min.m2), but VO2 did not change (166 +/- 68 to 176 +/- 74 ml/min.m2; NS). In pediatric septic shock patients, increasing CO2 by blood transfusion may not increase VO2.     

Gastric-arterial PCO2 gradient does not reflect systemic and splanchnic hemodynamics or oxygen transport after cardiac surgery

Gastric mucosal-arterial PCO2 gradient (P(g-a)CO2) is used to assess splanchnic perfusion and oxygenation. We evaluated whether P(g-a)CO2 reflects whole body (Q) and splanchnic (Qsp) blood flow, oxygen delivery (DO2) and consumption (VO2) after coronary artery by pass graft (CABG) operation. Thirty patients received dobutamine or dopexamine to increase cardiac index, 15 patients enalapril or sodium nitroprusside to lower blood pressure, and 30 patients were controls. We measured Q, Qsp (hepatic vein catheter and indocyanine green), and gastric mucosal PCO2 (nasogastric tonometer) before and after interventions. Multiple linear regression model showed that none of the changes in Q, Qsp, and splanchnic or systemic DO2 and VO2 significantly explained changes in P(g-a)CO2 (deltaP(g-a)CO2). All independent variables together explained only 7% of deltaP(g-a)CO2. Increased splanchnic blood flow (0.65 +/- .19 vs. 0.94 +/- .31 L/min/m2, P < 0.001) and increased splanchnic DO2 (101 +/- 28 vs. 143 +/- 42 mL/min/m2, P < 0.001) during catecholamine infusions were associated with increased P(g-a)CO2 (8 +/- 8 vs. 11 +/- 7 mmHg, P = 0.003). P(g-a)CO2 does not reflect whole body or splanchnic blood flow, DO2 or VO2 after CABG operations. The physiology of P(g-a)CO2 is complex and therefore it is difficult for clinicians to interpret changes in gastric mucosal-arterial PCO2 gradient in individual patients after cardiac surgery.     

Whole body oxygen consumption and critical oxygen delivery in response to prolonged and severe carbon monoxide poisoning

BACKGROUND: Carbon monoxide (CO) poisoning remains the leading cause of death by poisoning in the world. One of the major proposed mechanisms for CO toxicity is the binding of CO to cytochrome oxidase and interference with cellular oxygen utilization but evidence for this is inconclusive. AIM OF STUDY: This study examined the effects of prolonged CO exposure on the dynamics of whole body oxygen consumption (VO(2)) and oxygen delivery (DO(2)) in an attempt to observe if CO exposure results in a defect of oxygen utilization defect as determined by a reduction in VO(2) during the course of poisoning prior to reaching the point where VO(2) is directly dependent on DO(2). This critical level of DO(2) (DO(2)crit) produced by CO poisoning was compared to historical values produced by other insults, which decrease global body DO(2). METHODS: Five small dogs were ventilated for 2 h with 0.25% CO and room air followed by 0.5% CO until death. Cardiac index (Q), DO(2), VO(2), oxygen extraction ratio (OER), and systemic lactate were measured every 15 min until death. RESULTS: Carboxyhemoglobin (COHb) levels increased linearly over 2.5 h to values above 80% until death. VO(2) remained constant and not significantly different from baseline below a COHb of 80%. At COHb levels above 80%, VO(2) precipitously dropped. Similarly lactate levels were not significantly elevated from baseline until VO(2) dropped. DO(2) decreased by 78% (from 23+/-6 ml/kg/min to 5+/-4 ml/kg/min) over time despite an increase in Q by 58% until levels of COHb were above 80%. OER increased from 19+/-5% to 50+/-11% until death. The calculated DO(2)crit was 10.7+/-4 ml/min/kg, which is not significantly different from values ranging from 7 to 13 ml/min/kg reported in the literature due to other insults, which reduce DO(2). CONCLUSION: In this canine model of prolonged CO exposure, no gradual reduction in VO(2) or increase in systemic lactate prior to reaching DO(2)crit was noted. In addition, CO exposure does not appear to change the DO(2)crit. The combination of these findings does not support the theory that CO produces a whole body intracellular defect in oxygen utilization.     

Comparison between the Datex-Ohmeda M-COVX metabolic monitor and the Deltatrac II in mechanically ventilated patients

OBJECTIVE: To compare the M-COVX and the Deltatrac II metabolic monitors under clinical conditions. DESIGN: Prospective clinical comparison. SETTING: A general Intensive Care Unit of a university hospital. PATIENTS: Twenty mechanically ventilated critically ill patients. INTERVENTIONS: The monitors were compared at FiO(2) 0.3, 0.5, and 0.7 in each patient where possible. MEASUREMENTS AND RESULTS: Pulmonary gas exchange measurements were recorded using the two monitors sequentially (Deltatrac(before), M-COVX, Deltatrac(after)). Each measurement consisted of five consecutive 1-min readings of VO(2) and VCO(2). We compared the Deltatrac(before) with the Deltatrac(after) and the mean of the Deltatrac with the M-COVX. There was no clinically significant bias between the two monitors for VO(2) or VCO(2) but the limits of agreement (LOA) were wide (bias +/-95% LOA: VCO(2) -13 +/- 30 ml/min, -8 +/- 36 ml/min, 7 +/- 50 ml/min; VO(2) -7 +/- 50 ml/min, -5 +/- 56 ml/min, 6 +/- 64 ml/min, at FiO(2) 0.3, 0.5, and 0.7, respectively). The Deltatrac before and after measurements displayed good agreement for VCO(2) but poorer agreement for VO(2) (bias +/- 95% LOA: VCO(2) 0 +/- 18 ml/min, -6 +/- 16 ml/min, -1 +/- 12 ml/min; VO(2) 2 +/- 12 ml/min, 3 +/- 38 ml/min, 10 +/- 42 ml/min, at FiO(2) 0.3, 0.5, and 0.7, respectively). Using within-patient standard deviation as a measure of reproducibility suggested that for VO(2) the M-COVX performed better than the Deltatrac at high FiO(2), and for VCO(2) Deltatrac was better at lower FiO(2). CONCLUSIONS: The M-COVX is a suitable integrated device for measuring metabolic gas exchange in ventilated patients.     

Interleukin-1beta alters the oxygen delivery-oxygen consumption relationship in rabbits by increasing the slope of the supply-independent line

When systemic oxygen delivery (DO2) is reduced, oxygen consumption (VO2) is maintained until a critical level is reached (DO2crit). Sepsis is thought to shift DO2crit to the right and lengthen the supply-dependent portion. We tested the effect of interleukin (IL)-1beta, which is one of the key cytokines related to sepsis, on the DO2-VO2 relationship. Fifteen rabbits were subjected to stepwise cardiac tamponade to reduce DO2 to 10% by inflating a handmade balloon placed into the pericardial sac. Seven rabbits were given 10 microg/kg of IL-1beta intravenously (IL-1beta group) prior to the graded cardiac tamponade. The remainder received saline alone (control group). The DO2-VO2 relationship was analyzed by the dual-line method. IL-1beta significantly decreased mean arterial pressure (65 +/- 11 mmHg from baseline 85 +/- 7 mmHg) without altering cardiac output. The IL-1beta group showed significantly steeper supply-independent line slopes than did the control group (0.19 +/- 0.02 vs. 0.11 +/- 0.02, respectively), which resulted in a DO2crit shift to the left (IL-1beta group, 8.7 +/- 1.7 ml/kg x min vs. control, 11.7 +/- 0.7 ml/kg x min). The IL-1beta group also showed greater PO2 and plasma lactate levels in the portal vein than did the control group. These results indicate that IL-1beta impairs systemic oxygen uptake even before VO2 becomes supply-dependent, presumably due to maldistribution of the blood flow including the splanchnic circulation.     

Alterations in tissue oxygen consumption and extraction after trauma and hemorrhagic shock

OBJECTIVES: Although trauma and hemorrhage are associated with tissue hypoperfusion and hypoxemia, changes in oxygen delivery (DO2), oxygen consumption VO2), and oxygen extraction at the organ level in a small animal (such as the rat) model of trauma and hemorrhage have not been examined. Therefore, the objectives of this study were to determine whether blood flow, DO2, VO2, and oxygen extraction ratio in various organs are differentially altered after trauma-hemorrhagic shock and acute resuscitation in the rat. DESIGN: Prospective, randomized animal study. SETTING: A university research laboratory. SUBJECTS: Male Sprague-Dawley rats (n = 6-7 animals/group) weighing 275-325 g. INTERVENTIONS: Male rats underwent laparotomy (i.e., soft tissue trauma) and were bled to and maintained at a blood pressure of 40 mm Hg until 40% of shed blood volume was returned in the form of lactated Ringer's solution. They were then resuscitated with four times the volume of shed blood with lactated Ringer's solution for 60 mins. At 1.5 hrs postresuscitation, cardiac output and blood flow were determined by using strontium-85 microspheres. Blood samples (0.15 mL each) were collected from the femoral artery and vein and the hepatic, portal, and renal veins to determine total hemoglobin and oxygen content. Systemic and regional DO2, VO2, and oxygen extraction ratio were then calculated. MEASUREMENTS AND MAIN RESULTS: Both the systemic hemoglobin and systemic arterial oxygen content in hemorrhaged animals at 1.5 hrs postresuscitation were >50% lower as compared with sham-operated controls. Cardiac output and blood flow in the liver, small intestine, and kidneys decreased significantly, but blood flow in the brain and heart remained unaltered after hemorrhage and resuscitation. Systemic DO2 and VO2 were 73% and 54% lower, respectively, than controls at 1.5 hrs after resuscitation. Similarly, regional DO2 and VO2 in the liver, small intestine, and kidneys decreased significantly under such conditions. In addition, the liver had the most severe reduction in VO2 (76%) among the tested organs. However, the oxygen extraction ratio in the liver of sham animals was the highest (72%) and remained unchanged after hemorrhage and resuscitation. CONCLUSION: Because the liver experienced the most severe reduction in VO2 associated with an unchanged oxygen extraction capacity, this organ appears to be more vulnerable to hypoxic insult after hemorrhagic shock.     

Cardiorespiratory requirements and reproducibility of the six-minute walk test in elderly patients with coronary artery disease

OBJECTIVES: To measure the cardiorespiratory requirements of the six-minute walk test (6MWT), to compare this demand with the symptom-limited exercise test (SLET) at ventilatory threshold and at maximal level in elderly patients with coronary artery disease (CAD), and to assess the reproducibility of the 6MWT in cardiorespiratory exchanges in those patients. DESIGN: Comparative and reproducibility sample. SETTING: Cardiac rehabilitation service. PARTICIPANTS: Twenty-five people with CAD. INTERVENTIONS: Subjects performed an SLET and a 6MWT. To test 6MWT reproducibility, 9 patients performed 2 repeated 6MWTs. MAIN OUTCOME MEASURES: The 6MWT cardiorespiratory values, measured with a portable gas analyzer, were compared with the SLET data and with the data from the 2 repeated 6MWTs. RESULTS: The 6MWT peak oxygen uptake (VO2peak, 14.27+/-2.94 mL.min(-1).kg(-1)) and heart rate (94+/-14 beats/min) did not differ from the SLET values at ventilatory threshold (VO2, 13.4+/-2.65 mL.min(-1).kg(-1); heart rate, 91+/-17 beats/min), whereas the 6MWT ventilation (VEpeak, 36.72+/-10.03 L/min) was higher than the SLET at ventilatory threshold (Ve, 31.54+/-8.93 L/min, P<.03). Maximal 6MWT cardiorespiratory data were lower than the SLET maximal values. Cardiorespiratory values did not differ between the 2 repeated 6MWT (VO2peak, 15.33+/-3.52 mL.min(-1).kg(-1) vs 15.11+/-2.65 mL.min(-1).kg(-1); VEpeak, 39.07+/-12.33 L/min vs 39.07+/-12.13 L/min; heart rate, 95+/-21 beats/min vs 89+/-15 beats/min). CONCLUSIONS: The 6MWT cardiorespiratory requirement values did not differ from SLET values at ventilatory threshold except for ventilation, and 6MWT values are reproducible in elderly patients with CAD.     

Effects of hemorrhage on gastrointestinal oxygenation

OBJECTIVES: (1) To demonstrate that metabolic parameters are better indicators of tissue hypoxia than regional and whole oxygen consumption (VO(2)). (2) To compare intramucosal pH (pHi) in different gastrointestinal segments. DESIGN: Prospective, interventional study. SETTING: Research laboratory at a university center. SUBJECTS: Fourteen anesthetized, mechanically ventilated dogs. INTERVENTIONS: Twenty milliliters per kilogram bleeding. MEASUREMENTS AND MAIN RESULTS: We placed pulmonary, aortic and mesenteric venous catheters, and an electromagnetic flow probe in the superior mesenteric artery, and gastric, jejunal and ileal tonometers to measure flows, arterial and venous blood gases and lactate, and intramucosal PCO(2). We calculated systemic and intestinal oxygen transport (DO(2)) and consumption (VO(2)), pHi and arterial minus intramucosal PCO(2) (DeltaPCO(2)). Then, we bled the dogs and repeated the measurements after 30 min. Systemic and intestinal DO(2) fell (26.0+/-7.3 versus 8.9+/-2.6 and 71.9+/-17.3 versus 24.6+/-9.6 ml/min per kg, respectively, p<0.0001). Systemic and intestinal VO(2) remained unchanged (5.5+/-1.3 versus 5.4+/-1.3 and 15.7+/-5.0 versus 14.9+/-5.3 ml/min per kg, respectively). Gastric, jejunal and ileal pHi (7.13+/-0.11 versus 6.96+/-0.17, 7.18+/-0.06 versus 6.97+/-0.15, 7.12+/-0.11 versus 6.94+/-0.14, p<0.05) and DeltaPCO(2) (21+/-13 versus 35+/-23, 15+/-5 versus 33+/-16, 23+/-17 versus 38+/-20, p<0.05) changed accordingly. Arterial and mesenteric venous lactate and their difference, rose significantly (1.7+/-0.9 versus 3.7+/-1.4 and 1.8+/-0.8 versus 4.3+/-1.5 mmol/l, 0.1+/-0.6 versus 0.6+/-0.7 mmol/l, p<0.05). CONCLUSIONS: During hemorrhage, systemic and intestinal VO(2) remained stable. However, hyperlactatemia and intramucosal acidosis evidenced anaerobic metabolism. pHi changes paralleled in the three intestinal segments.     

Ex vivo evaluation of a new neonatal/infant oxygenator: comparison of the Terumo CAPIOX Baby RX with Dideco Lilliput 1 and Polystan Safe Micro in the piglet model

OBJECTIVE: A newly developed neonatal and infant oxygenator with a nonheparin biocompatible polymer coating, low priming volume (43 mL), high oxygen transfer, wide operating range (<1.5 L/min) and low pressure drop represents a promising solution for cardiac surgery in neonates and infants. We compared the new CAPIOX Baby RX, Terumo (BRX) with two commonly used neonatal oxygenators: Dideco Lilliput 1 (DL1) and Polystan Safe Micro (PSM) in a piglet model. METHODS: Fifteen piglets (5.6 +/- 1.3kg) were placed on standardized cardiopulmonary bypass (CPB) for 6 hours using one of the three oxygenators (n = 5 in each group). After 120 min, the system was cooled to 25 degrees C for 60 min and then returned to normothermia. Arterial and venous blood gas data and temperature were recorded continuously by a CDI500 System (Terumo). Pressure drop, FiO2 and gas flow were recorded. Blood samples were taken before CBP, after 10 min, before and after cooling, and at the end. Total blood counts, thrombin-antithrombin complex and plasma-free haemoglobin (PfHb) were measured. RESULTS: All oxygenators showed acceptable performance for the duration of CPB. The BRX had lower mean gas flow (0.33 +/- 0.05 L/min) and FiO2 (0.43 +/- 0.02%) throughout CPB than the DL1 (1.14 +/- 0.25 L/min, p = 0.006 and 0.60 +/- 0.02%, p = 0.009, respectively) or the PSM (1.47 +/- 0.87 L/min and 0.54 +/- 0.08%, p = ns). Pressure drop in the BRX group ranged from 12 to 22 mmHg. This was significantly lower than in the DL1 group (39-65 mmHg, p = 0.005). In the PSM group, values ranged between 24 and 33 mmHg (p = ns). The increase in PfHb at six hours was significantly lower in the BRX (11.3 +/- 4.2 ng/dL) versus the DL1 (42.2 +/- 6.1 ng/dL, p = 0.004) and the PSM (56.7 +/- 15.5 ng/dL, p = 0.045). CONCLUSIONS: The BRX is as safe as the DL1 and the PSM, with superior performance in pressure drop, efficient blood gas management and lower haemolysis. The BRX exhibited the lowest prime, hold-up volume and breakthrough time.     

Effect of dobutamine on oxygen consumption and fluid and protein losses after endotoxemia

OBJECTIVE: To determine the effect of a dobutamine infusion on the relationship between oxygen consumption (VO2) and oxygen delivery (DO2) after endotoxin administration, as well as the rate of fluid and protein loss from permeability-injured tissue. METHODS: Unanesthetized adult sheep with lung and soft-tissue lymph fistulas were given 5 micrograms/kg Escherichia coli endotoxin alone, or E. coli endotoxin plus a continuous infusion of dobutamine (10 to 15 micrograms/kg.min) beginning at 3 hrs. Lymph flow reflected the vascular permeability and surface area perfused. Data were compared with dobutamine alone and with controls. Filling pressures were maintained at baseline. RESULTS: Dobutamine alone produced a 75% increase in DO2, a transient 10 +/- 4% increase in VO2, but no increase in lung or soft-tissue lymph flow. Beginning at 3 hrs after endotoxin alone, a significant increase in protein-rich lung and soft-tissue lymph flow was noted, but only a transient 14 +/- 5% increase in VO2. Plasma proteins were slightly decreased. With the addition of dobutamine at 3 hrs postendotoxin, DO2 increased by greater than 50% for the 3-hr infusion period, while VO2 increased for a 30-min period by 25 +/- 8%, which was not different than endotoxin alone. Lung and soft-tissue lymph flow did not increase further, but plasma proteins did decrease significantly compared with controls and with endotoxin alone. CONCLUSION: Increasing DO2 with dobutamine postendotoxin does not increase the surface area perfused or the edema process, at least in lung and soft tissue. Therefore, no microvessels in these tissues are reopened with dobutamine when normal filling pressures are present. Dobutamine administration does not increase VO2 more than the increase seen with endotoxin alone.     

Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat.

Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR.     

End-tidal CO2 pressure determinants during hemorrhagic shock

OBJECTIVES: To examine the relationship between end-tidal CO2 (PETCO2) and its physiological determinants, pulmonary blood flow (cardiac output, CO) and CO2 production (VCO2), in a model of hemorrhagic shock during fixed minute ventilation. DESIGN AND SETTING: Prospective, observational study in a research laboratory at a university center. SUBJECTS AND INTERVENTIONS: Six anesthetized, intubated, and mechanically ventilated mongrel dogs. Progressive stepwise bleeding. MEASUREMENTS AND RESULTS: We continuously measured PETCO2 with a capnograph, pulmonary artery blood flow with an electromagnetic flow probe, arterial oxygen saturation (SaO2) with a fiberoptic catheter, and oxygen consumption (VO2) and VCO2 by expired gases analysis. Oxygen delivery (DO2) was continuously calculated from pulmonary blood flow and SaO2. We studied the correlation of PETCO2 with CO and VCO2 in each individual experiment. We also calculated the critical point in the relationships PETCO2/ DO2 and VO2/DO2 by the polynomial method. As expected, PETCO2 was correlated with CO. The best fit was logarithmic in all experiments (median r2 = 0.90), showing that PETCO2 decrease is greater in lowest flow states. PETCO2 was correlated with VCO2, but the best fit was linear (median r2 = 0.77). Critical DO2 for PETCO2 and VO2 was 8.0 +/- 3.3 and 6.3 +/- 2.5 ml x min(-1) kg(-1), respectively (NS). CONCLUSIONS: Our data reconfirm the relationship between PETCO2 and CO during hemorrhagic shock. The relatively greater decrease in PETCO2 at lowest CO levels could represent diminished CO2 production during the period of VO2 supply dependency.     

Lung fluid dynamics and supply dependency of oxygen uptake during experimental endotoxic shock and volume resuscitation

BACKGROUND AND METHODS: We studied the effect of volume resuscitation on lung fluid balance and systemic oxygen extraction during septic shock in eight anesthetized dogs. Sepsis was induced using a 2-hr continuous infusion of Escherichia coli endotoxin at 0.25 micrograms/min.kg. Relationships between oxygen uptake (VO2) and oxygen supply (DO2) were performed acutely during stepwise controlled decrements in cardiac output by progressive inflation of an intracardiac balloon. At each stage, DO2 and corresponding VO2 were measured independently and the individual critical DO2 level was referred to as the point below which the relationship held. The slope of such a constructed relationship was defined as the maximal oxygen extraction ratio. Lung fluid balance was assessed by measurements of extravascular lung water. All values were studied at baseline, after endotoxin insult, and after reversing hypotension by a 10% dextran infusion. RESULTS: Endotoxin infusion led to a shock state that associated hypotension (from 135 to 63 mm Hg) with increases in blood lactate (from 0.53 to 3.9 mmol/L). The mean critical DO2 and maximal oxygen extraction ratio were significantly altered from 7.9 to 17.8 mL/min.kg and from 0.81 to 0.38, respectively. After reversing hypotension by 28 mL/kg colloid infusion, the critical DO2 (11.4 mL/min.kg) and maximal oxygen extraction ratio (0.48) were significantly improved. However, restoration of normal values required a state of fluid overload by further dextran infusion (8 mL/kg). At the end of the fluid challenge, extravascular lung water significantly increased from 6.4 to 17.4 mL/kg. CONCLUSIONS: These data suggest that volume loading may reverse endotoxin-induced peripheral perfusion abnormalities. However, substantial pulmonary edema may occur, possibly jeopardizing the beneficial effects of fluid expansion.     

An in vitro study of the effects of isoflurane on oxygen transfer

A common anesthetic technique utilized during cardiopulmonary bypass (CPB) includes the use of various inhalation agents, such as isoflurane. The purpose of this study was to evaluate the effects of this agent on oxygen transfer during CPB. An in vitro model was designed using bovine blood. Blood flow was held constant at 2 l/min, while gas flow was manipulated at 1 and 3 l/min. The percentage of inspired oxygen (FiO2) was set at 50 and 100%, and isoflurane was manipulated to 1.0, 3.0 and 5.0%. Blood gas analysis, oxygen transfer, and inlet and outlet isoflurane concentrations were measured at each of the given conditions. A total of 12 trials with four oxygenators were conducted. In the four oxygenators used in our study, no significant differences in oxygenator performance were found. At conditions of 1 I/min gas flow, 50% FiO2 and 1% isoflurane, there were no significant changes in O2 transfer between baseline and measurements taken during isoflurane administration (100.18 +/- 12.49 vs 102.35 +/- 10.99 ml O2/min, p=0.8031). At 3 I/min gas flow, 100% FiO2 and 5% isoflurane, no significant differences were found (142.35 +/- 10.76 vs 154.04 +/- 8.95 ml O2/min, p=0.1459). The only significant differences found for oxygen transfer were between 50 and 100% FiO2, all other conditions being set equal (102.35 +/- 10.99 vs 137.68 +/- 8.62 ml O2/min, p=0.0023). In conclusion, increasing concentrations of isoflurane up to 5% does not affect the efficiency of oxygen transfer in an in vitro circuit. Further studies are necessary to evaluate the effects in an in vivo setting.     

Different dosages of dobutamine in septic shock patients: determining oxygen consumption with a metabolic monitor integrated in a ventilator

OBJECTIVE: Oxygen consumption (VO2) obtained from respiratory gases by indirect calorimetry (VO2,IC) with a metabolic monitor integrated in a ventilator were to be compared to VO2 obtained by the Fick principle (VO2,Fick) in septic patients following an increase in oxygen delivery (DO2) induced by positive inotropic support. DESIGN: Prospective clinical study. SETTING: University Hospital, Surgical Intensive Care Unit (ICU). PATIENTS: Thirty patients suffering from sepsis. INTERVENTIONS: DO2 was increased by dobutamine infusion, starting with an initial dosage of 5 microg x kg x min, increased to a maximum of 10 microg x kg x min. MEASUREMENTS AND MAIN RESULTS: Dobutamine infusion induced a dosage-related increase in DO2 (from 577 +/- 192 to 752 +/- 202 ml x min x m2, p < 0.01), which was associated with a statistically significant increase in VO2,IC (from 173 +/- 30 to 188 +/- 28 ml x min x m2, p < 0.01) and in VO2,Fick (from 140 +/- 25 to 156 +/- 24 ml x min x m2, p < 0.01). The comparison between VO2,IC and VO2,Fick revealed differences (bias and precision--33 +/- 32 ml x min x m2). CONCLUSIONS: With a metabolic monitor integrated in a ventilator it was possible to carry out continuous monitoring of calorimetric data under clinical conditions. In contrast to previous studies using indirect calorimetry, this study showed a moderate correlation between VO2 and DO2 in septic patients using either method. The clinical relevance of this finding requires further investigation. Different factors (e. g. injectant temperature, pulmonary VO2) produced substantial differences between VO2,IC and VO2,Fick as previously shown.     

Blood pressure development of the spontaneously hypertensive rat after concurrent manipulations of dietary Ca2+ and Na+. Relation to intestinal Ca2+ fluxes.

The blood pressure of the spontaneously hypertensive rat (SHR) is influenced by the Ca2+ content of its diet. As the SHR's greater dependence on dietary calcium may reflect a defect in intestinal calcium absorption, we measured in vitro unidirectional Ca2+ flux (J) in the duodenum-jejunum (four segments each) of the SHR (n = 6) and the normotensive Wistar-Kyoto rat (WKY; n = 6) by a modified Ussing apparatus. Because of the known and postulated interactions between Ca2+ and Na+ in both intestinal and vascular tissue, we assessed in vivo the influence of a concurrent manipulation of Na+ intake (three levels: 0.25%, 0.45%, and 1.0%) on the blood pressure development of SHRs (n = 35) and WKYs (n = 35), between 6 and 20 wk of age, exposed to three levels of dietary calcium (0.1, 1.0, and 2%). Net calcium flux (Jnet) (mean +/- SEM) was significantly (P less than 0.01) lower in the SHR (-2.8 +/- 6.3 nmol/cm2 X h) than in the WKY (34.6 +/- 8.8 nmol/cm2 X h). The SHR's decreased Jnet resulted from a significantly (P less than 0.03) lower mucosa-to-serosa flux (Jm-s) in the SHR (41.0 +/- 5.6 nmol/cm2 X h) compared with the Jm-s of the WKY (70.1 +/- 9.1 nmol/cm2 X h). Serosa-to-mucosa flux for calcium did not differ between the SHR (43.8 +/- 6.6 nmol/cm2 X h) and the WKY (35.5 +/- 8.0 nmol/cm2 X h). The SHR's decreased (P less than 0.002) Jm-s was confirmed by additional measurements in SHRs and WKYs. Jm-s was 36.2 +/- 3.7 nmol/cm2 X h in the SHRs (n = 11) and 64.4 +/- 6.7 nmol/cm2 X h in the WKYs (n = 9). The provision of an increased dietary Ca2+ (2% by weight) and increased Na+ (1%) to the SHR prevented the emergence of hypertension (P less than 0.001) (mean +/- SEM systolic blood pressure at 20 wk of age; 135 +/- 5 mmHg for the 2% Ca2+, 1% Na+ SHR vs. 164 +/- 2 mmHg for the control diet SHR). Ca2+ (0.1%) and Na+ (0.25%) restriction accelerated the SHR's hypertension (192 +/- 2 mmHg) (P less than 0.001) and was associated with higher pressures in the WKY (146 +/- 4 mmHg in the restricted WKY vs. 134 +/- 4 mmHg in the control WKY). In a parallel group of 24 SHRs and 24 WKYs fed one of three diets (2% Ca2+/1% Na+; 1% Ca2+/0.45% Na+; or 0.1% Ca2+/0.25% Na+), the heart (P < 0.05) and kidney (P = 0.08) weight of the SHRs varied depending on the diet at 20 wk of age. Low Ca2+ and Na+ intake was associated with increased heart weight (1.6+/-0.9 g) compared with the normal diet for SHR (1.51+/-0.07 g). Increased Ca2+ and Na+ intake was associated with a significantly (P = 0.05) lower heart weight in the SHR (1.37+/-0.03 g) and in the WKY (1.35+/-0.06 g) compared with their normal diet controls. These findings show one mechanism for the SHR's depressor response to supplemental dietary Ca2+ and, in part, explain the sodium dependence of calcium's cardiovascular protective effect.