Advantages of pyruvate-based fluids in preclinical shock resuscitation-A narrative review.

This review focuses on the innate beneficial effects of sodium pyruvate-based fluids, including pyruvate in intravenous solutions, oral rehydration solutions, and peritoneal dialysis solutions, on shock resuscitation with various animal models relative to current commercial fluids over the last two decades. Due to its superior pharmacological properties, pyruvate effectively sustains cytosolic glycolytic pathways and mitochondrial oxidative phosphorylation by restoration of redox potentials and reactivation of pyruvate dehydrogenase in hypoxia, even anoxia, and diabetes, reversing the Warburg effect and diabetic glucometabolic aberration. Pyruvate has been demonstrated to protect against multiorgan dysfunction and metabolic disturbance in numerous preclinical studies with various pathogenic injuries. The unique features of pyruvate potential clinical benefits encompass to efficiently correct lethal lactic acidosis via metabolically rapid consumption of intracellular [H+] and robustly protect multiorgan metabolism and function, particularly visceral organs in addition to the heart and brain, significantly prolonging survival in various animal models. Pyruvate protection of red blood cell function and preservation of the partial pressure of arterial oxygen should be highly concerned in further studies. Pyruvate is much advantageous over existing anions such as acetate, bicarbonate, chloride, and lactate in commercial fluids. Pyruvate-based fluids act as a therapeutic agent without causing iatrogenic resuscitation injury in addition to being a volume expander, indicating a potential novel generation of resuscitation fluids, including crystalloids and colloids. Pyruvate-based fluids have an enormous potential appeal for clinicians who face the ongoing fluid debate to readily select as the first resuscitation fluid. Clinical trials with pyruvate-based fluids in shock resuscitation are urgently warranted.

Pyruvate as a Potential Beneficial Anion in Resuscitation Fluids.

There have been ongoing debates about resuscitation fluids because each of the current fluids has its own disadvantages. The debates essentially reflect an embarrassing clinical status quo that all fluids are not quite ideal in most clinical settings. Therefore, a novel fluid that overcomes the limitations of most fluids is necessary for most patients, particularly diabetic and older patients. Pyruvate is a natural potent antioxidant/nitrosative and anti-inflammatory agent. Exogenous pyruvate as an alkalizer can increase cellular hypoxia and anoxia tolerance with the preservation of classic glycolytic pathways and the reactivation of pyruvate dehydrogenase activity to promote oxidative metabolism and reverse the Warburg effect, robustly preventing and treating hypoxic lactic acidosis, which is one of the fatal complications in critically ill patients. In animal studies and clinical reports, pyruvate has been shown to play a protective role in multi-organ functions, especially the heart, brain, kidney, and intestine, demonstrating a great potential to improve patient survival. Pyruvate-enriched fluids including crystalloids and colloids and oral rehydration solution (ORS) may be ideal due to the unique beneficial properties of pyruvate relative to anions in contemporary existing fluids, such as acetate, bicarbonate, chloride, citrate, lactate, and even malate. Preclinical studies have demonstrated that pyruvate-enriched saline is superior to 0.9% sodium chloride. Moreover, pyruvate-enriched Ringer's solution is advantageous over lactated Ringer's solution. Furthermore, pyruvate as a carrier in colloids, such as hydroxyethyl starch 130/0.4, is more beneficial than its commercial counterparts. Similarly, pyruvate-enriched ORS is more favorable than WHO-ORS in organ protection and shock resuscitation. It is critical that pay attention first to improving abnormal saline with pyruvate for ICU patients. Many clinical trials with a high dose of intravenous or oral pyruvate were conducted over the past half century, and results indicated its effectiveness and safety in humans. The long-term instability of pyruvate aqueous solutions and para-pyruvate cytotoxicity is not a barrier to the pharmaceutical manufacturing of pyruvate-enriched fluids for ICU patients. Clinical trials with sodium pyruvate-enriched solutions are urgently warranted.

Effects of sodium pyruvate supplementation on repeated sprint exercise performance and recovery in male college soccer players: a randomized controlled trial.

BACKGROUND: Sodium pyruvate (PYR) has been reported to improve aerobic metabolism and attenuate metabolic acidosis. Aerobic capacity and the ability to remove hydrogen ions affect the recovery from repeated high intensity activities. However, the effects of PYR supplementation on repeated sprint exercise (RSE) performance have not been elucidated. This study explored the effects of PYR ingestion on RSE ability and recovery. METHODS: A total of 14 male soccer athletes (aged 20±2 years) participated in this double-blinded crossover study. The subjects completed two experimental sessions after randomized ingestion of either PYR or the maltodextrin placebo (PLA) for 1 week. At each session, participants completed high-intensity interval exercise (HIIE) and RSE 60 minutes after supplementation. Additionally, acid-base parameters in venous blood, energy system contributions, and power output were assessed. RESULTS: Compared to PLA, PYR supplementation significantly increased the relative peak power output (PPO) of the first (P=0.034) and fifth (P=0.043) sprints, and the relative mean power output (MPO) of the fifth sprint (P=0.026). In addition, the mean PPO (P=0.031) and MPO (P=0.033) of sprints 1-6 were significantly elevated after PYR supplementation. After PYR administration, the phosphagen energy system [adenosine triphosphate (ATP)-phosphocreatine (PCr)] resynthesis of the fourth (P=0.034) and the overall recovery periods during HIIE (P=0.029) were higher than PLA administration. Additionally, the ATP-PCr resynthesis of the first (P=0.033) and fifth (P=0.019) recovery periods, and the mean of the six recovery periods during RSE (P=0.041) were increased in the PYR group compared to the PLA group. Furthermore, participants on the PYR regimen had higher blood pH, HCO3-, and base excess at pre-HIIE, post-HIIE, and pre-RSE (all P<0.05) compared to participants receiving PLA. CONCLUSIONS: PYR supplementation enhanced RSE performance, and the improvement may be attributed to accelerated restoration of the acid-base balance and ATP-PCr regeneration. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100053936.

NAD+, Senolytics, or Pyruvate for Healthy Aging?

In last decades, healthy aging has become one of research hotspots in life science. It is well known that the nicotinamide adenine dinucleotide oxidized form (NAD+) level in cells decreases with aging and aging-related diseases. Several years ago, one of NAD+ precursors was first demonstrated with its new role in DNA damage repairing in mice, restoring old mice to their physical state at young ones. The finding encourages extensive studies in animal models and patients. NAD+ and its precursors have been popular products in nutrition markets. Alternatively, it was also evidenced that clearance of cellular senescence by senolytics preserved multiorgan (kidney and heart) function and extended healthy lifespan in mice. Subsequent studies confirmed findings in elderly patients subjected with idiopathic pulmonary fibrosis. The senolytic therapy is now focused on various diseases in animal and clinical studies. However, pyruvate, as both a NAD+ substitute and a new senolytic, may be advantageous, on the equimolar basis, over current products above in preventing and treating diseases and aging. Pyruvate-enriched fluids, particularly pyruvate oral rehydration salt, may be a novel intervention for diseases and aging besides critical care. Albeit the direct evidence that benefits healthy aging is still limited to date, pyruvate, as both NAD+ provider and senolytic agent, warrants intensive research to compare NAD+ or senolytics for healthy aging, specifically on the equimolar basis, in effective blood levels. This review briefly discussed the recognition of healthy aging by comparing NAD+ and Senolytics with sodium pyruvate from the clinical point of view.

Pyruvate-Enriched Oral Rehydration Solution Improves Glucometabolic Disorders in the Kidneys of Diabetic db/db Mice.

Diabetes is prevalent worldwide, but ideally intensive therapeutic strategy in clinical diabetes and diabetic nephropathy (DN) is still lack. Pyruvate is protective from glucometabolic disturbances and kidney dysfunction in various pathogenic insults. Present studies focused on oral pyruvate effects on diabetes status and DN with 0.35% pyruvate in pyruvate-enriched oral rehydration solution (Pyr-ORS) and 1% pyruvate as drinking water for 8 weeks, using the model of diabetic db/db mice. Both Pyr-ORS and 1% pyruvate showed comparable therapeutic effectiveness with controls of body weight and blood sugar, increases of blood insulin levels, and improvement of renal function and pathological changes. Aberrant key enzyme activities in glucometabolic pathways, AR, PK, and PDK/PDH, were also restored; indexes of oxidative stress and inflammation, NAD+/NADH ratio, and AGEs in the kidneys were mostly significantly preserved after pyruvate treatments. We concluded that oral pyruvate delayed DN progression in db/db mice and the modified Pyr-ORS formula might be an ideal novel therapeutic drink in clinical prevention and treatment of type 2 diabetes and DN.

Pyruvate alleviates high glucose-induced endoplasmic reticulum stress and apoptosis in HK-2 cells.

Endoplasmic reticulum (ER) stress plays a critical role in the development of diabetic nephropathy (DN). We previously demonstrated that pyruvate (Pyr)-enriched oral rehydration solution improved glucometabolic disorders and ameliorated DN outcome in db/db mice. Here, we investigated the effects of Pyr on high glucose-induced ER stress and apoptosis in HK-2 cells. Our results suggest that high glucose can induce reactive oxygen species production, apoptosis and ER stress in HK-2 cells, and that Pyr treatment can ameliorate these effects and restore the expression of key proteins involved in ER stress. Thus, Pyr may have potential for the development of novel strategies for the prevention and treatment of clinical DN.

Pyruvate is a prospective alkalizer to correct hypoxic lactic acidosis.

Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be harmful. This paper reviewed data regarding lactic acidosis treatment and recommended that pyruvate might be a potential alkalizer to correct type A lactic acidosis in future clinical practice. Pyruvate is a key energy metabolic substrate and a pyruvate dehydrogenase (PDH) activator with several unique beneficial biological properties, including anti-oxidant and anti-inflammatory effects and the ability to activate the hypoxia-inducible factor-1 (HIF-1α) - erythropoietin (EPO) signal pathway. Pyruvate preserves glucose metabolism and cellular energetics better than bicarbonate, lactate, acetate and malate in the efficient correction of hypoxic lactic acidosis and shows few side effects. Therefore, application of pyruvate may be promising and safe as a novel therapeutic strategy in hypoxic lactic acidosis correction accompanied with multi-organ protection in critical care patients.

Pyruvate as a novel carrier of hydroxyethyl starch 130/0.4 may protect kidney in rats subjected to severe burns.

BACKGROUND: The carrier of hydroxyethyl starch (HES) may play a critical role in kidney injury in fluid resuscitation. This study aimed mainly to compare effects of pyruvate-enriched saline with normal saline (NS) and acetate Ringer's (AR) solution as a carrier in HES130/0.4 on kidney function in rats subjected to severe burns. METHODS: Using a lethal burn model, 140 rats were randomly allocated in seven groups (n = 20): sham group (group S); no fluid after burn (group N); burn resuscitated with NS (group NS); burn resuscitated with pyruvate saline (group PS); burn resuscitated with AR plus pyruvate-HES (group SP); burn resuscitated with AR plus acetate-HES (group SA), and burn resuscitated with AR plus NS-HES (group SN). A low volume (18.75 mL·kg-1 during 12 h) of HES130/0.4 was infused with the ratio of 1:1 to crystalloids. Renal surface blood flow, blood creatinine and blood urea nitrogen, early sensitive indicators of kidney function: alpha-1 microglobulin, cystatin-C, and neutrophil gelatinase-associated lipocalin in blood and urine, and kidney tissue water contents were determined. Renal histopathological alterations with Paller scores were also measured at 8 h and 24 h after burn (n = 10), respectively. RESULTS: The results showed in a comparable manner that group SP was the best in three HES groups and group PS was superior to group NS in renal preservation; group SP appeared significantly beneficial compared with group PS in renal surface blood flow, cystatin-C, neutrophil gelatinase-associated lipocalin, water contents, and Paller scores at 8-h or both time points after burn, respectively (all P < 0.05). CONCLUSIONS: The carrier of HES130/0.4 played a crucial role in kidney injury in fluid resuscitation of rats subjected to severe burns. Pyruvate-enriched HES130/0.4 was superior and HES130/0.4, per se, might be not renocytotoxic, but renoprotective. Further studies are warranted.

Pyruvate in reduced osmolarity oral rehydration salt corrected lactic acidosis in sever scald rats.

BACKGROUND: A novel pyruvate-based oral rehydration salt (Pyr-ORS) was demonstrated of superiority over bicarbonate- or citrate-based one to preserve organ function and correct lactic acidosis in rehydration of lethal shock in animals. This study further compared these effects between low-osmolar Pyr-ORS and equimolar citrate-based counterpart. METHODS: Eighty rats, using a fatal burn shock model, were randomized into four groups (two subgroups per group: n = 10): the sham group (group SR), Pyr-ORS group (group PR), WHO-ORS III group (group CR), and no rehydration group. ORS was delivered by manual gavage during 24 h following burns. Oral administration consisted of half of counted volume in the initial 8 h plus the rest in the later 16 h. Systemic hemodynamics, visceral organ surface blood flow, organ function, and metabolic acidosis were determined at 8 h and 24 h after burn. Another set of rats with identical surgical procedures without tests was observed for survival. RESULTS: Survival was markedly improved in the groups PR and CR; the former showed a higher survival rate than the latter at 24 h (40% versus 20%, P < 0.05). Systemic hemodynamics, visceral blood flow, and function of heart, liver, and kidney were greatly restored in group PR, compared with group CR (all P < 0.05). Hypoxic lactic acidosis was efficiently reversed in group PR, instead of group CR, (pH 7.36 versus 7.11, base excess 2.1 versus -9.1 mmol/L, lactate 4.28 versus 8.18 mmol/L; all P < 0.05) at 24 h after injury. CONCLUSIONS: Pyruvate was advantageous over citrate in low-osmolar ORS for protection of organs and survival; pyruvate, but not citrate, in the ORS corrected hypoxic lactic acidosis in rats subjected to lethal burn shock in 24 h.

Pyruvate in oral rehydration salt improves hemodynamics, vasopermeability and survival after burns in dogs.

BACKGROUND: To investigate whether pyruvate-enriched oral rehydration solution (Pyr-ORS), compared with citrate-enriched ORS (Cit-ORS), improves hemodynamics and organ function by alleviating vasopermeability and plasma volume loss during intra-gastric fluid rehydration in dogs with severe burn. METHODS: Forty dogs subjected to severe burn were randomly divided into four groups (n=10): two oral rehydrated groups with Pyr-ORS and Cit-ORS (group PR and group CR), respectively, according to the Parkland formula during the first 24h after burns. Other two groups were the intravenous (IV) resuscitation (group VR) with lactated Ringer's solution with the same dosage and no fluid rehydration (group NR). During the next 24h, all groups received the same IV infusion. The hemodynamics, plasma volume, vasopermeability and water contents and function of various organs were determined. Plasma levels of vascular endothelial growth factor (VEGF) and platelet activating factor (PAF) were detected by ELISA. RESULTS: Hemodynamics parameters were significantly improved in group PR superior to group CR after burns. Levels of VEGF and PAF were significantly lower in group PR than in group CR. Organ function parameters were also greatly preserved in group PR, relative to groups CR and NR. Lactic acidosis was fully corrected and survival increased in group PR (50.0%), compared to group CR (20.0%). CONCLUSION: Pyr-ORS was more effective than Cit-ORS in improving hemodynamics, visceral blood perfusion and organ function by alleviating vasopermeability-induced visceral edema and plasma volume loss in dogs with severe burn.

Effects of Hindlimb Unweighting on MBP and GDNF Expression and Morphology in Rat Dorsal Root Ganglia Neurons.

With the development of technology and space exploration, studies on long-duration space flights have shown that microgravity induces damage to multiple organs, including the dorsal root ganglia (DRG). However, very little is known about the effects of long-term microgravity on DRG neurons. This study investigated the effects of microgravity on lumbar 5 (L5) DRG neurons in rats using the hindlimb unweighting (HU) model. Male (M) and female (F) Sprague-Dawley rats were randomly divided into M- and F-control (CON) groups and M- and F-HU groups, respectively (n = 10). At the end of HU treatment for 4 weeks, morphological changes were detected. Myelin basic protein (MBP) and degenerated myelin basic protein (dgen-MBP) expressions were analyzed by immunofluorescence and western blot assays. Glial cell line-derived neurotrophic factor (GDNF) protein and mRNA expressions were also analyzed by immunohistochemistry, western blot, and RT-PCR analysis, respectively. Compared with the corresponding CON groups, the HU groups exhibited slightly loose junctions between DRG neurons, some separated ganglion cells and satellite cells, and lightly stained Nissl bodies that were of smaller size and had a scattered distribution. High levels of dgen-MBP and low MBP expressions were appeared and GDNF expressions were significantly decreased in both HU groups. Changes were more pronounced in the F-HU group than in the M-HU group. In conclusion, HU treatment induced damage of L5 DRG neurons, which was correlated with decreased total MBP protein expression, increased dgen-MBP expression, and reduced GDNF protein and mRNA expression. Importantly, these changes were more severe in F-HU rats compared with M-HU rats.

Pyruvate alleviates lipid peroxidation and multiple-organ dysfunction in rats with hemorrhagic shock.

OBJECTIVE: Pyruvate can reduce lipid peroxidation, which plays a critical role in organ injury, in various models. However, it is not fully understood if this inhibition occurs in resuscitation of hemorrhagic shock (HS). This study examines effects of pyruvate Ringer solution (PR) in this respect in rats. METHODS: Rats, subjected to 45% blood loss, were randomly allocated to the 3 groups (n = 18): HS with no fluid resuscitation (group NR), HS resuscitated with lactated Ringer solution (LR) (group LR), and HS resuscitated with PR (group PR). Mean arterial pressure, plasma levels of thiobarbituric acid reactive substances (TBARS), and superoxide dismutase were measured at various time points until 360 minutes after hemorrhage. Visceral organs were harvested at the end for evaluations of the TBARS, antioxidant enzyme, and tissue water content. Other 54 rats with identical procedures without sampling were documented for 24-hour survival rates (n = 18) after fluid resuscitation. RESULTS: Pyruvate Ringer solution significantly increased mean arterial pressure and decreased blood TBARS levels after lethal HS. It also reduced TBARS concentrations and glutathione peroxidase activities but significantly enhanced glutathione reductase activities in most organs and greatly improved the ratios of reduced glutathione over oxidized glutathione in various organs in group PR, compared to group LR. Furthermore, PR significantly improved various organ function and water contents relative to LR. Group PR showed a more than 2-fold higher 24-hour survival rate of group LR. CONCLUSIONS: Pyruvate Ringer solution alleviated organ edema and injury and prompted survival partially through inhibition of lipid peroxidation in various organs in severe HS rats.

Pyruvate Is Superior to Citrate in Oral Rehydration Solution in the Protection of Intestine via Hypoxia-Inducible Factor-1 Activation in Rats With Burn Injury.

BACKGROUND: Recent studies have suggested that pyruvate-enriched oral rehydration solution (Pyr-ORS) may be superior to the standard bicarbonate-based ORS in the protection of intestine from ischemic injury. The aim of this study was to compare the effects of Pyr-ORS with citrate-enriched ORS (Cit-ORS) on the intestinal hypoxia-inducible factor-1 (HIF-1)-erythropoietin (EPO) signaling pathway for enteral rehydration in a rat model of burn injury. METHODS: Rats were randomly assigned to 4 groups (N = 20, 2 subgroups each: n = 10): scald sham (group SS), scald with no fluid resuscitation (group SN), scald and resuscitation with enteral Cit-ORS (group SC), and scald and resuscitation with enteral Pyr-ORS (group SP). At 2.5 and 4.5 hours after a 35% total body surface area (TBSA) scald, intestinal mucosal blood flow (IMBF), contents of HIF-1, EPO, endothelial nitric oxide synthase (eNOS), nitric oxide (NO), barrier protein (ZO-1), levels of serum diamine oxidase (DAO), and intestinal mucosal histology injury score were determined. RESULTS: Serum DAO activities in the scalded groups were significantly elevated, but less raised in group SP than in group SC, at 2.5 hours and at 4.5 hours after the scald. Further, group SP more profoundly preserved intestinal HIF-1 expression compared with group SC at the 2 time points. Compared with group SC, group SP had markedly elevated intestinal EPO, eNOS, and NO levels at the same time points, respectively (P < .05). Similarly, IMBF and ZO-1 levels were significantly higher in group SP than in group SC. Intestinal mucosal histopathological scores were statistically higher at 2.5 hours and 4.5 hours after scalding but were more attenuated in group SP than in group SC (P < .05). Immunofluorescence expression of intestinal mucosal ZO-1 was consistent with the above changes. The above parameters were also significantly different between groups SC and SN (all P < .05). CONCLUSION: Pyr-ORS provides a superior option to Cit-ORS for the preservation of intestinal blood flow and barrier function and the attenuation of histopathological alterations in enteral resuscitation of rats with burn injury. Its underlying mechanism may be closely related to the pyruvate in activation of intestinal HIF-1-EPO signaling cascades.

Effects of pyruvate-enriched peritoneal dialysis solution on intestinal barrier in peritoneal resuscitation from hemorrhagic shock in rats.

BACKGROUND: To investigate protective effects of pyruvate-enriched peritoneal dialysis solution (P-PDS), compared with lactate-PDS (L-PDS), on the intestinal mucosal barrier in peritoneal resuscitation (PR) from severe hemorrhagic shock (HS) in rats. MATERIALS AND METHODS: Fifty male SD rats were randomly divided into five groups (n = 10): group sham, group control (HS without fluid resuscitation), group intravenous resuscitation (IVR) (HS with IVR only), group L-PDS (HS with i.v. infusion plus PR with L-PDS), and group P-PDS (HS with i.v. infusion plus PR with P-PDS). HS was induced by hemorrhage with mean arterial pressure 40 mm Hg for 60 min. In three groups with fluid rehydration, IVR included shed blood and dl-lactate Ringer solution equal to two times the volume of shed blood during 60 min; in two groups with PR, 20 mL of L-PDS, or P-PDS were infused when i.v. infusion started after HS into the peritoneal cavity in 20 min, respectively. Blood samples were taken for determinations of pH, base excess, PaCO2, PaO2, and D-LA 60 min post fluid resuscitation. After rats were sacrificed, a segment of intestine was harvested for the detection of expressions of intestinal barrier proteins: zonula occludens-1 (ZO-1) and phosphorylated vasodilator-stimulated phosphoprotein (p-VASP) by Western blot and immunohistochemistry. Intestinal morphologic alterations were also observed. RESULTS: Blood pH, base excess, and PaO2 were higher, whereas PaCO2 and D-LA were lower in group P-PDS than in other three HS groups (P < 0.05 and P < 0.01, respectively). Severe acidosis was nearly corrected in group P-PDS. Intestinal barrier proteins ZO-1 and p-VASP were significantly preserved in group P-PDS than in group L-PDS (P < 0.05) although they were improved in group L-PDS in comparison with other two HS groups (P < 0.05 or P < 0.01). Expressions of barrier proteins by Western blotting in group P-PDS were reversed to normal. The score of intestinal epithelial damage index was reduced in group L-PDS, compared with other two HS groups (P < 0.05), however, it was significantly lower in group P-PDS than in group L-PDS (P < 0.05). CONCLUSIONS: Pyruvate was superior to lactate in PDS in the correction of severe acidosis with PR. P-PDS was more preservative of expressions of intestinal ZO-1 and p-VASP and mucosal barrier function, compared with L-PDS in PR from severe HS in rats.

Pyruvate oral rehydration solution improved visceral function and survival in shock rats.

BACKGROUND: Recent findings showed advantages of a novel pyruvate-enriched oral rehydration solution (Pyr-ORS) in resuscitation of burns. This study focused on effects of Pyr-ORS on the visceral blood perfusion (VBP), gastrointestinal function, and survival rate, compared with the bicarbonate-based World Health Organization-guided oral rehydration solution (WHO-ORS), during intragastric rehydration of lethal hemorrhagic shock in rats. METHODS: Sixty adult rats were subjected to 45% total blood volume loss and were randomly allocated to the following three groups (n = 20): group NR (no fluid resuscitation), group PORS (oral Pyr-ORS rehydration), and group BORS (oral WHO-ORS rehydration), respectively. Other 10 rats were served as group NH (the sham group). Enteral rehydration lasted for 4 h after hemorrhage. The mean arterial pressure (MAP), VBP, and plasma enzymes activities of heart, liver, and kidney, and intestinal fatty acid binding protein were measured. Liver, kidney, and ileum were harvested for the evaluation of activities of oxidative enzymes and intestinal barrier protein (ZO-1). Other 84 rats with identical procedures without sampling were observed for their 24-h survival rates. RESULTS: Pyr-ORS was more effective in enhancing the MAP and VBP, inhibiting tissue oxidative damage, and improving organ function, compared with WHO-ORS. Hypoxic lactic acidosis was fully corrected in group PORS in 4 h, whereas it worsened in group BORS, and the 24-h survival rate was twice higher in group PORS than in group BORS (45.8 versus 20.8%, P < 0.05). CONCLUSIONS: A small amount of pyruvate in Pyr-ORS was more therapeutically beneficial than equivalent bicarbonate in WHO-ORS and greatly raised survival in enteral rehydration of lethal hemorrhagic shock. The Pyr-ORS may be an ideal oral fluid in resuscitation of hypovolemic shock, especially in prehospital and resource-poor settings.

Electroacupuncture at Zusanli (ST36) promotes gastric emptying and mucosal blood flow during oral resuscitation of scalded rats with a pyruvate-enriched ORS.

AIM: The aim of this study was to investigate the effect of electroacupuncture at ST36 (EA ST36) on gastric emptying and mucosal blood flow during intragastric resuscitation with pyruvate-enriched oral rehydration solution (Pyr-ORS) in scalded rats. METHODS: The rats were subjected to a 35% total body surface area (TBSA) of scald injury and randomly divided into five groups (N=24) and two subgroups (n=12) in each group. The Pyr-ORS was delivered intragastrically according to the Parkland formula immediately after scalding at a dose of 1 mL kg(-1) %TBSA(-1) in 1 h. In these animals, the bilateral Zusanli points (ST36) were electroacupunctured at a constant voltage (2 mA and 2-100 HZ) for 0.5 h immediately after intragastric resuscitation. At 2 and 4 h after scalding, the gastric emptying rate (GER) and gastric mucosal blood flow (GMBF) were determined, and the motilin levels of the plasma and gastric tissues were also analyzed at two time points, respectively. RESULTS: GER and GMBF were markedly decreased in groups with scalding and resuscitation, compared with the sham groups at two time points (P<0.05), but they were greatly improved in groups byEAST36 at 2 and 4 h after sustaining scald injuries (P<0.05). Bilateral vagotomy further aggravated the reduction of GER and GMBF in scalded rats. EA after gastric vagotomy failed to raise GER and GMBF. Neither EA nor vagotomy had effects on the reduced motilin levels of plasma and gastric tissues in animals after scalding. CONCLUSION: EA ST36 has a significant effect on improving gastric emptying and mucosal ischemia in the oral resuscitation of burn injury, possibly through the activation of a cholinergic nerve-dependent mechanism. In addition, EA ST36 showed no effects on motilin levels, but requires further investigations.

Pyruvate-enriched oral rehydration solution improved intestinal absorption of water and sodium during enteral resuscitation in burns.

AIM: To investigate alteration in intestinal absorption during enteral resuscitation with pyruvate-enriched oral rehydration solution (Pyr-ORS) in scalded rats. METHODS: To compare pyruvate-enriched oral rehydration solution (Pyr-ORS) with World Health Organisation oral rehydration solution (WHO-ORS), 120 rats were randomly divided into 6 groups and 2 subgroups. At 1.5 and 4.5 h after a 35% TBSA scald, the intestinal absorption rate, mucosal blood flow (IMBF), Na(+)-K(+)-ATPase activity and aquaporin-1 (AQP-1) expression were determined (n = 10), respectively. RESULTS: The intestinal Na(+)-K(+)-ATPase activity, AQP-1 expression and IMBF were markedly decreased in scald groups, but they were profoundly preserved by enteral resuscitation with WHO-ORS and further improved significantly with Pyr-ORS at both time points. Na(+)-K+-ATPase activities remained higher in enteral resuscitation with Pyr-ORS (Group SP) than those with WHO-ORS (Group SW) at 4.5 h. AQP-1 and IMBF were significantly greater in Group SP than in Group SW at both time points. Intestinal absorption rates of water and sodium were obviously inhibited in scald groups; however, rates were also significantly preserved in Group SP than in Group SW with an over 20% increment at both time points. CONCLUSION: The Pyr-ORS may be superior to the standard WHO-ORS in the promotion of intestinal absorption of water and sodium during enteral resuscitation.

Pyruvate is superior to reverse visceral hypoperfusion in peritoneal resuscitation from hemorrhagic shock in rats.

AIMS: The objective of this study was to investigate the effects of pyruvate-containing fluids on peritoneal resuscitation (PR), following intravenous fluid resuscitation from hemorrhagic shock (HS) in rats. METHODS: One hundred rats following 1-h HS with mean arterial pressure 35 ± 5 mmHg were randomly assigned to five groups (n = 10) in each of two comparable sets: group VR: intravenous resuscitation (VR) only and four groups with PR after VR: groups NS, LA, P1, and P2, resuscitated with normal saline, lactated peritoneal dialysis solution (PDS), pyruvated PDS, and 2.2% pyruvate, respectively. The splanchnic blood flow on surfaces of liver, kidney, and intestinal mucosa was detected. Blood samples were taken before HS and at T180 or T360 in these two animal sets after hemorrhage for function tests of liver, kidney, and intestinal mucosa, respectively. The intestinal mucosal barrier protein: zonula occludens 1 (ZO-1) and tissue water contents of these organs were also determined. RESULTS: Splanchnic blood flow was significantly preserved in all PR groups with hyperosmolar solutions: group P1 and group P2 with pyruvate were more advantageous than group LA. Group P2 was the most efficient among groups in reverse of visceral hypoperfusion. Organ function and tissue water contents of liver, kidney, and intestine and the intestinal barrier ZO-1 density were also improved in group P1 and group P2, compared with group LA. Among organs, the pyruvate protection of intestinal mucosa was the most apparent by reversing splanchnic blood flow and diamine oxidase close to reference ranges with the highest ZO-1 density. Group P2 showed the most pyruvate protection in all test parameters among four groups with PR. CONCLUSIONS: Peritoneal resuscitation with hyperosmolar fluids attenuated visceral vasoconstriction and splanchnic hypoperfusion and improved the intestinal barrier protein and organ function following conventional fluid resuscitation from severe HS in rats. Pyruvate was superior to lactate in PDS as PR fluids, and 2.2% pyruvate was the optimal fluid in PR.

Pyruvate Ringer's solution corrects lactic acidosis and prolongs survival during hemorrhagic shock in rats.

BACKGROUND: Lactic acidosis is a life-threatening complication of hemorrhagic shock. There is no ideal therapy for it in the clinical setting. OBJECTIVE: This study was designed to investigate whether pyruvate Ringer's solution could treat hypoxic lactic acidosis associated with lethal hemorrhagic shock in rats. METHODS: A total of 54 rats were subjected to hemorrhagic shock with mean arterial pressure (MAP) of 40 mm Hg for 1 h. They were then randomly divided into three groups (n = 18 each): Group N had no fluid resuscitation; Group L received lactated Ringer's solution infusion; and Group P received pyruvate Ringer's solution infusion. The survival rate was investigated after 24 h. In addition, a second set of 54 rats was selected for blood sampling, with identical methods for shock and resuscitation being followed, to determine arterial pH, blood gas analysis, lactate, pyruvate, and organs' enzyme activities at various time points. The MAP was monitored for 6 h in both populations. RESULTS: Pyruvate Ringer's solution significantly increased the survival rate of rats subjected to fatal shock and receiving pyruvate Ringer's solution (Group P) by 1.5 times the survival rate in Group L at 24 h after fluid resuscitation (55.6% vs. 22.2%, respectively; p < 0.05). Pyruvate infusion maintained a higher MAP and fully corrected severe acidosis 1 h after resuscitation in comparison to the lactated infusion, and markedly decreased blood lactate levels and the lactate-to-pyruvate ratio 4 h after resuscitation. It also significantly improved serum markers of organ dysfunction. CONCLUSION: Pyruvate Ringer's solution efficiently treated hypoxic lactic acidosis and significantly increased the survival rate in rats with lethal hemorrhagic shock. Pyruvate Ringer's solution is potentially applicable to clinical resuscitation in humans.