Perioperative Organ Protection Research Articles

Retracted: Effects of Different Anesthetics on Perioperative Organ Protection and Postoperative Cognitive Function in Patients Undergoing Cardiac Valve Replacement with Cardiopulmonary Bypass.

[This retracts the article DOI: 10.1155/2022/8994946.].

Open Thoracoabdominal Aortic Procedures following Endovascular Intervention.

Open conversion of thoracoabdominal aortic (TAA) disease after failed attempts of endovascular treatment is increasingly required. The main causes are endoleak, endograft failure, infection, disease progression, or persistent false lumen perfusion in dissected aortas. Mortality and morbidity rates are high, higher than after standard TAA open repair. Therefore, this surgery should be performed only in dedicated centers by experienced teams. Specific perioperative organ protection protocols, as well as surgical techniques, are crucial to guarantee acceptable results.

Effects of Different Anesthetics on Perioperative Organ Protection and Postoperative Cognitive Function in Patients Undergoing Cardiac Valve Replacement with Cardiopulmonary Bypass.

In this paper, we have carried out an experimental study to investigate the effects of different anesthetics on perioperative organ protection and postoperative cognitive function in patients undergoing cardiac valve replacement with cardiopulmonary bypass. To realize this idea, a total of 90 patients with single valve replacement under general anesthesia and hypothermic cardiopulmonary bypass from January 2020 to October 2021 were enrolled. These patients were assigned into three groups, with 30 cases in each group by the digital table method. Group A was anesthetized with sufentanil combined with dexmedetomidine. Group B was anesthetized with sufentanil combined with etomidate. Group C was anesthetized with sufentanil combined with propofol. Perioperative organ protection and postoperative cognitive function of the three groups were compared. At T0 time point, there was no significant difference in blood WBC, blood N, and CRP among groups A, B, and C (P > 0.05); At T4 and T5 time points, the indexes of blood WBC, blood N, and CRP in groups A, B, and C were higher compared to the T0 time point. At T4 and T5 time points, the indexes of blood WBC, blood N, and CRP in group A were significantly lower compared to group B and group C. Before treatment, there was no significant difference in ALT and AST among groups A, B, and C (P > 0.05). After treatment, the indexes of ALT and AST in group A were significantly lower compared to group B and group C at T4 and T5 time points (P < 0.05). Before treatment, there was no significant difference in urea and creatinine among groups A, B, and C (P > 0.05). After treatment, the urea and creatinine indexes of group A were significantly lower compared to group B and group C at T4 and T5 time points (P < 0.05). Before treatment, there was no significant difference in CK-MB and CTnl among groups A, B, and C (P > 0.05); After treatment, the indexes of CK-MB and CTnl in group A were significantly lower compared to group B and group C at T4 and T5 time points (P < 0.05). Before treatment, there was no significant difference in MOCA scores among groups A, B, and C (P > 0.05). After treatment, the MOCA scores of group A were significantly higher compared to group B and group C at T5 and T6 time points (P < 0.05). Sufentanil combined with dexmedetomidine for heart valve replacement under cardiopulmonary bypass can reduce the dosage of anesthetics during the operation and have a certain perioperative protective effect on important organs such as the heart, lung, liver, and kidney, which may be related to reducing intraoperative hemodynamic fluctuations and inhibiting inflammatory stress response.

Myocardial Expression of Estrogen Receptor-mRNA Is Associated With Lower Markers of Post-operative Organ Damage in Young Patients With Congenital Cardiac Defect.

Background: Estrogen receptors (ERs) relate to cardio-protection in adults, but their role in younger patients is not known. We aimed to assess the myocardial expression of ERα- and ERβ- mRNA in young patients with congenital cardiac disease and to analyze their putative protective role.Patients and Methods: Twenty children and young adults (seven females and 13 males) with a median age of 13.8 years (interquartile range: 12.3 years) were enrolled in this prospective study. The myocardial expression of ER-mRNA and genes involved in inflammation, growth, and stress response was assessed by real-time PCR and was correlated to post-operative (po) outcome.Results: ER-mRNA was detected in the myocardium of all patients, independently of gender and age. The expression of ER-mRNA correlated with that of mRNA coding for brain natriuretic peptide and for all cytokines tested. A higher ERα-mRNA expression correlated with lower troponin T concentrations at 24 h po (p = 0.032), higher PaO2/FiO2 ratio at 4 h po (p = 0.059), lower fluid retention at 4 h po (p = 0.048), and lower aspartate aminotransferase (AST) levels at 24 h po (p = 0.047). A higher ERβ-mRNA expression was also correlated with lower fluid retention at 24 h po (p = 0.048).Patients in whom the levels of ERα- and ERβ-mRNA were >P50 had lower troponin T (p = 0.003, respectively) and lower AST concentrations at 24 h po (p = 0.043, respectively) than the others.Conclusions: The expression of ERα- and ERβ-mRNA is present in the myocardium of children and young adults with congenital cardiac defect and is associated with lower markers of po organ damage. This suggests that ERs may provide perioperative organ protection in this population.

The concept of peri-operative medicine to prevent major adverse events and improve outcome in surgical patients: A narrative review.

: Peri-operative Medicine is the patient-centred and value-based multidisciplinary peri-operative care of surgical patients. Peri-operative stress, that is the collective response to stimuli occurring before, during and after surgery, is, together with pre-existing comorbidities, the pathophysiological basis of major adverse events. The ultimate goal of Peri-operative Medicine is to promote high quality recovery after surgery. Clinical scores and/or biomarkers should be used to identify patients at high risk of developing major adverse events throughout the peri-operative period. Allocation of high-risk patients to specific care pathways with peri-operative organ protection, close surveillance and specific early interventions is likely to improve patient-relevant outcomes, such as disability, health-related quality of life and mortality.

Activated Α7nachr Improves Postoperative Cognitive Dysfunction and Intestinal Injury Induced by Cardiopulmonary Bypass in Rats: Inhibition of the Proinflammatory Response Through the Th17 Immune Response

Backgrund/Aims: To investigate the effects of activated α7 nicotinic acetylcholine receptor (α7nAChR) on postoperative cognitive dysfunction (POCD) and intestinal injury induced by cardiopulmonary bypass (CPB) and its relationship with the Th17 response in order to provide a theoretical basis for organ protection and targeted drug therapy during the perioperative period. Methods: Sprague-Dawley rat models of CPB were established. Rat intestinal and brain injuries were observed after CPB using hematoxylin and eosin staining. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. Inflammatory factors and markers of brain injury in rat serum were measured using enzyme-linked immunosorbent assay. The expression levels of Bcl-2, Bax, caspase-3, ZO-1, occludin, AQP4, RORγT, and α7nAchR were examined using western blotting. Transcription factor RORγT expression was determined using real-time fluorescent quantitative polymerase chain reaction. Th17 cells in the peripheral blood and spleen were determined using flow cytometry. α7nAchR knockout rats were established. The Th17 response in the peripheral blood and spleen of α7nAchR knockout rats was further verified using flow cytometry. Results: CPB can induce POCD and intestinal injury in rats. α7nAchR activation markedly reduced intestinal injury, POCD, neuronal apoptosis, proinflammatory factor expression, and number of CD4⁺IL-17⁺ cells. α7nAchR knockout significantly increased serum D-lactic acid, FABP2, S-100β, NSE, TNF-α, IL-6, and IL-17 secretion. The number of CD4⁺IL-17⁺ cells was also significantly increased. Conclusion: α7nAchR activation markedly ameliorates the intestinal injury and POCD induced by CPB. Inhibition of the Th17 immune response can reduce the proinflammatory response, which could provide a new method for clinical perioperative organ protection and targeted drug therapy.

Progress and challenge of Stanford type A aortic dissection in China

In recent 20 years, the rapid development of acute Stanford type A aortic dissection in China has been mainly due to three aspects: (1) the refined classification of aortic dissection based on Stanford classification, (2) right axillary artery canal and selective cerebral perfusion technology become basic cardiopulmonary bypass strategy for Stanford type A aortic dissection, and (3) total aortic arch replacement and descending aortic stent graft surgery (Sun's surgery) become the standard treatment of Stanford type A aortic dissection. However, there are still many problems in the diagnosis and treatment of aortic dissection in China, such as: (1) unstandardized, lack of comprehensive guidelines of aortic dissection, (2) immature, perioperative organ protection and intraoperative blood protection technology remains a big flaw, and (3) it takes a long time to get patient prepared for surgery. In conclusion, as to the issue of the management of acute Stanford type A aortic dissection, there will be a long way for Chinese doctors to go. Peers should pay more attention to this problem and take more efforts, so that the outcome of acute Stanford type A aortic dissection surgical patients can be improved.

Abstract 15894: Adaptations of Innate Immunity in Hibernation: Mechanisms for Protection Against Acute Organ Injury

Introduction: Hibernation is a natural molecular adaptation to extreme environmental conditions with important implications for perioperative organ protection. Hypothesis: We hypothesized that the hibernator cardioprotective phenotype is accompanied by altered expression of innate immune pattern-recognition receptors (PRRs) and inflammatory pathways. Methods: LV myocardium, peripheral blood monocytes (PBMC), and plasma were collected from rat, summer AGS, and winter AGS after sham, 3h or 24h ischemia/reperfusion (I/R). Results: Plasma troponin I detection confirmed greater I/R injury in rat compared to AGS (Fig 1). Proteomic profiling of LV myocardium detected multiple differences including higher expression of MyD88 dependent toll-like receptors (TLR) in rat compared to AGS; average levels of TLRs were 1.8 fold higher in rat compared with hibernating AGS. Comparison of PBMCs from rat, summer, and hibernating AGS revealed increased PRR expression and cytokine production in the rat compared to the AGS, along the TLR3/TICAM (Fig2), TLR/MyD88, and AIM2/inflammasome axes. Conclusions: Compared to AGS, rats experience robust inflammasome activation in response to I/R as evidenced by &gt;30-fold increases in AIM2 and Caspase 1. Hibernation state differences in innate immunity exist, including reduced expression of PRRs(TLR1,3, and AIM2); additionally signaling via TLR 3 and 4 is greatly dampened in winter AGS due to nearly absent expression of TICAM1. Circulating immune effector cells in winter AGS have an abrogated response to DAMPs compared to cells from summer AGS or rat, as evidenced by reduced cytokine production.

Next generation of cardiovascular studies: transcriptional responses of the human myocardium during cardiac surgery.

Next generation of cardiovascular studies: transcriptional responses of the human myocardium during cardiac surgery.

Abstract 18884: Proteomic Profiling Reveals Reduction in Electron Transport Chain Proteins in the Hearts of Hibernating Arctic Ground Squirrels Compared with Rats after Surgical Ischemia and Reperfusion: A Convergence of Mammalian Cardio-protective Strategies

Introduction: Mammalian hibernation is a natural molecular adaptation to extreme environmental conditions with important applications for perioperative organ protection. We conducted an integrated proteomic analysis to identify species and season-specific correlates of the cardioprotective phenotype. Methods: Quantitative 2D-LC/LC-MS/MS was used in the myocardium of summer active arctic ground squirrels (AGS), winter hibernating AGS, and rats subjected to deep hypothermic cardiac arrest and reperfusion. Results: Hibernating AGS display robust cardioprotection in our model of I/R compared with rats using both biomarker (Fig 1) and echocardiographic assessment of cardiac injury. Proteomic analysis revealed significant reduction in subunits of all five electron transport chain (ETC) complexes in hibernating AGS compared with rats, only complex 5 showed increased expression of some subunits after I/R.Fig 2 Conclusions: Proteomic profiling revealed dichotomy in the cardioprotective adaptations employed by hibernating AGS and rat. The proteomic profile of hibernating AGS resembles that of myocardial hibernation in other mammals, with significant downregulation of mitochondrial ETC complexes. However, unlike myocardial hibernation in non-hibernators, AGS demonstrated downregulation of glycolytic and other myocardial energetic pathways with the exception of fatty acid oxidation. Sirtuin 3 - a key regulator of mitochondrial bioenergetics - was robustly upregulated in AGS, suggesting that preventing hyperacetylation of key metabolic enzymes may be a cardioprotective strategy employed by hibernators.

Abstract 18362: Proteomic and Metabolomic Profiling After Ischemia-Reperfusion Injury Reveals Bottlenecks That Underlie Cardioprotection in Hibernating Mammals

Introduction: Mammalian hibernation is a natural molecular adaptation to extreme environmental conditions with important applications for perioperative organ protection. We have previously shown in a surgical model of deep hypothermic circulatory arrest (DHCA) robust cardioprotection in hibernating arctic ground squirrels (AGS) compared with Brown Norway rats (Figure). We conducted an integrated proteomic and metabolomic analysis to identify species and season-specific correlates of the cardioprotective phenotype. Methods: Quantitative 5-fraction 2D-LC/LC-MS/MS was used to identify proteins expressed in the myocardium of summer active AGS, winter hibernating AGS, and rats subjected to DHCA followed by 3h or 24h of reperfusion, or sham (n=3-5/group). The complete sets of 5250 peptides for AGS and 8482 peptides for Rat were matched using an ENSEMBL referenced orthology map. Peptides from the same matched protein and species were log-transformed and summarized into protein level profiles by means of principal component analysis. Myocardial levels of 167 metabolites were quantified by MS. Results: Differentially expressed metabolic enzymes or transporters are paired with substrate and product in Table and reported as a ratio of change over baseline by species and hibernation status. Compared to AGS, rats developed metabolic TCA cycle substrate flux bottlenecks at the level of succinate dehydrogenase and malate transporter. Conclusions: Integration of observed changes in protein abundance with metabolic modules identified specific druggable targets for metabolic optimization that underlie the hibernator cardioprotective phenotype.

Targeting Purinergic Signaling for Perioperative Organ Protection

Targeting Purinergic Signaling for Perioperative Organ Protection

N-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery*

When used to prevent perioperative inflammation and ischemia-reperfusion injury, N-acetylcysteine may inadvertently impair hemostasis. We, therefore, performed a post hoc analysis of a recent randomized controlled trial in cardiac surgery to determine whether N-acetylcysteine was associated with increased blood loss and blood product transfusion. Blinded (patients, caregivers, outcome assessors) placebo-controlled parallel group randomized trial (www.ClinicalTrials.gov ID NCT00188630). Tertiary care hospital in Toronto, Ontario, Canada (September 2003 to October 2005). A total of 177 patients with preexisting moderate renal insufficiency (estimated glomerular filtration rate <or=60 mL/min) and undergoing cardiac surgery. Eighty-nine patients were randomized to receive intravenous N-acetylcysteine (100 mg/kg bolus; 20 mg.kg.hr infusion until 4 hours after cardiopulmonary bypass), and 88 were randomized to receive placebo. We used laboratory markers (hemoglobin, platelets, coagulation), chest-tube blood loss, and blood product transfusion to evaluate hemostasis. Compared with placebo, patients who received N-acetylcysteine arm experienced a mean 24-hour chest-tube blood loss that was 261 mL higher (95% confidence interval [CI] 93-488 mL, p = 0.008), and were transfused 1.6 more units of red blood cells (95% CI 0.4-3.1 units, p = 0.02) during hospitalization. The risk of receiving >or=5 units of red blood cells within 24 hours of surgery was significantly higher with N-acetylcysteine (relative risk 1.85, 95% CI 1.06-3.21, p = 0.03; adjusted relative risk 2.09, 95% CI 1.24-3.83, p = 0.005). In patients who have preexisting moderate renal insufficiency and are undergoing cardiac surgery, N-acetylcysteine was associated with important effects on blood loss and blood product transfusion. Clinicians and researchers should, therefore, consider the potential for impaired hemostasis when using N-acetylcysteine in the perioperative setting. Further research is needed to elucidate mechanisms by which N-acetylcysteine may impair hemostasis, and the risk-benefit profile of N-acetylcysteine for perioperative organ protection.

Best Practice &amp; Research: Clinical Anaesthesiology - Perioperative Organ Protection. Vol 22, No. 1, 2008.

Best Practice &amp; Research: Clinical Anaesthesiology - Perioperative Organ Protection. Vol 22, No. 1, 2008.

Invited commentary

The grave prognosis associated with post-cardiac surgery acute kidney injury (AKI) may be due, at least in part, to the distant effects of AKI on other organ function. An AKI requiring dialysis occurs in as many as 5% of cardiac surgery patients, while an additional 8% to 15% have moderate kidney injury (eg, >1.0 mg/dL peak creatinine rise in serum creatinine). Lesser renal injuries are even more common with as many as 50% of postoperative cardiac surgery patients in some studies having a 25% or greater rise in serum creatinine. The AKI in many settings, including cardiac surgery, has been independently linked with in-hospital mortality, even after adjustment for comorbid diseases and other complications [1Chertow G.M. Levy E.M. Hammermeister K.E. Grover F. Daley J. Independent association between acute renal failure and mortality following cardiac surgery.Am J Med. 1998; 104: 343-348Abstract Full Text Full Text PDF PubMed Scopus (1023) Google Scholar]. All degrees of AKI are associated with short-term mortality and other adverse outcomes [2Stafford-Smith M. Perioperative renal dysfunction: implications and strategies for protection.in: Newman M.F. Perioperative organ protection. Lippincott Williams & Wilkins, Baltimore, MD2003: 89-124Google Scholar]. However, only a few previous studies have focused on the relationship of perioperative AKI with long-term survival. Brown and colleagues [3Brown J.R. Cochran R.P. MacKenzie T.A. et al.Long-term survival after cardiac surgery is predicted by estimated glomerular filtration rate.Ann Thorac Surg. 2008; 86: 4-12Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar] compare mortality rates and postoperative renal dysfunction in a population of 13,593 isolated coronary artery bypass graft procedures in terms of lowest postoperative estimated glomerular filtration rate (eGFR). What is particularly elegant in the current study relative to any of the other studies in this area is that the authors have a sufficiently large dataset to demonstrate an association with long-term survival, even when this outcome is separated from short-term in-hospital, 30-day mortality. Their finding, linking eGFR rates less than 60 mL/min with decreased long-term survival (after 30 days postoperatively) is yet further validation of the importance of postoperative renal dysfunction, including AKI. As early biomarkers start to provide better information than serum creatinine and become validated as clinical tools to diagnose AKI, the hope is that early recognition and prompt intervention similar to the strategies developed for acute myocardial infarction (AMI) may redefine the therapeutic approach to AKI and potentially, as with AMI, lead to the development of interventions that may improve outcome including long-term survival. Studies such as the one from Brown and colleagues [3Brown J.R. Cochran R.P. MacKenzie T.A. et al.Long-term survival after cardiac surgery is predicted by estimated glomerular filtration rate.Ann Thorac Surg. 2008; 86: 4-12Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar] that provide measurable endpoints associated with AKI may become the benchmarks against which such renoprotective interventions are compared. Long-Term Survival After Cardiac Surgery is Predicted by Estimated Glomerular Filtration RateThe Annals of Thoracic SurgeryVol. 86Issue 1PreviewEstimated glomerular filtration rate (eGFR) before coronary artery bypass graft (CABG) surgery is a key risk factor of in-hospital mortality. However, in patients with normal renal function before CABG, acute kidney injury develops after the procedure, making postoperative renal function assessment necessary for evaluation. Postoperative eGFR and its association with long-term survival have not been well studied. Full-Text PDF

Perioperative outcome after Aortic arch repair with standardized deep hypothermic circulatory arrest: role of a multimodal protocol to enhance perioperative organ protection

Perioperative outcome after Aortic arch repair with standardized deep hypothermic circulatory arrest: role of a multimodal protocol to enhance perioperative organ protection

Inhibitors of the renin angiotensin system: implications for the anaesthesiologist

The major long-term benefits of angiotensin-converting enzyme (ACE) inhibitors have now clearly been demonstrated in patients with arterial hypertension, cardiac insufficiency, coronary artery disease and several renal diseases. Such long-term treatment markedly alters the cardiovascular response to anaesthesia and surgery, whereas preliminary data suggest that short-term renin angiotensin system blockade might provide perioperative organ protection and improved circulatory conditions. Besides the classic view that the conversion of angiotensin I to angiotensin II is mainly due to ACE, alternative pathways have recently been identified, including cathepsin G as well as chymostatin- and aprotinin-sensitive serine proteases that are released from mastocytes and endothelial cells and which are insensitive to the effects of ACE inhibitors. These proteases are thought to contribute to tissue perfusion under hypoxic conditions and to structural remodelling. In clinical practice, ACE inhibitors may be preferred to angiotensin II receptor antagonists since the former, besides reducing angiotensin II synthesis, also lead to an accumulation of kinins (e.g. bradykinin), which have important cardio- and renal protective effects through liberation of prostacyclin and nitric oxide in endothelial cells and through stimulation of guanylate cyclase to form cyclic GMP.