Vitamin B12 for the treatment of vasoplegia in cardiac surgery and liver transplantation: a narrative review of cases and potential biochemical mechanisms.

PURPOSE: Hydroxocobalamin, or vitamin B12 (V-B12), is frequently used to treat smoke inhalation and cyanide poisoning. Recent reports have also described its use to treat vasoplegia in cardiac surgery and liver transplantation. This narrative review discusses this "off-label" indication for V-B12, focusing on the potential biochemical mechanisms of its actions. SOURCE: PubMed, Cochrane, and Web of Science databases were searched for clinical reports on the use of V-B12 for vasoplegia in cardiac surgery and liver transplantation, with the biochemical mechanisms discussed being based on a survey of the related biochemistry literature. PRINCIPAL FINDINGS: Forty-four patients have been treated with V-B12 for vasoplegia in various isolated case reports and one series. Although 75% of patients have increased blood pressure in response to V-B12, there were some "non-responders". The true efficacy remains unknown because clinical trials have not been performed, and significant reporting bias likely exists. Plausible biochemical explanations exist for the potential beneficial effects of V-B12 in treating vasoplegia, including binding nitric oxide and other gasotransmitters. Additional research is required to clarify if and how these mechanisms are causally involved in effective clinical responders and non-responders. CONCLUSIONS: Although anecdotal reports utilizing V-B12 for vasoplegia are available, no higher-level evidence exists. Future work is necessary to further understand the dosing, timing, adverse events, and biochemical mechanisms of V-B12 compared with other therapies such as methylene blue.

Preliminary results from the use of intraoperative real-time biliary oxygen monitoring in liver transplantation.

BACKGROUND AND AIMS: Biliary anastomosis is a frequent area of complications after liver transplantation (LT) and a potential area of "microangiopathy". The concept of a "marginal bile duct" is unexplored. The main aim was to make a preliminary evaluation of the utility of an innovative real-time oxygen microtension (pO2mt) testing device for the assessment of bile duct viability during LT and to correlate these pO2mt values with microvascular tissue quality by histopathology and outcomes. PATIENTS AND METHODS: Observational prospective cohort study with 23 patients. Oxygen microtension measurements were made placing a micropO2 probe in different areas of recipient and donor's bile duct intraoperative. RESULTS: Mean pO2mt in the graft bile duct at the level of the anastomosis 103.82 (31-157) mm Hg, being 121.52 (55-174) mm Hg 1.5 cm proximal to the hilar plate (P < 0.001). Mean pO2mt in the recipient's bile duct was 117.87 (62-185) mm Hg, while a value of 137.30 (81-198) mm Hg was observed 1.5 cm distal to the anastomosis (P < 0.001). Cystic duct resection (12 cases) was also related with higher pO2mt values at anastomosis [117.8 (93-157) vs 88.54 (31-124) mm Hg] and distal to anastomosis [135.6 (111-174) vs 106.2 (55-133) mm Hg; P < 0.001]. Patients with 1-, 3-, and 12-month biliary complications had significantly lower pO2mt in the intraoperative measurements. CONCLUSION: Our preliminary results show that distal borders of donor and recipient bile ducts may be low-vascularized areas. Tissue pO2mt is significantly higher in areas close to the hilar plate and to the duodenum in donor and recipient's sides, respectively. Bile duct injury and biliary complications are associated with worse tissue pO2mt.

Targeting Hypoxia Signaling for Perioperative Organ Injury.

Perioperative organ injury has a significant impact on surgical outcomes and presents a leading cause of death in the United States. Recent research has pointed out an important role of hypoxia signaling in the protection from organ injury, including for example myocardial infarction, acute respiratory distress syndrome, acute kidney, or gut injury. Hypoxia induces the stabilization of hypoxia-inducible factors (HIFs), thereby leading to the induction of HIF target genes, which facilitates adaptive responses to low oxygen. In this review, we focus on current therapeutic strategies targeting hypoxia signaling in various organ injury models and emphasize potential clinical approaches to integrate these findings into the care of surgical patients. Conceptually, there are 2 options to target the HIF pathway for organ protection. First, drugs became recently available that promote the stabilization of HIFs, most prominently via inhibition of prolyl hydroxylase. These compounds are currently trialed in patients, for example, for anemia treatment or prevention of ischemia and reperfusion injury. Second, HIF target genes (such as adenosine receptors) could be activated directly. We hope that some of these approaches may lead to novel pharmacologic strategies to prevent or treat organ injury in surgical patients.

Crotalus helleri venom preconditioning reduces postoperative cerebral edema and improves neurological outcomes after surgical brain injury.

INTRODUCTION: Postoperative cerebral edema is a devastating complication in neurosurgical patients. Loss of blood-brain barrier integrity has been shown to lead to the development of brain edema following neurosurgical procedures. The aim of this study was to evaluate preconditioning with Crotalus helleri venom (Cv-PC) as a potential preventive therapy for reducing postoperative brain edema in the rodent SBI model. C. helleri venom is known to contain phospholipase A2 (PLA2), an enzyme upstream to cyclooxygenase-2 (COX-2) in the inflammatory cascade, acts to increase the production of inflammatory mediators, such as prostaglandins. We hypothesize that Cv-PC will downregulate the response of the COX-2 pathway to injury, thereby reducing the inflammatory response and the development of brain edema after SBI. MATERIALS AND METHODS: 75 male Sprague Dawley rats (280-330g) were divided to the following groups-naïve+vehicle, naïve+Cv-PC, sham, vehicle, Cv-PC, Cv-PC+NS398 (COX-2 inhibitor). Vehicle preconditioned and Cv-PC animals received either three daily subcutaneous doses of saline or C. helleri venom at 72h, 48h, and 24h prior to surgery. In Cv-PC+NS398 animals, NS398 was administered intraperitoneally 1h prior to each Cv-PC injection. Sham-operated animals received craniotomy only, whereas SBI animals received a partial right frontal lobectomy. Neurological testing and brain water content were assessed at 24h and 72h after SBI; COX-2 and PGE2 expression was assessed at 24h postoperatively by Western blot and immunohistochemistry, respectively. RESULTS: At 24h after SBI, the vehicle-treated animals were observed to have increased brain water content (83.1±0.2%) compared to that of sham animals (80.2±0.1%). The brain water content of vehicle-treated animals at 72h post-SBI was elevated at 83.3±0.2%. Cv-PC-treated animals with doses of 10% LD50 had significantly reduced brain water content of 81.92±0.7% and 81.82±0.3% at 24h and 72h, respectively, after SBI compared to that of vehicle-treated animals, while Cv-PC with 5% LD50 doses showed brain water content that trended lower but did not reach statistical significance. At 24h and 72h post-SBI, Cv-PC-treated animals had significantly higher neurological score than vehicle-treated animals. The COX-2 over-expression characterized in SBI was attenuated in Cv-PC-treated animals; NS398 reversed the protective effect of Cv-PC on COX-2 expression. Cv-PC tempered the over-expression of the inflammatory marker PGE2. CONCLUSION: Our findings indicate that Cv-PC may provide a promising therapy for reducing postoperative edema and improving neurological function after neurosurgical procedures.

Androgen Deprivation Accelerates the Prostatic Urethra Wound Healing After Thulium Laser Resection of the Prostate by Promoting Re-Epithelialization and Regulating the Macrophage Polarization.

BACKGROUND: Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. METHODS: Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. RESULTS: The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. CONCLUSION: Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc.

Low end-tidal CO2 as a real-time severity marker of intra-anaesthetic acute hypersensitivity reactions.

BACKGROUND: Prompt diagnosis of intra-anaesthetic acute hypersensitivity reactions (AHR) is challenging because of the possible absence and/or difficulty in detecting the usual clinical signs and because of the higher prevalence of alternative diagnoses. Delayed epinephrine administration during AHR, because of incorrect/delayed diagnosis, can be associated with poor prognosis. Low end-tidal CO2 (etCO2) is known to be linked to low cardiac output. Yet, its clinical utility during suspected intra-anaesthetic AHR is not well documented. METHODS: Clinical data from the 86 patients of the Neutrophil Activation in Systemic Anaphylaxis (NASA) multicentre study were analysed. Consenting patients with clinical signs consistent with intra-anaesthetic AHR to a neuromuscular blocking agent were included. Severe AHR was defined as a Grade 3-4 of the Ring and Messmer classification. Causes of AHR were explored following recommended guidelines. RESULTS: Among the 86 patients, 50% had severe AHR and 69% had a confirmed/suspected IgE-mediated event. Occurrence and minimum values of arterial hypotension, hypocapnia and hypoxaemia increased significantly with the severity of AHR. Low etCO2 was the only factor able to distinguish mild [median 3.5 (3.2;3.9) kPa] from severe AHR [median 2.4 (1.6;3.0) kPa], without overlap in inter-quartile range values, with an area under the receiver operator characteristic curve of 0.92 [95% confidence interval: 0.79-1.00]. Among the 41% of patients who received epinephrine, only half received it as first-line therapy despite international guidelines. CONCLUSIONS: An etCO2 value below 2.6 kPa (20 mm Hg) could be useful for prompt diagnosis of severe intra-anaesthetic AHR, and could facilitate early treatment with titrated doses of epinephrine. CLINICAL TRIAL REGISTRATION: NCT01637220.

Anesthetic Management of Patients With Inborn Errors of Metabolism.

Inborn errors of metabolism (IEM) are characterized by the body's inability to convert food into energy. The pathogenetic mechanism is based on defects in a variety of cellular enzymes. In addition to impairment of energy generation, accumulation of substrates may occur, which can deposit in tissue and lead to organ dysfunction. IEM can have profound implications for perioperative management, including difficult airway management, cardiac dysfunction, aspiration risk, seizures, and metabolic dysregulation. For the anesthesiologist, comprehensive knowledge is difficult to attain because of the heterogeneity of this group and the low prevalence of specific diseases. The first part of this article reviews intermediary metabolism, whereas the second part aims to highlight important aspects in perioperative management of patients with IEM. Instead of reviewing each single disorder within the vast group of IEM, we provide a conceptual framework that will facilitate the understanding of main problems encountered in each of the disease subgroups.

Brain Oxygen Supply Parameters in the Risk Assessment of Cerebral Complications During Carotid Endarterectomy.

OBJECTIVE: To determine whether preoperative regional cerebral oxygen saturation (rSO2) and the decrease in rSO2 during carotid clamping were predictive of the risk for neurologic complications in carotid endarterectomy and to determine the cutoff values of the studied parameters. DESIGN: Cohort, prospective, nonrandomized trial. SETTING: Research Institute of Circulation Pathology, Novosibirsk, Russia. PARTICIPANTS: The study comprised 466 adults who underwent carotid endarterectomy since 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, postoperative complications, and brain oxygen supply during carotid endarterectomy were analyzed. The primary endpoints were the perioperative and early postoperative neurologic complications. Ischemic stroke was diagnosed in 1.5% of patients, and cognitive disorders were reported in 2.6% of patients. Preoperative rSO2 of 50% was the cutoff value for the prediction of stroke outcome after carotid endarterectomy, with a sensitivity of 90.7% and specificity of 66.7%. A 20% decrease in rSO2 during temporary carotid clamping was the cutoff value for the prediction of stroke, with a sensitivity of 86.0% and specificity of 57.1%, and for the prediction of cognitive disorders, with a sensitivity of 88.1% and specificity of 58.3%. Preoperative rSO2 less than 50% and a decrease in rSO2 of at least 20% during temporary carotid artery clamping caused a significant increase in the hospitalization period. CONCLUSIONS: A 20% or more decrease in rSO2 during temporary internal carotid artery clamping during carotid endarterectomy caused a 10-fold increased risk of ischemic stroke and an 8-fold increased risk of cognitive disorders, whereas preoperative rSO2 less than 50% resulted in a 6-fold increased risk of ischemic stroke in the perioperative and early postoperative periods of carotid endarterectomy.

Simultaneous assessment of the synthesis rate and transcapillary escape rate of albumin in inflammation and surgery.

BACKGROUND: Better knowledge of albumin kinetics is needed to define the indications for albumin use in clinical practice. This study involved two approaches: the synthesis rate and transcapillary escape rate of albumin were measured simultaneously at different levels of plasma albumin concentration in relation to acute inflammation and surgery; and two different tracers were compared to determine plasma volume and the transcapillary escape rate. METHODS: Healthy volunteers (n = 10), patients with acute inflammatory abdominal disease (n = 10), and patients undergoing elective pancreatic resection (n = 10) were studied. The albumin synthesis rate was measured by the incorporation of deuterium-labeled phenylalanine. Plasma volume and the transcapillary escape rate were assessed using 123I-labeled and 125I-labeled albumin. RESULTS: A 50 % elevated de-novo albumin synthesis rate was seen in patients with acute inflammation and marked hypoalbuminemia, while patients with marginal hypoalbuminemia before the start of surgery had a normal albumin synthesis rate. The transcapillary escape rate was elevated intraoperatively during the reconstructive phase of pancreatic surgery, when plasma albumin was decreased but stable. In acute inflammation with marked hypoalbuminemia, the transcapillary escape rate was no different from normal. 123I-labeled and 125I-labeled albumin were found exchangeable for plasma volume determinations, but could be used only in groups of patients for the transcapillary escape rate. CONCLUSIONS: This observational study illustrates the limited information contained in albumin plasma concentrations to reflect albumin kinetics. On the contrary, single measurements of the synthesis rate and/or transcapillary escape rate of albumin obviously cannot explain the plasma level of albumin or the changes seen in plasma albumin concentration. TRIAL REGISTRATION: www.clinicaltrials.gov , study number NCT01686776 . Registered 13 September 2012.

High sensitive C-reactive protein and the risk of acute kidney injury among ST elevation myocardial infarction patients undergoing primary percutaneous intervention.

BACKGROUND: Elevated periprocedural high sensitive C-reactive protein (hs-CRP) was shown to be associated with an increased risk for acute kidney injury (AKI) in non-myocardial infarction (MI) patients undergoing percutaneous coronary intervention (PCI), however, no information to date is present regarding its predicting role for AKI in MI patients. We evaluated whether admission serum hs-CRP levels may predict risk of AKI among ST elevation MI (STEMI) patients undergoing primary PCI. METHODS: Five hundred and sixty-two patients that were admitted with STEMI and treated with primary PCI were included in the study. Serum hs-CRP levels were determined from blood samples taken prior to PCI. Patients' medical records were reviewed for occurrence of AKI, in-hospital complications and 30 days mortality. RESULTS: Mean age was 62 ± 16 and 455 (80 %) were males. Patients were divided into two groups, according to their admission hs-CRP values: group 1: hs-CRP ≤9 mg/l (n = 394) and group 2: hs-CRP >9 mg/l (n = 168). Patients with hs-CRP >9 mg/l had significantly higher rate of AKI following PCI (17 vs. 6 %; p < 0.001), more in-hospital complications and higher30 -day mortality rate (11 vs. 1 %; p = 0.02). In a multivariable logistic regression model admission hs-CRP level >9 mg/l was an independent predictor for AKI (OR 2.7, 95 % CI: 1.39-5.29; p = 0.001) and a strong trend for 30 day mortality (OR 4.27, 95 % CI: 0.875-21.10; p = 0.07). CONCLUSION: Admission serum hs-CRP level >9 mg/l is an independent predictor for AKI following primary PCI in STEMI patients.

Foreseeing the danger in the beach chair position: Are standard measurement methods reliable?

PURPOSE: The aim of this study is to show whether peripheral perfusion monitoring methods reflect central perfusion during shoulder arthroscopy at beach chair position. We hypothesized that mean arterial pressure (MAP), central heart rate (CHR) and peripheral oxygenation (SaO2) measurements individually will not parallel cerebral oximetry measurements by near-infrared spectroscopy (NIRS). METHODS: Between 2011 and 2012, 53 patients who had arthroscopic rotator cuff repair surgery in the beach chair position were enrolled prospectively. Median ages of the patients were 58 (range 42-68) years. The regional cerebral oxygen saturation value of each hemisphere was continuously monitored by the use of NIRS. MAP, CHR, SaO2 and both hemispheric cerebral oxygen saturation values were recorded at six time periods peri-operatively. Correlation and differences between parameters were evaluated. RESULTS: Cerebral oxygen saturation of right hemisphere was dropped >20 % in 28.3 and 45.3 % of the patients. At left hemisphere, cerebral oxygen saturation was dropped >20 % in 20.8 and 43.4 % of the patients. Peripheral saturation values were statistically different from cerebral saturation values (p < 0.001). On the other hand, there was a correlation between cerebral saturation and MAP values (p < 0.05). CONCLUSION: Cerebral oximetry by NIRS may prove useful as a monitor for cerebral ischaemia. In the absence of NIRS, CHR can partially detect abnormalities but not trustable, and MAP is the most reliable method for monitoring.

[Cerebral blood flow monitoring].

Cerebral ischemic events remain a major problem in patients undergoing cardiac and thoracic aortic surgery. Efforts to improve outcomes have been made in many aspects which include cerebral monitoring. New technology is making it possible to shed a light to the brain, which historically used to be a black box during general anesthesia in the operating room. Cerebral brain monitoring methods include cerebral oxymetry using near infrared spectroscopy, trans cranial Doppler, Jugular venous oxygen saturation, bispectral index, temporal artery pressure monitoring. Cerebral oxymetry probably is the most commonly used method among these based on its simplicity and reproducibility. Though it is easy to obtain numbers from cerebral oxymetry, it is important to understand the principle and the limitations to interpret the results, properly.

PAR-1 antagonist SCH79797 ameliorates apoptosis following surgical brain injury through inhibition of ASK1-JNK in rats.

Neurosurgical procedures inevitably produce intraoperative hemorrhage. The subsequent entry of blood into the brain parenchyma results in the release of large amounts of thrombin, a known contributor to perihematomal edema formation and apoptosis after brain injury. The present study seeks to test 1) the effect of surgically induced brain injury (SBI) on thrombin activity, expression of thrombin's receptor PAR-1, and PAR-1 mediated apoptosis; 2) the effect of thrombin inhibition by argatroban and PAR-1 inhibition by SCH79797 on the development of secondary brain injury in the SBI model on rats. A total of 88 Sprague-Dawley male rats were randomly divided into sham, vehicle-, argatroban-, or SCH79797-treated groups. SBI involved partial resection of the right frontal lobe under inhalation isoflurane anesthesia. Sham-operated animals received only craniotomy. Thrombin activity, brain water content, and neurological deficits were measured at 24 h following SBI. Involvement of the Ask1/JNK pathway in PAR-1-induced post-SBI apoptosis was characterized by using Ask1 or JNK inhibitors. We observed that SBI increased thrombin activity, yet failed to demonstrate any effect on PAR-1 expression. Argatroban and SCH79797 reduced SBI-induced brain edema and neurological deficits in a dose-dependent manner. SBI-induced apoptosis seemed mediated by the PAR-1/Ask1/JNK pathways. Administration of SCH79797 ameliorated the apoptosis following SBI. Our findings indicate that PAR-1 antagonist protects against secondary brain injury after SBI by decreasing both brain edema and apoptosis by inactivating PAR-1/Ask1/JNK pathway. The anti-apoptotic effect of PAR-1 antagonists may provide a promising path for therapy following SBI.

The usefulness of near-infrared spectroscopy in the anesthetic management of endovascular aortic aneurysm repair.

Near-infrared spectroscopy (NIRS) may be a useful method for monitoring the regional oxygen saturation (rSO(2)) of the lower extremity during endovascular aortic repair. Eighteen patients with thoracic descending and/or abdominal aortic aneurysm were enrolled in this study. NIRS probes were placed bilaterally on the calves. Muscular rSO(2) (mrSO(2)) was monitored every 30 s throughout the operation. In the leg in which the femoral artery was clamped, mrSO(2) values were selected at 3 or 4 points-just before clamping (control value), 30 min after clamping, 10 min after the first declamping, and 10 min after the second declamping following repair of the femoral artery, if necessary. In all patients, mrSO(2) decreased significantly during clamping, from 64 ± 11 % (mean ± SD) of the control value to 32 ± 15 %. After declamping, mrSO(2) recovered to 69 ± 14 % of the control value in 16 patients. In the 2 other patients, however, mrSO(2) did not recover after the first declamping, because of femoral artery dissection. After additional repair, mrSO(2) recovered quickly to the control value. These data suggested NIRS may objectively and quantitatively reflect oxygenation of the lower extremities, and may indicate an ischemic event that needs additional repair during endovascular aortic repair.

Global metabolic phenotyping in an experimental laparotomy model of surgical trauma.

Surgical trauma initiates a complex series of metabolic host responses designed to maintain homeostasis and ensure survival. (1)H NMR spectroscopy was applied to intraoperative urine and plasma samples as part of a strategy to analyze the metabolic response of Wistar rats to a laparotomy model. Spectral data were analyzed by multivariate statistical analysis. Principal component analysis (PCA) confirmed that surgical injury is responsible for the majority of the metabolic variability demonstrated between animals (R² Urine = 81.2% R² plasma = 80%). Further statistical analysis by orthogonal projection to latent structure discriminant analysis (OPLS-DA) allowed the identification of novel urinary metabolic markers of surgical trauma. Urinary levels of taurine, glucose, urea, creatine, allantoin, and trimethylamine-N-oxide (TMAO) were significantly increased after surgery whereas citrate and 2-oxoglutarate (2-OG) negatively correlated with the intraoperative state as did plasma levels of betaine and tyrosine. Plasma levels of lipoproteins such as VLDL and LDL also rose with the duration of surgery. Moreover, the microbial cometabolites 3-hydroxyphenylpropionate, phenylacetylglycine, and hippurate correlated with the surgical insult, indicating that the gut microbiota are highly sensitive to the global homeostatic state of the host. Metabonomic profiling provides a global overview of surgical trauma that has the potential to provide novel biomarkers for personalized surgical optimization and outcome prediction.

Oxygen concentration and characteristics of progressive atelectasis formation during anaesthesia.

BACKGROUND: atelectasis is a common consequence of pre-oxygenation with 100% oxygen during induction of anaesthesia. Lowering the oxygen level during pre-oxygenation reduces atelectasis. Whether this effect is maintained during anaesthesia is unknown. METHODS: during and after pre-oxygenation and induction of anaesthesia with 60%, 80% or 100% oxygen concentration, followed by anaesthesia with mechanical ventilation with 40% oxygen in nitrogen and positive end-expiratory pressure of 3 cmH(2) O, we used repeated computed tomography (CT) to investigate the early (0-14 min) vs. the later time course (14-45 min) of atelectasis formation. RESULTS: in the early time course, atelectasis was studied awake, 4, 7 and 14 min after start of pre-oxygenation with 60%, 80% or 100% oxygen concentration. The differences in the area of atelectasis formation between awake and 7 min and between 7 and 14 min were significant, irrespective of oxygen concentration (P<0.05). During the late time course, studied after pre-oxygenation with 80% oxygen, the differences in the area of atelectasis formation between awake and 14 min, between 14 and 21 min, between 21 and 28 min and finally between 21 and 45 min were all significant (P<0.05). CONCLUSION: formation of atelectasis after pre-oxygenation and induction of anaesthesia is oxygen and time dependent. The benefit of using 80% oxygen during induction of anaesthesia in order to reduce atelectasis diminished gradually with time.

[The pathogenesis factors of intraoperative hemolysis in cardiac surgery].

As shown in various studies, hemolysis is revealed in all extracorporeal circuits showing the increasing levels of plasma-free hemoglobin (PfHb) during and after cardiopulmonary bypass (CPB). The pathogenesis factors and mechanisms of intraoperative hemolysis are observed in this article. The role of mechanical blood trauma, oxygen free radical generation, activation of complement, preoperative defects erythrocytes, infusion preparations and other medicaments in postperfusion hemolysis are discussed. Along with the complete red blood cell (RBC) destruction (hemolysis), RBCs can also be damaged on a sublethal level, resulting in altered rheological properties, decreased microcirculation and organ dysfunction caused by hypoxia. The severity of the consequences of RBC damage, the high incidence of this complication and the lack of interventional strategies in cases of suspected or confirmed RBC damage are considered, there may be a need for a treatment algorithm for this phenomenon.

Metabolomic profiling reveals distinct patterns of myocardial substrate use in humans with coronary artery disease or left ventricular dysfunction during surgical ischemia/reperfusion.

BACKGROUND: Human myocardial metabolism has been incompletely characterized in the setting of surgical cardioplegic arrest and ischemia/reperfusion. Furthermore, the effect of preexisting ventricular state on ischemia-induced metabolic derangements has not been established. METHODS AND RESULTS: We applied a mass spectrometry-based platform to profile 63 intermediary metabolites in serial paired peripheral arterial and coronary sinus blood effluents obtained from 37 patients undergoing cardiac surgery, stratified by presence of coronary artery disease and left ventricular dysfunction. The myocardium was a net user of a number of fuel substrates before ischemia, with significant differences between patients with and without coronary artery disease. After reperfusion, significantly lower extraction ratios of most substrates were found, as well as significant release of 2 specific acylcarnitine species, acetylcarnitine and 3-hydroxybutyryl-carnitine. These changes were especially evident in patients with impaired ventricular function, who exhibited profound limitations in extraction of all forms of metabolic fuels. Principal component analysis highlighted several metabolic groupings as potentially important in the postoperative clinical course. CONCLUSIONS: The preexisting ventricular state is associated with significant differences in myocardial fuel uptake at baseline and after ischemia/reperfusion. The dysfunctional ventricle is characterized by global suppression of metabolic fuel uptake and limited myocardial metabolic reserve and flexibility after global ischemia/reperfusion stress in the setting of cardiac surgery. Altered metabolic profiles after ischemia/reperfusion are associated with postoperative hemodynamic course and suggest a role for perioperative metabolic monitoring and targeted optimization in cardiac surgical patients.

The Activation of Phosphatidylserine/CD36/TGF-ß1 Pathway prior to Surgical Brain Injury Attenuates Neuroinflammation in Rats.

Neuroinflammation plays an important pathological role in experimental surgical brain injury (SBI). Apoptotic associated with phosphatidylserine (PS) externalization promotes anti-inflammatory mediator TGF-ß1 release. In the present study, we investigated the anti-neuroinflammation effect of PS liposome or isoflurane pretreatment via PS/CD36/TGF-ß1 signaling in a rat model of SBI. A total of 120 male Sprague-Dawley rats (weighing 280-330 gms) were used. SBI was induced by partial right frontal lobe corticotomy. Intranasal PS liposome or isoflurane inhalation was administered prior to SBI induction. CD36 small interfering RNA (siRNA) was administered intracerebroventricularly. Recombinant Annexin V protein (rAnnexin V) was delivered intranasally. Post-SBI assessments included neurological tests, brain water content, Western blot, and immunohistochemistry. Endogenous CD36 protein levels but not TGF-ß1 was significantly increased within peri-resection brain tissues over 72 h after SBI. SBI rats were associated with increased brain water content surrounding corticotomy and neurological deficits. PS liposome pretreatment significantly reduced brain water content and improved some neurological deficits at 24 hours and 72 hours after SBI. PS liposome increased CD36 and TGF-ß1 protein levels, but decreased IL-1ß and TNFα protein levels in peri-resection brain tissues at 24 hours after SBI. CD36 siRNA or rAnnexin V partially countered the protective effect of PS liposome. Isoflurane pretreatment produced similar antineuroinflammation and neurological benefits in SBI rats partially by upregulating CD36/Lyn/TGF-ß1 signaling. Collectively, our findings suggest that the activation of PS/CD36/TGF-ß1 pathway by PS liposome or isoflurane prior to SBI could attenuate neuroinflammation and improve neurological outcomes in rats. PS liposome or isoflurane pretreatment may serve as an effective preventive strategy to minimize the brain injury caused by neurosurgical procedures in patients.

Non-toxicity of IV injected perfluorocarbon oxygen carrier in an animal model of liver regeneration following surgical injury.

Lethal dose experiments in animals have demonstrated that second-generation perfluorocarbon oxygen carriers are remarkably non-toxic. However, this non-toxicity has not previously been demonstrated in a liver failure scenario. A surgical liver damage and regeneration model in rats was selected using a well-controlled cross tabulated study design. A large number of physiological, biochemical, and hematological parameters were measured. No indications were found that intravenously injected perfluorooctyl bromide emulsion was toxic at the concentrations employed, in either healthy or severe liver injury scenarios. Neither was there any significant impact on the rate of liver regeneration following the injuries. Bearing in mind prior human clinical studies, it is therefore safe to assume that perfluorocarbon emulsions are also non-toxic in bioartificial liver treatments.