The immune response to anesthesia: Part 2 sedatives,opioids, and injectable anesthetic agents

ObjectiveTo review the immune response to injectable anesthetics and sedatives and to compare the immunomodulatory properties between inhalation and injectable anesthetic protocols.Study designReview.Methods and databasesMultiple literature searches were performed using PubMed and Google Scholar from March 2012 through November 2013. Relevant anesthetic and immune terms were used to search databases without year published or species constraints. The online database for Veterinary Anaesthesia and Analgesia and the Journal of Veterinary Emergency and Critical Care were searched by issue starting in 2000 for relevant articles.ConclusionSedatives, injectable anesthetics, opioids, and local anesthetics have immunomodulatory effects that may have positive or negative consequences on disease processes such as endotoxemia, generalized sepsis, tumor growth and metastasis, and ischemia-reperfusion injury. Therefore, anesthetists should consider the immunomodulatory effects of anesthetic drugs when designing anesthetic protocols for their patients.     

半滑舌鳎免疫球蛋白对黄芪多糖的免疫应答

采用单因素6水平3重复的试验方法,研究半滑舌鳎免疫球蛋白对黄芪多糖(APS)的免疫应答水平变化,确定半滑舌鳎免疫球蛋白对APS产生最强免疫应答时的APS最佳添加剂量。结果表明,随着试验时间的延长,试验组半滑舌鳎鳃黏液、肠黏液、血液及皮肤黏液免疫球蛋白对APS的免疫应答水平呈先升高后降低的变化趋势,且均显著高于对照组(P<0.05),皮肤黏液免疫球蛋白含量在第18 d时达到最高水平,鳃黏液、肠黏液和血液中的免疫球蛋白含量则于第54 d时达到最高水平;随着APS添加剂量的增加,试验组半滑舌鳎血液、皮肤黏液、鳃黏液及肠黏液免疫球蛋白对APS的免疫应答水平呈逐渐升高的变化趋势,且大部分显著高于对照组(P<0.05);半滑舌鳎鳃黏液、肠黏液、血液及皮肤黏液免疫球蛋白对APS产生最强免疫应答时的APS最佳添加剂量为1 800 mg/kg。     

Kinetics of immune response to foot-and-mouth disease virus (type Asia 1) in experimental cattle

Humoral and mucosal (secretory antibody)immune response to FMDV type Asia 1 in cattle was analyzed after vaccination and infection using virus neutralizing test (VNT). Vaccination (1/16th the usual dose) failed to protect cattle from generalized clinical disease following experimental FMDV Asia 1 infection. Our results showed that infection induced higher and prolonged serum antibody titres indicating antigen mass is important for optimal immune response. Experimental FMDV infection induced significant secretory antibody (mucosal) response in cattle. Though, there was no difference in the serum antibody response between the cattle that developed generalized infection (unprotected) and those with only localized infection (protected), secretory antibody response differed, wherein the unprotected cattle had higher secretory response than protected cattle. Thus, FMDV Asia 1 infection stimulates a similar serum antibody response and a unique secretory antibody response among the infected cattle. An erratum to this article can be found at     

Acute lung injury and acute respiratory distress syndromes in veterinary medicine: consensus definitions: The Dorothy Russell Havemeyer Working Group on ALI and ARDS in Veterinary Medicine

Background: As veterinary medicine has become more sophisticated, with greater numbers of veterinary patients receiving intensive care, more patients with an acute respiratory distress (ARDS)‐like syndrome have been recognized. Methods: A consensus definition meeting was held for the purpose of developing veterinary‐specific definitions for acute lung injury (ALI) and ARDS. Results/conclusions: Three clinically based definitions for acute lung injury and acute respiratory distress‐like syndromes occurring in veterinary patients were described. Neonatal equine respiratory distress syndrome (NERDS) was defined separately due to the specific requirement for primary developmental surfactant dysfunction and lack of an inflammatory component. Five diagnostic criteria categories were established for Veterinary ALI/ARDS (Vet ALI/ARDS) with 4 required and a fifth highly recommended criteria. A strong consensus was reached that onset of respiratory distress must have been acute and that known risk factors must be present. Additional criteria included evidence of pulmonary capillary leak with no evidence of increased pulmonary capillary pressure, evidence of inefficient gas exchange and, finally, evidence of inflammation. Some features of ALI/ARDS in the neonatal horse were recognized as unique, therefore, equine neonatal ALI/ARDS (EqNALI/EqNARDS) was similarly defined but with a graded gas exchange inefficiency table to allow for normal developmental changes in gas exchange. Use of these definitions in planning prospective studies of these problems in veterinary patients should allow for more direct comparisons of studies and clinical trials, with a larger goal of improving outcome in veterinary patients.     

Impact of nutrition on the innate immune response to infection in poultry

Viral and bacterial diseases remain a threat to the poultry industry and countermeasures to prevent and control them are needed due to production losses. With the continued threat of exotic and emerging diseases and concern over the use of antibiotics in animal production, there is a serious and urgent need to find safe and practical alternatives to prevent or control pathogens. Identification of new tools for the design of new immunological interventions or therapeutic antimicrobials to reduce microbial pathogens in poultry is now required more than ever. Immunological interventions to reduce microbial pathogens in poultry would be of great value to the poultry industry and to the consumer. We have been advocating boosting immunity and encouraging the host to utilize its innate immune system to control and clear infections. Our research has addressed the use of innate immune mechanisms and components to develop new immune modulators (prophylactic and therapeutic) and the characterization and production of antimicrobial peptides as potential immune modulators in poultry. Dietary bioactive food components that interact with the immune response have considerable potential to reduce susceptibility to infectious diseases. With this premise, this paper asks and answers a series of pertinent questions on the utilization of avian immunity for increasing resistance to a variety of potential pathogens problematic in today's commercial poultry industry. Using experimental data to provide answers to these questions, we hope to stimulate a dialog between avian immunologists and nutritionists that results in coordinating and integrating their expertise into specific practical solutions that will benefit the industry and improve the well-being of commercial poultry.     

Controversies related to red blood cell transfusion in critically ill patients

Objective – To review the evolution of and controversies associated with allogenic blood transfusion in critically ill patients. Data sources – Veterinary and human literature review. Human Data Synthesis – RBC transfusion practices for ICU patients have come under scrutiny in the last 2 decades. Human trials have demonstrated relative tolerance to severe, euvolemic anemia and a significant outcome advantage following implementation of more restricted transfusion therapy. Investigators question the ability of RBCs stored longer than 2 weeks to improve tissue oxygenation, and theorize that both age and proinflammatory or immunomodulating effects of transfused cells may limit efficacy and contribute to increased patient morbidity and mortality. Also controversial is the ability of pre‐ and post‐storage leukoreduction of RBCs to mitigate adverse transfusion‐related events. Veterinary Data Synthesis – While there are several studies evaluating the transfusion trigger, the RBC storage lesion and transfusion‐related immunomodulation in experimental animal models, there is little research pertaining to clinical veterinary patients. Conclusions – RBC transfusion is unequivocally indicated for treatment of anemic hypoxia. However, critical hemoglobin or Hct below which all critically ill patients require transfusion has not been established and there are inherent risks associated with allogenic blood transfusion. Clinical trials designed to evaluate the effects of RBC age and leukoreduction on veterinary patient outcome are warranted. Implementation of evidence‐based transfusion guidelines and consideration of alternatives to allogenic blood transfusion are advisable.     

The equine immune response to equine herpesvirus-1: the virus and its vaccines

Equine herpesvirus-1 (EHV-1) is an alphaherpesvirus which infects horses, causing respiratory and neurological disease and abortion in pregnant mares. Latency is established in trigeminal ganglia and lymphocytes. Immunity to EHV-1 lasts between 3 and 6 months. Current vaccines, many of which contain inactivated virus, have reduced the incidence of abortion storms in pregnant mares but individual animals, which may be of high commercial value, remain susceptible to infection. The development of effective vaccines which stimulate both humoral and cellular immune responses remains a priority. Utilising data generated following experimental and field infections of the target species, this review describes the immunopathogenesis of EHV-1 and the interaction between the horse's immune system and this virus, both in vivo and in vitro, and identifies immune responses, highlighting those which have been associated with protective immunity. It then goes on to recount a brief history of vaccination, outlines factors likely to influence the outcome of vaccine administration and describes the immune response stimulated by a selection of commercial and experimental vaccines. Finally, based on the available data, a rational strategy designed to stimulate protective immune responses by vaccination is outlined.     

Identification and examination of a novel 9‐bp insert/deletion polymorphism on porcine SFTPA1 exon 2 associated with acute lung injury using an oleic acid‐acute lung injury model

The pulmonary surfactant‐associated protein (SFTPA1, SP‐A) gene has been studied as a candidate gene for lung disease resistance in humans and livestock. The objective of the present study was to identify polymorphisms of the porcine SFTPA1 gene coding region and its association with acute lung injury (ALI). Through DNA sequencing and the PCR‐single‐strand conformation polymorphism method, a novel 9‐bp nucleotide insertion (+) or deletion (‐) was detected on exon 2 of SFTPA1, which causes a change in three amino acids, namely, alanine (Ala), glycine (Gly) and proline (Pro). Individuals of three genotypes (?/?, +/? and +/+) were divided into equal groups from 60 Rongchang pigs that were genotyped. These pigs were selected for participation in the oleic acid (OA)‐ALI model by 1‐h and 3‐h injections of OA, and there were equal numbers of pigs in the control and injection groups. The lung water content, a marker for acute lung injury, was measured in this study; there is a significant correlation between high lung water content and the presence of the 9‐bp indel polymorphism (P < 0.01). The lung water content of the OA injection group was markedly higher than that of the control group and lung water content for the +/+ genotype was significantly higher than that of the others in the 1‐h group (P < 0.01). No differences in the expression of the SFTPA1 gene were found among individuals with different SFTPA1 genotypes, indicating that the trait is not caused by a linked polymorphism causing altered expression of the gene. The individuals with the ?/? genotype showed lower lung water content than the +/+ genotype pigs, which suggests that polymorphism could be a potential marker for lung disease‐resistant pig breeding and that pig can be a potential animal model for human lung disease resistance in future studies.     

Evaluation of a risk-screening questionnaire to detect equine lung inflammation: results of a large field study

Reasons for performing study: The diagnosis of equine recurrent airway obstruction (RAO) and inflammatory airway disease (IAD) is based on clinical signs and increased inflammatory cell percentages in the bronchoalveolar lavage (BAL) fluid. Since a BAL is an invasive procedure, a risk‐screening questionnaire (RSQ) would be a valuable screening tool for lung inflammation. Objective: To evaluate the accuracy of a RSQ to detect lower airway inflammation (LAI) in a large population of horses. Methods: A standardised BAL was performed in the field on 167 horses in Alberta, Canada. Horses were separated into 3 categories: 1) BAL normal; 2) BAL mild to moderate LAI (MLAI), and 3) BAL severe LAI (SLAI). The horse owners were asked to complete a RSQ. The RSQ scores were compared to the BAL results to determine the likelihood of a horse having MLAI, SLAI or no LAI. Results: Based on BAL cytology, 28 (17%) horses were normal and 139 (83%) were abnormal, with 110 (66%) showing MLAI and 29 (17%) SLAI. Horses with SLAI and MLAI had a mean RSQ score of 0.95 and 0.70, respectively, compared to 0.60 for normal BAL horses. Horses with SLAI showed more clinical signs than normal and MLAI horses. The sensitivity and negative predictive values of the RSQ for detecting SLAI using a cut‐off score of 0.87, were excellent at 0.90 (95%CI 0.73–0.98) and 0.96 (95%CI 0.82–1.00). Questions on the clinical signs typically found in RAO cases differed significantly between horses with BAL SLAI and those with BAL normal. Conclusions: Prevalence of MLAI was high in this population. Although the RSQ did not allow differentiating normal horses from horses with MLAI, it has a high sensitivity to detect horses with SLAI and is therefore a good screening tool for SLAI.     

Genome‐wide association study of cell‐mediated immune response in chicken

Cell‐mediated immunity (CMI) causes the intracellular destruction of the antigen or elimination of the host cell to make animals resistant against exogenous antigens and cancers. In this study, a genome‐wide association study (GWAS) was carried out to identify genomic regions associated with CMI in chicken using chicken 60k high‐density single nucleotide polymorphism (SNP) array. Genomic relationships were taken into account to adjust for population structure. In order to account for multiple testing, chromosome‐wise false discovery rate was controlled at 5% and 10% levels. Moreover, a comparison of the power of fixed and mixed linear models based on genomic inflation factor was carried out. Mixed linear model (MLM) had better inflation rate, and therefore the results from MLM were used for subsequent analysis. Three significantly associated SNPs (FDR < 0.05) on chromosome 24 and linkage group E22C19W28_E50C23, and three suggestively associated SNPs (FDR < 0.1) on chromosome 1, 5 and 16 were identified. Pathway analysis showed that two biological pathways, which are related to immune response, were strongly associated with the candidate genes surrounding identified SNPs, and their influences were mostly on antigen processing and presentation, and cellular structure.     

参麦注射液对大鼠急性肺损伤保护作用及机制的研究

试验旨在探讨参麦注射液对大鼠肺组织的保护作用及可能机制,为临床治疗急性肺损伤(acute lung injury,ALI)提供理论依据。将Wister大鼠随机分为模型组、参麦治疗组和空白对照组,每组采用经典尾静脉注射油酸方法建立急性肺损伤模型。观察肺体系数、病理切片、超微结构及肺组织匀浆中TNF-α、ICAM-1的含量变化,探讨参麦注射液对大鼠肺组织急性肺损伤的保护作用。结果发现,与模型组相比参麦治疗组可以明显改变大鼠急性肺损伤的肺体系数,减轻肺组织形态学及超微结构的病理改变,同时降低肺组织匀浆中TNF-α、ICAM-1的表达。证实参麦注射液对大鼠急性肺损伤具有保护作用,其机制可能通过降低肺组织匀浆中TNF-α、ICAM-1的含量,而发挥抗炎作用。     

The use of lingual venous blood to determine the acid‐base and blood‐gas status of dogs under anesthesia

ObjectiveTo assess the suitability of lingual venous blood (LBG) as an alternative to arterial blood (ABG) samples in determining acid–base balance and blood–gas status in dogs anesthetized for elective procedures and with medetomidine and isoflurane administration under experimental conditions.Study designProspective, randomized clinical and experimental study.AnimalsClinical population of 18 ASA I/II dogs for elective surgery and five healthy Beagles (3 females and 2 males) for the experimental study.MethodsBlood sampling was simultaneously performed at dorsal pedal arterial and lingual venous sites, generating paired data. Two paired samples were collected from each dog in the clinical part and four from each dog in the experimental part (two during isoflurane anesthesia and two during isoflurane plus medetomidine). A modified Bland and Altman method was used to examine data from the clinical part and the experimental data were subjected to a paired sign's test following transformation where appropriate.ResultsThe pH of LBG overestimated ABG, with limits of agreement of (?0.01, 0.02). The partial pressure of carbon dioxide (PCO₂) of LBG overestimated ABG by 0.6 mmHg [0.1 kPa], with limits of agreement of (?3.5, 4.6) mmHg [?0.5, 0.6 kPa]. The partial pressure of oxygen (PO₂) of LBG underestimated ABG by 86.3 mmHg [?11.5 kPa], with limits of agreement of (?199.8, 27.3) mmHg [?26.6, 3.6 kPa]. During medetomidine administration values for PO₂ (p = 0.03) and lactate (p = 0.03) were lower for LBG when compared with ABG. The LBG value of PO₂ was lower (p = 0.03) during medetomidine and isoflurane administration versus isoflurane alone.Conclusions and clinical relevanceThe pH and PCO₂ of LBG samples provide clinically acceptable substitutes of ABG samples in the dog population studied. The wider limits of agreement for PO₂ render it less reliable as a substitute for ABG. The difference in PO₂ identified between LBG and ABG during medetomidine administration may not preclude the use of LBG as substitutes for ABG samples.     

The relationship between cellular immune response to foot-and-mouth disease virus Asia 1 and viral persistence in Indian cattle (Bosindicus)

Foot-and-mouth disease (FMD), the most contagious animal disease, is associated with persistent viral infection in ruminants, despite the induction of systemic immune response. The present study was performed to decipher the relation between the persistent FMD virus (FMDV) infection and cellular immune response in Indian cattle (Bosindicus) following experimental inoculation of FMDV Asia 1. Persistent viral infection (carriers) was detected by antigen capture RT-PCR on the oesophageal-pharyngeal fluid. Viral excretion was found to be intermittent and strongly variable among the persistently infected Indian cattle. Lymphocyte proliferative (LP) response, assessed as reactivity of peripheral blood mononuclear cells to FMDV Asia 1 antigen (Ag) was of low magnitude indicating a weak primary cellular immune response following infection. LP response to FMDV Ag was higher among the non-carriers than carriers of FMDV Asia 1. An enhanced LP response was associated with the lack of virus shedding in the OPF. The findings of this study are suggestive of relationship between cellular immune response and virus excretion during persistence of FMDV Asia 1 in infected cattle.     

家禽H5亚型禽流感(Re-6株)疫苗免疫抗体消长规律研究

为了解H5亚型重组禽流感Re-6株灭活疫苗在鸡、鸭免疫后的抗体消长规律,本实验分别选择一个鸡场和鸭场开展了临床免疫实验。实验鸡群于14日龄首免单价疫苗(Re-6株)和H5亚型二价疫苗(Re-6株+Re-4株)后,在30日龄~200日龄不同时间点采血检测Re-6抗体,结果表明,二价疫苗比单价疫苗免疫后的Re-6免疫抗体产生早、效价高、抗体整齐度好;40日龄二免后20 d,二价疫苗和单价疫苗的Re-6免疫抗体消长规律趋于一致。实验鸭群于17日龄分别采用禽流感(H5+H9)双价灭活疫苗和单价灭活疫苗(H5N1亚型,Re-6株)进行免疫,免后45日龄~205日龄不同时间点检测Re-6抗体,结果表明,双价疫苗与单价疫苗均可以诱导免疫鸭产生高水平抗体,而且两种疫苗的消长规律相似。此外,45日龄二免Re-6株疫苗的免疫程序要优于70日龄二免的免疫程序。本研究评估Re-6疫苗的防控效果,为家禽H5亚型禽流感免疫防制提供了实验依据。     

Use of C-reactive protein to predict outcome in dogs with systemic inflammatory response syndrome or sepsis

Background – There is a high mortality rate in patients with systemic inflammatory response syndrome (SIRS) or sepsis. Therefore, an early diagnosis and prognostic assessment is important for optimal therapeutic intervention. The objective of the study was to evaluate if baseline values and changes in serum C-reactive protein (CRP) might predict survival in dogs with SIRS and sepsis.
Design – Prospective study; July 2004 to July 2005.
Setting – Small Animal Clinic, Berlin, Clinic of Small Animal Medicine, Munich.
Animals – Sixty-one dogs.
Measurements and Main Results – For the CRP analysis blood was drawn on day 0, 1, and 2; CRP was measured using a commercial ELISA test kit. Thirteen dogs suffered from nonseptic SIRS and 48 dogs from sepsis. The 14-day survival rate was 61% (69% nonseptic SIRS, 58% sepsis). Serum CRP was higher in sick dogs compared with controls ( P <0.001). Over the 3-day period surviving dogs ( n =31) displayed a significantly greater decrease in CRP than nonsurvivors ( n =10) ( P =0.001). No correlation was found between the initial CRP concentrations and the survival rate. The changes in CRP corresponded to the survival rate ( P =0.01).
Conclusion – There was no significant relationship between the survival rate in dogs with nonseptic SIRS or sepsis and the initial serum CRP concentrations. There was a correlation between decreasing CRP concentrations and recovery from disease. However, the changes in CRP concentrations over a 3-day period correctly predicted survival in 94% of dogs and death in 30% of the dogs (false positive rate 22%).     

Gender differences in non-specific immune response to exercise in the lactate threshold: a study in equine athletes

Gender differences have not been shown in relation to the immune system in athletic horses. The aim of the present paper was to elucidate gender differences in the non-specific immune response of the polymorphonuclear neutrophil (PMN), plasma glucose and in hormones before and after an exercise in the lactate threshold (LT). A group of 12 Anglo-Arabian horses (6 females and 6 males, 4-7 years old) was observed. A submaximal exercise test was carried out at the LT. The results showed that males had a higher PMN percentage, plasma glucose values, Adherence index (AI) and random migration than females. Also, females showed significant negative correlations between cortisol and catecholamines with PMN and glucose with phagocytosis, and positive ones between AI and catecholamines. In males, negative correlations were established between random migration and chemotaxis with cortisol, and positive ones between cortisol and phagocytosis.