Systemic and muscle oxygen uptake/delivery after dopexamine infusion in endotoxic dogs.

BACKGROUND AND METHODS: This study was designed to test whether dopexamine, a dopaminergic and beta 2-adrenergic agonist, would a) increase systemic oxygen delivery (DO2) in endotoxic dogs, and b) interfere with the ability of resting skeletal muscle to extract oxygen. There were three treatment groups (n = 6 in each group): control, endotoxin alone (E) 4 mg/kg iv, and endotoxin + dopexamine (E + D) 12 micrograms/kg.min. Data were analyzed between and within groups by split-plot analysis of variance with significance of identified differences tested post hoc by Duncan's multiple range test. Donor RBC and dextran were used after endotoxin to maintain adequate perfusion pressures, with Hct kept near 40%. Blood flow to left hindlimb muscles was decreased in controlled steps of 15 min each after stabilization. RESULTS: In E group, cardiac output (Qt), mean arterial pressure (MAP), systemic DO2, and oxygen uptake (VO2) decreased despite blood volume expansion. In E + D group with similar volume expansion, dopexamine maintained Qt, systemic DO2, and VO2 near the control levels, although MAP and systemic vascular resistance were reduced. In comparison with control subjects, endotoxin increased critical DO2 in the isolated limb muscles from 4.6 to 7. mL/kg.min and decreased critical oxygen extraction from 81% to 68%. The pressure/flow relationship in the limb became flattened, indicating loss of vascular reactivity. In the E + D group, there was no further change in the pressure/flow curve nor in the critical oxygen extraction level. CONCLUSIONS: Dopexamine provided hemodynamic support for endotoxic dogs, thereby increasing total DO2 and VO2, while not altering oxygen extraction in the muscle.     

Systemic oxygen delivery and consumption during acute lung injury in dogs

When oxygen delivery (QO₂ = Qt × CaO₂) is reduced in healthy animals, oxygen uptake by tissues (VO₂) is maintained by an increase in the O₂ extraction ratio ((CaO₂ − CvO₂)/CaO₂) until a critical level of delivery QO₂C is reached, below which VO₂ becomes dependent on QO₂. In patients with adult respiratory distress syndrome (ARDS), VO₂ becomes dependent on O₂ delivery even at high levels of QO₂ implying a systemic O₂ extraction defect. To determine whether lung injury, or its management with positive end-expiratory pressure (PEEP) and high inspired oxygen fractions (F1O₂), might disrupt O₂ extraction by peripheral tissues, we compared the critical O₂ delivery and extraction ratio in 30 anesthetized and paralyzed dogs in four groups. One group (n = 7) received oleic acid to produce an acute lung injury (F_lO₂ = 1.0) and a second group (n = 7) was maintained with PEEP (F_lO₂ = 1.0) after receiving oleic acid. A third group (n = 8) received no oleic acid (F_lO₂ = 1.0), and a fourth group received no oleic acid and was ventilated with room air. The critical O₂ delivery was determined in each animal as QO₂ was lowered in a stepwise manner by controlled blood removal. Neither the critical QO₂ nor critical O₂ extraction ratios were different (P> .05) among oleic acid, PEEP-treated, or hyperoxic control animals. Similarly, the critical QO₂ determined from the point at which arterial lactate began to increase showed no difference among groups. Thus, neither acute lung injury produced with oleic acid nor its treatment with PEEP was associated with a peripheral O₂ extraction defect. However, a linear regression across all groups demonstrated a positive correlation between the arterial PO₂ and corresponding critical O₂ delivery (r = < P < .05). These results suggest that high arterial O₂ tensions may contribute to an impairment of peripheral O₂ extraction.     

己酮可可碱对内毒素休克犬的影响

目的 :研究己酮可可碱 (PTX)在内毒素休克时所起的作用。方法 :选用成年杂种犬 12只 ,随机分成 2组 ,第一组 (n =6 )按 2 5 0 μg/kg持续静注内毒素 30min ,第二组 (n =6 )除用同样的方法静注内毒素外 ,在静注内毒素前按 2 0mg/kg静推PTX后按 2 0mg·kg- 1 ·h- 1 持续静注PTX。两组动物从开始到结束持续静注生理盐水维持CVP及PCWP在基础水平。每隔半小时测量一次MAP、MPAP、CVP、PCWP、HR、CO、肠系膜上动脉的血流量。并于 0′、 90′、 180′、 2 40′作动脉血、肺动脉血、肠系膜上静脉血血气分析 ,计算CI,SVI,SVRI,PVRI和DO2 ,VO2 ,O2 ER等。结果 :两组实验动物均产生休克 ,平均动脉压下降 30 %以上。与对照组相比 ,PTX能进一步降低内毒素休克犬的外周血管阻力 ,并使心脏指数及肠系膜上动脉的血流量增加。增加全身及肠系膜上动脉所供胃肠组织的氧输送 (P <0 0 5 )。结论 :己酮可可碱可显著改善内毒素休克犬的血液动力学及缺血脏器的血供、氧供。对感染性休克治疗有益。     

犬心跳骤停复苏后脑和全身氧供需关系的观察

目的　观察和比较犬心跳骤停 (CA)复苏后脑和全身氧利用率 (O2 UC)的变化。方法　 5只犬采用经胸壁电击致室颤 /心跳骤停 (VF/CA) 8min ,开胸心肺复苏 (OCCPR)恢复自主循环 (RSC)后同时观察 4h内脑和全身O2 UC的变化。结果　 5只犬均CPR成功后维持稳定的血流动力学状态 ,仅RSC后 12 0min心输出量 (CO)较CA前明显降低 (2 1± 0 .8L/minvs 3 4± 1 4L/min ,P <0 0 5 )。RSC后 30min脑O2 UC即显著高于CA前 (0 5 7± 0 11vs 0 43± 0 0 8,P <0 0 5 ) ,RSC后 6 0、12 0和 2 40min时脑O2 UC则渐进性升高 ,且非常显著高于CA前 (0 6 5± 0 0 9、0 72± 0 0 9和 0 78± 0 0 6vs 0 43± 0 0 8,P均 <0 0 1) ;而直至RSC后 12 0min全身O2 UC才显著高于CA前 (0 36± 0 10vs 0 2 0± 0 0 5 ,P <0 0 5 )。结论　CA经OCCPR后脑和全身均发生氧供相对于氧需的不足 ,而且脑氧供需失衡的发生较全身更早、更严重 ,提示CPR后应力求尽早改善脑氧输送 ,同时脑氧代谢的监测可为脑复苏提供有力的指导     

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.     

浅麻醉下犬脑组织对异丙酚的摄取及其分布

目的:研究异丙酚浅麻醉时在犬脑不同区域的摄取及分布。方法:6条成年雄犬,静脉注射异丙酚4.5mg/kg,达到有效麻醉深度后3min,取颈内动脉和颈内静脉血并断头法将犬处死,解剖犬脑,分别取额叶、顶叶、颞叶、海马、扣带回、丘脑、中脑、桥脑、小脑组织。高效液相色谱-紫外线法测定血浆浓度及组织浓度。结果:各个脑区药物浓度分布呈桥脑>中脑>丘脑>小脑>扣带回>额叶>颞叶>顶叶>海马的趋势,动脉血药浓度明显高于静脉血药浓度。结论:异丙酚浅麻醉时在犬脑不同区域分布不同,其中以脑干和丘脑最高,可能在异丙酚静脉麻醉中发挥着重要作用。     

Systemic and regional hemodynamic effects of high-dose epinephrine infusion in hypoxic piglets resuscitated with 100% oxygen

Shock and poor regional perfusion are common in asphyxiated neonates. We compared the systemic and regional hemodynamic effects of high-dose epinephrine (E) with those of dopamine combined with low-dose epinephrine (DE) infusions in a neonatal model of hypoxia-reoxygenation. Neonatal piglets (1-3 days, 1.5-2.5 kg) were acutely instrumented to continuously monitor systemic arterial pressure (SAP), pulmonary artery pressure, cardiac index (CI), and blood flows at the left common carotid, superior mesenteric, and renal arteries. Either epinephrine (1 microg.kg(-1).min(-1)) or dopamine (10 microg.kg(-1).min(-1)) and epinephrine (0.2 microg.kg(-1).min(-1)) were given for 2 h in hypoxic piglets resuscitated with 100% oxygen (n = 8 per group) in a randomized blinded fashion. Control piglets received hypoxia and reoxygenation but no catecholamine infusion (n = 7). Alveolar hypoxia (PaO2, 33-37 mmHg) caused reduced CI (89-92 vs. 171-186 mL.kg(-1).min(-1) of baseline, P < 0.05), hypotension (SAP, 28-32 mmHg) with pH 7.05 to 7.10, and decreased regional flows. Upon reoxygenation, CI and SAP improved but gradually deteriorated to 131 to 136 mL.kg(-1).min(-1) and 41 to 49 mmHg at 2 h of reoxygenation, respectively. E and DE administration similarly improved CI (167 +/- 60 and 166 +/- 55 vs. 121 +/- 35 mL.kg(-1).min(-1) of controls) and SAP (53 +/- 7 and 56 +/- 10 vs. 39 +/- 8 mmHg of controls), respectively, and the pulmonary vascular resistance (vs. controls, all P < 0.05). Heart rate and pulmonary artery pressure were not different between groups. Systemic oxygen delivery and consumption were increased in E- and DE-treated groups with no difference in extraction ratio between groups. There were no differences in regional blood flows and oxygen delivery between groups. After hyperlactatemia with hypoxia, plasma lactate levels decreased with no difference between groups. Epinephrine given as the sole agent is as effective as dopamine and low-dose epinephrine combined in treating shock and hypotension that follow the resuscitation of hypoxic neonatal piglets, with no reduction in regional perfusion.     

Correlation of transconjunctival PO2 with cerebral oxygen delivery during cardiopulmonary resuscitation in dogs

The relationship between transconjunctival PO2 (PcjO2) and cerebral oxygen delivery (DO2) was examined in dogs during sinus rhythm and CPR with an inflatable vest. Microsphere-determined cerebral blood flow (CBF), DO2, and PcjO2 readings were normal during sinus rhythm. During CPR, with carotid pressure of 82 +/- 11/25 +/- 5 (SEM) mm Hg, cerebral perfusion and DO2 fell by 53% and 57%, respectively, while PcjO2 fell by 87%. After epinephrine administration, carotid pressure increased to 128 +/- 13/48 +/- 9 mm Hg, and CBF and DO2 rose to 130% and 115% of pre-arrest levels, respectively, but PcjO2 readings remained at 11% of control values. Thus, PcjO2 failed to reflect accurately either CBF or DO2 during CPR. In the presence of epinephrine, PcjO2 does not seem to provide an accurate index of the effectiveness of CPR.     

Increased concentrations of plasma lactate predict pathologic dependence of oxygen consumption on oxygen delivery in patients with adult respiratory distress syndrome

We asked whether increasing systemic oxygen delivery by blood transfusion could identify pathologic dependence of oxygen consumption on oxygen delivery in patients who have adult respiratory distress syndrome (ARDS) with and without increased concentrations of plasma lactate. Twenty-four ARDS patients were divided into normal (n = 11, lactate ≤ 1.8 mmol/L) and increased (n = 13, lactate > 1.8 mmol/L) plasma lactate groups. After transfusion of two units of packed red blood cells, oxygen delivery index increased significantly in both the normal and increased plasma lactate groups. In the increased plasma lactate group, this was associated with a significant increase in oxygen consumption index and an unchanged oxygen extraction ratio. In contrast, in the normal plasma lactate group, oxygen consumption index did not change from the baseline value and the oxygen extraction ratio decreased significantly. We conclude that increasing systemic oxygen delivery by blood transfusion identifies pathologic dependence of oxygen consumption on oxygen delivery in patients who have ARDS and increased concentrations of plasma lactate.     

Hypertonic sodium lactate improves fluid balance and hemodynamics in porcine endotoxic shock

Introduction

Based on the potential interest in sodium lactate as an energy substrate and resuscitative fluid, we investigated the effects of hypertonic sodium lactate in a porcine endotoxic shock.

Methods

Fifteen anesthetized, mechanically ventilated pigs were challenged with intravenous infusion of E. coli endotoxin. Three groups of five animals were randomly assigned to receive 5 mL/kg/h of different fluids: a treatment group received hypertonic sodium lactate 11.2% (HSL group); an isotonic control group receiving 0.9% NaCl (NC group); a hypertonic control group with the same amount of osmoles and sodium than HSL group receiving hypertonic sodium bicarbonate 8.4% (HSB group). Hemodynamic and oxygenation variables, urine output and fluid balance were measured at baseline and at 30, 60, 120, 210 and 300 min. Skin microvascular blood flow at rest and during reactive hyperemia was obtained using a laser Doppler flowmetry technique. Results were given as median with interquartile ranges.

Results

Endotoxin infusion resulted in hypodynamic shock. At 300 min, hemodynamics and oxygenation were significantly enhanced in HSL group: mean arterial pressure (103 [81–120] mmHg vs. 49 [41–62] in NC group vs. 71 [60–78] in HSB group), cardiac index (1.6 [1.2–1.8] L/min/m² vs. 0.9 [0.5–1.1] in NC group vs. 1.3 [0.9–1.6] in HSB group) and partial pressure of oxygen (366 [308–392] mmHg vs. 166 [130–206] in NC group vs. 277 [189–303] in HSB group). At the same time, microvascular reactivity was significantly better in HSL group with a lower venoarterial CO₂ tension difference (5.5 [4–10] mmHg vs. 17 [14–25] in NC group vs. 14 [12–15] in HSB group). The cumulative fluid balance was lower in HSL group (-325 [-655; -150] mL) compared to NC (+560 [+230; +900] mL, p = 0.008) and HSB (+185 [-110; +645] mL, p = 0.03) groups.

Conclusions

In our hypodynamic model of endotoxic shock, infusion of hypertonic sodium lactate improves hemodynamic and microvascular reactivity with a negative fluid balance and a better oxygenation.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0467-3) contains supplementary material, which is available to authorized users.     

Evaluation of oxygen uptake and delivery in critically ill patients: A statistical reappraisal

Objective The evaluation of oxygen consumption (VO₂) and oxygen delivery (DO₂) has gained increasing importance in the monitoring of critically ill patients. They can be obtained from either direct measurements or by indirect calculations based on the Fick principle. However the choice between these two approaches remains controversial. The aim of the study was to investigate whether these 2 methods provide similar results, and if not, to define the best one in terms of reproducibility. Design Oxygen delivery and oxygen consumption were prospectively analyzed in 171 consecutive critically ill patients. Metabolic data were obtained simultaneously. Setting The study was completed in the intensive care unit as part of the management of the patients studied. Patients A first “group” of 279 evaluations was carried out in 73 consecutive critically ill patients. The results were subsequently validated by 423 observations performed in the 98 following patients. Interventions Before and during each evaluation, the patients were kept in stable hemodynamic and metabolic conditions. All were mechanically ventilated. Measurements and results VO₂ was evaluated by calculation (Fick principle) and direct measurement using indirect calorimetry. Cardiac output was both measured by the thermodilution technique and calculated (Fick principle) and the data were used for the evaluation of the directly measured and indirectly calculated DO₂. For both VO₂ and DO₂ the agreement between direct and indirect evaluations was not satisfactory. Differences as great as 55 ml/min·m² and 267 ml/min·m² between simultaneously measured and calculated VO₂ and DO₂ respectively may be expected. Finally, the indirect calculated methods were less reproducible than the measured ones. These observations resulted mainly from the cumulative effects of the random errors in the metabolic data entering into the calculation of VO₂ and DO₂. Conclusions Our data suggested that the indirect calculation (Fick equation) and the direct measurement (indirect calorimetry, thermodilution) of both VO₂ and DO₂ did not provide similar results. Direct measurements are more reproducible methods and must be preferred.     

Hemodynamic effects of continuous norepinephrine infusion in dogs with and without hyperkinetic endotoxic shock

We compared, at constant preload maintained by polygeline (gelatin) infusion, the hemodynamic effects of continuous infusion of norepinephrine (0.5, 1, and 1.5 micrograms/kg X min) in anesthetized dogs with and without hyperdynamic endotoxic shock. In both groups, norepinephrine infusion increased systolic, diastolic and mean aortic BP, cardiac index, stroke index, index of myocardial contractility, and mean pulmonary artery pressure. No significant change in right atrial pressure, left ventricular end-diastolic pressure, heart rate, systemic vascular resistance, or pulmonary vascular resistance was observed. Oxygen consumption index and oxygen extraction ratio remained unchanged. Increases in systolic aortic BP were dose-related, whereas maximal effects on other variables were obtained at 0.5 to 1 microgram/kg X min. The rise in aortic pressure resulted from an increased cardiac index but not from an increased systemic vascular resistance. Stroke index increased as contractility improved. The slight alpha-adrenergic effect of continuous, low-dose norepinephrine infusion did not impede the beneficial effects of the marked beta-adrenergic stimulation on cardiac function. The combination of these two effects improved hemodynamic disturbances of hyperdynamic endotoxic canine shock.     

Scaling of lactate threshold by peak oxygen uptake and by fat-free mass 0 x 67

The lactate threshold (LT) represents the onset of metabolic acidosis during cardiopulmonary exercise testing (CPET). It is measured as a O(2) in the units of ml min(-1). In order to make comparisons among subjects, LT is often scaled or normalized by O(2) peak resulting in the LT/O(2) peak ratio. Ratio variables have underlying assumptions. One assumption is that the relationship between the numerator and denominator is linear with a zero y-intercept. If the relationship has a positive y-intercept, then the ratio will decrease with increasing values of the scaling variable thereby penalizing subjects with larger values of the scaling variable. Our purpose was to examine the validity of scaling LT by O(2) peak and by fat-free mass raised to 0 x 67 power (FFM(0 x 67)) as dimensional analysis predicts that LT is proportional to FFM(0 x 67). Cycle ergometer CPET was administered to 204 healthy, sedentary subjects (103 males) to the limit of tolerance. Lactate threshold was estimated noninvasively using the V-slope technique. Fat-free mass was assessed by skinfolds. The relationship of LT versus O(2) peak was linear with a positive y-intercept for both sexes. Consequently, the LT/O(2) peak ratio decreased as O(2) peak increased for both sexes. The relationship of LT versus FFM(0 x 67)was linear with a zero y-intercept for both sexes. Consequently, the plot of the LT/FFM(0 x 67) ratio versus FFM resulted in a straight line with a slope of zero for both sexes. The results of this study support the conclusion that FFM(0 x 67), but not O(2) peak, is a valid scaling variable for LT.     

Comparison of systemic and regional effects of dobutamine and dopexamine in norepinephrine-treated septic shock

Objectives: To compare the effects of dobutamine and dopexamine on systemic hemodynamics, lactate metabolism, renal function and the intramucosal-arterial PCO₂ gap in norepinephrine-treated septic shock. Design: A prospective, interventional, randomized clinical trial. Setting: Adult medical/surgical intensive care unit in a university hospital. Patients: After volume resuscitation, 24 patients were treated with norepinephrine alone titrated to obtain a mean arterial pressure of 75 mmHg and a cardiac index greater than 3.5 l/min^-1· m^-2. Interventions: Patients were randomized to receive an infusion of dobutamine (n = 12) (5 μg/kg per min) or dopexamine (n = 12) (1 μg/kg per min). Measurements and main results: Baseline measurements included: hemodynamic parameters, renal parameters (diuresis, creatinine clearance and urinary sodium excretion), gastric mucosal-arterial PCO₂ gap, arterial and mixed venous gases and arterial lactate and pyruvate levels. These measurements were repeated after 1 (H₁), 4 (H₄) and 24 (H₂₄) h. No difference was found between dobutamine and dopexamine among H₀ and H₁, H₄ and H₂₄ values for hemodynamics. Dobutamine and dopexamine at low doses had no significant effect on mean arterial pressure, heart rate, cardiac index, oxygen delivery, oxygen consumption and pulmonary artery occlusion pressure. No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia. After 4 and 24 h lactate concentration decreased in the dobutamine group from 2.4 ± 1 mmol/l to 1.7 ± 0.7 mmol/l and 1.5 ± 0.4 mmol/l, respectively, while it increased in the dopexamine group from 2.3 ± 1 mmol/l to 2.7 ± 1 mmol/l after 4 h and returned to baseline values after 24 h (2.2 ± 0.6). After 24 h the lactate/pyruvate ratio decreased in the dobutamine group from 15 ± 5 to 12 ± 3 (p < 0.05) while it was unchanged in the dopexamine group (from 16 ± 6 to 17 ± 4). Arterial pH increased in the dobutamine group from 7.35 ± 0.05 to 7.38 ± 0.07 (p < 0.05) while it was unchanged in the dopexamine group (from 7.34 ± 0.01 to 7.35 ± 0.10). The PCO₂ gap decreased after 1 and 4 h in both the dobutamine and dopexamine groups (p < 0.05 with respect to baseline). When looking at individual responses, however, patients from both groups exhibited an increased gastric PCO₂ gap. No difference was found between dobutamine and dopexamine for renal parameters. Conclusions: In norepinephrine-treated septic shock, low doses of neither dobutamine nor dopexamine caused significant effects on systemic hemodynamics and renal function and both dobutamine and dopexamine inconsistently improved the PCO₂ gap. The present results support the need for individual measurement of the effects of catecholamine on the PCO₂ gap. Received: 26 October 1998 Final revision received: 11 April 1999 Accepted: 8 June 1999     

Systemic and renal macro- and microcirculatory responses to arginine vasopressin in endotoxic rabbits

OBJECTIVE: Arginine vasopressin is being used increasingly to treat vasodilatory hypotension, although little is known of its effects on regional perfusion. Arginine vasopressin hemodynamic effects in physiology are mainly mediated through the V1a receptor on blood vessels. To investigate this further, we studied the effect of arginine vasopressin on systemic and renal blood flow in anesthetized, ventilated rabbits given either intravenous saline or endotoxin, and the impact of blocking V1a receptors. DESIGN: Prospective, randomized, controlled study. SETTING: Animal research laboratory. SUBJECTS: Male White New Zealand rabbits. INTERVENTIONS: Measurement was made of mean arterial blood pressure, aortic and renal blood flow velocities (pulsed Doppler), and renal cortical and medullary flow (laser Doppler). MEASUREMENTS AND MAIN RESULTS: In a first series of animals, incremental intravenous boluses of arginine vasopressin ranging from 1 to 1000 ng were administered 90 mins postendotoxin or saline. In control rabbits (n = 9), increasing doses of arginine vasopressin elevated mean arterial blood pressure but reduced both aortic and renal blood flow velocity and renal cortical flow (p <.05). In endotoxic animals (n = 6), arginine vasopressin produced a similar increase in mean arterial blood pressure although aortic flow was maintained while renal blood flow velocity increased, mostly in its diastolic component (p <.05). Pretreatment with the V1a receptor antagonist in a second series of animals blunted all the effects observed in both control (n = 5) and endotoxic (n = 6) animals, suggesting that arginine vasopressin acted mainly through V1a subtype in this early phase of sepsis. CONCLUSIONS: Preservation of renal blood flow with arginine vasopressin during endotoxemia, in particular to the cortex, suggests it could be a promising agent for hemodynamic support during septic shock.     

多巴胺对内毒素休克犬肺动脉压力的影响

目的 通过观察多巴胺对内毒素休克犬肺动脉压力的影响,评价多巴胺用于内毒素休克治疗的临床意义.方法 选择健康雄性杂种犬20只,随机分为4组,每组5只.以静脉注射脂多糖(LPS)1 mg/kg制备内毒素休克模型,2 h后分别静脉泵人生理盐水5 ml/h(模型组)和多巴胺5、10、20 μg·kg-1·min-1(分别记为D5组、D10组、D20组).经股动、静脉及开胸行肺动脉穿刺测压,记录制模前、给药前及给药后5、10、30、60及120 min时平均动脉压(MAP)及平均肺动脉压(MPAP).结果 不同浓度多巴胺均能升高MPA和MPAP,与模型组比较差异均有统计学意义(P<0.05或P<0.01);且D10组和D20组MAP较D5组升高幅度大,D20组MPAP较D5组和D10组升高幅度大(P<0.05或P<0.01).给予多巴胺后120 min各组MAP/MPAP比值均高于模型组,以高剂量组显著(P均<0.05).结论 不同浓度的多巴胺均能在升高MAP的同时使肺循环阻力增加致肺动脉压力也升高,且体动脉压力升高幅度明显大于肺动脉压力.     

Systemic oxygen transport in patients with myelotoxic agranulocytosis

The paper presents data on central hemodynamics, blood pulmonary shunting and evaluation of oxygen transport in 30 patients with myelotoxic agranulocytosis. In early agranulocytosis (fourteen cases) there was evidence of a drastic increase in pulmonary shunting, reduced stroke and cardiac indices, oxygen transport and its tissue utilization. By day 5-6 the disturbed parameters returned to normal values. It is noted that a phasic course of agranulocytosis implies time-related differential therapy.     

Effects of continuous positive-pressure ventilation on hepatic blood flow and intrahepatic oxygen delivery in dogs

The effect of mechanical ventilation with PEEP of 0, 10, and 20 cm H2O (continuous positive-pressure ventilation [CPPV]) on hepatic blood flow (HBF) and intrahepatic oxygen delivery was studied in 26 mongrel dogs anesthetized with fentanyl. Hepatic arterial and portal venous blood flow was measured by an electromagnetic flowmeter. CPPV caused a significant decrease in HBF, which was related to the PEEP level. A linear correlation was seen between HBF and cardiac output. Intrahepatic oxygen delivery decreased more than HBF and cardiac output. The reduced oxygen delivery was due mainly to the decrease in portal venous oxygen content.     

Comparison of systemic oxygen delivery and uptake with NIR spectroscopy of brain during normovolemic hemodilution in the rabbit.

Incremental hyperoxic normovolemic hemodilution was utilized to progressively decrease oxygen delivery (DO2) in anesthetized rabbits. At decreasing DO2, we compared systemic responses related to the adequacy of DO2, i.e. mixed venous oxygen saturation (SvO2), oxygen consumption (VO2), and arterial lactate concentrations, to near infrared spectroscopy (NIRS) of the brain, a regional measure of intracellular oxygen availability. We sought concomitantly to define critical SvO2 and DO2, beyond which whole body VO2 begins to decline and arterial lactate concentrations increase. NIR Spectroscopy provided the means to test the hypothesis that systemic indicators of inadequate DO2 would not accurately reflect the oxygenation of a critical organ such as the brain. In thirteen rabbits anesthetized with fentanyl, paralyzed and artificially ventilated at an FIO2 of 0.60, hemodilution produced an early decrease in mixed venous oxygen saturation. When mixed venous oxygen saturation decreased below approximately 50%, arterial lactate concentrations began to increase significantly. Further decreases in oxygen delivery precipitated a decline in systemic VO2. Finally, NIRS revealed an increase in the reduction level of brain cytochrome a,a3 after systemic parameters of oxygen delivery had been altered. Analysis of the data indicated that falling SvO2 predicted inadequate DO2 to tissue during early hemodilution under narcotic/relaxant anesthesia and that the brain showed evidence of intracellular hypoxia only after systemic parameters such as SvO2 were affected markedly.     

Systemic and hepatosplanchnic macro- and microcirculatory dose response to arginine vasopressin in endotoxic rabbits

OBJECTIVE: Arginine vasopressin (AVP) is being used increasingly to treat vasodilatory hypotension, although its effects on hepatosplanchnic perfusion have been debated. DESIGN: Prospective study in a university-based experimental research laboratory. SUBJECTS AND INTERVENTIONS: We compared the effect of AVP on systemic, gut, and liver blood flow in anesthetized and ventilated rabbits given either saline or endotoxin. Incremental i.v. boluses of AVP ranging from 1 to 1,000[Symbol: see text]ng were administered 90[Symbol: see text]min post-endotoxin or saline. MEASUREMENTS AND RESULTS: Endotoxin induced a shock state with a transient decrease of mesenteric artery blood flow velocity (pulsed Doppler, in centimeters per second, V(mes)) but had no effect on liver surface microcirculation (laser Doppler in TPU, MicroFl(liver)). Gut microcirculatory (MicroFl(gut)) changes became independent of mean arterial pressure (MAP) after endotoxin. In control rabbits (n = 5), increasing doses of AVP elevated MAP but reduced aortic blood flow (pulsed Doppler, VAo), V(mes), and MicroFl(gut) (p < 0.05). In endotoxic animals (n = 6), AVP produced a similar rise in MAP (p < 0.05), while V(mes) and MicroFl(gut) only decreased for AVP doses above 100[Symbol: see text]ng (p < 0.05). Liver microcirculation was only minimally affected by AVP, although significantly, both in control and endotoxin animals. CONCLUSION: Preservation of mesenteric blood flow as well as gut and liver microcirculation, with therapeutic doses of AVP during endotoxemia, supports its use as a hemodynamic agent during septic shock.