Differential alterations in systemic and regional oxygen delivery and consumption during the early and late stages of sepsis.

BACKGROUND: Studies have indicated that regional changes in oxygen utilization during sepsis cannot be predicted from the changes in the whole body oxygen delivery (DO2) and consumption (VO2). The aim of this study, therefore, was to determine whether differential alterations in systemic and regional DO2 and VO2 occur during the early and late stages of sepsis. METHODS: Adult male Sprague-Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 hours (i.e., the early, hyperdynamic phase of sepsis) or 20 hours (i.e., the late, hypodynamic phase) after CLP, cardiac output, and organ blood flow were measured by radioactive microspheres. Systemic and regional DO2 and VO2 were determined and plasma levels of lactate were measured. RESULTS: Cardiac output and blood flow to the liver, small intestine, and kidneys increased at 5 hours and decreased at 20 hours after CLP. Although both systemic DO2 and VO2 increased at 5 hours after CLP, systemic DO2 but not VO2 decreased at 20 hours. At 5 hours after CLP, intestinal and renal DO2 increased. However, DO2 in all the tested organs decreased at 20 hours after CLP. VO2 increased in the liver, small intestine, and kidneys at 5 hours after CLP but decreased only in the liver and small intestine at 20 hours after the onset of sepsis. Moreover, plasma lactate levels increased at the late stage of sepsis. CONCLUSION: Because hepatic and intestinal VO2 but not systemic and renal VO2 decreased at 20 hours after CLP, the liver and small intestine seem to be more vulnerable to the hypoxic insult during the hypodynamic stage of polymicrobial sepsis.     

Effects of indomethacin on hemodynamics of dogs in refractory hemorrhagic shock.

We examined the effects of indomethacin upon anesthetized control dogs and dogs in refractory hemorrhagic shock. Systemic arterial pressure, central venous pressure, cardiac output, and blood flow to the kidney, the heart, the brain, a small intestinal segment, and a piece of skeletal muscle were measured. Systemic vascular resistance and resistances of the vascular beds of the kidney, the heart, the brain, a small intestinal segment, and a piece of skeletal muscle were calculated. Blood flow distribution within the renal cortex was also examined. Indomethacin treatment had little effect upon dogs that were not in shock. Blood flow to the skeletal muscle was decreased. There was also a redistribution of blood flow within the renal cortex with a greater proportion of renal cortical flow going to the outer cortex. However, systemic vascular resistance, cardiac output, and blood flow to the heart, kidneys, brain, and small intestine were unchanged.The refractory shock state was characterized by low systemic arterial pressure and cardiac output with vascular resistance identical to control. Blood flow to the kidney and brain appears to be decreased while coronary flow is maintained. In addition, the ratio of outer renal cortical blood flow to inner renal cortical blood flow, which in the control dog was about 1.5, decreases to 1.Indomethacin treatment largely reversed the hypotension of refractory shock. The increase in arterial pressure following indomethacin treatment is the result of an increase in systemic vascular resistance. Indomethacin treatment had no effect upon cardiac output. The vascular resistances of the kidney, heart, brain, and small intestine increased following treatment of dogs in refractory shock with indomethacin. Renal blood flow was decreased 57%. The renal cortical blood flow distribution was shifted toward the outer cortex as in the controls.Substances dependent upon prosta glandin synthetase may be involved in the hypotension that is characteristic of refractory hemorrhagic shock and may be important in maintaining blood flow to the kidneys and gut.     

Continuous resuscitation after hemorrhage and acute fluid replacement improves cardiovascular responses

BACKGROUND: Although acute fluid replacement after trauma and severe hemorrhage remains the cornerstone in the management of trauma victims, it remains unknown whether continuous resuscitation after trauma-hemorrhage and acute fluid replacement produces salutary effects on cardiovascular function and reduces proinflammatory cytokine release. METHODS: Adult male rats underwent laparotomy (ie, soft tissue trauma) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the shed blood volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with 4 times the volume of shed blood with RL for 60 minutes, followed by continuous resuscitation with RL at 5 mL/h/kg for 48 hours after the acute fluid replacement. At 48 hours after hemorrhage, mean arterial pressure, cardiac output, and left ventricular contractility parameters, such as the maximal rates of ventricular pressure increase (+dP/dt(max)) and decrease (-dP/dt(max)), were determined. Microvascular blood flow in the intestine and kidney was assessed by laser Doppler flowmetry. In addition, plasma levels of TNF-alpha were assayed by enzyme-linked immunosorbent assay. RESULTS: The mean arterial pressure and cardiac output were decreased by 34% and 18%, respectively, at 48 hours after hemorrhage and acute resuscitation. Continuous resuscitation, however, markedly improved these parameters. Similarly, +dP/dt(max) and -dP/dt(max) decreased significantly after hemorrhage and acute fluid replacement but was restored to sham values after continuous resuscitation. Microvascular blood flow in the gut and kidneys was decreased after hemorrhage and acute resuscitation by 34% and 35%, respectively. However, intestinal and renal perfusion was maintained at the sham levels at 48 hours after continuous resuscitation. In addition, the upregulated TNF-alpha after acute resuscitation alone was reduced after continuous resuscitation. CONCLUSIONS: Continuous resuscitation after acute fluid replacement appears to be a useful approach for restoring and maintaining cardiovascular function and organ perfusion after trauma and severe hemorrhage.     

Effects of carbon dioxide (hypocapnia and hypercapnia) on tissue blood flow and oxygenation of liver, kidney and skeletal muscle in the dog

We investigated the effects of carbon dioxide on the splanchnic visceral organs (liver and kidney) as well as skeletal muscle in the anesthetized dog. Thirty two adult mongrel dogs were anesthetized with sodium pentobarbital, intubated and ventilated mechanically with 100% oxygen to maintain normocapnia. After laparotomy, miniature Clark-type polarographic oxygen electrodes were placed on the surfaces of liver, kidney and rectus femoris muscle. Electromagnetic blood flow (BF) probes were also applied to hepatic artery (HA), portal vein (PV), left renal artery (RA) and left femoral artery (FA). After a stable normocapnic ventilation, the hypocapnia was produced by increasing respiratory rate, and the hypercapnia was induced by adding the exogenous carbon dioxide. Results: Hyperventilation resulted in a significant decrease in HABF, PVBF, liver surface PO2 and kidney surface PO2 in parallel with the decreased PaCO2, but these parameters increased dose dependently when the carbon dioxide was added to the inspired gas (hypercapnic hyperventilation). On the contrary, FABF and skeletal muscle surface PO2 increased by hypocapnia and decreased during hypercapnia. Neither PaCO2 or cardiac output showed any significant change during the entire experiment. Arterial PCO2 appears to exert significant effects on both splanchnic and skeletal muscle perfusion as well as corresponding changes in tissue oxygenations. It is possible that injudicious and prolonged hypocapnic hyperventilation may seriously compromise splanchnic organ perfusion and oxygenation.     

The effects of thoracic aortic cross-clamping and declamping on visceral organ blood flow.

Blood flow was measured using radioactive microspheres in 11 macaque monkeys 1) before hemorrhage shock, 2) after onset of shock, 3) after aortic cross-clamping and resuscitation, and 4) after release of the cross-clamp and stabilization. Hemodynamic parameters (cardiac output, arterial, right atrial and left atrial pressure) and blood gases were also monitored. Total abdominal organ flow fell with hemorrhage and fell further with aortic clamping. Reinfusion of shed volume did not restore abdominal organ flow (4.7% baselines) but increased LAP and cardiac output to the upper body. Release of the cross-clamp produced profound acidosis that was treated effectively with NcHCO3. After stabilization of blood, flow to kidney remained low (49% baseline) although intestinal flow was increased threefold (320% of baseline). It is clear that thoracic aortic cross-clamping in shock further compromises already reduced visceral blood flow and may contribute to the problem of ischemic multiple organ failure after resuscitation from hemorrhagic shock.     

Intramucosal pH and pCO(2) do not strictly correlate with intestinal energy metabolism in experimental peritonitis

This study aimed to investigate tissue hypoxia on the cellular level in sepsis. Eighteen pigs weighing 18-27 kg were studied. Intramucosal-arterial PCO(2) gradient (PCO(2)-gap) and intramucosal pH (pH(i)) were calculated using tonometry. A blind loop of the small intestine was constructed for repeated tissue biopsies to measure intestinal energy-related metabolites and lactate concentration. Six animals served as controls. In 12 animals, faecal peritonitis was induced. Six of these animals were studied without further interventions, while the others were resuscitated with dextran to maintain cardiac index at baseline level. Untreated peritonitis caused an increase in PCO(2)-gap and a drop in pH(i). The intestinal energy metabolism was not disturbed until the end of the experimental period, with a decreased energy charge value and a moderately increased lactate concentration. In peritonitis-dextran animals, PCO(2)-gap and pH(i) remained at baseline level and the energy metabolism was not disturbed. We conclude that in peritonitis, PCO(2)-gap - like pH(i) - can be influenced by other factors than strictly anaerobic tissue metabolism.     

急性中度等容血液稀释对小肠氧输送和氧耗的影响

目的 探讨术中急性中度等容血液稀释对小肠血流灌注和氧输送,氧耗的影响。方法 １５只雄性家猫,用多聚明胶将血红蛋白稀释至８４ｇ／Ｌ在血液稀释前后分别测定肠系膜上动脉血流量,肠系膜上静脉血乳酸量,作肠系膜上动脉,静脉血气分析,分析计算血液稀释前后的小肠氧输送量,氧耗量和氧摄取率。结果 血液稀释后肠系膜上动脉血流量及小肠氧耗量较称释前有显著意义的升高（Ｐ〈０．０５）,小肠氧输送量和小肠氧摄取率无显著性变     

The effect of hypertonic saline resuscitation on responses to severe hemorrhagic shock by the skeletal muscle, intestinal, and renal microcirculation systems: seeing is believing

BACKGROUND: Decompensated hemorrhagic shock is often refractory to resuscitation, and we show here that it is associated with loss of vascular tone in skeletal muscle precapillary arterioles. We tested the hypothesis that microvascular derangements in the skeletal muscle, intestinal, and renal microcirculation systems would be reversed by initial hypertonic saline-dextran infusion. METHODS: Male Sprague-Dawley rats underwent precollicular brain stem transection without anesthesia for study. Parameters measured by in vivo videomicroscopy included cardiac output, mean arterial pressure, and microvascular responses in the skeletal muscle, ileum, and renal (i.e., the hydronephrotic kidney) microcirculation systems. Hemorrhaged was induced to a mean arterial pressure of 50 mmHg until decompensation occurred. The rats were then initially resuscitated with (1) 4 mL/kg 7.5% NaCl in 6% dextran 70, (2) 33 mL/kg .9% NaCl in 6% dextran 70, or (3) 33 mL/kg .9% NaCl. Twenty minutes later they received shed blood plus 33 mL/kg .9% NaCl to maintain mean arterial pressure at baseline levels. RESULTS: Decompensated hemorrhagic shock decreased cardiac output to between 24% and 35% of baseline values and profoundly decreased microvascular blood flow to between 10% and 19% of baseline. At the completion of resuscitation cardiac output increased to greater than baseline in all groups. Microvascular blood flow increased toward baseline transiently but then progressively deteriorated to between 36% and 69% of baseline in the 3 tissues. There was no significant difference between the three resuscitative fluids. CONCLUSIONS: Despite return of cardiac output to greater than baseline levels, muscle, intestinal, and renal microvascular blood flows remained significantly depressed. Hypertonic saline and/or dextran did not improve these deficits.     

去乙酰毛花甙与依那普利拉单用及配伍应用对烫伤大鼠脏器早期损害的影响

目的 了解去乙酰毛花甙与依那普利拉单用及两药配伍应用对严重烫伤大鼠心、肝、肾、肠早期损害的影响. 方法 将40只雄性Wistar大鼠按随机数字表法分为假伤组(模拟烫伤)、烫伤对照组、去乙酰毛花甙组、依那普利拉组、去乙酰毛花甙+依那普利拉组,每组8只.大鼠麻醉后给予背部30%TBSAⅢ度烫伤,伤后30 min腹腔注射乳酸钠林格液(4 mL·kg-1·1%TBSA-1)复苏治疗.补液同时去乙酰毛花甙组静脉注射去乙酰毛花甙0.2 mg/kg;依那普利拉组静脉注射依那普利拉1 mg/kg;去乙酰毛花甙+依那普利拉组静脉注射去乙酰毛花甙及依那普利拉,剂量同前.伤后6h,以多道生理信号采集处理系统记录各组大鼠心肌力学指标;以激光多普勒血流仪记录肝、肾、肠血流量;取大鼠静脉血检测心肌肌钙蛋白I(cTnI)、总胆汁酸(TBA)、β2微球蛋白(β2-MG)、二胺氧化酶(DAO). 结果 与假伤组比较,烫伤对照组大鼠各项心肌力学指标均显著降低;肝血流量为(158±32)血流灌注单位(PU)、肾(156±46)PU、肠(119±30)PU,亦显著降低(P＜0.05);血清cTnl(5.0±0.3)μg/L、TBA(82±23)μmol/L、β-MG(2.55±0.15)mg/L、DAO(1.52±0.08)kU/L,明显高于假伤组(P＜0.05).与烫伤对照组比较,去乙酰毛花甙组和依那普利拉组心肌力学指标均有不同程度提升,肝、肾、肠血流量增加(P＜0.05),血清cTnl、TBA、β2-MG浓度和DAO活性降低(P＜0.05).去乙酰毛花甙+依那普利托组大鼠心肌力学指标全部升高,血流量分别为肝(240±49)PU、肾(239±75)PU、肠(194±55)PU,明显升高(P＜0.05),血清cTnI为(3.4±0.2)μg/L、TBA(47±8)μmol/L、β2-MG(2.01±0.16)mg/L、DAO(1.17±0.15)kU/L,均明显降低(P＜0.05). 结论 严重烫伤后早期单用去乙酰毛花甙或依那普利拉,均能改善大鼠心功能,对肝、肾、肠损害有一定防治作用,两药配伍应用可产生协同作用.     

Assessment of graded intestinal hypoperfusion and reperfusion using continuous saline tonometry in a porcine model.

OBJECTIVE: To evaluate effects of graded intestinal hypoperfusion and reperfusion on intestinal metabolic parameters as assessed by a modified continuous saline tonometry technique. MATERIALS: Twelve barbiturate-anaesthetized female pigs. METHODS: Measurements were performed prior to and during three predefined levels of superior mesenteric mean arterial blood pressure (P(SMA) 70, 50 and 30 mmHg, respectively, each 80 min long), obtained by an adjustable clamp around the origin of the superior mesenteric artery, and during reperfusion. We continuously measured jejunal mucosal perfusion (laser Doppler flowmetry), jejunal tissue oxygen tension (PO(2TISSUE); microoximetry) and intramucosal PCO(2) (continuous saline tonometry) and calculated net intestinal lactate production, mesenteric oxygenation, PCO(2) gap (jejunal mucosal PCO(2)-arterial PCO(2)) and pHi. RESULTS: At P(SMA) 70 and 50 mmHg mesenteric oxygen uptake and net lactate production remained unaltered, in spite of decreased oxygen delivery. At these P(SMA) levels PCO(2) gap increased, while pHi and PO(2TISSUE) decreased. At P(SMA) 30 mmHg pronounced increases in PCO(2) gap and mesenteric net lactate production as well as marked decreases in PO(2TISSUE) and pHi were demonstrated. Data indicate absence of anaerobic conditions at an intestinal perfusion pressure (IPP)> or =41 mmHg, a pHi> or =7.22 or PCO(2) gap< or =15.8 mmHg. CONCLUSIONS: Continuous saline tonometry detected intestinal ischemia as induced by graded reductions in IPP. A threshold could be defined above which intestinal ischemia does not occur.     

Tissue oxygen tension and other indicators of blood loss or organ perfusion during graded hemorrhage

Currently employed clinical indicators of perfusion provide inadequate warning of developing hazards caused by marginal perfusion in certain vital organs or "peripheral" tissues that are pivotal to postsurgical wound healing. In this study, mean arterial blood pressure, cardiac output, and transcutaneous and subcutaneous oxygen tensions (PtcO2 and PsqO2) were investigated during serial hemorrhage, as indicators of the degree of both hypovolemia and perfusion to specific tissues. Blood was removed in stages (10%, 20%, 30%, 40%, 55%, 60%, and 65% of original volume) from anesthetized dogs. Injections of variously radiolabeled microspheres allowed assessment of blood flow at each stage of hemorrhage in bone, brain, colon, heart, kidney, liver, muscle, pancreas, skin, small intestine, spleen, stomach, and subcutaneous tissue. PsqO2 was correlated more highly with blood volume lost than was PtcO2. Furthermore PsqO2 was more sensitive to blood loss than was either cardiac output or PtcO2 and, also during the early loss (0% to 40%), was more sensitive than mean arterial pressure. Some organs (e.g., pancreas) appeared to lose considerable blood flow with only small loss of blood volume, but their blood flow then stabilized at a low level despite further hemorrhage. Other organs, notably the kidney, appeared to be relatively unaffected by substantial loss of blood volume (20% to 40%), after which, however, their blood flow quite abruptly became sensitive to further hypovolemia. This explains why blood flow-related performance of the kidney (e.g., urine volume) may not adequately predict a developing hazard or peripheral perfusion. Some indicators were found to be better indexes of blood flow in some organs than in others (e.g., cardiac output and PsqO2 correlated more closely with skin, spleen, and intestinal flows [and one another] than with vital organ flows).     

Supraceliac aortic cross-clamping and declamping. Effects of dopexamine and dopamine on systemic and mesenteric hemodynamics, metabolism and intestinal tonometry in a rat model

BACKGROUND: The effects of dopexamine and dopamine on mesenteric ischemia during reperfusion following aortic cross-clamping are not known. We determined intramucosal tonometric PCO2 and PCO2 gap using a rat model of supraceliac aortic cross-clamping and declamping. METHODS: Under pentobarbital and fentanyl anesthesia, 24 rats were surgically instrumented with arterial, right atrial, and portal venous catheters, ultrasonic flowprobes for measurements of abdominal aortic, superior mesenteric and carotid artery blood flow, and a pediatric tonometer for intestinal mucosal PCO2 measurements. Rats were randomized to receive a continuous infusion of dopexamine (10 x microg(-1) x kg(-1) x min(-1), n=8), dopamine (10 microg x kg(-1) x min(-1), n=8 ), or physiologic saline (control, n= 8), infused at a rate of 4 ml x kg(-1) x h(-1), administered throughout the experimental protocol. After 30 min of drug infusion, the aorta was cross-clamped at the supraceliac level for 30 min. Reperfusion following declamping was observed for 180 min. RESULTS: Intestinal tonometric PCO2 remained unchanged during drug treatment before aortic cross-clamping, increased similarly in all groups following declamping during early reperfusion, and recovered to baseline within 30 min of reperfusion. Dopexamine treatment was associated with higher lactate levels and increased heart rate (P<0.05) during aortic cross-clamping. CONCLUSIONS: 1) Mesenteric ischemia, determined by intestinal tonometric PCO2 and PCO2 gap, recovers within 30 min of reperfusion following 30 min of aortic cross-clamping irrespective of drug treatment and, 2) dopexamine induced higher lactate levels and increased heart rate during aortic cross-clamping and should be carefully analyzed for potentially adverse effects on cardiac function.     

Hypoxia is not the sole cause of lactate production during shock

BACKGROUND: Traditionally, elevated blood lactate after hemorrhage is interpreted as tissue hypoperfusion, hypoxia, and anaerobic glycolysis. The severity and duration of the increase in blood lactate correlate with death. Recent in vitro studies indicate that epinephrine stimulates lactate production in well-oxygenated skeletal muscle by increasing activity of the Na+-K+-adenosine triphosphatase (ATPase), which derives a significant amount of adenosine triphosphate from glycolysis. Using in vivo microdialysis, we tested whether inhibiting the Na+-K+ pump with ouabain could reduce muscle lactate production during local exposure, via the microdialysis probe, to epinephrine or during hemorrhage in rats. METHODS: Microdialysis catheters were placed in the muscle of both thighs of pentobarbital-anesthetized male Sprague-Dawley rats (275-350 g) and perfused (1 microL/min) with Krebs-phosphate buffer (pH 7.4) containing ethanol (5 mmol/L) to permit assessment of changes in local blood flow. To inhibit the Na+-K+-ATPase, ouabain (2-3 mmol/L) was added to the perfusate of one leg. In one series of studies, epinephrine was added to the perfusate. In another series, rats were hemorrhaged to a mean arterial pressure of 45 mm Hg for 30 minutes, followed by resuscitation with shed blood and 0.9% sodium chloride. Dialysate fractions were analyzed for lactate and ethanol fluorometrically. RESULTS: Lactate rose during epinephrine exposure or during hemorrhage and resuscitation. Treatment with ouabain reduced dialysate lactate concentration significantly in both series of studies. Local blood flow was reduced by either epinephrine or hemorrhage, but returned toward baseline afterward. Ouabain had no apparent effect on local blood flow. CONCLUSION: Increased Na+-K+ATPase activity during epinephrine treatment or hemorrhage contributes to muscle lactate production. Hypoxia is not necessarily the sole cause of hyperlactatemia during and after hemorrhagic shock.     

Effective organ blood flow and bioenergy status in murine peritonitis

Whether organ dysfunction frequently encountered in overwhelming bacterial sepsis is a result of a direct cellular "toxic" effect or diminished cellular perfusion remains controversial. To assess the effects of peritonitis on cellular energy status and visceral blood flow, peritonitis was induced in rats by means of cecal ligation and perforation. Five, 10, or 20 hours after cecal ligation and perforation, cardiac outputs were determined by thermodilution, effective hepatic blood flow was determined by low-dose galactose clearance, and effective renal plasma flow was determined by paraminohippuric acid clearance. In similar groups of rats with peritonitis or sham controls, tissue samples of liver, kidney, and skeletal muscle were obtained by freeze-clamp technique for analysis of adenine nucleotides, energy charge, pyruvate, lactate, and pyruvate/lactate ratios (P/L). Despite an increase in cardiac output (p less than 0.05), results indicated in this model that effective hepatic blood flow and effective renal plasma flow were significantly reduced (p less than 0.05). The energy charge and P/L ratios of hepatic (p less than 0.01) and renal (p less than 0.05) tissues were also decreased. In contrast, skeletal muscle energy charge and P/L ratio were unchanged by 20 hours duration. These data support the hypothesis of diminished visceral perfusion as contributory to the cellular dysfunction observed in sepsis. Skeletal muscle appears either nonischemic or more tolerant of ischemia in sepsis.     

The important role of the gut in initiating the hyperdynamic response during early sepsis

BACKGROUND: Although the initial response to sepsis includes a hyperdynamic phase and although the increased hepatic perfusion in early sepsis is due solely to the increased portal blood flow, it remains unknown whether the gut plays an important role in producing such a response. MATERIALS AND METHODS: Adult male Sprague-Dawley rats underwent a complete enterectomy (ER) before being subjected to sepsis by cecal ligation and puncture (CLP; the cecum was excised from the removed gut and stitched to the posterior peritoneum in ER groups) or sham operation. At 2 h after CLP (i.e., the early, hyperdynamic phase of sepsis), cardiac output and heart performance (+/-dP/dt(max)), as well as hepatic and renal blood flow, were measured. Systemic and regional oxygen delivery (DO(2)) and oxygen consumption (VO(2)) were also determined. RESULTS: Cardiac output, heart performance, organ blood flow, as well as DO(2) and VO(2), increased significantly 2 h after CLP. ER prior to the onset of sepsis, however, prevented the elevation of those parameters. ER in sham animals did not alter the measured parameters with the exception that portal blood flow decreased by 85% and hepatic arterial blood flow increased by 368%, resulting in no significant reduction in hepatic DO(2) and VO(2). There were no changes in circulating blood volume among groups, indicating that the effect of ER on hemodynamics after CLP was not due to alterations in blood volume. CONCLUSION: Since ER immediately before the onset of sepsis prevents the increase in cardiac output and regional hemodynamics, the gut appears to play an important role in producing the hyperdynamic response during the early stage of polymicrobial sepsis.     

Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock

We studied the intestinal microvascular blood flow responses to hemorrhage and resuscitation with pentoxifylline by in vivo video microscopy. Male Sprague-Dawley rats were hemorrhaged to 50% of baseline mean arterial pressure for 45 minutes and then blindly randomized to receive pentoxifylline (25 mg/kg bolus + 0.2 mg/kg/minute) or an equivalent volume of saline plus return of shed blood and an additional bled volume of Ringer's lactate solution. Hemorrhage caused intestinal microvascular blood flow to decrease to 10% to 15% of baseline values. In the control group, resuscitation restored cardiac output and mean arterial pressure to baseline values, but intestinal microvascular blood flow remained at 30% of baseline values. In contrast, addition of pentoxifylline to the resuscitation regimen resulted in an immediate hyperemic response with an increase in intestinal microvascular blood flow to significantly greater than baseline values followed by return to baseline. Arteriolar dilation was not responsible for the improvement in flow implicating improved flow dynamics between erythrocytes, granulocytes, and vascular endothelia within the microcirculation. We conclude that addition of pentoxifylline to resuscitation from hemorrhagic shock restores intestinal microvascular blood flow.     

Intracompartmental pressure, PO2, PCO2 and blood flow in the human skeletal muscle

Measurement of PO2, PCO2, and blood flow in skeletal muscle could be a supplement to examination in clinical practice. Mass spectrometry was utilized to measure these parameters in the resting anterior tibial muscle of healthy adults. The partial pressures of oxygen and carbon dioxide were 21 +/- 3.6 and 46 +/- 2.5 Torr, respectively. The intracompartmental pressure was 8 +/- 1.1 Torr. The oxygen tension in muscle varied only slightly when arterial partial pressure was increased. The blood flow (tissue perfusion coefficient) estimated by washout of an inert gas was 5.4 +/- 0.8 ml/100 g/min. The results are in accordance with those from animal studies of skeletal muscle. The study demonstrates the feasibility of measuring PO2, PCO2, and blood flow in skeletal muscle by mass spectrometry.     

A novel approach to maintaining cardiovascular stability after hemorrhagic shock: beneficial effects of adrenomedullin and its binding protein

BACKGROUND: Vascular responsiveness to adrenomedullin (AM), a recently discovered vasodilator peptide, is depressed after hemorrhage and resuscitation. Downregulation of AM binding protein-1 (ie, AMBP-1) appears to be responsible for this hyporesponsiveness. Therefore, we hypothesize that administration of AM/AMBP-1 improves cardiovascular responses after hemorrhagic shock and resuscitation. METHODS: Male rats were bled to and maintained at a mean blood pressure of 40 mm Hg for 90 minutes. The animals were then resuscitated with 4 times the volume of shed blood with Ringer's lactate over 60 minutes. At 15 minutes after the beginning of resuscitation in hemorrhaged animals, AM alone, AMBP-1 alone, AM in combination with AMBP-1, or vehicle (phosphate-buffered saline solution) was administered intravenously over 45 minutes. At 4-hour postresuscitation, in vivo left ventricular contractility parameters, maximal rates of ventricular pressure increase (+dP/dt max ) and decrease (-dP/dt max ), were determined. Cardiac output and organ blood flow were measured with the use of radioactive microspheres. In an additional group of animals, cardiac tumor necrosis factor-alpha (TNF-alpha) levels were measured by an enzyme-linked immunosorbent assay. RESULTS: Four hours after resuscitation, +dP/dt max , -dP/dt max , cardiac output, and organ blood flow in the liver, small intestine, and kidneys were decreased while treatment with AM/AMBP-1 increased these parameters ( P < .05). Moreover, cardiac TNF-alpha levels were elevated at 4 hours after hemorrhage and resuscitation, while AM/AMBP-1 treatment reduced them to sham levels ( P < .05). CONCLUSIONS: Administration of AM/AMBP-1 appears to be a useful approach for restoring and maintaining cardiovascular stability after severe hemorrhagic shock and crystalloid resuscitation.     

The effect of alpha(2) agonist-induced sedation and its reversal with an alpha(2) antagonist on organ blood flow in sheep

We investigated changes in cardiac output and organ blood flow induced by medetomidine in sheep and determined changes in cardiac output and organ blood flow after reversal of medetomidine-induced sedation by atipamezole. Eight sheep were chronically instrumented. Medetomidine was infused IV to target plasma levels of 0, 0.8, 1.6, 3.2, 6.4, and 12.8 ng/mL for 25 min each, followed by a 5-min infusion of atipamezole. Hemodynamic values and organ blood flow (using colored microspheres) were measured just before medetomidine infusion (baseline), at the end of each medetomidine infusion step, and 30 min after the administration of atipamezole. Medetomidine (12. 8 ng/mL) decreased cardiac output from 6.3 +/- 1.0 to 3.2 +/- 0.7 L/min (P < 0.0001) and increased systemic vascular resistance from 1310 +/- 207 to 3467 +/- 1299 dynes. s(-1). cm(-5) (P < 0.0001). Blood flow decreased in the cerebral cortex from 1.29 +/- 0.40 to 0. 66 +/- 0.12 mL. g(-1). min(-1) (P < 0.0001), left ventricle from 2. 11 +/- 0.61 to 1.40 +/- 0.40 mL. g(-1). min(-1) (P < 0.0001), kidney from 8.28 +/- 3.17 to 6.07 +/- 2.65 mL. g(-1). min(-1) (P < 0.0001), skin from 0.09 +/- 0.04 to 0.05 +/- 0.02 mL. g(-1). min(-1) (P < 0. 0001), intestine from 0.56 +/- 0.13 to 0.27 +/- 0.07 mL. g(-1). min(-1) (P < 0.0001), and skeletal muscle from 0.28 +/- 0.15 to 0.04 +/- 0.01 mL. g(-1). min(-1) (P < 0.0001). Blood flow in the liver (hepatic artery) increased from 0.05 +/- 0.03 to 0.24 +/- 0.16 mL. g(-1). min(-1) (P < 0.0001). After atipamezole infusion, cardiac output and systemic vascular resistance returned to baseline, but the cerebral cortex, left ventricle, and renal blood flows remained below baseline at 0.89 +/- 0.22, 1.37 +/- 0.50, and 6.25 +/- 2.76 mL. g(-1). min(-1), respectively; skeletal muscle blood flow increased above baseline to 0.44 +/- 0.27 mL. g(-1). min(-1), spleen blood flow decreased below baseline to 1.65 +/- 0.61 mL. g(-1). min(-1) (P < 0.0001), and liver, intestine, and lung blood flows returned to baseline values. In conclusion, medetomidine decreased and redistributed organ blood flow in sheep. Atipamezole reversed the medetomidine-induced hemodynamic changes, but redistributed blood flow from the brain, heart, and kidney to the skeletal muscle.     

山莨菪碱对失血性休克兔小肠微循环血量及血液酸碱度的影响

目的观察山莨菪碱对失血性休克兔小肠微循环血流量及血液酸碱度变化情况。方法大白兔16只随机分为2组,分别是山莨菪碱治疗组(S组,n=8)和生理盐水对照组(C组,n =8)。复制兔重度失血性休克及复苏的动物模型,在休克期间分别予等容量的山莨菪碱注射液和生理盐水治疗,复苏60 min。观察放血前、放血后10、30、60 min小肠黏膜微循环血流量、动脉平均血压、中心静脉压。在放血前、放血后10、30、60 min取颈动脉、肠系膜上静脉血液少量进行血气分析。结果放血后两组动物休克期小肠黏膜微循环血流量均比放血前明显降低(P<0.05);回输血液后S组动物小肠微循环血流量恢复,与放血前比较差异无统计学意义(P>0.05);C组动物在再灌注10、30、60 min时的微循环血流量明显低于放血前(P<0.05)。在再灌注60 min时S组的颈动脉血pH值、BE值高于C组(P<0.05);而对肠系膜上静脉血,S组在再灌注30、60 min时的pH值高于C组,在再灌注10、30、60 min时的BE值高于C组(P<0.05)。结论山莨菪碱能改善失血性休克时肠黏膜微循环,有利于更快清除肠微循环蓄积的酸性物质。