Gui-Zhen Yang

Combined morphine and limb remote ischemic perconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury by antiapoptosis

BACKGROUND Both morphine and limb remote ischemic perconditioning (RIPer) can protect against myocardial ischemia/reperfusion injury (IRI). This experiment was designed to assess whether combined morphine and limb RIPer could provide and enhanced protection against myocardial IRI in an in vivo rat model. METHODS One hundred male Sprague-Dawley rats were randomly allocated to six groups: sham, ischemia/reperfusion (IR), ischemic preconditioning, RIPer, morphine (M), and combined morphine and remote ischemic perconditioning (M + RIPer). Ventricular arrhythmias that occurred during ischemia and early reperfusion were scored, and serum creatine kinase isoenzyme and cardiac troponin I levels were assayed. The infarct size was determined by Evans blue and triphenyl tetrazolium chloride staining. The apoptosis in the myocardial ischemic core, ischemic border, and nonischemic areas was assessed through real-time polymerase chain reaction for Bax and Bcl-2 and with the transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay. RESULTS The infarct size, serum cardiac troponin I level, incidence, and score of the arrhythmias during the initial reperfusion were significantly reduced in the M + RIPer group compared with the IR group but did not differ significantly between the ischemic preconditioning and M + RIPer groups. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling-positive cells were significantly decreased, and the Bcl-2/Bax ratio was significantly increased in the M + RIPer group compared with the IR group. CONCLUSIONS This experiment demonstrates that combined morphine and limb RIPer provides an enhanced protection against myocardial IRI by the Bcl-2-linked apoptotic signaling pathway.

Assessing interaction between dexmedetomidine and propofol

1. Yoo JY, Kwak HJ, Kim YB, Park CK, Lee SY, Kim JY. The effect of dexmedetomidine pretreatment on the median effective bolus dose of propofol for facilitating laryngeal mask airway insertion. J Anesth. 2016. doi:10.1007/s00540-016-2245-7. 2. Afonso J, Reis F. Dexmedetomidine: current role in anesthesia and intensive care. Rev Bras Anestesiol. 2012;62:118–33. 3. Rolly G, Versichelen L, Huyghe L, Mungroop H. Effect of speed of injection on induction of anaesthesia using propofol. Br J Anaesth. 1985;57:743–6. To the Editor:

Current Evidences for the Use of UEscope in Airway Management

Objective: UEscope is a new angulated videolaryngoscope (VL). This review aimed to describe the features of UEscope and provide clinical evidences regarding the efficacy and safety of this video device in adult tracheal intubation and its roles in airway management teaching. Data Sources: The Wan Fang Data, CNKI, PubMed, Embase, Cochrane Library, and Google Scholar were searched for relevant English and Chinese articles published up to January 15, 2017, using the following keywords: “HC video laryngoscope”, “UE videolaryngoscope”, “video laryngoscope”, and “videolaryngoscopy”. Study Selection: Human case reports, case series, observable studies, and randomized controlled clinical trials were included in our search. The results of these studies and their reference lists were cross-referenced to identify a common theme. Results: UEscope features the low-profile portable design, intermediate blade curvatures, all-angle adjustable monitor, effective anti-fog mechanisms, and built-in video recording function. During the past 5 years, there have been a number of clinical studies assessing the application and roles of UEscope in airway management and education. As compared with direct laryngoscope, UEscope improves laryngeal visualization, decreases intubation time (IT), and increases intubation success rate in adult patients with normal and difficult airways. These findings are somewhat different from the previous results regarding the other angulated VLs; they can provide an improved laryngeal view, but no conclusive benefits with regard to IT and intubation success rate. Furthermore, UEscope has extensively been used for intubation teaching and shown a number of advantages. Conclusions: UEscope can be used as a primary intubation tool and may provide more benefits than other VLs in patients with normal and difficult airways. However, more studies with large sample are still needed to address some open questions about clinical performance of this new VL.

Association between intraoperative blood product transfusions and acute kidney injury following cardiac surgery

With great interest, we read the recent article by Kindzelski et al.1 assessing the association between intraoperative blood product transfusions and acute kidney injury (AKI) following cardiac surgery. By binary logistic regression analysis, they show that intraoperative blood product transfusions are independently associated with an increased risk of postoperative AKI. Furthermore, there is a stepwise increase in the probability of postoperative 30-day mortality with escalating AKI severity. In this study, the authors had used appropriate statistical methods to evaluate the influence of intraoperative blood transfusion on the occurrence of AKI and determine the association between postoperative AKI stages and mortality. However, this study is a retrospective analysis, which potentially introduces a number of confounders. Other than the limitations described in the discussion, we note that several issues of this study were not well addressed. First, when determining the association of intraoperative blood transfusion with postoperative AKI stages by logistic regression analysis, intraoperative variables used for risk adjustments only included type of surgery (CABG, valvular, both) and cross-clamp time, but not other important intraoperative variables associated with AKI, especially for hemoglobin levels during cardiopulmonary bypass. It has been shown that hemodilution anemia during cardiopulmonary bypass is independently associated with AKI after cardiac surgery, especially when prolonged cardiopulmonary bypass time and intraoperative transfusion are needed.2 Furthermore, the simultaneous occurrence of both hemodilution anemia and hypotension during cardiopulmonary bypass can synergistically act to increase the risk of AKI after cardiac surgery.3 We are concerned that the neglect of important intraoperative factors for risk adjustments would have biased the true contribution of intraoperative blood transfusion to the occurrence of postoperative AKI. Second, this study only focused on the influence of intraoperative blood transfusion on the development of postoperative AKI. The available evidence shows that blood transfusion after cardiac surgery is also an independent risk factor of postoperative AKI.4,5 Finally, when evaluating the association of escalating AKI severity with postoperative 30-day mortality by logistic regression analysis, postoperative anemia and blood transfusion were not included in the model for risk adjustment. Similarly, postoperative blood transfusion has also been associated independently with the increased risk of adverse events and mortality after cardiac surgery.6 Furthermore, postoperative anemia is common and frequently persists for months after cardiac surgery. When the postoperative hemoglobin level is considered as a continuous variable, every 1 mg/dl decrease in hemoglobin level is associated with a 13% increase in adverse cardiovascular events and a 22% increase in all-cause mortality.7 Thus, not taking postoperative anemia and blood transfusion into account would have tampered with the inference of the logistic regression model for adjusted impacts of AKI stages on postoperative 30-day mortality.

Effects of enteral different-dose levothyroxinesodium pretreatment on serum thyroid hormone levels and myocardial ischemia-reperfusion injury

Introduction: The available evidence shows that perioperative oral thyroid hormone can significantly attenuate the postoperative decline in the serum hormone level and improve postoperative hemodynamic and prognostic parameters. However, there has been no study assessing the effects of preoperative oral different-dose thyroid hormone on serum hormone levels and myocardial ischemia-reperfusion injury (IRI) after cardiac surgery. Methods: Forty-eight healthy Wistar rats, aged 35 days, were randomly allocated into six groups: Group BC, Group C and four pretreatment groups in which the rats were given levothyroxine-sodium of 10 μg, 20 μg, 40 μg and 80 μg/100 g. On the eighth day, the serum thyroid hormone levels were determined and then an isolated heart ischemia-reperfusion model was established with a Langendorff apparatus. Results: Compared with Groups BC and C, serum thyroid hormone levels on the eighth day did not significantly change in Group 10 μg, but were significantly increased in Groups 20 μg, 40 μg and 80 μg. The cardiac enzyme myocardial-bound creatine kinase levels in the coronary effluent during reperfusion were significantly lower in Groups 10 μg and 20 μg and 40 μg than in Group C. The recovery rates of +dp/dtmax and -dp/dtmax at 30 min during reperfusion were significantly lower in Groups 40 μg and 80 μg than in Groups 10 μg and 20 μg. Compared with Group C, myocardial expressions of heat shock protein 70 and myosin heavy chain α were increased in the four experiment groups and myocardial expression of thyroid hormone receptor α1 was significantly increased in Groups 20 μg, 40 μg and 80 μg. Conclusions: The pretreatment with enterally smaller doses levothyroxine-sodium does not significantly affect serum thyroid hormone levels and produces protection against myocardial IRI, whereas pretreatment with enterally larger doses of levothyroxine-sodium can only provide an attenuated or insignificant cardioprotection because of hyperthyroxinemia. Cardioprotection by levothyroxine-sodium pretreatment is probably attributable to increased myocardial expression of heat shock protein 70 and myosin heavy chain α.

Comparing bougie-guided and conventional nasotracheal intubations using videolaryngoscopy

In a randomised controlled trial comparing bougie-guided and conventional nasotracheal intubation using videolaryngoscopy in older children and adults, Abrons et al. [1] showed that a bougie-guided technique resulted in significantly less nasal trauma and the need to use Magill forceps compared with a conventional technique, but led to prolonged intubation time and no difference in intubation success rate. To differentiate the effect of one factor on primary study end-points in a randomised controlled trial, however, all of the other factors have to be standardised for avoidance of potential bias. We would like to invite the authors to address the following comments about their study. The authors stated in their methods that they used a size-4 GlideScope videolaryngoscope (Verathon, Bothell, WA, USA), an angulated-type videolaryngoscope, but showed a C-MAC videolaryngoscope (Karl Storz Endoscopy, Tuttlingen, Germany), a Macintosh-type videolaryngoscope, in their Figures 1 and 3. Obviously, a size-4 GlideScope blade would not be suitable for the paediatric patients included in this study. The design of the blade can affect the performance of videolaryngoscopy for nasotracheal intubation [2], in particular, acute distal angulation and the large size of the GlideScope blade, which can complicate use of the straight Magill forceps, in comparison with the Macintosh blade of the C-MAC videolaryngoscope; Boedeker curved forceps are recommended instead when an angulated-typed videolaryngoscope is used for nasotracheal intubation [3]. In addition, could the authors state which type of GlideScope videolaryngoscope was used in this study – Original, Cobalt, Ranger or Titanium – as different GlideScope videolaryngoscopes can have an effect [4]? Secondly, only a paediatric bougie was used as a Seldinger nasotracheal intubation guide, which can be inadequate for guiding a large nasotracheal tube past the nasal cavity and glottis in adult patients. Do the authors concur with our experience, that the selection of a bougie size based on the patients age can facilitate nasotracheal tube passage, decrease nasopharyngeal trauma and improve tube navigability, as effectively as fiberoptic bronchoscopeguided nasotracheal intubation [5]? Finally, and most importantly, the authors described how many of the participants had not had training in the bougie-guided technique before the study, and were anaesthesia residents or year one-student nurse anaesthetists. Every airway technique has a learning curve, and in a randomised controlled trial, equal proficiency using a standardised technique is necessary to avoid mapping the learning curves of inexperienced novices, instead of measuring the efficacy of the techniques studied [6]. Could the authors quantify, therefore, how many of the participants had had experience in performing nasotracheal intubation?

Evaluating LMA-ProSeal insertion techniques: A call for methodological clarification

In the recent article by Ishio et al. [1] evaluating the insertion efficacy of the LMA-ProSeal by novice doctors with or without a 90° bend created by an intubating stylet in anesthetized patients, they demonstrate that a 90° bend re-figuration facilitates LMA-ProSeal insertion, as shown by a higher successful insertion rate, a higher sealing pressure, and a lower subjective difficulty of insertion. To rightly compare effect of insertion techniques on performance of the studied device in a randomized controlled trial, however, standardization of equipment and rational design of study are crucial. In our opinion, there are several issues in their study that would have made interpretation of their findings questionable. First, in method, the authors did not specify the LMA-ProSeal insertion procedure, particularly at the control group. It must be emphasized that standardization of equipment is associated with improved performance. Given that all of 15 novice doctors participated in this study only had limited experience in the use of LMAProSeal, we would like to knowwhether they received formal teaching and training about the use of this device before this study. According to the manufacturers instructions, the LMA-ProSeal insertion can be performed with a digital method or a metal introducer technique [2]. When using a digital method, the doctors index finger is placed in the retaining strap of LMA-ProSeal: this is made easier by lateral compression of the body of the mask to bow the strap outward. When using a metal introducer, it distal end is located in the retaining strap of LMA-ProSeal and its proximal end is placed in the notch between airway tube and drain tube. Furthermore, what should be noted is that insertion of the LMA-ProSeal using a digital method is similar to the classic LMA, whereas the insertion with an introducer technique resembles the intubating LMA-Fastrach. We are concerned that no pre-study teaching and training would have resulted in a poor insertion technique of the LMA-ProSeal and then influence the final end-point of performance. Second, as to the Fig. 2 provided in this article, the shape of the LMA-ProSeal created by an intubating stylet was similar to that made by a metal introducer. Thus, a rational design of control group would be that the LMA-ProSeal was inserted with using a metal introducer, as performed in previous study [3]. Third, in this study, the cuff of the LMA-ProSeal was inflated to a pressure of 30 cm H2O with a pressure transducer. As to the manufacturers instructions, inflation to an intracuff pressure of 60 cm H2O is preferred for the LMA-ProSeal [2]. It has been shown that cuff inflation volume and intracuff pressure can significantly change airway sealing pressure of the LMA-ProSeal [4].

Controlling tip of nasotracheal tube under video laryngoscopy

vision on the monitor (Supplementary Figure 1A). After the tube has been advanced to pass the glottis, the cuff is deflated and the tube is inserted into the trachea. Use of a surgical suture to control the distal tip of the nasotracheal tube under video laryngoscopy has recently been reported by Hung et al. [2]. In our experience, this method is effective in correcting the posterior or lateral tube tip location (Supplementary Figure 1B).

Use of a meta-analysis to assess the preventive effect of dexmedetomidine on cardiac surgery-associated acute kidney injury

Shi and Tie [1] concluded in their meta-analysis that dexmedetomidine might be a promising prevention strategy for cardiac surgery-associated acute kidney injury (CSA-AKI). In a meta-analysis, the results from many studies are synthesized mathematically by complex statistical methods to assess the diversity among results and to estimate a common pooled effect with increased precision. Thus, the results of a meta-analysis are only as good as the quality of the collected data. We noted that some defects of the studies included in this metaanalysis would have made interpretation of their conclusions questionable. First, there is a high heterogeneity among seven included studies, such as studied subjects (pediatric and adult patients), definitions of primary outcomes (creatinine rise, biomarkers, and renal complications), intervention times (unclear, intraoperative, intraoperative and postoperative, and postoperative), doses of dexmedetomidine, and so on. Second, four of seven included studies were observational studies with significant methodological limitations and a number of confounders, such as a retrospective design or single-center recruitment. There was no attempt in some studies to control most of the risk factors for CSA-AKI, including intraoperative transfusions, hemodynamic instability, use of vasopressors, hemodilution anemia, and so on [2, 3]. Third, most of included studies did not assess the effect of dexmedetomidine on the severity and duration of CSA-AKI, although these have highly been associated with postoperative outcomes [4]. Finally, this analysis did not include the recent randomized controlled trial (RCT) by Zhai et al. [5], in which dexmedetomidine decreased the incidence and severity of CSA-AKI in patients undergoing cardiac surgery. The findings of Zhai et al. support the conclusion of this meta-analysis that dexmedetomidine may be beneficial for prevention of CSA-AKI.

Feasibility Analysis of Oxygen-Glucose Deprivation-Nutrition Resumption on H9c2 Cells In vitro Models of Myocardial Ischemia-Reperfusion Injury

Background: Oxygen-glucose deprivation-nutrition resumption (OGD-NR) models on H9c2 cells are commonly used in vitro models of simulated myocardial ischemia-reperfusion injury (MIRI), but no study has assessed whether these methods for establishing in vitro models can effectively imitate the characteristics of MIRI in vivo. This experiment was designed to analyze the feasibility of six OGD-NR models of MIRI. Methods: By searching the PubMed database using the keywords “myocardial reperfusion injury H9c2 cells,” we obtained six commonly used OGD-NR in vitro models of MIRI performed on H9c2 cells from more than 400 published papers before January 30, 2017. For each model, control (C), simulated ischemia (SI), and simulated ischemia-reperfusion (SIR) groups were assigned, and cell morphology, lactate dehydrogenase (LDH) release, adenosine triphosphate (ATP) levels, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and inflammatory cytokines were examined to evaluate the characteristics of cell injury. Subsequently, a coculture system of cardiomyocyte-endothelial-macrophage was constructed. The coculture system was dealt with SI and SIR treatments to test the effect on cardiomyocytes survival. Results: For models 1, 2, 3, 4, 5, and 6, SI treatment caused morphological damage to cells, and subsequent SIR treatment did not cause further morphological damage. In the models 1, 2, 3, 4, 5 and 6, LDH release was significantly higher in the SI groups than that in the C group (P < 0.05), and was significantly lower in the SIR groups than that in the SI groups (P < 0.05), except for no significant differences in the LDH release between C, SI and SIR groups in model 6 receiving a 3-h SI treatment. In models 1, 2, 3, 4, 5, and 6, compared with the C group, ATP levels of the SI groups significantly decreased (P < 0.05), ROS levels increased (P < 0.05), and MMP levels decreased (P < 0.05). Compared with the SI group, ATP level of the SIR groups was significantly increased (P < 0.05), and there was no significant ROS production, MMP collapse, and over inflammatory response in the SIR groups. In a coculture system of H9c2 cells-endothelial cells-macrophages, the proportion of viable H9c2 cells in the SIR groups was not reduced compared with the SI groups. Conclusion: All the six OGD-NR models on H9c2 cells in this experiment can not imitate the characteristics of MIRI in vivo and are not suitable for MIRI-related study.