Increased oxygen consumption after cardiac surgery is associated with the inflammatory response to endotoxemia

Objective The aim of this study was to determine whether the increase in post-operative oxygen consumption (VO₂) in cardiac surgery patients in related to endotoxemia and subsequent cytokine release and whether VO₂ can be used as a parameter of post-perfusion syndrome.Design Prospective study.Setting Operating room and intensive care unit of a university hospital.Patients Twenty-one consecutive male patients undergoing elective coronary artery bypass surgery without major organ dysfunction and not receiving corticosteroids.Measurements and results Plasma levels of endotoxin, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were measured before, during and for 18 h after cardiac surgery. Oxygen consumption, haemodynamics, the use of IV fluids and dopamine, body temperature and the time of extubation were also measured. Measurements from patients with high VO₂ (median value of the entire group) were compared with measurements from patients with low VO₂ (2 had higher levels of circulating endotoxin (P=0.004), TNF (P=0.04) and IL-6 (P=0.009) received more IV fluids and dopamine while in the ICU, and were extubated later than patients with low VO₂. Several hours after VO₂ the patient's body temperature rose, Forward stepwise regression analysis showed that circulating endotoxin and TNF explained 50% of the variability of VO₂.Conclusions This study demonstrates that patients with high post operative oxygen comsumption after elective cardiac surgery have higher circulating levels of endotoxin, TNF and IL-6 and also have more symptoms of post-perfusion syndrome. Early detection of high VO₂ might be used as a clinical signal to improve circulation in order to meet the high oxygen demand of inflammation. In addition, continuous measurement of VO₂ provides us with a clinical parameter of inflammation in interventional studies aiming at a reduction of endotoxemia or circulating cytokines.Part of this study was supported financially by Jaussen Pharmaceutica B.V. (Tilburg, The Netherlands)     

Myocardial oxygen consumption during dobutamine infusion in endotoxemic pigs

PURPOSE: Dobutamine infusion is used to increase whole-body oxygen delivery in septic patients to satisfy unmet oxygen demand of hypoxic tissues. However, dobutamine infusion also increases myocardial work and myocardial oxygen consumption. Our goal was to determine the importance of this effect as a fraction of the increase in whole-body oxygen consumption, in a porcine model of septic shock. MATERIALS AND METHODS: Four hours after a 50 microg/kg infusion of Escherichia coli endotoxin (0111: B4, Sigma) in eight anesthetized pigs, whole-body oxygen delivery and myocardial oxygen delivery and consumption were calculated from blood flow and arterial and venous oxygen content measurements. We directly measured whole-body oxygen consumption by analysis of inhaled and exhaled gases using a metabolic cart. Then dobutamine 10 and 20 microg/kg/min was infused and measurements were repeated. RESULTS: Dobutamine infusion increased whole-body oxygen delivery but did not increase metabolic cart measured whole-body oxygen consumption. Dobutamine infusion of 10 and 20 microg/kg/min increased myocardial oxygen consumption by 7.0 +/- 0.6 (80 +/-10%) and 12.0 +/- 2.0 mL O2/min (142 +/- 30%), respectively (P < .01). CONCLUSIONS: In this porcine model of sepsis, dobutamine infusion significantly increases myocardial oxygen consumption. Because whole-body oxygen consumption does not change, dobutamine infusion may fail to increase and may decrease oxygen consumption by other organs.     

Effects of dobutamine on oxygen transport and consumption in the adult respiratory distress syndrome

Objective To determine if oxygen consumption (VO₂) in patients with adult respiratory distress syndrome (ARDS) is dependent on, and thus limited by, oxygen transport (TO₂) rather than O₂ demand.Design Prospective study.Setting Intensive care unit of a tertiary referral center.Patients 12 patients with ARDS and sepsis syndrome.Interventions Routine intensive care unit monitoring including pulmonary and radial artery catheters.Measurements Dobutamine was used to increase cardiac output, thereby directly varying TO₂ under conditions of constant O₂ demand. After baseine measurements of TO₂ and VO₂, dobutamine was infused intravenously at progressively increasing doses of 5, 10, 15 and 20 g/kg/min and measurements of TO₂ and VO₂ were repreated after 30 min at each dose.Results Dobutamine increased TO₂ in 8 of the 12 patients, by 29% at 5 g/kg/min and by 45% (net) at 10 g/kg/min, but not at higher doses. In these 8 patients dobutamine also increased VO₂ by 15% at 5 g/kg/min, but did not further increase VO₂ at higher doses. There was no correlation between baseline blood lactate concentration and the response of either TO₂ or VO₂ to dobutamine.Conclusions In some but not all patients with ARDS and sepsis syndrome, short-term infusion of low-dose dobutatmine can increase both TO₂ and VO₂. Achievement of a TO₂-independent level of VO₂ could not be convincingly demonstrated in any individual patient. The response of TO₂ and VO₂ to dobutamine could not be predicted from baseline blood lactate concentration. Determination of the impact on patient outcome of a more prolonged infusion of dobutamine requires further study.     

Increased systemic oxygen consumption offsets improved oxygen delivery during dobutamine infusion in newborn lambs

OBJECTIVE: To determine: 1) if dobutamine elicited a thermogenic response during postnatal development; and 2) if this response impacted on the balance between systemic O(2) delivery (DO(2)) and O(2) consumption (VO(2)), and involved one or a combination of adrenoceptor subtypes. DESIGN: Prospective non-randomized unblinded study. SETTING: University research laboratory. Subjects: Thirty-five Border-Leicester cross lambs used in a main study performed at 1-2 days (n=7), 7-10 days (n=7), and 6-8 weeks (n=8), and in a adrenoceptor blockade substudy performed at 1-2 days (n=13). INTERVENTIONS: Lambs were instrumented under anaesthesia and dobutamine was infused at incremental rates of 1-40 microg/kg per minute. In separate subgroups of 1-2 day-old lambs, dobutamine was infused after selective or combined alpha1, beta 1, and beta 2-adrenoceptor blockade. MEASUREMENTS: Cardiac output, aortic and pulmonary arterial blood gases, and body temperature were measured. DO(2) and VO(2) were calculated. MAIN RESULTS: Dobutamine increased DO(2) similarly at all three ages. Dobutamine also increased VO(2) in the absence of muscle shivering, but the average rise in 1-2 day-old lambs was sevenfold to 12-fold greater (P<0.001) than in 7-10 day-old and 6-8 week-old animals, was associated with an increase in systemic O(2) extraction, and accounted for approximately 90% of the rise in DO(2). Body temperature rose by 1.3+/-0.5 degrees C in 1-2 day-old animals (P<0.001), but was unchanged in 7-10 day-old or 6-8 week-old lambs. In 1-2 day-old lambs, rises in DO(2), VO(2), and body temperature induced by dobutamine were not affected by selective alpha1, beta1 or beta2 adrenoceptor blockade, but were markedly attenuated by combined adrenoceptor blockade. CONCLUSIONS: A substantial rise in VO(2) which accompanied a pronounced thermogenic effect of dobutamine in newborn lambs utilized most of the associated increase in DO(2) and appeared to be dependent on activation of multiple adrenoceptor subtypes.     

The relationship between oxygen delivery and oxygen consumption during fluid resuscitation of burn-related shock

Although burn-related shock resuscitation based on invasive hemodynamic monitoring has been reported at an increased rate, little is known about appropriate hemodynamic end points. Shock resuscitation based on oxygen transport criteria has been widely used for patients with trauma and patients who undergo surgery, and supranormal values of oxygen delivery (DO2) have been reported in association with an improved survival rate. This improved survival rate has been attributed to a shifting of the critical threshold of DO2 to higher values in these patients. In patients with thermal injuries, the effects of the manipulation of hemodynamics to optimize oxygen transport have not been proven. It is still unclear whether these patients exhibit delivery-dependent oxygen consumption (VO2) during the shock phase. The goal of this study was to evaluate the existence of oxygen supply dependency and to determine critical levels of DO2 in patients with burns. In a prospective study that included 16 patients with serious thermal injuries, we studied the effects of volume loading on DO2 and VO2. A transpulmonary double dilution technique was used for hemodynamic monitoring, and resuscitation end points included a normalization of preload and cardiac output parameters within 24 hours of the thermal injury. Fluid loading with crystalloids and colloids, according to our resuscitation protocol, was used to augment cardiac output and DO2. Of the 16 patients with a mean of 46% total body surface area burned (range, 22%-80%), 8 patients survived and 8 patients died. With the use of progressive fluid loading, cardiac index was restored within 24 hours of admission in all of the patients. Successful resuscitation was associated with increased levels of DO2 and VO2 and with declining serum lactate levels. VO2 appeared to be dependent on DO2 during the resuscitation period (r = 0.596), and the correlation was significantly stronger in the patients who survived (r = 0.744) than in the patients who died (r = 0.368; P < .05). A critical threshold of oxygen supply could not be identified. We concluded that increasing DO2 by fluid resuscitation increases VO2 during hypovolemic shock after a severe burn injury.     

The relationship between oxygen delivery and consumption in the conscious rat before and after expansion of body fluid volumes

Oxygen consumption and delivery (defined as the product of cardiac output, haemoglobin concentration and arterial oxygen saturation) and haemodynamic variables were examined in the conscious resting rat throughout the day and after the expansion of body fluid volumes. Cardiac output was measured in arbitrary units by electromagnetic flowmetry and oxygen consumption by respirometry. The variability of blood pressure in the basal state was significantly less than that of cardiac output. Oxygen consumption was significantly correlated with cardiac output and oxygen delivery. In studies undertaken throughout the day, both oxygen consumption and delivery fell in the afternoon and there was evidence that the relationship between these two variables was curvi- rather than recti-linear. During oral sodium chloride administration for 7 days, blood pressure rose and some evidence was found for an alteration in the relationship between oxygen consumption and delivery, with an excess of delivery relative to consumption, particularly on the first day of salt loading. Intravenous injection of sodium chloride solution (0.171 mol/l) did not alter the relationship between oxygen consumption and delivery. Expansion of blood volume, while the packed cell volume was maintained nearly constant, raised oxygen delivery transiently and evidence was obtained that the relationship between oxygen consumption and delivery was altered, with oxygen delivery rising relatively more than oxygen consumption. The findings are discussed in relation to the autoregulatory hypothesis of circulatory control and for the role of autoregulation in hypertensive states. The importance of relating oxygen delivery to metabolic requirements in studies of the role of autoregulation is emphasized.     

Effect of intraoperative dobutamine on splanchnic tissue perfusion and outcome after Whipple surgery

Purpose

Splanchnic hypoperfusion during abdominal surgery contributes to postoperative gut sepsis and mortality. Dobutamine is an inotrope with vasodilator properties that improve hepatosplanchnic perfusion. The aim of this study was to examine the effect of intraoperative dobutamine infusion during Whipple surgery on splanchnic perfusion, hemodynamic, and overall postoperative outcome.

Methods

Sixty patients were randomly allocated to receive intraoperatively (3 μg/kg per minute or 5 μg/kg per minute) doses of dobutamine or saline. Baseline measurements included hemodynamic parameters, gastric tonometric parameters, and arterial and mixed venous gases. These patients had a follow-up for development for in-hospital morbidity and mortality.

Results

Intraoperative use of dobutamine increased oxygen-derived parameters as evidenced by increased mixed venous oxygen saturation. Tonometered gastric mucosal pH, a surrogate for splanchnic perfusion, increased in patients who received intraoperative dobutamine. Patients in the dobutamine groups demonstrated significant higher heart rates, premature ventricular contraction arrhythmias, and electrocardiographic signs of ischemia. Mean arterial blood pressure demonstrated no significant difference among groups. The overall incidence of postoperative complications was higher in control group 70 % vs 20% to 40% in dobutamine groups.

Conclusion

Intraoperative use of dobutamine improved global oxygen delivery, splanchnic perfusion, and postoperative outcome after Whipple surgery. These findings may be of clinical importance when the therapeutic goal is to improve gut perfusion.     

多巴胺多巴酚丁胺治疗毛细支气管炎的疗效观察

目的　了解多巴胺、多巴酚丁胺治疗毛细支气管炎的疗效。方法　将 62例患毛细支气管炎的病儿随机分成两组 ,观察组 3 2例 ,对照组 3 0例 ,观察组在常规治疗的基础上加用多巴胺、多巴酚丁胺注射液 0 .6～ 1mg/kg加入 5 %葡萄糖注射液 3 0ml静滴 ,每日 1次 ,每 1疗程 5天。结果　两组疗效经统计学处理 ,总有效率 χ2 =5 .98,P <0 .0 5 ,治疗组效果明显优于对照组。结论　多巴胺、多巴酚丁胺治疗毛细支气管炎临床效果显著 ,值得推广。     

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.     

热休克蛋白27对内毒素血症所致心功能不全的保护作用

目的 探讨心肌特异性高表达热休克蛋白27(Hsp27)对内毒素血症所致心功能不全的影响,并初步探讨其机制.方法 所有实验均在南京医科大学第一附属医院老年医学科研究室和南京大学模式动物研究所完成.(1)心肌特异性高表达Hsp27转基因鼠(Hsp27Tg)基因型和表达鉴定:分别采用PCR法和western blot法;(2)心功能测定:HspZ7 Tg和野生型(WT)对照鼠均被腹腔注射内毒素(LPS,10 mg/kg),24 h后以超声心动图测定心功能,n=6/组;(3)死亡率:Hsp27Tg和WT鼠腹腔注射内毒素(LPS,20 mg/kg),密切监测70 h内的累积死亡率,n=37/WT,n=27/Hsp27Tg;(4)NF-kB活性测定:心肌组织样本采用凝胶迁移电泳法,细胞样本采用双报告基因法,n=4/组;(5)多组间的两两比较采用ANOVA和Seheffe检验,生存曲线分析采用log-rank检验,P＜0.05设为相差显著性界值.结果 (1)Hsp27 Tg小鼠心肌有丰富的Hsp27表达,WT则没有;(2)LPS使WT和Hsp27 Tg鼠心功能均显著下降,但与WT比较,Hsp27 Tg的心功能显著改善(P＜0.01或P＜0.05),其中EF增加27.3%.FS增加37.1%;(3)至LPS注射后70 h,WT和Hsp27Tg小鼠死亡率分别为37.84%和11.11%,与WT鼠比较,Hsp27TG生存率显著提高(P＜0.05);(4)Hsp27显著抑制LPS诱导的NF-kB激活(P＜0.01或P＜0.05).结论 Hsp27心肌特异性高表达显著抑制内毒素血症所致的心功能不全,改善生存率,其机制可能与Hsp27下调LPS诱导的NF-kB激活有关.     

Effect of increasing oxygen delivery postburn on oxygen consumption and oxidant-induced lipid peroxidation in the adult sheep

We studied the relationship between oxygen delivery (DO2) and oxygen consumption (VO2) in the early post-burn period. Unanesthetized sheep with a 15% total body surface (TBS) third-degree burn were resuscitated back to baseline VO2 and vascular pressures. DO2 was adjusted further by infusion and removal of whole blood. The response was compared to the same maneuver in nonburned sheep. We found that increasing DO2 after burns resulted in a 32% increase in VO2, while the same maneuver in controls produced no change in VO2. We then determined whether the increase in VO2, caused by volume loading, resulted in a further increase in postburn oxidant release and lipid peroxidation measured as conjugated dienes. Plasma conjugated dienes increased significantly and equally by 30% in burns maintained at baseline VO2 vs. the increased VO2. Therefore, the increased oxygen used is not simply resulting in further oxidant damage. VO2 was maintained equally in both burned animals and controls with a decrease in DO2 by increased oxygen extraction from Hgb. We conclude that standard burn resuscitation does not restore adequate DO2 for oxygen demands. The 30% increase in VO2 achieved by increasing DO2 does not lead to a further release of oxidants from burn tissue and is therefore potentially beneficial for cell function.     

Effect of sequential early burn wound excision and closure on postburn oxygen consumption

OBJECTIVE: To determine the effect of early excision and closure of burns on postburn hypermetabolism, measured as oxygen consumption (VO2). METHODS: Twelve patients with deep burns of 30% to 50% of total body surface underwent sequential excisions and wound coverage, beginning 1 to 3 days after burn. The majority of the deep burn was removed by day 7, but with the addition of a donor site area of 20% to 25% of total body surface. RESULTS: No decrease in VO2 was noted in relation to the percent removal of burn tissue. In addition, a transient further increase in VO2 was noted early after excision, especially with surgical procedures performed after 5 days. This response could not be attributed to wound manipulation-induced bacteremias. CONCLUSION: We conclude that early surgical excision and closure of burns in excess of 30% to 50% of total body surface do not decrease postburn hypermetabolism in proportion to the area closed. It is possible that remaining open wounds in the form of donor sites and nonexcised burn are sufficient to perpetuate the hypermetabolic process, once established.     

Effect of tetracyclines and UV light on oxygen consumption by human leukocytes.

When polymorphonuclear leukocytes were stimulated with zymosan, a sharp rise in oxygen consumption was observed. In the presence of doxycycline, we observed a further increase in oxygen consumption when the phagocytosing cells were exposed to UV light. When the light was turned off, oxygen consumption of the cells almost ceased, indicating photodamage to polymorphonuclear leukocytes during irradiation. Irradiation of the polymorphonuclear leukocytes for 20 min in the presence of doxycycline (10 micrograms/ml) before phagocytosis completely abolished the rise in oxygen consumption initiated by zymosan. Demethylchlortetracycline and light exposure also caused a marked reduction of polymorphonuclear leukocyte oxygen consumption, whereas oxytetracycline, lymecycline, chlortetracycline, and minocycline had only a slight or no photosensitizing effect. The photodamage induced by doxycycline and demethylchlortetracycline was inhibited by azide and enhanced in deuterium oxide. This was in accordance with singlet oxygen-mediated damage.     

容量复苏对早期严重创伤性休克患者血流动力学和氧输送的影响

目的 探讨大容量复苏对早期严重创伤性休克患者血流动力学和氧输送的影响.方法 监测24例严重腹部创伤患者不同容量复苏时的血流动力学和氧代谢指标.结果 容量复苏收缩压从80～90mm Hg(1 mm Hg=0.133 kPa)上升到100～120 mm Hg时,平均复苏容量分别为(2286±521)ml(1 h)和(3486±758)ml(2 h).心脏指数(CI)从(2.0±0.5)L/(min·m2)上升为(3.2±0.6)L/(min·m2)(P<0.05),体循环阻力指数(SVRI)从(1857.6±750.2)dyn·s/(cm5·m2)上升为(3741.5±862.1)dyn·s/(cm5·m2)(P<0.05),与之相对应,氧输送指数(DO2)从(301.1±74.1)ml/(min·m2)升为(554.1±80.0)ml/(min·m2)(P<0.05),氧耗指数(VO2)为(99.7±51.4)ml/(min·m2)升为(147.2±60.1)mL/(min·m2)(P<0.05),氧摄取指数(O2ext)为(33.1±9.1)%下降至(26.6±8.0)%(P<0.05).结论 在急诊抢救中,早期大容量复苏能改善血流动力学和氧代谢.     

Effect of carbon dioxide on systemic oxygenation, oxygen consumption, and blood lactate levels after bidirectional superior cavopulmonary anastomosis

OBJECTIVE: We sought to assess the effects of four different CO2 tensions on systemic oxygenation, oxygen consumption, and arterial blood lactate levels early after bidirectional superior cavopulmonary anastomosis. DESIGN: Prospective study. SETTING: Quaternary pediatric cardiac critical care unit. PATIENTS: Nine children aged 2-23 months (median, 7 months). INTERVENTIONS: All patients were sedated, muscle relaxed, and mechanically ventilated. Baseline Paco2 was adjusted to 35 mm Hg by changing tidal volume. CO2 was added via the inlet port of the ventilator to maintain the Paco2 at 45 and 55 mm Hg. Measurements were repeated after discontinuing additional CO2 gas at a Paco2 of 40 mm Hg. Arterial blood gases and lactate were measured at each level of Paco2. We measured oxygen consumption continuously by respiratory mass spectrometry. MEASUREMENTS AND MAIN RESULTS: Mean (95% confidence interval) Paco2 increased from 35 (34-36) to 45 (44-46) to 55 (54-56) mm Hg (4.7 [4.5-4.9] to 6 [5.7-6.3] to 7.3 [7.2-7.4] kPa), arterial pH decreased from 7.43 (7.39-7.47) to 7.35 (7.31-7.39) to 7.28 (7.24-7.32). Pao2 increased from 36 (32-40) to 44 (40-48) to 50 (45-55) mm Hg (4.8 [4.3-5.3] to 5.9 [5.4-6.4] to 6.7 [6.2-7.2] kPa), and oxygen saturation increased from 72% (67-79%) to 77% (73-81%) to 80% (76-84%). Oxygen consumption decreased significantly, with each increase in Paco2, from 146 (125-167) to 132 (112-152) to 126 (107-145) mL.min.m (p = .0001), and lactate decreased from 1.5 (1-2.0) to 1.2 (0.8-1.6) to 0.8 (0.5-1.1) mmol/L (p < .01). These changes returned toward baseline at a Paco2 of 40 mm Hg. CONCLUSIONS: Moderate hypercapnia with respiratory acidosis improved arterial oxygenation and reduced oxygen consumption and arterial lactate levels, thus improving overall oxygen transport in children after bidirectional superior cavopulmonary anastomosis.     

Effects of diltiazem on oxygen delivery and consumption after asphyxial cardiac arrest and resuscitation.

BACKGROUND AND METHODS: Calcium-channel blockers may attenuate vasospasm after transient ischemia and improve organ blood flow after resuscitation. Our aim was to assess the effect of diltiazem on systemic oxygen delivery and consumption, hemodynamics, electroencephalogram (EEG), and organ blood flow after restoration of spontaneous circulation. After a 3-min period of asphyxial cardiac arrest, 14 pigs (20 to 27 kg) were randomly allocated to treatment with either diltiazem (0.1 mg/kg bolus followed by an iv infusion of 0.025 mg/min/kg over 120 mins) or placebo, given at 5 mins after successful resuscitation. Organ blood flow was measured using tracer microspheres 120 mins after resumption of spontaneous circulation. RESULTS: Median systemic oxygen delivery index values at 30, 60, and 120 mins after restoration of spontaneous circulation were 18.2 mL/min/kg (range 14.8 to 20.7), 16.8 mL/min/kg (13.2 to 20.8), and 19.6 mL/min/kg (16.9 to 21.0), respectively, in the diltiazem group and 13.1 mL/min/kg (11.2 to 14.6), 11.9 mL/min/kg (10.3 to 13.3), and 14.7 mL/min/kg (11.4 to 17.2), respectively, in the control group (p less than .05 for all three comparisons). At the same points in time, median systemic oxygen consumption indices were 3.2 mL/min/kg (range 2.2 to 3.7), 2.1 mL/min/kg (1.9 to 3.0), and 2.6 mL/min/kg (1.8 to 3.8) in the diltiazem group and 2.8 mL/min/kg (2.1 to 4.0), 2.7 mL/min/kg (1.7 to 4.3), and 2.3 mL/min/kg (1.6 to 3.8) in the placebo group (NS). Diltiazem enhanced the postarrest recovery of EEG total power. Right and left cerebral blood flow 120 mins after restoration of spontaneous circulation was significantly (p less than .01) higher in the diltiazem group in comparison with the control group. CONCLUSIONS: Diltiazem causes an increase in systemic oxygen delivery index by promoting vasodilation, but it does not change systemic oxygen consumption index in comparison to placebo treatment. It may be that an impairment in local autoregulation and/or in oxidative metabolism at the cellular or subcellular level was the reason why diltiazem did not improve these derangements. The observed increase in cerebral blood flow and in EEG recovery may be beneficial to the brain after a period of asphyxia.     

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.     

Effect of vasoactive agents on intestinal oxygen consumption and blood flow in dogs.

A comparison study of several vasoconstrictor and vasodilator agents was conducted measuring changes in intestinal blood flow and oxygen consumption during 10-min periods of intra-arterial infusion. Blood flow was measured in a branch of the superior mesenteric artery of anesthetized dogs with an electromagnetic blood flow meter, and the arteriovenous oxygen content difference across the gut segment was determined photometrically. Vasopressin (4 x 10(-3) and 7x 10(-4) U/kg-min) diminished blood flow 60 and 28% and reduced oxygen consumption 54 and 22%, respectively (all P less than 0.001). In a dose which did not lower blood flow, vasopressin still caused a decline in oxygen consumption (P less than 0.01). Epinephrine (5 x 10(-2) mug/kg-min) decreased blood flow 19% (P less than 0.001) but did not reduce oxygen consumption. After beta-adrenergic blockade, however, the same dose of epinephrine decreased blood flow 41% and oxygen consumption 33% (both P less than 0.001). Responses to angiotension II, calcium chloride, and prostaglandin F2alpha resembled effects of vasopressin rather than those of epinephrine, namely decreased blood flow and decreased oxygen consumption. The vasodilator agents, prostaglandin E1, is isoproterenol, and histamine, increased (P less than 0.001) both blood flow (130, 80, and 98%, respectively) and oxygen consumption (98, 64, and 70%, respectively). Vasopressin, angiotensin II, calcium chloride, and prostaglandin F2alpha appear to contract arteriolar and precapillary sphincteric smooth muscle indiscriminately to evoke both intestinal ischemia and hypoxia. Epinephrine is the exceptional constrictor in this case, producing diminished blood flow without a reduction in oxygen uptake.