PPARγ expression is increased in systemic lupus erythematosus patients and represses CD40/CD40L signaling pathway.

Systemic lupus erythematosus (SLE) is a heterogeneous disease involving several immune cell types and pro-inflammatory signals, including the one triggered by binding of CD40L to the receptor CD40. Peroxisome-proliferator activated receptor gamma (PPARγ) is a transcription factor with anti-inflammatory properties. Here we investigated whether CD40 and PPARγ could exert opposite effects in the immune response and the possible implications for SLE. Increased PPARγ mRNA levels were detected by real-time PCR in patients with active SLE, compared to patients with inactive SLE PPARγ/GAPDH mRNA = 2.21 ± 0.49 vs. 0.57 ± 0.14, respectively (p < 0.05) or patients with infectious diseases and healthy subjects (p < 0.05). This finding was independent of the corticosteroid therapy. We further explored these observations in human THP1 and in SLE patient-derived macrophages, where activation of CD40 by CD40L promoted augmented PPARγ gene transcription compared to non-stimulated cells (PPARγ/GAPDH mRNA = 1.14 ± 0.38 vs. 0.14 ± 0.01, respectively; p < 0.05). This phenomenon occurred specifically upon CD40 activation, since lipopolysaccharide treatment did not induce a similar response. In addition, increased activity of PPARγ was also detected after CD40 activation, since higher PPARγ-dependent transcription of CD36 transcription was observed. Furthermore, CD40L-stimulated transcription of CD80 gene was elevated in cells treated with PPARγ-specific small interfering RNA (small interfering RNA, siRNA) compared to cells treated with CD40L alone (CD80/GAPDH mRNA = 0.11 ± 0.04 vs. 0.05 ± 0.02, respectively; p < 0.05), suggesting a regulatory role for PPARγ on the CD40/CD40L pathway. Altogether, our findings outline a novel mechanism through which PPARγ regulates the inflammatory signal initiated by activation of CD40, with important implications for the understanding of immunological mechanisms underlying SLE and the development of new treatment strategies.

Enhanced expression of Fc alpha receptor I on blood phagocytes of patients with gram-negative bacteremia is associated with tyrosine phosphorylation of the FcR-gamma subunit.

Sepsis caused by gram-negative bacteria is a common finding having high incidence and mortality. Fc alpha RI (CD89), a receptor for immunoglobulin A (IgA), has been shown to mediate bacterial phagocytosis, which might play a role in the pathogenesis of sepsis. In this study the expression and function of Fc alpha RI were analyzed on blood monocytes and neutrophils of patients with bacteremia. We found a marked increased in expression of the alpha- and gamma-subunits of the Fc alpha RI on both types of cells in patients with gram-negative bacteremia, but not in patients with gram-positive bacteremia. This increase was independent of serum IgA levels. Fc alpha RI M(r) was lower on cells from gram-negative patients than on cells from controls (50-65 kDa versus 55-75 kDa), despite a similar 32-kDa backbone, indicating altered glycosylation. Increased levels of Fc alpha RI on blood phagocytes correlated with enhanced serum IL-6 levels, but not with IFN gamma or TNF-alpha. FcR-gamma chain associated with Fc alpha RI was phosphorylated in patients neutrophils, indicating functional engagement of this receptor during gram-negative sepsis. Increased expression and activation of Fc alpha RI-gamma 2 complexes following gram-negative infections suggests its involvement in host defense against bacteria.

Refeeding procedures after 43 days of total fasting.

Refeeding syndrome encompasses fluid and electrolyte imbalances and metabolic, intestinal, and cardiorespiratory derangements associated with appreciable morbidity and mortality. Although refeeding syndrome has been well documented in concentration-camp subjects, and more recently during parenteral therapy of critically ill patients, little is known about the importance of refeeding syndrome during recovery from a hunger strike. Thus, we studied the response to a four-step dietary replenishment routine in eight hunger strikers who refused food for 43 d. In this retrospective, observational study, we assessed the safety and efficacy of the refeeding procedure and analyzed the clinical and nutritional course of the cohort during both starvation and refeeding, mainly on the basis of clinical as well as a few biochemical determinations. During starvation, average weight loss was about 18% and, with the exception of occasional oral vitamins and electrolytes, the subjects consumed only water. Available body-composition and biochemical profiles showed no clinically significant changes during starvation, but one-half of the group displayed spontaneous diarrhea at some time before refeeding. Stepwise nutritional replenishment lasted for 9 d, after which all patients tolerated a full, unrestricted diet. Only one episode of diarrhea occurred during this phase, and both clinical and biochemical indexes confirmed a favorable clinical course, without any manifestation of refeeding syndrome. In conclusion, we observed the following: 1) Hypophosphatemia and other micronutrient imbalances did not occur, nor was macronutrient intolerance detected. 2) Despite some episodes of diarrhea, nutritional replenishment was not associated with significant enteral dysfunction. 3) There was some fluid retention, but this was mild. 4) Acute-phase markers were abnormally elevated during the refeeding phase, without associated sepsis or inflammation.

The role of the vagus nerve in hypertonic resuscitation of hemorrhagic shocked dogs.

Previous studies have suggested a critical role for the vagi during the hypertonic resuscitation of hemorrhagic shocked dogs. Vagal blockade prevented the full hemodynamic and metabolic recovery and increased mortality. This interpretation, however, was challenged on the grounds that the blockade also abolished critical compensatory mechanisms and therefore the animals would die regardless of treatment. To test this hypothesis, 29 dogs were bled (46.0 +/- 6.2 ml/kg, enough to reduce the mean arterial pressure to 40 mmHg) and held hypotensive for 45 min. After 40 min, vagal activity was blocked in a reversible manner (0 masculine C/15 min) and animals were resuscitated with 7.5% NaCl (4 ml/kg), 0.9% NaCl (32 ml/kg), or the total volume of shed blood. In the vagal blocked isotonic saline group, 9 of 9 dogs, and in the vagal blocked replaced blood group, 11 of 11 dogs survived, with full hemodynamic and metabolic recovery. However, in the hypertonic vagal blocked group, 8 of 9 dogs died within 96 h. Survival of shocked dogs which received hypertonic saline solution was dependent on vagal integrity, while animals which received isotonic solution or blood did not need this neural component. Therefore, we conclude that hypertonic resuscitation is dependent on a neural component and not only on the transient plasma volume expansion or direct effects of hyperosmolarity on vascular reactivity or changes in myocardial contraction observed immediately after the beginning of infusion.

Hypertonic saline resuscitation is prevented by intracerebroventricular saralasin but not by captopril.

Hypertonic saline resuscitation (HR, 7.5% NaCl, 4 ml/kg) effectively reverts severe hemorrhage, but a central neural component is probably involved in the survival response. This experiment examines the role of central angiotensinergic pathways in hemorrhage-hypertonic resuscitation interaction. Severely bled (43 +/- 2 ml/kg) pentobarbital-anesthetized dogs with chronically implanted cerebral ventricular cannulae were resuscitated with 4 ml/kg 7.5% NaCl, iv 10 min after intracerebroventricular injection of 0.5 ml normal saline (CT), 150 micrograms saralasin (in 0.5 ml saline, SR), or 10 mg captopril (in 0.5 ml saline, CP). All 10 SR-treated dogs died 2-6 h after HR. Their arterial pressure and cardiac index initially recovered to near pre-hemorrhage levels, but gradually decreased thereafter, base excess remaining at severe metabolic acidosis levels throughout. All CT- and 8/10 CP-treated dogs survived indefinitely, with near normal arterial pressure, cardiac index and base excess levels. It is therefore concluded that the inhibition of central angiotensinergic sites with the competitive antagonist saralasin effectively prevents survival after HR, whereas inhibition of angiotensin converting enzyme by captopril in cerebrospinal fluid is virtually ineffective.

Hypertonic NaCl antagonizes cardiac arrhythmia induced by bupivacaine.

We studied the effects of pretreatment with hypertonic solutions on the conduction disturbances and cardiac arrhythmias caused by iv injection of bupivacaine in anesthetized mongrel dogs. Bupivacaine was injected in doses of 3 mg/kg and 6.5 mg/kg. The hypertonic solutions used were: 7.5% NaCl, 5.4% LiCl, 50% Glucose (5 ml/kg) and 20% mannitol (10 ml/kg). Bupivacaine induced severe conduction disturbances, as reflected by significant increases in QRS complex duration, HV interval and IV interval, and severe hypotension. The arrhythmias observed were: sinus node dysfunction, nonsustained ventricular tachycardia, sustained ventricular tachycardia and ventricular fibrillation. These effects were dose dependent, and were more evident with the higher dose of bupivacaine. Among all the hypertonic solutions tested, only 7.5% NaCl effectively protected against conduction disturbances and cardiac arrhythmias. These findings suggest an important role for sodium overload in these situations and provide a potentially harmless tool for the treatment of anesthetic accidents with bupivacaine during regional anesthesia.

[Early hemodynamic effects of the rapid infusion of sodium chloride Dextran-70 hypertonic solution as treatment for hemorrhagic shock in dogs]. / Efeitos hemodinâmicos imediatos da infusão rápida de solução hipertônica de cloreto de sódio-dextran-70 para tratamento de choque hemorrágico em cães.

PURPOSE: To study the early hemodynamic effects of the rapid infusion of 7.5g/dl NaCl/ 6g/dl dextran-70 solution in dogs submitted to hemorrhagic shock. METHODS: Mongrel dogs were anesthetized with pentobarbital and a electromagnetic flowmeter probe was placed around the ascending aorta or the portal vein. By external bleeding the arterial pressure was lowered to 40mmHg and held for 30min. The animals received a 4ml/kg infusion of the hypertonic solution in 90s. Arterial blood pressure and flow were registered continuously during 3min and the derived hemodynamic variables were calculated at regular time intervals. RESULTS: The total plasma protein concentration decreased and the cardiac output showed a continuous elevation during the infusion. The arterial blood pressure showed two oscillations and then decreased during a short period of time. This moment was coincident with the initial increase of the portal flow and preceded the elevation of the systemic vascular resistance and the arterial pressure. CONCLUSION: The rapid infusion of hypertonic NaCl/dextran solution to dogs in hemorrhagic shock determines immediate and intense hemodynamic effects. During the infusion period there is volemic expansion and the cardiac output increases rapidly. The arterial pressure shows oscillations and decreases as a consequence of visceral arterial dilation before starting its final elevation that occurs as the vascular resistance increases.

Immune cells and oxidative stress in the endotoxin tolerance mouse model.

Sepsis is a systemic inflammatory response that can lead to tissue damage and death. In order to increase our understanding of sepsis, experimental models are needed that produce relevant immune and inflammatory responses during a septic event. We describe a lipopolysaccharide tolerance mouse model to characterize the cellular and molecular alterations of immune cells during sepsis. The model presents a typical lipopolysaccharide tolerance pattern in which tolerance is related to decreased production and secretion of cytokines after a subsequent exposure to a lethal dose of lipopolysaccharide. The initial lipopolysaccharide exposure also altered the expression patterns of cytokines and was followed by an 8- and a 1.5-fold increase in the T helper 1 and 2 cell subpopulations. Behavioral data indicate a decrease in spontaneous activity and an increase in body temperature following exposure to lipopolysaccharide. In contrast, tolerant animals maintained production of reactive oxygen species and nitric oxide when terminally challenged by cecal ligation and puncture (CLP). Survival study after CLP showed protection in tolerant compared to naive animals. Spleen mass increased in tolerant animals followed by increases of B lymphocytes and subpopulation Th1 cells. An increase in the number of stem cells was found in spleen and bone marrow. We also showed that administration of spleen or bone marrow cells from tolerant to naive animals transfers the acquired resistance status. In conclusion, lipopolysaccharide tolerance is a natural reprogramming of the immune system that increases the number of immune cells, particularly T helper 1 cells, and does not reduce oxidative stress.

Purine nucleotides reduce superoxide production by nitric oxide synthase in a murine sepsis model.

Sepsis involves a systemic inflammatory response of multiple endogenous mediators, resulting in many of the injurious and sometimes fatal physiological symptoms of the disease. This systemic activation leads to a compromised vascular response and endothelial dysfunction. Purine nucleotides interact with purinoceptors and initiate a variety of physiological processes that play an important role in maintaining cardiovascular function. The purpose of the present study was to investigate the effects of ATP on vascular function in a lipopolysaccharide (LPS) model of sepsis. LPS induced a significant increase in aortic superoxide production 16 h after injection. Addition of ATP to the organ bath incubation solution reduced superoxide production by the aortas of endotoxemic animals. Reactive Blue, an antagonist of the P2Y receptor, blocked the effect of ATP on superoxide production, and the nonselective P2Y agonist MeSATP inhibited superoxide production. Nitric oxide synthase (NOS) inhibition by L-NAME blocked vascular relaxation and reduced superoxide production in LPS-treated animals. In the presence of L-NAME there was no ATP effect on superoxide production. A vascular reactivity study showed that ATP increased maximal relaxation in LPS-treated animals compared to controls. The presence of ATP induced increases in Akt and endothelial NOS phosphorylated proteins in the aorta of septic animals. ATP reduces superoxide release resulting in an improved vasorelaxant response. Sepsis may uncouple NOS to produce superoxide. We showed that ATP through Akt pathway phosphorylated endothelial NOS and "re-couples" NOS function.

Treatment of hemorrhagic shock with hypertonic saline solution modulates the inflammatory response to live bacteria in lungs.

Shock and resuscitation render patients more susceptible to acute lung injury due to an exacerbated immune response to subsequent inflammatory stimuli. To study the role of innate immunity in this situation, we investigated acute lung injury in an experimental model of ischemia-reperfusion (I-R) followed by an early challenge with live bacteria. Conscious rats (N = 8 in each group) were submitted to controlled hemorrhage and resuscitated with isotonic saline (SS, 0.9% NaCl) or hypertonic saline (HS, 7.5% NaCl) solution, followed by intratracheal or intraperitoneal inoculation of Escherichia coli. After infection, toll-like receptor (TLR) 2 and 4 mRNA expression was monitored by RT-PCR in infected tissues. Plasma levels of tumor necrosis factor alpha and interleukins 6 and 10 were determined by ELISA. All animals showed similar hemodynamic variables, with mean arterial pressure decreasing to nearly 40 mmHg after bleeding. HS or SS used as resuscitation fluid yielded equal hemodynamic results. Intratracheal E. coli inoculation per se induced a marked neutrophil infiltration in septa and inside the alveoli, while intraperitoneal inoculation-associated neutrophils and edema were restricted to the interseptal space. Previous I-R enhanced lung neutrophil infiltration upon bacterial challenge when SS was used as reperfusion fluid, whereas neutrophil influx was unchanged in HS-treated animals. No difference in TLR expression or cytokine secretion was detected between groups receiving HS or SS. We conclude that HS is effective in reducing the early inflammatory response to infection after I-R, and that this phenomenon is achieved by modulation of factors other than expression of innate immunity components.

Immune cells and oxidative stress in the endotoxin tolerance mouse model

Sepsis is a systemic inflammatory response that can lead to tissue damage and death. In order to increase our understanding of sepsis, experimental models are needed that produce relevant immune and inflammatory responses during a septic event. We describe a lipopolysaccharide tolerance mouse model to characterize the cellular and molecular alterations of immune cells during sepsis. The model presents a typical lipopolysaccharide tolerance pattern in which tolerance is related to decreased production and secretion of cytokines after a subsequent exposure to a lethal dose of lipopolysaccharide. The initial lipopolysaccharide exposure also altered the expression patterns of cytokines and was followed by an 8- and a 1.5-fold increase in the T helper 1 and 2 cell subpopulations. Behavioral data indicate a decrease in spontaneous activity and an increase in body temperature following exposure to lipopolysaccharide. In contrast, tolerant animals maintained production of reactive oxygen species and nitric oxide when terminally challenged by cecal ligation and puncture (CLP). Survival study after CLP showed protection in tolerant compared to naive animals. Spleen mass increased in tolerant animals followed by increases of B lymphocytes and subpopulation Th1 cells. An increase in the number of stem cells was found in spleen and bone marrow. We also showed that administration of spleen or bone marrow cells from tolerant to naive animals transfers the acquired resistance status. In conclusion, lipopolysaccharide tolerance is a natural reprogramming of the immune system that increases the number of immune cells, particularly T helper 1 cells, and does not reduce oxidative stress.

Pressure-driven hemorrhage: a new experimental design for the study of crystalloid and small-volume hypertonic resuscitation in anesthetized dogs.

Fifty pentobarbital anesthetized dogs were subjected to pressure driven hemorrhage (PDH) in which (a) an initial bleeding rate (25 ml/min) was set, and (b) reset min-to-min in proportion to prevailing mean arterial pressure (MAP). When blood loss reached 40 ml/kg, experimental time was set to zero and dogs were divided into five groups: (1) CTR (untreated controls); (2) HSD (NaCl 7.5%-Dextran70 6%, 6 ml/kg, at zero time); (3) LR (lactated Ringers, 25 ml/min from 0-60 min); (4) HSD-LR (combines HSD and LR); (5) DBL-HSD-LR (as HSD-LR, plus second HSD injection, 4 ml/kg, at 30 min). PDH was continued throughout the postresuscitation period. CTR dogs bled 55.5 +/- 2.1 ml/kg and survived to 34.7 +/- 5.0 min postzero; HSD dogs bled 78.6 +/- 2.0 ml/kg, and survived to 51.2 +/- 2.9 min with transient recovery of MAP, cardiac output (CO), and O2 availability (O2A); LR dogs bled 94.5 +/- 3.4 ml/kg and survived for over 60 min, with sustained, partial recovery of MAP, CO, and O2A. HSD-LR dogs bled 111.5 +/- 3.7 ml/kg and survived for over 60 min with improved hemodynamic and metabolic response. In DBL-HSD-LR dogs, the second HSD produced higher MAP, CO, and O2A, but hematocrit was lowered to a critical level. Thus, standard LR resuscitation is effective in PDH, in spite of increased blood loss; a single HSD lengthens survival when used alone and improves recovery when added to LR.

Effect of hypertonic sodium chloride (7.5%) on uncontrolled hemorrhage in rats and its interaction with different anesthetic procedures.

Small volumes (4-6 ml/kg) of hypertonic NaCl (7.5%, HS) have been shown to correct the hemodynamic alterations caused by severe blood loss, but it has been claimed that its use is detrimental to rats undergoing uncontrolled arterial bleeding. The interaction between uncontrolled hemorrhage and HS was reexamined in experiments performed on male Wistar rats anesthetized with neurolidol-ketamine (NK), pentobarbital (P), chloralose (C), or urethane (U), (n = 20 in each group), half of them treated with HS (4 ml/kg IV) 15 min after start of bleeding. Uncontrolled hemorrhage was induced by cutting the tail at 12% (T12%) or 50% (T50%) from its tip. NK induced large blood loss (T50%, 32.6 ml/kg; T12%, 16.2 ml/kg) and hypotension (T50%, 70 mmHg drop, T12%; 25 mmHg). Mortality was 3/10 (T50%) and 2/10 (T12%). HS produced a significant transient recovery of mean arterial pressure (MAP) and increased blood loss to 38.9 and 21.8 ml/kg for T50% and T12% respectively, but mortality was not significantly different (T50%, 5/10; T12%, 3/10). The other three anesthetics with a T50% cut produced mild blood loss and slight hypotension, unaffected by HS. Only three of 60 rats died under these anesthetics (two HS, one untreated). In a supplementary P-anesthetized group (P-MIMIC), blood was forcibly removed from a large artery to mimic the loss observed in the NK-T50% group. Hypotension and death rates in P-MIMIC (four HS, one control) were comparable to those observed in NK-T50%. It is concluded that the effects of NK are probably due to its powerful vasodilator effect, apparently sufficient to impede the normal vasoconstrictor response to shock.

Hypertonic NaCl solution prevents bupivacaine-induced cardiovascular toxicity.

The effects of various hypertonic solutions on the intraventricular conduction disturbances and on the cardiac arrhythmias caused by the intravenous (i.v.) injection of bupivacaine were studied in sodium pentobarbital anesthetized mongrel dogs. Bupivacaine was injected in 2 doses: 3.0 mg/kg and 6.5 mg/kg. Hypertonic solutions, given intravenously 5 minutes before bupivacaine, were 7.5% NaCl, 5.4% LiCl or 50% glucose (2,400 mOsm/l, 5 ml/kg), or 20% mannitol (1,200 mOsm/l, 10 ml/kg). The highest dose of bupivacaine induced severe cardiac arrhythmias and intraventricular conduction disturbances, as reflected by significant increases in QRS complex duration, HV interval and IV interval, as well as a severe hemodynamic impairment. Significant prevention against intraventricular conduction disturbances and ventricular arrhythmias was observed with 7.5% NaCl (QRS complex duration percent increase: 164 +/- 21% in the non pretreated group vs. 75 +/- 14% in the pretreated group, P less than .01; HV interval percent increase: 131 +/- 16% in the non pretreated group vs. 58 +/- 7% in the pretreated group, P less than .01; cardiac index percent decrease: 46 +/- 6% in the non pretreated group vs. 28 +/- 5% in the pretreated group, P less than .025). The three other hypertonic solutions were ineffective. These findings suggest an involvement of sodium ions in the mechanism of hypertonic protection.

Hyperosmotic NaCl and severe hemorrhagic shock.

Intravenous infusions of highly concentrated NaCl (2,400 mosmol/l; infused volume 4 ml/kg; equivalent to 10% of shed blood), given to lightly anesthetized dogs in severe hemorrhagic shock, rapidly restore blood pressure and acid base equilibrium toward normality. No appreciable plasma volume expansion occurs for at least 12 h, indicating that fluid shift into the vascular bed plays no essential role in this response. Initial effects wee sustained indefinitely; long term survival was 100%, compared to 0% for a similar group of controls treated with saline. Hemodynamic analysis of the effects of hyperosmotic NaCl showed that these infusions substantially increase mean and pulse arterial pressure, cardiac output and mesenteric flow, whereas heart rate was slightly diminished. These effects immediately follow infusions with no tendency to dissipate with time (6-h observation). We conclude that hyperosmotic NaCl infusions increase the dynamic efficiency of the circulatory system, enabling it to adequately handle oxygen supply and metabolite clearance, despite a critical reduction of blood volume.

Hyperosmotic NaCl and severe hemorrhagic shock: role of the innervated lung.

Infusions of hyperosmotic NaCl (2,400 mosmol/l; 4 ml/kg) were given to dogs in severe hemorrhagic hypotension by intravenous injection (72 expts) or intra-aortic injection (25 expts). In 46 experiments intravenous infusions were given during bilateral blockage of the cervical vagal trunks (local anesthesia or cooling). Intravenous infusions (without vagal blockade) restore arterial pressure, cardiac output, and acid-base equilibrium to normal and cause mesenteric flow to overshoot prehemorrhage levels by 50%. These effects are stable, and indefinite survival was observed in every case. Intra-aortic infusions of hyperosmotic NaCl produce only a transient recovery of arterial pressure and cardiac output but no long-term survival. Intravenous infusions with vagal blockage produce only a transient recovery of cardiac output, with non long-term survival. Measurement of pulmonary artery blood osmolarity during and after the infusions shows that a different pattern is observed in each of these three groups and strongly indicates that the first passage of hyperosmotic blood through the pulmonary circulation at a time when vagal conduction is unimpaired is essential for the production of the full hemodynamic-metabolic response, which is needed for indefinite survival.

Central angiotensinergic system and hypertonic resuscitation from severe hemorrhage.

Single injections of 4 ml/kg hypertonic NaCl (7.5%) resuscitate dogs from severe blood loss (40-45 ml/kg). Mechanisms involve osmolarity-dependent volume expansion, increased myocardial contractility, and vasodilation. The role of central angiotensinergic pathways in the hemorrhage-hypertonic resuscitation interaction was investigated through experiments performed on male pentobarbital sodium-anesthetized dogs bled to, and held at, 40 mmHg for 30 min. Dogs were treated with 4 ml/kg of 7.5% NaCl or 32 of 0.9% NaCl iv preceded by intracerebroventricular (ICV) injections of 150 micrograms saralasin, 20 micrograms arginine vasopressin inhibitor (AVPI), or 10 micrograms morphine. ICV saralasin and morphine inhibited the full recovery response to hypertonic NaCl, whereas AVPI had no such effect. Saralasin did not inhibit the recovery from hemorrhagic shock produced by large volume isotonic saline reexpansion. These data demonstrate an interaction between the central angiotensin system and small volume hypertonic resuscitation from severe hemorrhagic shock but not between this central system and large volume isotonic reexpansion of circulatory volume. In contrast, the central vasopressinergic system does not appear to be similarly involved.

Hypertonic saline resuscitation: saturated salt-dextran solutions are equally effective, but induce hemolysis in dogs.

Hypertonic saline, or saline-dextran resuscitation is normally achieved with an Na+ load of 4.8 to 7.2 mEq/kg given in a small volume (typically 4 to 6 ml/kg NaCl 7.5%). Na+ can also be administered saturated in a smaller volume, e.g., 1 to 1.5 ml/kg NaCl 25%, with similar results. Such reduction in administered volume would be an asset in prehospital trauma management. In the present experiments, severely bled (45 ml/kg) dogs were treated with one of three NaCl/dextran-70 solutions: S1, 25% NaCl + 24% dextran (1.5 ml/kg); S2, 15% NaCl + 14.4% dextran (2.5 ml/kg); S3, 7.5% NaCl + 6% dextran (5 ml/kg). S1, S2, and S3 were pump-infused in 10 min into a peripheral vein; S1 and S2 were also given into the right atrium. S1, S2, or S3 produced a number of similar responses irrespective of the route of administration; arterial pressure, cardiac index, and base excess reverted to near control levels, plasma Na+ was raised to 155-158 mEq/L, and 5-day survival was high and comparable. Plasma volume, and total and mean red cell volumes were similarly affected in all groups; however, peripheral injections of S1 and S2 induced severe hemolysis (plasma Hgb: 53 +/- 6 and 34 +/- 4 mg/dl, respectively), while right atrial S1 and S2 caused mild hemolysis (22 +/- 3 and 14 +/- 3 mg/dl, respectively). In contrast, S3 never induced hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in body fluid and energy compartments during prolonged hunger strike.

UNLABELLED: Prolonged total food deprivation in non-obese adults is rare, and few studies have documented body composition changes in this setting. In a group of eight hunger strikers who refused alimentation for 43 days, water and energy compartments were estimated, aiming to assess the impact of progressive starvation. Measurements included body mass index (BMI), triceps skinfold (TSF), arm muscle circumference (AMC), and bioimpedance (BIA) determinations of water, fat, lean body mass (LBM), and total resistance. Indirect calorimetry was also performed in one occasion. The age of the group was 43.3+/-6.2 years (seven males, one female). Only water, intermittent vitamins and electrolytes were ingested, and average weight loss reached 17.9%. On the last two days of the fast (43rd-44th day) rapid intravenous fluid, electrolyte, and vitamin replenishment were provided before proceeding with realimentation. Body fat decreased approximately 60% (BIA and TSF), whereas BMI reduced only 18%. Initial fat was estimated by BIA as 52.2+/-5.4% of body weight, and even on the 43rd day it was still measured as 19.7+/-3.8% of weight. TSF findings were much lower and commensurate with other anthropometric results. Water was comparatively low with high total resistance, and these findings rapidly reversed upon the intravenous rapid hydration. At the end of the starvation period, BMI (21.5+/-2.6 kg/m2) and most anthropometric determinations were still acceptable, suggesting efficient energy and muscle conservation. CONCLUSIONS: 1) All compartments diminished during fasting, but body fat was by far the most affected; 2) Total water was low and total body resistance comparatively elevated, but these findings rapidly reversed upon rehydration; 3) Exaggerated fat percentage estimates from BIA tests and simultaneous increase in lean body mass estimates suggested that this method was inappropriate for assessing energy compartments in the studied population; 4) Patients were not morphologically malnourished after 43 days of fasting; however, the prognostic impact of other impairments was not considered in this analysis.