Prothrombin and activated partial thromboplastin times, thromboelastography, hematocrit, and platelet count in a feline hemorrhage/over-resuscitation model using lactated Ringer's solution or 6% tetrastarch 130/0.4.

OBJECTIVE: To describe and compare prothrombin time (PT), activated partial thromboplastin time (aPTT), thromboelastography (TEG), HCT, and platelet count measurements in a hemorrhage/over-resuscitation model. DESIGN: Randomized crossover study. SETTING: University teaching hospital. ANIMALS: Six cats. INTERVENTIONS: Anesthetized cats underwent 3 treatments at 2-month intervals. The treatments were as follows: NHR-no controlled hemorrhage and sham resuscitation; LRS-controlled hemorrhage and lactated Ringer's solution (LRS) for resuscitation; and Voluven-controlled hemorrhage and 6% tetrastarch 130/0.4 for resuscitation. The LRS and Voluven were administered at 60 and 20 mL/kg/h, respectively, for 120 minutes. Blood samples were drawn for PT, aPTT, TEG, HCT, and platelet count measurements at a healthy check (T - 7d), after controlled hemorrhage (T0), at 60 and 120 minutes of resuscitation (T60 and T120), and at 24 hours after completion of resuscitation (T24h). Data were analyzed using a general linear mixed model approach (significance was P < 0.05). MEASUREMENTS AND MAIN RESULTS: Total median blood loss (controlled hemorrhage and blood sampling from T0 to T120) at T120 was 11.4, 31.0, and 30.8 mL/kg for NHR, LRS, and Voluven, respectively. PT and aPTT during LRS and Voluven were prolonged at T60 and T120 compared to NHR (P < 0.001). On TEG, the reaction time, kinetic time, and alpha-angle were within reference intervals for cats at all time points in all treatments, while maximum amplitude was less than the reference interval (40 mm) at T0, T60, and T120 during Voluven and at T60 and T120 during LRS compared to NHR (both P < 0.001). The HCT and platelet count were significantly lower at T60 and T120 during LRS and Voluven compared to NHR (P < 0.001). CONCLUSIONS: Hypocoagulopathy was observed during hemorrhage and liberal fluid resuscitation. Prolongation of PT and aPPT and decreased clot strength may have been caused by hemodilution and platelet loss.

Elaborate cooperation of poly(rC)-binding proteins 1/2 and glutathione in ferroptosis induced by plasma-activated Ringer's lactate.

Reactive species are involved in various aspects of neoplastic diseases, including carcinogenesis, cancer-specific metabolism and therapeutics. Non-thermal plasma (NTP) can directly provide reactive species, by integrating atmospheric and interjacent molecules as substrates, to represent a handy strategy to load oxidative stress in situ. NTP causes apoptosis and/or ferroptosis specifically in cancer cells of various types. Plasma-activated Ringer's lactate (PAL) is another modality at the preclinical stage as cancer therapeutics, based on more stable reactive species. PAL specifically kills malignant mesothelioma (MM) cells, employing lysosomal ·NO as a switch from autophagy to ferroptosis. However, the entire molecular mechanisms have not been elucidated yet. Here we studied cytosolic iron regulations in MM and other cancer cells in response to PAL exposure. We discovered that cells with higher catalytic Fe(II) are more susceptible to PAL-induced ferroptosis. PAL caused a cytosolic catalytic Fe(II)-associated pathology through iron chaperones, poly (rC)-binding proteins (PCBP)1/2, inducing a disturbance in glutathione-regulated iron homeostasis. PCBP1/NCOA4-mediated ferritinophagy started at a later phase, further increasing cytosolic catalytic Fe(II), ending in ferroptosis. In contrast, PCBP2 after PAL exposure contributed to iron loading to mitochondria, leading to mitochondrial dysfunction. Therapeutic effect of PAL was successfully applied to an orthotopic MM xenograft model in mice. In conclusion, PAL can selectively sensitize MM cells to ferroptosis by remodeling cytoplasmic iron homeostasis, where glutathione and PCBPs play distinct roles, resulting in lethal ferritinophagy and mitochondrial dysfunction. Our findings indicate the clinical application of PAL as a ferroptosis-inducer and the potential of PCBPs as novel targets in cancer therapeutics.

Effects of a fortified balanced salt solution and Ringer's lactate solution on anterior chamber inflammation after phacoemulsification in diabetes.

PURPOSE: To compare the effects of a fortified balanced salt solution (fSS) and Ringer's lactate solution (Ringer) on anterior chamber (AC) inflammation in patients undergoing phacoemulsification. SETTING: Tianjin Medical University Eye Hospital, Tianjin, China. DESIGN: Prospective masked controlled trial. METHODS: 80 patients (40 patients with regular cataract and 40 cataract patients with diabetes mellitus [DM]) were randomized to receive either fSS (n = 40) or Ringer's solution (n = 40). Anterior-segment optical coherence tomography was used to evaluate AC cells and flare. Transepithelial electrical resistance (TEER) and zonula occludens-1 (ZO-1) immunofluorescence were used for tight junction examination. Monocytic leukemia cell line (Tohoku Hospital Pediatrics-1 [THP-1]) transmigration assay was performed to observe the effects of the 2 perfusates on the inflammatory response in vitro. RESULTS: In patients with regular cataracts, postoperative AC cells and flare on the 1st and 7th days were not significantly different between the Ringer and fSS groups. However, in cataract patients with DM, AC cells were higher in the Ringer group than in the fSS group ( P = .003) on postoperative day 1. The AC flare was also significantly higher in the Ringer group than in the fSS group ( P < .0001). No significant differences between the groups were observed on day 7. Compared with Ringer, fSS increased the TEER value and ZO-1 content and reduced the adhesion of THP-1 cells. CONCLUSIONS: The results of this study indicated that early postoperative AC inflammation is more severe in patients with cataracts and DM. In addition, fSS attenuates inflammation by protecting the blood-aqueous barrier and inhibiting the exudation of inflammatory cells.

Efficacy of periodic cold plasma treatment in a paddy to produce white-core grains in brewer's rice cultivar Yamadanishiki.

We investigated the effect of cold plasma application on the yield and grain quality of rice (Oryza sativa L.), focusing on the brewer's rice cultivar, Yamadanishiki. Two treatment methods were examined in a paddy; direct plasma irradiation of seedlings and indirect treatment with plasma-activated Ringer's lactate solution (PAL) during the vegetative growth phase. Periodic direct irradiation for 30 s increased whole plant weight and grain yield. Treatment with PAL promoted some growth of panicles relatively and partially suppressed the growth of culms and leaves. Both treatments affected the grain quality; an increase of the ratio of white-core grains to total number of grains, which is suited for producing Japanese sake rice, as well as a decrease of the ratio of immature grains. The results showed that the effective production of rice grains for sake production can be improved by the application of cold plasma treatment of rice seedlings in a paddy.HighlightRice plants of brewer's rice cultivar in a paddy were treated with cold plasma, by the direct irradiation of plants and the immersed of plants in plasma-activated Ringer's lactate (PAL).Direct plasma irradiation promoted plant weight, grain ripening, and increased yield.PAL treatment affected the growth of main stem and promoted the growth of panicles relatively.Both treatments improved the producing white-core grains, in addition to promotion of grain ripening.Cold plasma treatment can be applied to produce stable and high-quality food in various agriculture and food industries, which can achieve the sustainable developmental goals (SDGs).

EFFECT OF IRRIGATION FLUID COMPOSITION ON HEMOSTASIS IN MOUSE BLEEDING MODELS.

ABSTRACT: Introduction: Intraoperative irrigation, usually with normal saline (NS), aids in bleeding identification and management. We investigated the effect of different irrigation fluids, with additives, on hemostasis using two bleeding models. Methods: C57BL/6 J mice were subjected to a tail bleed model or uncontrolled abdominal hemorrhage via liver laceration followed by abdominal cavity irrigation. We compared NS, lactated Ringer's (LR), and PlasmaLyte. We examined NS and LR at different temperatures. Normal saline or LR with calcium (Ca 2+ ) or tranexamic acid (TXA) was studied. Results: Compared with room temperature (RT), increasing the temperature of the irrigation fluid to 37°C and 42°C reduced tail vein bleeding times substantially in both NS and LR (all P < 0.001), with no significant differences between the two fluids. At RT, LR, but not PlasmaLyte, substantially reduced bleeding times in comparison to NS ( P < 0.0001). Liver injury blood loss was lower with LR ( P < 0.01). Normal saline supplemented with 2.7 mEq/L of Ca 2+ decreased bleeding time and blood loss volume ( P < 0.001 and P < 0.01, respectively) to similar levels as LR. Normal saline with 150 mg/mL of TXA markedly reduced bleeding time ( P < 0.0001), and NS with 62.5 mg/mL TXA decreased blood loss ( P < 0.01). Conclusion: Whereas Ca 2+ - and TXA-supplemented NS reduced bleeding, LR remained superior to all irrigation fluid compositions. As LR contains Ca 2+ , and Ca 2+ -supplemented NS mirrored LR in response, Ca 2+ presence in the irrigation fluid seems key to improving solution's hemostatic ability. Because warming the fluids normalized the choice of agents, the data also suggest that Ca 2+ -containing fluids such as LR may be more suitable for hemostasis when used at RT.

Dispelling myths and misconceptions about the treatment of acute hyperkalemia.

Hyperkalemia represents a widespread and potentially lethal condition that affects millions of people across their lives. Despite the prevalence and severity of the condition, there are no consensus guidelines on the treatment of hyperkalemia or even a standard definition. Herein, we provide a succinct review of what we believe to be the most significant misconceptions encountered in the emergency care of hyperkalemia, examine current available literature, and discuss practical points on several modalities of hyperkalemia treatment. Additionally, we review the pathophysiology of the electrocardiographic effects of hyperkalemia and how intravenous calcium preparations can antagonize these effects. We conclude each section with recommendations to aid emergency physicians in making safe and efficacious choices for the treatment of acute hyperkalemia.

Non-thermal plasma-activated lactate solution kills U251SP glioblastoma cells in an innate reductive manner with altered metabolism.

Ringer's lactate solution irradiated by non-thermal plasma, comprised of radicals, electrons, and ions, is defined as plasma-activated lactate (PAL). PAL exhibited antitumor effects in glioblastoma U251SP cells, which we termed PAL-specific regulated cell death. In contrast to the oxidative stress condition typical of cells incubated in plasma-activated medium (PAM), U251SP cells treated with Ringer's lactate solution or PAL exhibited changes in intracellular metabolites that were reductive in the redox state, as measured by the ratio of oxidative/reductive glutathione concentrations. In the metabolomic profiles of PAL-treated cells, the generation of acetyl-CoA increased for lipid metabolism from alanine and asparagine. PAL thus induces regulated death of U251SP glioblastoma cells in more innate microenvironments than PAM.

Reperfusion using lactate Ringer's mixture partially eliminates IGF II receptor involved cardiac damage caused by hemorrhagic shock in diabetic rats.

Diabetes is a metabolic disorder that damages many organs. We investigated the effects of reperfusion using lactate Ringer's solution (LR) in a diabetic animal model. Eight-week-old rats were divided into groups: control, hemorrhagic shock induced (HS), diabetes mellitus (DM), DM plus HS (DM + HS) and DM rats that received LR after HS (DM + HS + LR). HS was induced by withdrawing blood from the femoral artery and arterial pressure was maintained at 40 mm Hg for 1 h. Animals were perfused with either withdrawn blood or LR. Rats were sacrificed and hearts were collected from all groups. Histopathological studies were performed using left ventricles and western blotting analysis was performed using protein extracted from the left ventricle. Using the TUNEL assay, we found more apoptotic cells in the DM + HS group compared to the control group, whereas in animals resuscitated with LR, the number of apoptotic cells was reduced. Western blotting showed a significant reduction in apoptotic markers, cyt c, cas 9 and cas 3, and increased survival markers, pPI3K and pAKT, in the DM + HS + LR group. Reperfusion with LR may have therapeutic effects on trauma induced HS by blocking the IGF II R facilitated apoptosis pathway in diabetic rats.

In vitro effects of lactated Ringer's solution, hypertonic saline, hydroxyethyl starch, hypertonic saline/hydroxyethyl starch, and mannitol on thromboelastographic variables of canine whole blood.

OBJECTIVE: To assess the in vitro effects of crystalloid and colloid IV fluids on the thromboelastographic (TEG) variables of canine whole blood. DESIGN: In vitro experimental study. SETTING: Veterinary teaching hospital. ANIMALS: Twenty-two healthy dogs. INTERVENTION: Citrated whole blood samples collected from healthy dogs were diluted with 3.4% hypertonic saline (HTS 3.4), 7% hypertonic saline (HTS 7), and 20% mannitol at 8% and 16% dilutions; hydroxyethyl starch 130/0.4 (HES 130/0.4) at 16% dilution; lactated Ringer's solution (LRS) at 16%, 33%, and 66% dilutions; and HTS 7-HES 130/0.4 at 25% and 50% dilutions. Kaolin-activated TEG analysis was concurrently performed on diluted and control (undiluted) samples. MEASUREMENTS AND MAIN RESULTS: Dilution of canine whole blood with LRS compared to control reduced α angle and MA at both 33% (P = 0.009 and P = 0.011, respectively) and 66% dilution (P < 0.001 and P < 0.001, respectively), and prolonged K time at 66% dilution (P = 0.003). At 16% dilution, HTS 3.4, prolonged R time (P = 0.007), while mannitol, a fluid iso osmolar to HTS 3.4, prolonged K time (P = 0.006), reduced α angle (P < 0.001), MA (P = 0.046), and LY60 (P = 0.015). At 8% dilution, HTS 7, a fluid of high osmolarity and tonicity, prolonged R time (P = 0.009) and reduced MA (P = 0.015), while all measured TEG variables were altered at the 16% dilution (P < 0.01 for all variables). HES 130/0.4 reduced α angle (P = 0.031) and MA (P = 0.001) and increased LY60 (P < 0.001) at 16% dilution. Comparing different fluid types, HES 130/0.4 and HTS 3.4 had no to minor, mannitol intermediate, and HTS 7 profound effects on TEG variables (P < 0.05) when compared to LRS at the same dilution. CONCLUSIONS: In vitro dilution of canine whole blood with commonly used IV fluids leads to thromboelastographic changes consistent with hypocoagulability in a dose dependent manner for all fluid types tested. Viscoelastic changes are also influenced by fluid characteristics, specifically tonicity and osmolarity.

Hypertonic saline and seawater solutions damage sinonasal epithelial cell air-liquid interface cultures.

BACKGROUND: Nasal irrigation (NI) is commonly used to treat several sinonasal diseases, including chronic rhinosinusitis with nasal polyps (CRSwNP); however, the effects of NI on the sinonasal epithelium are not fully known. The aim of this study was to investigate the effects of commonly used NI solutions on epithelial mucociliary and barrier functionality in primary cultured human nasal epithelial cells (HNECs). METHODS: HNECs from control subjects and patients with CRSwNP were established as air-liquid interface (ALI) cultures. Differentiated cultures were treated with different NI solutions, including isotonic 0.9% and hypertonic 3.0% saline, isotonic and hypertonic seawater, and Ringer lactate solution. The changes in ciliary beat frequency (CBF), numbers of ciliated and goblet cells, and cytotoxicity were measured. Epithelial barrier functionality was assessed by measuring the transepithelial electric resistance (TER), paracellular flux, and expression of tight junction protein zonula occludens-1 (ZO-1) and occludin. RESULTS: Isotonic saline, isotonic seawater, and Ringer lactate solutions did not affect epithelial mucociliary and barrier function in either control or CRSwNP-derived ALI cultures; however, hypertonic saline induced a significant disruption of these cell functions in both cultures. Hypertonic seawater caused a transient decrease of CBF and TER in CRSwNP-derived ALI cultures, in contrast to inducing an obvious mucociliary and barrier dysfunction and cytotoxicity in control ALI cultures. CONCLUSION: Although isotonic NI solutions appear to not affect epithelial mucociliary and barrier function in control and CRSwNP-derived ALI cultures, hypertonic saline and seawater solutions damaged sinonasal epithelial cells in ALI cultures. The safety and efficacy of these solutions requires further investigation.

Population-based volume kinetics of crystalloids and colloids in healthy volunteers.

We characterized the volume kinetics of crystalloid solutions (Ringer's lactate solution and 5% dextrose water) and colloid solutions (6% tetrastarch and 10% pentastarch) by nonlinear mixed-effects modeling in healthy volunteers. We also assessed whether the bioelectrical impedance analysis parameters are significant covariates for volume kinetic parameters. Twelve male volunteers were randomly allocated to four groups, and each group received the four fluid solutions in specified sequences, separated by 1-week intervals to avoid any carryover effects. Volunteers received 40 ml/kg Ringer's lactate solution, 20 ml/kg 5% dextrose water, 1000 ml 6% tetrastarch, and 1000 ml 10% pentastarch over 1 h. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. Bioelectrical impedance spectroscopy (BIS, INBODY S10, InBody CO., LTD, Seoul, Korea) was also carried out at preset time points. In total, 671 hemoglobin-derived plasma dilution data points were used to determine the volume kinetic characteristics of each fluid. The changes in plasma dilution induced by administration of crystalloid and colloid solutions were well-described by the two-volume and one-volume models, respectively. Extracellular water was a significant covariate for the peripheral volume of distribution at baseline in the volume kinetic model of Ringer's lactate solution. When the same amount was administered, the colloid solutions had ~4 times more plasma expansion effect than did the crystalloid solutions. Starches with larger molecular weights maintained the volume expansion effect longer than those with smaller molecular weights.

Comparing the treatment effect of narrow spectrum antimicrobial, probiotic and fluid with amoxicillin in mink kits (Neovison vison) with pre-weaning diarrhea.

Pre-weaning diarrhea in mink kits (PWD), also known as "sticky kits" is a multifactorial syndrome of considerable concern in the mink production. Evidence based treatment protocols are not available, and treatment is therefore empirical and often based on the use of antimicrobials. The purpose of the study was to test the effect of 3 alternative treatments to a standard antibiotic treatment, to characterize the study groups microbiologically, and finally to compare the intestinal microbiota of the different treatment groups at the age of 42 days. In total, 226 one to three week old mink kits with PWD from 36 litters were treated with either 1) Lactobacillus reuteri, 2) benzylpenicillin, 3) Ringer lactate or 4) amoxicillin (controls). Effects of the treatments were measured as weight gain from day 0 to day 15 and mortality. Multivariable linear mixed model regression showed no significant difference in weight gain between probiotic-, penicillin or fluid-treated mink kits and the amoxicillin treated controls. There was also no significant difference in mortality risk between the treatment groups. Bacterial culture and next generation sequencing of the viral contents showed that the study groups were uniform with a high frequency of Staphylococcus intermedius group (SIG) bacteria, Escherichia coli, Enterococcus hirae, Mamastrovirus and Sapovirus which were representative for mink kits with PWD. 16S sequencing results of the bacterial microbiota, when the kits were 42 days old were dominated by clostridia in all groups and showed no clear differences in the bacterial composition between the different treatment groups.

Fluid management in patients undergoing cardiac surgery: effects of an acetate- versus lactate-buffered balanced infusion solution on hemodynamic stability (HEMACETAT).

BACKGROUND: Recent evidence suggests that acetate-buffered infusions result in better hemodynamic stabilization than 0.9% saline in patients undergoing major surgery. The choice of buffer in balanced crystalloid solutions may modify their hemodynamic effects. We therefore compared the inopressor requirements of Ringer's acetate and lactate for perioperative fluid management in patients undergoing cardiac surgery. METHODS: Using a randomized controlled double-blind design, we compared Ringer's acetate (RA) to Ringer's lactate (RL) with respect to the average rate of inopressor administered until postoperative hemodynamic stabilization was achieved. Secondary outcomes were the cumulative dose of inopressors, the duration of inopressor administration, the total fluid volume administered, and the changes in acid-base homeostasis. Patients undergoing elective valvular cardiac surgery were included. Patients with severe cardiac, renal, or liver disease were excluded from the study. RESULTS: Seventy-five patients were randomly allocated to the RA arm, 73 to the RL. The hemodynamic profiles were comparable between the groups. The groups did not differ with respect to the average rate of inopressors (RA 2.1 mcg/kg/h, IQR 0.5-8.1 vs. RL 1.7 mcg/kg/h, IQR 0.7-8.2, p = 0.989). Cumulative doses of inopressors and time on individual and combined inopressors did not differ between the groups. No differences were found in acid-base parameters and their evolution over time. CONCLUSION: In this study, hemodynamic profiles of patients receiving Ringer's lactate and Ringer's acetate were comparable, and the evolution of acid-base parameters was similar. These study findings should be evaluated in larger, multi-center studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT02895659 . Registered 16 September 2016.

Influence of systemic hemodynamics on microcirculation during sepsis.

PURPOSE: During sepsis, improvement of hemodynamic may not be related to improvement of microcirculation. The aim of this study was to investigate influence of systemic circulation on microcirculation in septic ICU patients. METHODS: This is a prospective cohort study of septic ICU patients. Microcirculation was investigated with Near infrared spectrometry (NIRS) measuring tissue oxygen saturation (StO2). StO2 desaturation (desStO2) and resaturation (resStO2) slopes were determined. Analyses were made at baseline and after fluid challenges. RESULTS: Seventy-two patients were included. One hundred and sixty measures were performed at baseline. StO2 was 77.8% [72.4-85.0] and resStO2 was 87.3%/min [57.8-141.7]. Univariate analysis showed an association between resStO2 and diastolic arterial pressure (DAP) (p = .001), and norepinephrine dose (p = .033). In multivariate linear regression, there was an association between resStO2 and DAP (ß = 1.85 (0.64 to 3.08), p = .004). Fluid challenges (n = 60) increased CO, and resStO2 (all p < .001). In multivariate analysis, variation of stroke volume was associated with variation of resStO2 (p = .004) after fluid challenge. There was no association between CVP and resStO2. CONCLUSIONS: DAP was the only independent determinant of resStO2 in septic patients. Fluid challenges may improve microcirculation. CVP did not influence resStO2.

Hypertonic saline resuscitation protects against kidney injury induced by severe burns in rats.

BACKGROUND: Proper fluid resuscitation can relieve visceral damage and improve survival in severely burned patients. This study compared the effectiveness of resuscitation with 400mEq/L hypertonic saline (HS) and sodium lactate Ringer's solution (LR) in rats with kidney injury caused by burn trauma. METHODS: Rats (Sprague-Dawley) underwent burn injury and were randomized into sham, LR, and HS groups. Samples from the kidney were assayed for water content ratio, histopathology, and oxidative stress (superoxide dismutase (SOD) and malondialdehyde (MDA)). Serum sodium, renal function (creatinine and cystatin (Cys)-C), and inflammatory response (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and high mobility group protein box (HMGB)-1) were also examined as serum markers. RESULTS: Hypertonic saline resuscitation reduced the renal water content ratio and improved renal histopathology caused by severe burns. This effect was accompanied by reductions in serum creatinine and Cys-C as well as TNF-α, IL-1ß, and HMGB1. Serum sodium concentration and SOD activity were increased, whereas MDA content was decreased in the kidney tissue of the HS group. CONCLUSIONS: The data indicate that 400mEq/L HS solution reduces hyponatremia and renal edema, inhibits the release of inflammatory mediators, and alleviates oxidative stress injury, thus protecting against kidney injury induced by severe burns.

Enhanced ability of plasma-activated lactated Ringer's solution to induce A549 cell injury.

Non-thermal plasma (NTP) is applicable to living cells and has emerged as a novel technology for cancer therapy. Plasma-activated medium (PAM), which is prepared by the irradiation of culture medium with NTP, induces cell death in cancer cells. However, difficulties are associated with applying PAM to the clinical phase because culture media cannot be used for medical treatments. The objectives of the present study were to demonstrate the inhibitory effects of plasma-activated lactated Ringer's solution (PAL) on the viability of the A549 cancer cell line and elucidate the underlying mechanisms. The anti-tumor activity of PAL was significantly stronger than that of PAM, whereas their concentrations of H2O2 and nitrite were similar. Lactated Ringer's solution (Lac-R) consists of lactate and three types of inorganic salts. The results showing that NTP irradiation of the lactate solution rather than the inorganic salt solution induced the inactivation of catalase were dependent on the presence or absence of nitrite in these solutions. We detected nitrotyrosine in A549 cells treated with PAM or PAL, and the addition of catalase to PAM rather than to PAL reduced its production. The PAL treatment of A549 cells led to mitochondrial dysfunction with the down-regulation of NF-κB-Bcl2 signaling.

Protection of cerebral microcirculation, mitochondrial function, and electrocortical activity by small-volume resuscitation with terlipressin in a rat model of haemorrhagic shock.

BACKGROUND: During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer's solution (LR) on early recovery of microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. METHODS: Animals treated with LR replacing three times (3LR) the volume bled (n=26), terlipressin (n=27), terlipressin plus 1LR (n=26), 2LR (n=16), or 3LR (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials, spinal cord dorsum potential, and peripheral electromyography. RESULTS: Compared with sham treatment, haemorrhagic shock reduced the mean (SD) area of perfused vessels [82% (sd 10%) vs 38% (12%); P<0.001] and impaired oxygen concentration, mitochondrial redox state [99% (4%) vs 59% (15%) of baseline; P<0.001], and somatosensory evoked potentials [97% (13%) vs 27% (19%) of baseline]. Administration of terlipressin plus 1LR or 2LR was able to recover these measures, but terlipressin plus 3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. CONCLUSIONS: Resuscitation from haemorrhagic shock using terlipressin with small-volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological functions.