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Mechanism of cerebral blood flow augmentation by hemodilution in rabbits.

BACKGROUND AND PURPOSE: Hemodilution is known to increase cerebral blood flow, but it is not known whether the increase in flow is a direct result of a decrease in viscosity or whether it may be due to compensatory vasodilatation in response to the decrease in oxygen carrying capacity that results from hemodilution. This study is designed to investigate this question. METHODS: Changes in regional cerebral blood flow were studied in normal and ischemic brains of 15 and 18 rabbits, respectively. In one group of rabbits graded hemodilution was used to reduce arterial oxygen content progressively in stages; in the second group the arterial oxygen content was reduced in similar stages by progressively larger reductions in the concentration of inspired oxygen (hypoxic hypoxia). In the ischemic animals focal ischemia was produced by embolic occlusion of the right middle cerebral artery. RESULTS: In the normal rabbits, hypoxic hypoxia and hemodilution resulted in similar progressive increases in cerebral blood flow as arterial oxygen content fell. In the ischemic animals, there was a significant fall in cerebral blood flow in the ischemic region in all groups after arterial occlusion. Hemodilution resulted in a progressive increase in cerebral blood flow in both ischemic and nonischemic regions. With hypoxic hypoxia, however, cerebral blood flow in the ischemic region showed no increase or a slight decrease. CONCLUSIONS: Even though hypoxic hypoxia results in a marked increase in cerebral blood flow in normal brain, it does not significantly change cerebral blood flow in ischemic brain. In contrast, hemodilution resulting in a comparable degree of hypoxemia is capable of significantly increasing cerebral blood flow in ischemic brain. Therefore, the mechanism of blood flow augmentation by hemodilution in ischemic brain is probably related to a direct hemorheologic effect rather than to the resulting hypoxemia.

Animals↗

The perfluorocarbon fluoromethyloadamantane offers cerebral protection in a model of isovolemic hemodilution in rabbits.

BACKGROUND AND PURPOSE: Perfluorocarbons (PFCs) are considered promising cerebral protection agents because they could combine the beneficial effects of decreased blood viscosity with enhanced oxygen-carrying capacity and oxygen tissue delivery, but trials of PFCs as hemodilutants have been very limited. We evaluated fluoromethyloadamantane (FMA), a new perfluorocarbon compound, as an isovolemic hemodilutant and compared it with low-molecular-weight dextran 40 (D40) and a control group. METHODS: Through a transorbital craniectomy, the internal carotid, anterior, and middle cerebral arteries were coagulated to create a cerebral infarction in anesthetized, mechanically ventilated rabbits. No other experimental procedure was performed in control animals. In the two other groups, hemodilution was commenced 30 minutes after the arterial occlusion with either D40 or FMA. Hemodynamic parameters and brain and systemic temperature were monitored throughout the experiments. All animals were killed 6 hours after the arterial occlusion. RESULTS: Hemodynamic and metabolic parameters and blood oxygen content were not affected by the infusion of either FMA or D40. Brain and systemic temperature remained constant. The ratio of infarct volume to the hemispheric volume was 19.6 +/- 3.7% in the FMA group (n = 17), 19.9 +/- 4.6% in the D40 group (n = 16), and 40.3 +/- 5.7% in the control group (n = 17). The difference in infarct volume of both FMA and D40 animals compared with controls was statistically significant (P < .01) when tested with Student's t test. There was no significant difference between FMA and D40 groups. CONCLUSIONS: These results suggest that FMA has cerebral protective properties and should be purified, optimized, and further tested experimentally to develop a stable, efficient, and safe oxygen carrier, potentially suitable for clinical trials.

Adamantane↗

Analytical identification of ideal pulmonary-systemic flow balance in patients with bidirectional cavopulmonary shunt and univentricular circulation: oxygen delivery or tissue oxygenation?

BACKGROUND: In the present study, we extended previous mathematical modeling work on patients with bidirectional cavopulmonary ("bidirectional Glenn") anastomosis to assess the potential utility of several descriptors of oxygen status. We set out to determine which of these descriptors best represents the overall tissue oxygenation. We also introduce a new descriptor, SO2min, defined as the lower of the superior and inferior vena cava oxygen saturations. METHODS AND RESULTS: The application of differential calculus to a model of oxygen physiology of patients with bidirectional Glenn allowed simultaneous assessment of all possible distributions of blood flow and metabolic rate between upper and lower body, across all cardiac outputs, total metabolic rates, and oxygen-carrying capacities. When total cardiac output is fixed, although it may intuitively seem best to distribute flow to maximize oxygen delivery (total, upper body, or lower body), we found that for each variable, there are situations in which its maximization seriously deprives flow to the upper or lower circulation. In contrast, maximizing SO2min always gives physiologically sensible results. If the majority of metabolism is in the upper body (typical of infancy), then oxygenation is optimized when flow distribution matches metabolic distribution. In contrast, if the majority of metabolism is in the lower body (typical of older children and during exercise), oxygenation is optimal when flows are equal. CONCLUSIONS: In patients with bidirectional cavopulmonary anastomosis, because there is a tradeoff between flow distribution and saturation, it is unwise to concentrate on maximizing oxygen delivery. Maximizing systemic venous saturations (especially SO2min) is conceptually different and physiologically preferable for tissue oxygenation.

Blood Circulation↗

All-blood (miniplegia) versus dilute cardioplegia in experimental surgical revascularization of evolving infarction.

BACKGROUND: The advantages of blood cardioplegia include the oxygen-carrying capacity, superior oncotic and buffering properties, and endogenous antioxidants contained in blood. However, the partial dilution of blood in 4:1 (blood:crystalloid) cardioplegic solutions may nullify these advantages and progressively dilute blood during continuous retrograde delivery. This study tested the hypothesis that all-blood (66:1) cardioplegia provides superior myocardial protection compared with dilute (4:1) cardioplegia delivered in a continuous retrograde modality during surgical reperfusion of evolving myocardial infarction. METHODS AND RESULTS: After 60 minutes of left anterior descending coronary artery (LAD) occlusion, anesthetized canines were placed on cardiopulmonary bypass and randomized to either all-blood cardioplegia (AB group) or dilute blood cardioplegia (Dil group). After cross clamping, arrest was induced with 5 minutes of tepid (30 degrees C) antegrade potassium all-blood or dilute blood cardioplegia and maintained with tepid retrograde coronary sinus cardioplegia for a total of 1 hour. The LAD was released after 30 minutes of arrest, simulating revascularization. The cardioplegia hematocrit for the Dil group was lower than that for the AB group (7+/-1% versus 12+/-2%, P<0.05); at the end of bypass, systemic hematocrit was lower in the Dil group than in the Ab group (15+/-1% versus 20+/-1%, P<0.05). Infarct size (triphenyltetrazolium chloride staining) was comparable between the AB and Dil groups (29.6+/-2.9% versus 30.3+/-3.9% of area at risk), and there was no difference in area-at-risk myocardium systolic shortening (by sonomicrometry, -0.3+/-1% versus -0.4+/-1%). Tissue edema after bypass tended to be greater in the Dil group compared with the AB group in the heart (82+/-0% versus 81+/-1%), lung (79+/-1% versus 78+/-1%), liver (75+/-1% versus 74+/-0%), and skeletal muscle (76+/-1% versus 73+/-2%) and was significantly greater in the duodenum (80+/-1% versus 79+/-1%, P<0.05) and kidney (82+/-1% versus 79+/-1%, P<0.05). Postexperimental endothelial function (relaxation of acetylcholine) was impaired in LADs of the AB group versus the Dil group (59+/-6% versus 77+/-5%, P<0.05). CONCLUSIONS: Both all-blood cardioplegia and dilute cardioplegia have disadvantages, but these do not have an impact on the pathogenesis of infarct size or recovery of regional contractile function.

Animals↗

Dissociation of temperature-gradient and evaporative heat loss during cold gas hyperventilation in cold-induced asthma.

We examined temperature-gradient and evaporative energy losses during cold gas inhalation challenges in patients with exercise-induced asthma by using gases with similar water-carrying capacities but significantly different volume heat capacities. Seven subjects were asked to hyperventilate mixtures of 80% helium/20% oxygen (HeO2) or 80% sulfur hexafluoride/20% oxygen (SF6O2) for 5 min at a fixed target minute ventilation of 20 x FEV1 and an inspired gas temperature of 0 degrees C. Each subject equilibrated his or her lungs with the appropriate gas mixture prior to testing: PETCO2 and FIO2 were monitored and maintained at constant values (CO2 = 0.05; O2 = 0.20) by CO2 scrubbing and addition of compressed gas to the system. Gas composition, inspired and expired flow rates, and gas temperatures at the airway opening were recorded in real time using a computer-based data collection system that calculated respiratory heat loss on a per breath basis. Bronchoconstriction was quantitated using specific airway conductance measured before and serially after each challenge. The degree of bronchoconstriction correlated closely with evaporative respiratory heat loss (r = 0.658 p less than 0.05), but poorly with both temperature-gradient (r = 0.114, p greater than 0.20) and total (r = 0.268, p greater than 0.15) heat loss. These findings suggest that total respiratory heat loss is not the primary stimulus in exercise-induced asthma, and further suggest that total water loss, or focal heat/water loss, may be important in inducing bronchospasm in this subset of asthmatics.

Adult↗

Erythrocyte function and marrow regulation in hemoglobin Bethesda (beta-145 histidine).

Hemoglobin Bethesda (beta145 histidine) is one of the two mutants known to affect the penultimate hemoglobin tyrosines. The result of this substitution is extreme disorganization of the oxygenation function of the molecule. Red cells containing 45% Hb Bethesda and 55% Hb A have increased oxygen affinity but, paradoxically, a normal Bohr effect. As is usually seen with other hemoglobins with increased oxygen affinity, Hb Bethesda clinically is manifest in heterozygotes by erythrocytosis. Red cell production in affected individuals is erythropoietin dependent. The reciprocal interdependence of oxygen delivery and effective erythropoiesis was documented by alterations in erythropoietin excretion, quantitative iron kinetics, and reticulocyte production in response to phlebotomy-induced reduction in the oxygen-carrying capacity.

Adult↗

Rheology of leukocytes, leukocyte suspensions, and blood in leukemia. Possible relationship to clinical manifestations.

Suspensions of leukemic lymphocytes and myeloblasts and blood of leukemic patients were studied to examine (a) the effect of leukemic cells on blood viscosity and (b) the ability of leukemic cells to traverse channels of capillary diameter. The viscosity of suspensions of leukemic cells was dependent logarithmically on (a) shear strain rate and (b) cytocrit, although, suspensions of small lymphocytes and of myeloblasts had a similar viscosity at equivalent shear rates and cytocrit. The minimum apparent viscosity (MAV) of leukemic cells and red blood cells, measured over shear rates of 2.3-230 s(-1) was dependent logarithmically on cytocrit. However, MAV was slightly greater for leukemic cells than for red cells at cytocrits up to 20%. At cytocrits above 20%. MAV of leukemic cells increased more rapidly than that of erythrocytes. For example, at a 15% cytocrit MAV(WBC) (1.85 centipoise) was only slightly greater than MAV(RBC) (1.59); whereas, at 45% cytocrit MAV(WBC) (14.9) was markedly greater than MAV(RBC) (3.81). The blood of subjects with leukemia with marked elevation of leukocyte concentration (leukocrits of 6-32%) had 24% higher mean MAV (3.72) than blood with a similar total cytocrit composed of red cells (3.00). A negative correlation was present between leukocrit and erythrocrit in chronic lymphocytic (r = - 0.82) and chronic granulocytic (r = - 0.81) leukemia. Therefore, the modest increase in whole blood MAV in leukemia can be explained by (a) the negative association of leukocrit and erythrocrit and (b) the rarity of leukocrits over 20% and total cytocrits over 45%. However, the MAV of blood of leukemic patients was 71% greater than expected on the basis of their packed red cell volume. Hence, the ratio of hemoglobin concentration (O(2) carrying capacity) to MAV was abnormally low in the subjects with leukemia studied. Individual leukemic leukocytes were nearly rigid. The mean deformability index (DI) of leukemic myeloblasts (1.22; 1.18) and lymphocytes (1.22; 1.40) as measured by filtration and elastometry, respectively, at 50 mm H(2)O negative pressure, approached that of a rigid body (1.0) as compared to red cells studied by filtration (3.09) or elastometry (4.23). The ability of leukemic cells to traverse nucleopore filter or micropipette channels was related to cell diameter. The relevance of the rheology of leukemic cells to the interruption of blood flow and of tissue oxygen delivery and thereby to clinical manifestations of leukemia is considered.

Blood Viscosity↗

Hematopoiesis in the grey collie dog: studies of the regulation of erythropoiesis.

Hematopoiesis in the grey collie dog undergoes periodic fluctuations which involve reticulocytes, granulocytes, platelets, lymphocytes, and monocytes. This syndrome is inherited in an autosomal recessive manner and can be transmitted or abolished by appropriate bone marrow transplantation experiments, thus demonstrating this to be a primary marrow defect. Investigation of humoral regulation in this setting indicates that serum erythropoietin (ESF) also undergoes cyclic fluctuation and that shortly after the increase and peak in serum ESF levels recognizable red cell precursors appear in the marrow. Erythropoiesis in the grey collie is reciprocally related to the blood O2 carrying capacity. With phlebotomy, ESF activity and reticulocytes increase but continue to cycle, while hypertransfusion eliminates reticulocyte production completely. Neither phlebotomy nor hypertransfusion alter the underlying cycle time (11-12 days) nor influence the peaks of peripheral blood granulocytes. Thus, in these experiments, no direct evidence of competition between reticulocyte and granulocyte production is observed. In vitro studies of canine hemoglobin synthesis fail to demonstrate evidence of an inhibitor to ESF. These results indicate that periodic fluctuation of serum ESF is an integral part of the grey collie syndrome and are most consistent with some form of feedback regulation of ESF production.

Animals↗

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39 +/- 5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (VO2) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v O2 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7 +/- 2.1) despite normal oxygen carrying capacity and Hgb-O2 P50. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Qmax, patient = 303 ml/min per kg, normal men 238 +/- 36) and the slope of increase in Q relative to VO2 (i.e., delta Q/delta VO2) from rest to exercise was exaggerated (delta Q/delta VO2, patient = 29, normal men = 4.7 +/- 0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle.

Aconitate Hydratase↗

Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds.

Inhaled nitric oxide (NO) is being used more and more in intensive care units as a modality to improve the outcome of patients with pulmonary complications. Our objective was to demonstrate that inhaled NO could impact upon a distally inflamed microvasculature-improving perfusion, leukocyte adhesive interactions, and endothelial dysfunction. Using intravital microscopy to visualize ischemia/reperfusion of postcapillary venules, we were able to demonstrate that the reduction in perfusion, the dramatic increase in leukocyte rolling, adhesion, and emigration, and the endothelial dysfunction could all be significantly abrogated with 80 ppm, but not 20 ppm inhaled NO. Perfusing whole blood directly over an inert P-selectin and CD18 ligand substratum incorporated in a flow chamber recruited the same number of rolling and adhering leukocytes from NO-ventilated and non-NO-ventilated animals, suggesting that inhaled NO was not directly affecting leukocytes. To demonstrate that inhaled NO was actually reaching the peripheral microvasculature in vivo, we applied a NO synthase inhibitor locally to the feline mesentery and demonstrated that the vasoconstriction, as well as leukocyte recruitment, were essentially abolished by inhaled NO, suggesting that a NO-depleted peripheral microvasculature could be replenished with inhaled NO in vivo. Finally, inhaled NO at the same concentration that was effective in ischemia/reperfusion did not affect vascular alterations, leukocyte recruitment, and endothelial dysfunction associated with endotoxemia in the feline mesentery. In conclusion, our data for the first time demonstrate a role for inhaled NO as a therapeutic delivery system to the peripheral microvasculature, showing tremendous efficacy as an antiadhesive, antivasoconstrictive, and antipermeabilizing molecule in NO-depleted tissues, but not normal microvessels or vessels that have an abundance of NO (LPS-treated). The notion that blood borne molecules have NO carrying capacity is conceptually consistent with our observations.

Administration, Inhalation↗

Effects of venesection on leg blood flow in claudicants with high-normal haematocrit.

Patients with intermittent claudication frequently have high-normal levels of haematocrit and hence blood viscosity, which may contribute to decreased calf blood flow on exercise, and hence to the symptom of claudication. Reduction in haematocrit and viscosity by serial venesection in eight patients with stable claudication and high-normal haematocrit (mean 0.50) was performed, and the effects on claudication, calf blood flow, and calf oxygen delivery were studied. Following reduction in haematocrit to low-normal levels (mean 0.44), resting calf blood flow was unchanged; peak flow after ischaemic exercise increased slightly (+17%), but peak oxygen delivery (peak flow X haemoglobin concentration) was unchanged. Hence any increase in calf blood flow in the symptomatic leg is balanced by a decrease in oxygen-carrying capacity after venesection. No increase in claudication time would therefore be expected, and none was observed in the present study.

Adult↗

Robust motor speed control under time varying loads in moving actuator type artificial heart (AnyHeart).

The Moving Actuator type artificial heart(AnyHeart) as well as many other artificial hearts uses a motor as its power source. For controllability of control parameters such as pump rate, pump output, blood pressure profile and flow form, the precise motor speed control is important. However, because the implantable device has limited carrying capacity of hardware components in size and number, applying diverse motor control methods are not possible. In addition, the existing PI (Proportional-Integral) motor controller does not show satisfactory performance. A new controller that is sufficiently robust for the changes of load and physical system parameters has been designed and tested. The robust speed controller is based on the sliding mode control method that is applicable to a system of which the ranges of uncertainty in physical parameters are known. In a mock circulation system test, the actual speed showed good tracking characteristics in respect to the reference speed. Fast follow-up characteristics were also observed under high afterload and speed conditions. The speed error, current and power consumption were reduced by about 40%. The proposed control technique overcomes the limitations of the PI controller, and makes important improvements in both performance and stability.

Algorithms↗

The efficacy of ergogenic agents in athletic competition. Part II: Other performance-enhancing agents.

OBJECTIVE: To summarize the literature describing the epidemiology, pharmacology, efficacy, and adverse effects associated with growth hormone (GH), caffeine, aerobic metabolism facilitator (AMF), and sympathomimetic use among athletes. DATA SOURCES: Relevant articles were identified from a MEDLINE search using the search terms "Doping in Sports," "Blood," "Caffeine," "Cocaine," "Erythropoietin," "Somatotropin," and "Sympathomimetics (exploded)." Additional references were found in bibliographies of these articles. STUDY SELECTION/DATA EXTRACTION: We reviewed studies of ergogenic drug (ED) use among athletes. Interpretation of these studies is difficult because of poor research design and the paucity of information available. This necessitated the inclusion of many anecdotal or conjectural reports in our review. DATA SYNTHESIS: There are no studies documenting an ergogenic effect associated with GH use in humans or animals. It is still unknown whether GH abuse causes adverse effects in healthy adults, although GH-induced acromegaly has been suspected. Amphetamines, cocaine, and caffeine are thought to improve performance via enhanced concentration among athletes. Amphetamines and cocaine may increase aggressiveness. The ergogenic effects of other sympathomimetics including ephedrine and phenylpropanolamine are unclear. AMFs (e.g., blood doping, epoetin) enhance aerobic metabolism and endurance by increasing the oxygen-carrying capacity of the blood. Risks associated with excessive AMF use include increased blood viscosity and clotting. CONCLUSIONS: Athletes view EDs as an essential component for success. Without adequate intervention measures, ED abuse is likely to continue unchecked.

Amphetamines↗

Red cell exchange in sickle cell disease.

Red cell exchange transfusions remain an effective but possibly underutilized therapy in the acute and chronic treatment of sickle cell disease. In sickle cell disease, increased blood viscosity can cause complications when the hemoglobin exceeds 10 g/dL even if this is due to simple transfusion. Red cell exchange can provide needed oxygen carrying capacity while reducing the overall viscosity of blood. Acute red cell exchange is useful in acute infarctive stroke, in acute chest and the multi-organ failure syndromes, the right upper quadrant syndrome, and possibly priapism. Neither simple or exchange transfusions are likely to hasten resolution of an acute pain episode.

Anemia, Sickle Cell↗

On the expected relationship between inbreeding, fitness, and extinction.

We assessed the expected relationship between the level and the cost of inbreeding, measured either in terms of fitness, inbreeding depression or probability of extinction. First, we show that the assumption of frequent, slightly deleterious mutations do agree with observations and experiments, on the contrary to the assumption of few, moderately deleterious mutations. For the same inbreeding coefficient, populations can greatly differ in fitness according to the following: (i) population size; larger populations show higher fitness (ii) the history of population size; in a population that recovers after a bottleneck, higher inbreeding can lead to higher fitness and (iii) population demography; population growth rate and carrying capacity determine the relationship between inbreeding and extinction. With regards to the relationship between inbreeding depression and inbreeding coefficient, the population size that minimizes inbreeding depression depends on the level of inbreeding: inbreeding depression can even decrease when population size increases. It is therefore clear that to infer the costs of inbreeding, one must know both the history of inbreeding (e.g. past bottlenecks) and population demography.

Adaptation, Physiological↗

Wildlife reintroduction: considerations of habitat quality at the release site.

BACKGROUND: Assessing the suitability of a habitat prior to the release of animals is vital. Proper assessment of the flora will allow reintroduction programmes to determine whether the area will be capable of supporting the released animals in the long-term. Here data are presented from an island in Central Kalimantan, Indonesia which has been used as a release site for agile gibbons (Hylobates agilis albibarbis) since January 2003. RESULTS: Methods and results regarding fruit abundance, fruit productivity, tree density and diversity are presented. This information is then analysed in the context of the island's suitability to sustain released gibbons and without impact on the resident fauna. Based on the above ecological characteristics, the final carrying capacity of the island is estimated to be between 3 and 19 gibbons. CONCLUSION: These data highlight the need to survey areas being considered for release of gibbon prior to the release taking place. For reintroductions to be successful, long-term habitat assessment is vital, both pre- and post-release.

Adaptation, Physiological↗

Influence of intravenous nutrients on bilirubin transport. II. Emulsified lipid solutions.

The effects of an emulsified intravenous fat preparation (Intralipid) on bilirubin transport were analyzed by cholestyramine extraction, spectrophotometric analysis, Sephadex gel filtration, peroxidase assay, bilirubin uptake by red blood cells, and by toxicity in tissue culture (L-929) cells. Intralipid is capable of binding bilirubin, but does not compete effectively with bilirubin bound to high affinity sites on albumin. The emulsified fat appears to have a higher affinity for bilirubin than for cell membranes. Red blood cells become coated with Intralipid, resulting in an increased association of bilirubin with the cell surface, but a decrease in pigment actually incorporated into the red cell membrane. In tissue culture experiments, Intralipid protected the cells from bilirubin toxicity. It is concluded that Intralipid may enhance the carrying capacity of serum for bilirubin, and thus exert a protective effect on tissues.

Albumins↗

Hemodilution during cardiopulmonary bypass increases cerebral infarct volume after middle cerebral artery occlusion in rats.

Although the optimal hematocrit during cardiopulmonary bypass (CPB) is not defined, excessive hemodilution may lead to organ ischemia via a reduction in oxygen-carrying capacity uncompensated by autoregulatory and/or rheologic increases in organ blood flow. As a result, the consequences of hemodilution in patients at risk for cerebral ischemia are not clearly understood. We designed this study to evaluate the effects of hemodilution in the setting of focal cerebral ischemia during CPB. Wistar rats surgically prepared for CPB were randomized to either hemodilution (hemoglobin (Hb), 6 g/dL; n = 9) or control (Hb, 11 g/dL; n = 8) groups and subsequently exposed to focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Immediately after the onset of MCAO (maintained for 90 min), 65 min of hypothermic (28 degrees C) CPB was initiated. Twenty-four hours later, functional neurological outcome and cerebral infarct volume were determined. Compared with controls, the hemodilution group had worse neurological performance (new score = 8 [2], hemodilution; versus 10 [2], control; P = 0.030) and larger total cerebral infarct volumes (182 +/- 84 mm(3), hemodilution; versus 103 +/- 58 mm(3), control; P = 0.043). In this experimental model of CPB with reversible MCAO-induced focal cerebral ischemia, hemodilution worsened neurological function and increased cerebral infarct volume.

Animals↗