Resuscitation from hemorrhagic shock with diaspirin cross-linked hemoglobin, blood, or hetastarch

BACKGROUND: An oxygen-transporting hemoglobin solution should be more effective than a nonhemoglobin solution for resuscitation from hemorrhagic shock. A way to evaluate this effectiveness is to determine whether a hemoglobin solution can reverse the base deficit accumulated during hemorrhage at a faster rate than a nonhemoglobin solution. Using this criterion, we compared the resuscitative powers of autologous blood, hetastarch (Het), and diaspirin cross-linked hemoglobin (DCLHb). METHODS: Fifteen sedated, spontaneously breathing sheep (37.5 +/- 10.2 kg) were bled until base deficits fell to -5 to -10 mEq/L, and plasma lactate concentrations rose to 6 to 9 mg/L. The animals were resuscitated with autologous blood (n = 5), Het (n = 5), or DCLHb (n = 5) (3.5-4.0 mL/kg every 15 minutes) until base deficits returned to prehemorrhage baseline. RESULTS: Exsanguination to target base deficits required removal of an average of 41.4 +/- 5.5 mL blood/kg (estimated total blood volume, 80 mL/kg). Resuscitation required 18 +/- 3, 38 +/- 2 (different from blood), and 35 +/- 1 (different from blood) mL/kg of autologous blood, Het and DCLHb, respectively, over periods of 78 +/- 8, 163 +/- 10 (different from blood), and 129 +/- 9 minutes (different from blood and different from Het (p < or = 0.05)). Based on regression analysis, autologous blood, Het, and DCLHb corrected the base deficit at rates of, respectively, 0.074 (different from Het (p < or = 0.05)), 0.016, and 0.056 (different from Het (P < or = 0.05)) mEq/L/min. CONCLUSIONS: Based on the rate of base deficit correction and the volume of solution required, autologous blood was the most effective resuscitation solution. However, DCLHb was more effective than Het. DCLHb may be an attractive alternative to blood for resuscitation from hemorrhagic shock.     

Redefining cardiovascular performance during resuscitation: ventricular stroke work, power, and the pressure-volume diagram

OBJECTIVES: (1) To compare left ventricular stroke work index (SW) and left ventricular power output (LVP), hemodynamic variables that encompass blood pressure as well as blood flow, with the purely flow-derived hemodynamic and oxygen transport variables as markers of perfusion and outcome in critically injured patients during resuscitation. (2) To use the ventricular pressure-volume diagram to define characteristic hemodynamic patterns in the determinants of SW and LVP that are associated with survival. METHODS: This was a cohort study at a university Level I trauma center during the course of 1 year. A consecutive series of patients was monitored with a volumetric pulmonary artery catheter during the initial 48 hours of resuscitation. Heart rate, SW, LVP, cardiac index, and oxygen delivery and consumption during resuscitation were compared using multivariate logistic regression analysis with regard to the ability to clear lactate in less than 24 hours and survival. Receiver operating characteristic curves were constructed to determine threshold values for SW and LVP. Ventricular pressure-volume diagrams were used to describe characteristic patterns in the determinants of SW and LVP in survivors and nonsurvivors. Preload was expressed as left ventricular end-diastolic volume index, afterload as aortic input impedance (Ea), and contractility as ventricular end-systolic elastance (Ees). The ratio of Ea/Ees (RATIO) was used as a measure of ventricular-arterial coupling, which describes the efficacy of energy transfer from the heart to the vascular system. RESULTS: One hundred eleven patients (87 survivors, 24 nonsurvivors) met study criteria. Survivors had a significantly higher SW (4,510 +/- 1,070 vs. 3,440 +/- 980 mm Hg x mL x m(-2); p < 0.0001) and LVP (370 +/- 94 vs. 270 +/- 81 mm Hg x L x min(-2) x m(-2); p < 0.0001) than nonsurvivors. Heart rate, SW, and LVP were the only studied variables that were significantly related to lactate clearance and survival by logistic regression. Threshold values determined by the receiver operating characteristic curves were 4,000 mm Hg x mL x m(-2) for SW and 320 mm Hg x L x min(-1) x m(-2) for LVP. Survivors had better ventricular-arterial coupling than nonsurvivors, indicated by a lower RATIO (0.32 +/- 0.22 vs. 0.54 +/- 0.38; p = 0.003). This lower RATIO was attributable to lower levels of Ea (2.7 +/- 0.7 vs. 3.4 +/- 0.8 mm Hg x mL(-1) x m(-2); p = 0.0003) and a trend toward higher levels of Ees (13 +/- 11 vs. 9.9 +/- 7.3 mm Hg x mL(-1) x m(-2); p = 0.12). CONCLUSION: Thermodynamic perfusion variables that encompass both pressure and flow, such as SW and LVP, are more closely related to perfusion and outcome than the purely flow-derived variables. The higher SW and LVP in survivors is related to better ventricular-arterial coupling, and therefore more efficient cardiac function. Cutoff values for LVP of 320 mm Hg x L x min(-1) x m(-2) and for SW of 4,000 mm Hg x mL x m(-2) may be useful thresholds for evaluating hemodynamic performance during resuscitation.     

Early isotonic saline resuscitation from uncontrolled hemorrhage in rats

BACKGROUND: Attempts to modify traditional fluid resuscitation have been based on animal models that evaluate several variables including anesthesia. This study presents the effects of early saline resuscitation from severe uncontrolled hemorrhage unanesthetized rats. METHODS: Sixty-three female Sprague-Dawley rats were equally divided into three groups: group A, nonresuscitated; and groups B and C, resuscitated ;with isotonic saline (40 and 80 mL/kg, respectively). Hemodynamics, blood loss, survival time, and mortality were recorded for 360 minutes after the hemorrhage, which was initiated by 75% resection of the tail. RESULTS: In group C, 80 mL/kg of saline significantly lowered mortality (24% vs 76% and 71% for groups A and B, respectively) with concomitant increases in mean survival time (241 +/- 103 min vs 146 +/- 108 and 175 +/- 92 min for groups A and B, respectively). There were no statistically significant differences in blood loss, hematocrit, or hemodynamic parameters among the groups. CONCLUSIONS: Early and adequate isotonic saline resuscitation of unanesthetized rats improved outcome despite continuing hemorrhage. The significantly lower mortality rate and increased survival time were not a result of transiently improved arterial pressure and did not correlate with blood loss. No significant bleeding increases were noted in the resuscitated groups.     

Uncontrolled hemorrhage from parenchymal injury: is resuscitation helpful?

Fluid resuscitation increases blood pressure and may increase hemorrhage. We tested this hypothesis in a model of liver injury. After standardized injury, rats were randomized into four groups: no resuscitation (NR, n = 30), small volume lactated Ringer's solution (SVLR, 4 mL/kg, n = 30), large volume lactated Ringer's solution (LVLR, 24 mL/kg, n = 30), and hypertonic saline (HS, 4 mL/kg, n = 30). Terminal circulating volume was estimated using controlled hemorrhage experiments. Survival times and mortality rates were significantly lower in HS animals (10%) than in NR (50%) or SVLR (47%) animals. Blood pressure was significantly higher after HS, and this difference was sustained. Intraperitoneal blood volume was significantly higher with HS (26.0 +/- 0.7 mL/kg) and LVLR (26.9 +/- 0.6 mL/kg) compared with NR (21.5 +/- 0.7 mL/kg) and SVLR (22.5 +/- 0.7 mL/kg). Estimated terminal blood volume was significantly decreased in LVLR (29.3 +/- 0.6 mL/kg) compared with NR (33.3 +/- 0.7 mL/kg), SVLR (33.7 +/- 0.8 mL/kg), and HS (31.7 +/- 0.7 mL/kg). CONCLUSION: Vigorous resuscitation increases bleeding from solid viscus injury. Small volume HS improves blood pressure and survival compared with no resuscitation. Results of large vessel hemorrhage models may not apply to parenchymal viscus injury.     

Elevated arterial base deficit in trauma patients: a marker of impaired oxygen utilization

BACKGROUND: In trauma patients, the admission value of arterial base deficit stratifies injury severity, predicts complications, and is correlated with arterial lactate concentration. In theory, elevated base deficit and lactate concentrations after shock are related to oxygen transport imbalance at the cellular level. The purpose of this study was to test the hypothesis that an elevated base deficit in trauma patients is indicative of impaired systemic oxygen utilization and portends poor outcomes. METHODS: This study was a retrospective analysis of a prospectively collected database. The study population included all patients admitted to the trauma intensive care unit at a Level 1 trauma center during a 12-month period who were monitored with a pulmonary artery catheter and serial measurements of lactate and base deficit, and who achieved a normal arterial lactate concentration (< 2.2 mmol/L) with resuscitation. The patients were divided into those who maintained a persistently high base deficit (> or = 4 mmol/L) and those who achieved a low base deficit (< 4 mmol/L) during resuscitation. RESULTS: One-hundred patients (mortality 20%) were monitored with a pulmonary artery catheter and achieved a normal arterial lactate concentration. The mean age+/-SD (SEM) of the group was 37+/-17 years and the Injury Severity Score was 25+/-11. Subgroup analysis revealed that patients with a persistently high base deficit (n=26) had higher rates of multiple organ failure (35% versus 5%, p < 0.001) and death (50% versus 9%, p < 0.00001) compared with patients who achieved a low base deficit. Patients with a persistently high base deficit also had lower oxygen consumption (126+/-40 mL/m2 versus 156+/-30 mL/m2, p=0.01 at 48 hours) and a lower oxygen utilization coefficient (0.20+/-0.05 versus 0.24+/-0.03, p=0.01 at 48 hours) compared with patients with a low base deficit. At 48 hours, both oxygen consumption (r=-0.44, [r, correlation coefficient] p=0.002) and oxygen utilization (r=-0.46, p=0.001) had a significant negative correlation with base deficit. CONCLUSIONS: In trauma patients, a persistently high arterial base deficit is associated with altered oxygen utilization and an increased risk of multiple organ failure and mortality. Serial monitoring of base deficit may be useful in assessing the adequacy of oxygen transport and resuscitation.     

Differing effects of anesthetics on splanchnic arterial blood flow during hemorrhagic shock

The effect of anesthesia on splanchnic blood flow was examined during hemorrhagic shock and resuscitation. Sprague-Dawley rats were anesthetized with the inhalation anesthetic, methoxyflurane, or pentobarbital (65 mg/kg). Transonic Doppler flow probes were placed around the superior mesenteric artery (SMA) and the abdominal aorta, and the animals were subjected to acute hemorrhage (or sham) to 30 mmHg for 90 min followed by 30 min of resuscitation with shed blood (n = 6/group). At 90, 105, and 120 min, sham animals in both anesthetic groups showed comparable blood pressures with a 50% decrease in SMA and aortic blood flow. Acute hemorrhage decreased SMA blood flow by 94.5 +/- 0.01 and 86.0 +/- 2.8%, respectively, in the pentobarbital and methoxyflurane groups, with similar changes occurring in aortic blood flow. During resuscitation, arterial pressure remained significantly depressed and SMA blood flow decreased by 65% in the pentobarbital group, whereas blood pressure returned to control levels and SMA blood flow increased to 56% of control values (P < 0.001) in the methoxyflurane group. The findings indicate that the choice of anesthetic agent may significantly impact splanchnic blood flow and needs to be taken into account when designing experiments examining effects of hemorrhagic shock.     

Significant reduction of medical costs by differentiation therapy with all-trans retinoic acid during remission induction of newly diagnosed patients with acute promyelocytic leukemia. The Japan Adult Leukemia Study Group

OBJECTIVE: For resuscitation of hemorrhagic hypovolemia, we compared the effectiveness of (1) isotonic lactated Ringer's solution (LRS), (2) 2400 mOsm of 7.5% NaCl:6% dextran 70 (HSD), and (3) 2400 mOsm of 7.9% sodium acetate:1.9% NaCl:6% dextran 70 (HAD). DESIGN: In six randomized, blinded experiments for each solution, conscious instrumented adult sheep were hemorrhaged by removing approximately 1.8 L (42 +/- 3 mL/kg) of blood, while maintaining the mean arterial pressure (MAP) at 50 mm Hg for 2 hours. METHODS: Test solutions were infused as needed to restore the cardiac index to baseline. RESULTS: Volume requirements with HAD (236 +/- 29 mL) and HSD (244 +/- 39 mL) were significantly less (p < 0.05) than LRS (3463 +/- 234 mL). Mean arterial pressure was normalized with HSD and LRS, but not with HAD, which resulted in MAPs of 20 to 25 mm Hg less than baseline resulting from a reduced peripheral resistance. Oxygen delivery, however, was significantly higher with HAD during the resuscitation period. Acid-base balance (pH) and oxygen consumption were normalized within 5 minutes of infusion only with HAD. CONCLUSIONS: Small-volume infusion with HAD resulting in "high-flow-low-pressure" resuscitation may offer unique hemodynamic and metabolic advantages for the initial treatment of hemorrhage from trauma.     

Insulin resistance and hypertension in non-obese Africans in Tanzania

OBJECTIVE: This study was done to evaluate the differences in base deficit (BD) clearance, pH normalization, and the occurrence of complications between survivors and nonsurvivors after trauma. DESIGN: Concurrent data entry with retrospective review. METHODS: Trauma patients meeting registry criteria from July 1990 through August 1995 with arterial blood gases performed within 1 hour of admission and admission BD < or = -6 were included. Data was grouped by BD category (moderate, -6 to -9; severe, < or = -10). Group means +/- SEM were compared with a two-tailed t test. MEASUREMENTS and MAIN RESULTS: Six hundred seventy-four patients met entry criteria. Survivors in both the moderate and severe BD groups had improved their BD within 4 hours and normalized their BD by 16 hours. Nonsurvivors did not improve their BD category until 8 hours (for the severe group) and 16 hours (for the moderate group) and did not normalize BD before 24 hours. The BD differences between survivors and nonsurvivors were significant at each time interval, whereas pH differences were significant at 2 hours in the moderate group and at 2, 16, and 24 hours in the severe group. Patients who failed to improve their BD > -6 had an increased frequency of adult respiratory distress syndrome, multiple organ failure, and mortality. CONCLUSION: Base deficit reveals differences in metabolic acidosis between survivors and nonsurvivors not shown by pH determinations and is clearly a better marker of acidosis clearance after shock.     

Low-volume resuscitation with a hemoglobin-based oxygen carrier after hemorrhage improves gut microvascular oxygenation in swine

Using palladium-porphyrin quenching of phosphorescence, we investigated the influence of diaspirin cross-linked hemoglobin (DCLHb) on gut microvascular oxygen pressure (microPO2) in anesthetized pigs. Values of gut microPO2 were studied in correlation with regional intestinal as well as global metabolic and circulatory parameters. A controlled hemorrhagic shock (blood withdrawal of 40 mL/kg) was followed by resuscitation with either a combination of lactated Ringer's solution (75 mL/kg) and modified gelatin (15 mL/kg)(lactR/Gel) or 10% DCLHb (5 mL/kg). After resuscitation, gut microPO2 was similarly improved in the lactR/Gel group (from 25 +/- 10 mm Hg to 53 +/- 8 mm Hg) and the DCLHb group (from 23 +/- 9 mm Hg to 46 +/- 6 mm Hg), which was associated with increased gut oxygen delivery. However, the improvement after resuscitation with DCLHb was sustained for longer periods of time (75 vs 30 min). Mesenteric venous PO2 was increased after resuscitation with lactated Ringer's solution and modified gelatin but not with DCLHb, which was associated with an increased gut oxygen consumption in the latter group. We conclude that measurement of microPO2 by the palladium-porphyrin phosphorescence technique revealed DCLHb to be an effective carrier of oxygen to the microcirculation of the gut. Also, this effect can be achieved with a lower volume than is currently used in resuscitation procedures.     

Preconditioning improves myocardial function and reflow, but not vasodilator reactivity, after ischaemia and reperfusion in anaesthetized dogs

1. The present study examines whether three cycles of brief coronary artery occlusion and reperfusion (i.e. ischaemic preconditioning; PC) can prevent vasodilator dysfunction and the impairment of myocardial reflow caused by prolonged ischaemia. Coronary blood flow, left ventricular dP/dt, systemic arterial blood pressure and heart rate were measured in open-chest anaesthetized dogs. 2. Sixty minute occlusion of the left circumflex coronary artery (LCx) and 60 min LCx reperfusion (ISC/REP; group 1) significantly reduced resting coronary blood flow (CBF, initial 29 +/- 3 mL/min; ISC/REP 20 +/- 3 mL/min, P < 0.05 vs initial) and increased coronary vascular resistance (CVR, initial 4.1 +/- 0.6 mmHg/min per mL; ISC/REP 5.8 +/- 1.0 mmHg/min per mL, P < 0.05 vs initial). By contrast CBF and CVR were not affected in dogs subjected to preconditioning before ischaemia (group 2: CBF, initial 24 +/- 4 mL/min; PC+ISC/REP 23 +/- 4 mL/min; CVR, initial 4.7 +/- 0.6 mmHg/min per mL; PC+ ISC/REP 5.3 +/- 1.0 mmHg/min per mL). These data suggest that ischaemic preconditioning prevents the ischaemia-induced impairment of myocardial reflow. 3. Ischaemia and reperfusion impaired coronary dilator responses to the endothelium-dependent dilator acetylcholine (delta CBF, after ISC/REP: 50 +/- 6% of initial) and the endothelium-independent dilator glyceryl trinitrate (delta CBF, ISC/REP: 46 +/- 6% of initial). Despite the improvement in reperfusion in the preconditioned group, there was no significant improvement in responses to acetylcholine (PC+ISC/REP 52 +/- 6% of initial) or glyceryl trinitrate (PC+ISC/REP 59 +/- 6% of initial) after ischaemia and reperfusion. 4. The reduction in left ventricular dP/dt after ischaemia and reperfusion was significantly smaller in the preconditioned group indicating a lower level of impairment of cardiac contractility. In addition, we confirmed that preconditioning caused a significant reduction in infarct size and a reduction in the release of lactate dehydrogenase indicating less cardiac injury. 5. These results suggest that although ischaemic preconditioning was able to improve both myocardial reperfusion and contractility, it was not able to preserve vasodilator function. Such a reduction in vasodilator reserve could prevent adequate myocardial perfusion under conditions of elevated oxygen demand.     

Effects of partial liquid ventilation with perfluorocarbons on pressure-flow relationships, vascular compliance, and filtration coefficients of isolated blood-perfused rabbit lungs

OBJECTIVES: The density of perfluorocarbons is almost twice that of blood. Therefore, we hypothesized that partial liquid ventilation with these fluids markedly affects pulmonary hemodynamics and filtration coefficients. To test these hypotheses we studied pressure-flow relationships, vascular compliances, capillary pressures, and filtration coefficients in normal and perfluorocarbon-ventilated rabbit lungs. DESIGN: Controlled animal study with an ex-vivo isolated lung preparation. SETTING: Research laboratory for experimental anesthesiology at the Heinrich-Heine-University of Düsseldorf. SUBJECTS: Fourteen New Zealand White rabbits. INTERVENTIONS: The lungs were perfused under zone 3 flow conditions with autologous blood at various flow rates (50 to 250 mL/min, closed circuit, roller pump, 37 degrees C) and ventilated with 5% CO2 in air (positive end-expiratory pressure: 2 cm H2O, tidal volume: 10 mL/kg, respiratory rate: 30 breaths/min) without (control group, n=7) and with (n=7) perfluorocarbon administered intratracheally (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial, left atrial, and airway pressures, as well as blood reservoir volume (reflecting changes in pulmonary blood volume) and lung weight, were measured continuously. Inconsistent with our hypothesis, we found no significant differences between both groups in the slopes and intercepts of the pressure-flow relationships. There were no significant differences in capillary pressures determined by double occlusion (6.7+/-1.2 vs. 6.3+/-1.3 cm H2O for control group, p=.53), vascular compliances (0.51+/-0.10 vs. 0.47+/-0.09 mL/cm H2O for control group, p=.38), and filtration coefficients (0.33+/-0.06 vs. 0.37+/-0.07 mL/min/mm Hg/100 g wet weight for control group, p=.80, Mann-Whitney). CONCLUSIONS: Partial liquid ventilation with perfluorocarbons has no relevant effects on pulmonary filtration coefficients and global hemodynamic variables of isolated zone 3 lungs. These findings suggest that right ventricular afterload is not changed with partial liquid ventilation. It is likely, however, that intrapulmonary blood flow is redistributed toward less-dependent regions, although relevant global hemodynamic changes are absent during partial liquid ventilation.     

No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage

OBJECTIVES: To determine the effect of massive intracerebral hemorrhage (ICH) on regional cerebral blood flow (rCBF) and metabolism, and to test the hypothesis that there is persistent ischemia in the perihematoma region after ICH. BACKGROUND: Cerebral ischemia is postulated to be one of the mechanisms of neural injury after ICH. Presumably the hematoma induces ischemia by mechanical compression of the surrounding microvasculature. METHODS: The authors induced ICH in eight anesthetized mongrel dogs by autologous blood injection (7.5 mL) under arterial pressure in the deep white matter adjacent to the left basal ganglia. They measured serial rCBF using radiolabeled microspheres in regions around and distant to the hematoma, as well as cerebral oxygen extraction, oxygen consumption (CMRO2), glucose utilization, and lactate production by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were monitored continuously. All measurements were recorded at 0.5, 1.0, 2.0, 3.5, and 5.0 hours after induction of ICH and compared with prehematoma values. Evans Blue dye was injected at the end of the experiment, and intensity of staining was compared with three control animals. RESULTS: Compared with prehematoma ICP (12.5+/-2.0 mm Hg, mean+/-standard error), significant elevation in ICP was observed after ICH peaking at 5 hours (34.4+/-5.2 mm Hg). Compared with prehematoma MAP (125.8+/-7.0 mm Hg), significant elevation in MAP was observed at 120 minutes after onset of hematoma (139.1+/-4.6 mm Hg), with return to the prehematoma value by 5 hours. There were no significant changes observed in cerebral oxygen extraction (51.4+/-4.3% versus 44.8+/-4.9%) and CMRO2 (1.8+/-0.3 versus 1.64+/-0.2 mL O2/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. There were no significant differences observed in rCBF in the perihematoma gray (18.2+/-0.9 mL/100 g/min versus 20.1+/-1.5 mL/100 g/min) or white matter (15.6+/-1.4 mL/100 g/min versus 15.3+/-1.1 mL/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. No changes were observed in cerebral glucose utilization, lactate production, and rCBF in other regions after introduction of ICH. Permeability of the blood-brain barrier was more prominent in the ipsilateral hemisphere in animals with ICH compared with control animals. CONCLUSIONS: Despite a prominent increase in ICP and MAP after ICH, the authors found no evidence to support the presence of an ischemic penumbra in the first 5 hours after ICH. Thus, other mechanisms for acute neural injury and late rCBF changes after ICH must be investigated.     

Hepato-splanchnic blood flow and oxygen extraction capabilities during experimental tamponade: effects of endotoxin

We studied the hepato-splanchnic vascular response and changes in O2 extraction capabilities to a reduction in blood flow following endotoxemia. Fourteen anesthetized and mechanically ventilated dogs were divided into two groups of seven each. Group 1 received 2 mg/kg of E. coli endotoxin, and group 2 served as a control. After initial fluid resuscitation following endotoxic shock, regional blood flow estimated by an ultrasonic technique increased similarly in the hepatic artery, portal vein, and mesenteric artery, but microvascular blood flow estimated by a laser Doppler technique was lower in the liver than in the intestinal mucosa. When blood flow was reduced by cardiac tamponade, endotoxin-treated animals had greater whole body and regional critical O2 delivery (DO2crit) and lower whole body, liver, and intestinal critical O2 extraction ratios (O2ERcrit). DO2crit was higher in the liver than in intestine but O2ERcrit was similar in the two organs. Whole body DO2crit at the onset of organ O2 supply dependency was similar under control (9.4 +/- 1.9 mL/kg. min for whole body, 10.3 +/- 4.7 mL/kg. min for liver, and 10.0 +/- 2.6 mL/kg. min for intestine) and endotoxic conditions (13.6 +/- 3.2 mL/kg. min for whole body, 15.6 +/- 2.7 mL/kg. min for liver, and 15.4 +/- 8.7 mL/kg. min for intestine). We conclude that fluid-resuscitated endotoxic shock in dogs is characterized by blood flow redistribution within the liver and intestine. Microvascular depression may be more severe in the liver than in the intestinal mucosa, although the whole body, the liver, and the intestine became O2 supply-dependent simultaneously.     

Dopexamine improves liver oxygenation during crystalloid resuscitation from experimental hemorrhagic shock

OBJECTIVE: To evaluate the effects of dopexamine administration on hemodynamic variables and tissue oxygen tensions during crystalloid resuscitation from hemorrhagic shock. DESIGN: Randomized, control trial. SETTING: An animal laboratory at a university center. SUBJECTS: Twelve piglets, mean weight 22 kg. INTERVENTIONS: The animals were anesthetized and bled to a state of hemorrhagic shock and resuscitated, using a crystalloid solution infused at a rate of approximately 2.6 mL/min/kg (total amount 208 mL/kg). Cardiac output and mean arterial pressure (MAP were measured as indicators of volume filling during the 20- to 30-min resuscitation period and during the follow-up period until 80 mins from the start of resuscitation. Dopexamine was administered by infusion at 6 micrograms/kg-min from the start of volume replacement (dopexamine group, n = 6). The rest of the animals (control group, n = 6) were given volume replacement only. MEASUREMENTS AND MAIN RESULTS: Systemic oxygen transport variables were calculated. Tissue oxygen tensions were continuously recorded from the liver, conjunctival layer, and via subcutaneous and transcutaneous electrodes in the abdominal region. MAP decreased from 119 +/- 2 (SEM) to 44 +/- 2 mm Hg and cardiac output decreased by 77% during the shock period. During resuscitation, cardiac output was restored in both groups. MAP increased close to the baseline during the early resuscitation period and decreased slowly during follow-up. Oxygen delivery remained at 46% of baseline, whereas systemic oxygen consumption was restored during resuscitation in both groups. Liver tissue oxygen tension increased well above baseline during resuscitation in the dopexamine group, and liver tissue oxygen tension was significantly higher than in the control group. After 60 mins of resuscitation, the liver oxygen tension decreased to control group values. None of the other tissue oxygen tensions showed any differences between groups. CONCLUSIONS: Dopexamine administration during crystalloid resuscitation from hemorrhagic shock was well tolerated and resulted in significant and specific, although transient, improvement in liver oxygenation.     

Effects of hypertonic sodium lactate dextran resuscitation in severely burned dogs

12 dogs with 35% TBSA third degree burns received HLD resuscitation (HLD group, n = 6) or LR resuscitation (LR group, n = 6). Fluid resuscitation started one hour postburn. The amount of fluid infused with HLD resuscitation was calculated by that after giving HLD 19.6 ml/kg in 3 hours and 6 ml/kg/% TBSA lactate Ringer's solution followed. The amount of fluid infused with LR resuscitation was calculated by 8 ml/kg/% TBSA lactate Ringer's solution. Infusion of lactated Ringer's solution in both groups was adjusted by maintaining urinary output 0.5-1 ml/kg/h. The volume of fluid infused in HLD group (5.05 +/- 1.11 ml/kg/% TBSA) was much less than that of LR group (10.03 +/- 1.30 ml/kg/%TBSA) (P < 0.01). There was no significant difference in urinary output, serum Na+ and albumin, and plasmacrystalloid osmolarity between two groups. Plasma level of MDA decreased after resuscitation with HLD, which (0.81 +/- 0.20 mmol/g Hb) was much lower than that (1.39 +/- 0.44 mmol/g Hb) of LR group 4 hours postburn (P < 0.05). Plasma SOD activity (7.22 +/- 0.68 u/g Hb) of HLD group were much higher than that of LR group (4.86 +/- 0.53 u/g Hb) 4 hours postburn (P < 0.05). HLD resuscitation could significant reduce the amount of fluid infused comparing with lactate Ringer's solution. HLD resuscitation could attenuate postburn damage to tissue induced by lipid peroxide by elevating plasma SOD activity.     

Genetic analysis of adult-onset cataract in a city-based ophthalmic hospital

When oxygen delivery (DO2) critically decreases, oxygen consumption (VO2) becomes supply dependent. We examined whether end-tidal PCO2 (PetCO2) would identify supply dependency during shock. Five dogs (Group I) underwent progressive hemorrhage to decrease DO2 until they could no longer maintain a stable blood pressure. Five additional animals (Group II) were bled until VO2 decreased to 70% of baseline, followed by resuscitation. The PetCO2 versus time inflection point was compared with the DO2 at onset of supply dependency (DO2crit). DO2crit for Groups I and II were 6.9 +/- .4 and 8.1 +/- 1.3, respectively (p = NS), and not statistically different from the DO2 values at which PetCO2 decreased (6.6 +/- .7 and 6.3 +/- .7 mL/kg per min, respectively). AT constant minute volume, PetCO2 effectively indicated the onset of supply dependency and rapidly increased during resuscitation, paralleling the changes in VO2 in this model of hemorrhagic shock.     

The promoter of the plant defensin gene PDF1.2 from Arabidopsis is systemically activated by fungal pathogens and responds to methyl jasmonate but not to salicylic acid

OBJECTIVES: Hemoglobin-based oxygen carriers are designed to replace blood volume and to increase oxygen delivery to tissues after blood loss. The goals of the present study were two-fold: a) to determine the systemic and regional vascular effects of resuscitation with recombinant human hemoglobin (rHb1.1) in rats during controlled hemorrhage; and b) to determine whether nitric oxide (NO) or prostaglandins were involved in the observed responses. DESIGN: Paralyzed, ventilated rats were hemorrhaged (18 mL blood/kg body weight) during halothane anesthesia and allowed to stabilize for 30 mins. Systemic and regional hemodynamics and oxygen delivery were monitored at three time points, using the radioactive microsphere method. Microspheres were first infused at the end of the hemorrhage stabilization period (t=0 min). rHb1.1 (1 g/kg body weight) or rHb1.1 diluent (phosphate buffered saline, 36 mL/kg body weight) were infused over 20 mins and microspheres were administered again, 30 mins later (t=50 mins). Saline (0.5 mL), indomethacin (5 mg/kg to inhibit cyclooxygenase), or NG-monomethyl-L-arginine (L-NMMA, 100 mg/kg, to inhibit NO synthase) were then infused in rHb1.1-treated rats and microspheres injected once more (t=80 mins). SETTING: Research laboratory. SUBJECTS: Male Wistar rats (n=37). INTERVENTIONS: Recombinant human hemoglobin (rHb1.1), rHb1.1 diluent (phosphate buffered saline) resuscitation of hemorrhaged rats. Saline, L-NMMA, or indomethacin treatment after resuscitation. MEASUREMENTS AND MAIN RESULTS: Resuscitation with rHb1.1 increased mean arterial pressure (MAP), cardiac output, and systemic oxygen delivery significantly when compared with diluent. After rHb1.1 resuscitation, regional blood flows were significantly increased in skin, kidney, spleen, and heart compared with diluent resuscitation. Compared with saline treatment after rHb1.1 resuscitation, L-NMMA increased MAP and regional resistances in virtually all tissues; indomethacin did not alter MAP, but increased resistance in the brain. CONCLUSIONS: These data indicate that rHb1.1 resuscitation was more effective than diluent in improving systemic and regional hemodynamics and oxygen delivery, suggesting that rHb1.1 may be of benefit in the treatment of acute blood loss. Increased resistance after L-NMMA in the presence of rHb1.1 indicated that rHb1.1 resuscitation did not eliminate NO dependent circulatory control. Increased resistance after indomethacin in brain indicated that vasodilator prostanoids were important in regulating vascular resistance in these tissues after rHb1.1 resuscitation.     

Myocardial uptake and release of lactate after high dose neurolept endotracheal intubation in coronary surgery

To evaluate the relationship between the hemodynamic and ECG variables used in routine surveillance of coronary surgery and myocardial lactate metabolism, 23 middle-aged, male, beta 1-blocked patients about to undergo coronary surgery were monitored before and after endotracheal intubation with high dose (30 micrograms/kg) fentanyl-midazolam anesthesia. The induction of anesthesia was followed by a mean arterial pressure decrease (from 98 +/- 4 to 76 +/- 3 mm Hg) and heart rate increase (from 53 +/- 3 to 66 +/- 2 beats/min). After intubation the hemodynamic variables were stable except for a further, transient increase in heart rate (to 69 +/- 2 beats/min). The myocardial uptake of lactate decreased after intubation, from 48 +/- 5 mumol/min to a lowest level of 24 +/- 3 mumol/min. A lactate release was exhibited in 7/23 patients (30%). No ST-segment changes were observed. The correlation between the myocardial lactate uptake/release and hemodynamic or ECG variables was unimpressive or non-existent (r < or = 0.20). Thus, a reduced uptake and even a release of lactate occurred irrespective of the ST-segment, heart rate, or systemic or pulmonary artery pressures. In conclusion, endotracheal intubation in patients with coronary disease was consistently (17/23 patients) followed by a reduced myocardial uptake of lactate, in spite of high dose neurolept anesthesia and beta 1-blockade. This metabolic event was not consistently related to hemodynamic changes.     

Effects of nalmefene, CG3703, tirilazad, or dopamine on cerebral blood flow, oxygen delivery, and electroencephalographic activity after traumatic brain injury and hemorrhage

Hemorrhage after traumatic brain injury (TBI) in cats produces significant decreases in cerebral oxygen delivery (DcereO2) and electroencephalographic (EEG) activity. To determine whether effective treatments for the separate insults of TBI and hemorrhagic shock would also prove effective after the clinically relevant combination of the two, we measured the effects of a kappa-opiate antagonist (nalmefene), an inhibitor of lipid peroxidation (tirilazad), a thyrotropin-releasing hormone analog (CG3703), a clinically useful pressor agent (dopamine) or a saline placebo on cerebral blood flow (CBF), and EEG activity after TBI and mild hemorrhagic hypotension. Cats (n = 40, 8 per group) were anesthetized with 1.6% isoflurane in N2O:O2 (70:30) and prepared for fluid-percussion TBI and microsphere measurements of CBF. Cats were randomized to receive nalmefene (1 mg/kg), tirilazad (5 mg/kg), CG3703 (2 mg/kg), dopamine (20 microg x kg(-1) x min[-1]) or a saline placebo (2 ml, 0.9% NaCl). Animals were injured (2.2 atm), hemorrhaged to 70% of preinjury blood volume, treated as just described and resuscitated with a volume of 10% hydroxyethyl starch equal to shed blood. CBF was determined and EEG activity recorded before injury, after hemorrhage, and 0, 60, and 120 min after resuscitation (R0, R60, and R120). CBF increased significantly after resuscitation (R0) in the nalmefene- and CG3703-treated groups. CBF did not differ significantly from baseline in any group at R60 or R120. DcereO2 was significantly less than baseline in the saline-, dopamine-, and tirilazad-treated groups at R60 and in the dopamine-, tirilazad-, and CG3703-treated groups at R120. EEG activity remained unchanged in the nalmefene-treated group but deteriorated significantly at R60 or R120 compared to baseline in the other groups. Nalmefene and CG3703 preserved the hyperemic response to hemodilution (otherwise antagonized by TBI), and nalmefene prevented the deterioration in DcereO2 and EEG activity that occurs after TBI and hemorrhage.     

Lactated ringer's is superior to normal saline in a model of massive hemorrhage and resuscitation

BACKGROUND: Previous models comparing normal saline (NS) with lactated Ringer's solution (LR) for resuscitation use only mild or moderate hemorrhage and do not address the clinical situation of massive hemorrhage and resuscitation (MHR). This work compares NS and LR by using a new rat model of MHR. METHODS: NS and LR were compared by using both a traditional model of moderate pressure-controlled hemorrhage and a model of MHR. Moderate hemorrhage animals were bled to mean arterial pressure (MAP) = 60 mm Hg x 2 hour then resuscitated with crystalloid (NS or LR) for 1 hour. MHR animals were bled at a rate of 1 estimated blood volume (EBV) per hour for 2 hours with simultaneous resuscitation by using washed red blood cells (B) and crystalloid (LR+B or NS+B). MAP was kept at 60 mm Hg during the 2 hours of hemorrhage. Bleeding was then stopped, and animals were resuscitated for 1 additional hour with blood and crystalloid to MAP more than 90 mm Hg or until 10x EBV was given. Group means were compared with Student's t test (p < 0.01 significant) and 2-week survival rates were compared by using Fisher's exact test (p < 0.05 significant). RESULTS: The moderate hemorrhage group was bled 36% of EBV. In this setting, resuscitation with NS and LR was equivalent. The final hematocrit, pH, and base excess were not different, and all animals survived in both groups. MHR animals were bled 218% of EBV. Animals resuscitated with NS+B were significantly more acidotic than animals resuscitated with equal volumes of LR+B (pH 7.14+/-.06 vs. 7.39+/-.04, respectively) and had significantly worse survival (50% vs. 100%, respectively). CONCLUSION: With moderate hemorrhage, NS and LR are equivalent, but in the setting of massive hemorrhage and resuscitation, significantly more physiologic derangement and mortality occurs with NS than LR. LR is superior to NS for use in massive resuscitation.