Effect Of Preconditioning Research Articles

Material properties and effect of preconditioning of human sclera, optic nerve, and optic nerve sheath

The optic nerve (ON) is a recently recognized tractional load on the eye during larger horizontal eye rotations. In order to understand the mechanical behavior of the eye during adduction, it is necessary to characterize material properties of the sclera, ON, and in particular its sheath. We performed tensile loading of specimens taken from fresh postmortem human eyes to characterize the range of variation in their biomechanical properties and determine the effect of preconditioning. We fitted reduced polynomial hyperelastic models to represent the nonlinear tensile behavior of the anterior, equatorial, posterior, and peripapillary sclera, as well as the ON and its sheath. For comparison, we analyzed tangent moduli in low and high strain regions to represent stiffness. Scleral stiffness generally decreased from anterior to posterior ocular regions. The ON had the lowest tangent modulus, but was surrounded by a much stiffer sheath. The low-strain hyperelastic behaviors of adjacent anatomical regions of the ON, ON sheath, and posterior sclera were similar as appropriate to avoid discontinuities at their boundaries. Regional stiffnesses within individual eyes were moderately correlated, implying that mechanical properties in one region of an eye do not reliably reflect properties of another region of that eye, and that potentially pathological combinations could occur in an eye if regional properties are discrepant. Preconditioning modestly stiffened ocular tissues, except peripapillary sclera that softened. The nonlinear mechanical behavior of posterior ocular tissues permits their stresses to match closely at low strains, although progressively increasing strain causes particularly great stress in the peripapillary region.

Down-regulation of NAA10 mediates the neuroprotection induced by sevoflurane preconditioning via regulating ERK1/2 phosphorylation

ObjectiveIn the present study, the regulation mechanism of NAA10 (N-Alpha-Acetyltransferase 10) in sevoflurane preconditioning induced neuroprotective effect was explored. MethodsFirstly, si-NAA10 or negative control (NC) were constructed for cell transfection and injected into intracerebroventricular of rats. Oxygen-glucose deprivation/reperfusion (OGD/R) model in vitro and middle cerebral artery occlusion (MCAO) model in vivo were established to simulate cerebral I/R injury. QRT-PCR analysis and western blotting assay were performed to assess the expression of NAA10. TTC staining, neurological evaluation and cell counting kit-8 (CCK-8) were performed to evaluate the effect of NAA10 on sevoflurane induced neuroprotection. TUNEL assay and flow cytometry were used to detect the apoptosis in vivo and in vitro. ResultsIt showed that sevoflurane preconditioning increased the expression of NAA10 in MCAO rats. TTC staining, TUNEL assay and neurological evaluation results suggested that si-NAA10 attenuated the neuroprotective effect of sevoflurane preconditioning against MCAO. CCK-8 assay, flow cytometry, qRT-PCR and western blot results showed that NAA10 mediated sevoflurane preconditioning-induced neuroprotection in vitro. Furthermore, western blot results showed that down-regulation of NAA10 could reverse the attenuation of ERK1/2 phosphorylation induced by sevoflurane preconditioning in vivo or in vitro. ConclusionDown-regulation of NAA10 regulated ERK1/2 phosphorylation mediating sevoflurane preconditioning induced neuroprotective effects. The results revealed the regulatory mechanism of NAA10 in the neuroprotective effect of sevoflurane preconditioning.

The Effect of Remote Ischemic Preconditioning on Serum Creatinine in Patients Undergoing Partial Nephrectomy: A Randomized Controlled Trial.

Renal function declines after partial nephrectomy due to ischemic reperfusion injury induced by surgical insult or renal artery clamping. The effect of remote ischemic preconditioning (RIPC) on reducing renal injury after partial nephrectomy has not been studied regarding urinary biomarkers. Eighty-one patients undergoing partial nephrectomy were randomly assigned to either RIPC or the control group. RIPC protocol consisted of four cycles of five-min inflation and deflation of a blood pressure cuff to 250 mmHg. Serum creatinine levels were compared at the following time points: preoperative baseline, immediate postoperative, on the first and third days after surgery, and two weeks after surgery. The incidence of acute kidney injury, other surgical complication rates, and urinary biomarkers, including urine creatinine, β-2 microglobulin, microalbumin, and N-acetyl-beta-D-glucosaminidase were compared. Split renal functions measured by renal scan were compared up to 18 months after surgery. There was no significant difference in the serum creatinine level on the first postoperative day (median (interquartile range) 0.87 mg/dL (0.72–1.03) in the RIPC group vs. 0.92 mg/dL (0.71–1.12) in the control group, p = 0.728), nor at any other time point. There was no significant difference in the incidence of acute kidney injury. Secondary outcomes, including urinary biomarkers, were not significantly different between the groups. RIPC showed no significant effect on the postoperative serum creatinine level of the first postoperative day. We could not reveal any significant difference in the urinary biomarkers and clinical outcomes. However, further larger randomized trials are required, because our study was not sufficiently powered for the secondary outcomes.

Mature Adult Mice With Exercise-Preconditioning Show Better Recovery After Intracerebral Hemorrhage.

Physical exercise offers therapeutic potentials for several central nervous system disorders, including stroke and cardiovascular diseases. However, it is still mostly unknown whether and how exercise preconditioning affects the prognosis of intracerebral hemorrhage (ICH). In this study, we examined the effects of preconditioning on ICH pathology in mature adult mice using treadmill exercise. Male C57BL/6J (25-week old) mice were subjected to 6 weeks of treadmill exercise followed by ICH induction. Outcome measurements included various neurological function tests at multiple time points and the assessment of lesion volume at 8 days after ICH induction. In addition, plasma soluble factors and phagocytotic microglial numbers in the peri-lesion area were also measured to determine the mechanisms underlying the effects of exercise preconditioning. The 6-week treadmill exercise preconditioning promoted recovery from ICH-induced neurological deficits in mice. In addition, mice with exercise preconditioning showed smaller lesion volumes and increased numbers of phagocytotic microglia. Furthermore, the levels of several soluble factors, including endostatin, IGFBP (insulin-like growth factor-binding protein)-2 and -3, MMP (matrix metallopeptidase)-9, osteopontin, and pentraxin-3, were increased in the plasma samples from ICH mice with exercise preconditioning compared with ICH mice without exercise. These results suggest that mice with exercise preconditioning may suffer less severe injury from hemorrhagic stroke, and therefore, a habit of physical exercise may improve brain health even in middle adulthood.

Exosomes Secreted from Hypoxia-Preconditioned Mesenchymal Stem Cells Prevent Steroid-Induced Osteonecrosis of the Femoral Head by Promoting Angiogenesis in Rats.

Recent studies have suggested that exosomes exert similar therapeutic effects to those of mesenchymal stem cells (MSCs) in regenerative medicine and MSCs-derived exosomes exhibit therapeutic effects on steroid-induced osteonecrosis of the femoral head (ONFH). Furthermore, reparative functions of exosomes from MSCs are enhanced by hypoxia treatment of the cells. However, there are no related reports about whether exosomes derived from hypoxia-preconditioned MSCs could show better therapeutic effects on steroid-induced ONFH. In vitro, we investigated the effects of hypoxia precondition on exosomes derived from bone marrow mesenchymal stem cells (BMMSCs) from rats and the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs. In vivo, we investigated the role of exosomes from hypoxia-preconditioned BMMSCs on angiogenesis and protecting osteonecrosis in a rat ONFH model. We found that the potential of the proangiogenic ability of exosomes derived from hypoxia-preconditioned BMMSCs was higher than exosomes derived from BMMSCs cultured under normoxia. Exosomes derived from hypoxia-preconditioned BMMSCs significantly promoted proliferation, migration, vascular endothelial growth factor (VEGF) expression, and tube formation of human umbilical vein endothelial cells (HUVECs) compared with exosomes derived from BMMSCs cultured under normoxia. Administration of exosomes derived from hypoxia-preconditioned BMMSCs significantly prevented bone loss and increased vessel volume in the femoral head compared with exosomes derived from BMMSCs cultured under normoxia. Taken together, our data suggest that exosomes derived from hypoxia-preconditioned BMMSCs exert better therapeutic effects on steroid-induced ONFH by promoting angiogenesis and preventing bone loss.

Динамика хемилюминесценции в тонкой кишке на фоне анестетического прекондиционирования при геморрагической гипотензии

Introduction. The major pathogenetic factor of massive blood loss is hypoxia, which triggers activation of free-radical oxidation (FRO) processes in organs and tissues and the systemic inflammatory response. A universal factor of multiple organ dysfunction in blood loss is altered intestinal wall permeability with translocation of microflora and toxins into the systemic circulation during reperfusion. Recently, much of the attention has been focused on effects of anesthetic preconditioning, including during operations associated with hemorrhagic hypotension (HH). The aim of this study was to evaluate in experiment the dynamics of small intestinal FRO in HH during the use of the anesthetic sevoflurane, which has an effect of anesthetic preconditioning. Methods. Experiments were performed on 105 white male rats divided into two groups; groups 1 and 2 were exposed to HH with ether or sevoflurane as the anesthetic, respectively. Two groups of intact animals treated with ether or sevoflurane were used as the controls. Five animals died during the experiment. To evaluate FRO processes, samples of the duodenum, jejunum, and ileum were taken at 15 min, 30 min, 1 h, and 2 h of HH. The chemiluminescence (CL) study of small intestine homogenates was performed according to the Farukhutdinov method on a Fluorate ABLF-2T chemiluninometer. The following FRO indexes were recorded: spontaneous luminosity (SL), flash (F), and light sum (L∑). Significance of differences was determined with the Mann-Whitney test. Results. In the sevoflurane group 2 compared to the ether group after 15 min of HH, SL was increased in the jejunum by 33%; F was decreased in the duodenum by 50%, in the jejunum by 24%, and in the ileum by 36%; L∑ was decreased in the duodenum by 36%, in the jejunum by 45%, and in the ileum by 52%. At 30 min, SL in the jejunum was increased by 80%. In the HH+sevoflurane group, F was decreased in the duodenum by 38%, in the jejunum by 22%, and in the ileum by 27%; L∑ in the duodenum was decreased by 44%, in the jejunum by 45%, and in the ileum by 67%. After 1 h of HH+sevofluran, SL was increased in the jejunum twofold, in the duodenum by 38% and in the ileum by 15%; F was decreased in the duodenum by 67% and in the jejunum by 43%; L∑ in the duodenum was decreased by 62%, in the jejunum by 60%, and in the ileum by 70% compared to the ether group. After 2 h of HH+sevofluran, SL was increased in the jejunum and ileum by 80% and 67%, respectively, compared to the ether group. In this process, L∑ in the duodenum was decreased by 24% and in the jejunum by 15%. Conclusion. The HH+diethyl ether exposure was associated with activation of FRO processes in the small intestine. The sevoflurane preconditioning provided a significant restriction of oxidative stress in the rat small intestine due to activation of the antioxidant system in the duodenum, jejunum, and ileum at 1 h, 15 min, and 30 min of HH, respectively.

Down-Regulation of Nogo-A and PirB in Ischemic Cortex with Remote Ischemic Preconditioning in Mice

Objectives: The present study aims to investigate the effect of Limb Remote Ischemic Preconditioning (LRIP) on the expression of Nogo-A and PirB in the cortex of mice with focal cerebral ischemia, and related pathways involving in axonal regeneration and neurological function recovery after cerebral ischemia. Methods: Adult male C57/BL6 mice were divided into sham-operated (sham), transient Middle Cerebral Artery Occlusion (MCAO), LRIP and anti- PirBAb treatment group. Samples were collected 48h after cerebral ischemia. The histopathologic changes were assessed by 1,3,5-Triphenyl-2H-Tetrazolium Chloride (TTC), and Hematoxylin and Eosin (HE) staining and TUNEL method. The expression of Nogo-A and PirB were determined by immunofluorescence, RT-PCR and Western blot respectively. Results: TTC staining showed that LRIP treatment reduced the infarct size of mice and anti-PirBAb treatment further decline the infarct size, which was accompanied with the decline of neurological deficit score and reduction of neuronal damage. LRIP treatment also reduced the TUNEL positive cells induced by MCAO and anti-PirBAb treatment further strengthened the effect of LRIP. Except sham group, the expressions of Nogo-A and PirB in other three groups all increased with varying degrees, among which MCAO group was the highest, LRIP group was the second and the anti-PirBAb group was the lowest. The expressions of growth associated protein 43 (GAP43) showed opposite tendency. Conclusions: LRIP plays beneficial influence on cerebral ischemia. LRIP and PirB inhibition combination has a better protective effect on nervous system after cerebral ischemia in mice.

Effect of ischemic preconditioning on radiation damage to the submandibular gland in rats.

To investigate the effects of radiation on rat submandibular glands and the possible protective effects of ischemic preconditioning, the submandibular glands of Wistar rats were subjected to in situ radiation after ischemic preconditioning. The glands were exposed to X-radiation at a single dose of 20Gy. Ischemic preconditioning was achieved by three min of ischemia and three min of reperfusion, repeated three times before irradiation. Salivary secretion, histological changes, alterations in tight junctions, and the levels of oxidative stress, pro-inflammatory cytokines, and water secretion proteins mediated by the muscarinic acetylcholine M3 subtype receptor were determined at 1 and 12weeks post-irradiation. In glands subjected to irradiation only, the secretion, superoxide dismutase activity, tight junction width, acinar cell number, and M3 receptor and aquaporin-5 levels were lower at 1 and 12weeks than seen in the ischemically preconditioned irradiated glands. In contrast, tumor necrosis factor-α, malondialdehyde, myeloperoxidase activity, and the expression of the tight junction protein claudin-4 were significantly higher in the irradiated only glands. Our study revealed that radiation caused a series of injury-stress responses, especially damage to the water secretion pathway mediated by the M3 receptor that ultimately led to hyposecretion, which might play an important role in the dysfunction of the irradiated only glands. Ischemic preconditioning reduced the radiation-induced injury to submandibular glands and ameliorated salivary hyposecretion.

Protocol-Specific Effects of Intermittent Hypoxia Pre-Conditioning on Phrenic Motor Plasticity in Rats with Chronic Cervical Spinal Cord Injury.

"Low-dose" acute intermittent hypoxia (AIH; 3-15 episodes/day) is emerging as a promising therapeutic strategy to improve motor function after incomplete cervical spinal cord injury (cSCI). Conversely, chronic "high-dose" intermittent hypoxia (CIH; > 80-100 episodes/day) elicits multi-system pathology and is a hallmark of sleep apnea, a condition highly prevalent in individuals with cSCI. Whereas daily AIH (dAIH) enhances phrenic motor plasticity in intact rats, it is abolished by CIH. However, there have been no direct comparisons of prolonged dAIH versus CIH on phrenic motor outcomes after chronic cSCI. Thus, phrenic nerve activity and AIH-induced phrenic long-term facilitation (pLTF) were assessed in anesthetized rats. Experimental groups included: 1) intact rats exposed to 28 days of normoxia (Nx28; 21% O2; 8 h/day), and three groups with chronic C2 hemisection (C2Hx) exposed to either: 2) Nx28; 3) dAIH (dAIH28; 10, 5-min episodes of 10.5% O2/day; 5-min intervals); or 4) CIH (IH28-2/2; 2-min episodes; 2-min intervals; 8 h/day). Baseline ipsilateral phrenic nerve activity was reduced in injured versus intact rats but unaffected by dAIH28 or IH28-2/2. There were no group differences in contralateral phrenic activity. pLTF was enhanced bilaterally by dAIH28 versus Nx28 but unaffected by IH28-2/2. Whereas dAIH28 enhanced pLTF after cSCI, it did not improve baseline phrenic output. In contrast, unlike shorter protocols in intact rats, CIH28-2/2 did not abolish pLTF in chronic C2Hx. Mechanisms of differential responses to dAIH versus CIH are not yet known, particularly in the context of cSCI. Further, it remains unclear whether enhanced phrenic motor plasticity can improve breathing after cSCI.

Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18.

Cardiac hypertrophic preconditioning (HP) signifies cardioprotection induced by transient pressure overload to resist hypertrophic effects of subsequently sustained pressure overload. Although it is recently found that inflammation triggers the development of nonischemic cardiomyopathy, whether inflammation plays a role in the antecedent protective effects of HP remains unknown. Caspase-1 is a critical proinflammatory caspase that also induces pyroptosis; thus, we investigated the role of caspase-1 using a unique model of HP in mice subjected longitudinally to 3 days of transverse aortic constriction (TAC 3d), 4 days of de-constriction (De-TAC 4d), and 4 weeks of Re-TAC (Re-TAC 4W). Echocardiography, hemodynamics, histology, PCR, and western blot confirmed preserved cardiac function, alleviated myocardial hypertrophy and fibrosis, and less activated hypertrophic signaling effectors in Re-TAC 4W mice, compared with TAC 4W mice. Mechanistically, caspase-1 and its downstream targets IL-1β and IL-18, but not GSDMD, were less activated in Re-TAC 4W mice. Furthermore, in HP mice with AAV-9-mediated cardiac-specific caspase-1 overexpression, the salutary effects of HP were remarkably abrogated, as evidenced by exacerbated cardiac remodeling, dysfunction, and activation of IL-1β and IL-18. Collectively, this study revealed a previously unrecognized involvement of caspase-1 in cardiac HP by regulation of IL-1β and IL-18 and shed light on caspase-1 as an antecedent indicator and target for cardiac hypertrophy.

Effects of remote ischemic preconditioning on contrast-induced acute kidney injury after percutaneous coronary intervention in patients with chronic total occlusion

Objective: To investigate the effect of remote ischemic preconditioning (RIPC) on contrast-induced acute kidney injury (CI-AKI) in patients with chronic total occlusion (CTO) after percutaneous coronary intervention (PCI). Methods: A total of 282 patients undergoing PCI at Zhongda Hospital Affiliated to Southeast University between June 2017 and January 2019 were prospectively enrolled. The patients were randomly divided into RIPC group (n=142) and control group (n=140). CI-AKI was defined as an increase in level of cystatin C (CysC)≥10% above baseline at 24 h after contrast administration. Baseline characteristics and the incidence of CI-AKI were compared between the two groups. The multivariate logistic regression analysis was further used to analyze the independent risk factors of CI-AKI. Results: There were no significant differences in age, gender, smoking, hypertension, diabetes, stroke and old myocardial infarction, coronary artery bypass graft surgery, previous PCI history and laboratory test indicators, target vessel and pathological characteristics of CTO lesions, contrast agent dosage, J-CTO (Multicenter CTO Registry in Japan) score, SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score, PCI success rate and stent number between the two groups (P>0.05). The incidence of CI-AKI was significantly lower (18.3% vs 29.3%, P=0.036) in RIPC group than that of control group. Multivariate logistic analysis found that creatinine [odds ratio (OR)=1.018,95%CI: 1.006-1.030, P=0.003], CysC (OR=5.200, 95%CI:2.714-9.963, P<0.001),contrast agent dosage (OR=1.013,95%CI: 1.007-1.019, P<0.001) and J-CTO score (OR=1.834, 95%CI: 1.145-2.939, P=0.012) were independent risk factors of CI-AKI. However, RIPC was an independent protective factor of CI-AKI (OR=0.391, 95%CI: 0.199-0.765, P=0.006). Conclusion: RIPC before contrast agent administration prevents CI-AKI in CTO patients undergoing PCI.

Neuroprotective effect of hypoxic preconditioning and neuronal activation in a in vitro human model of the ischemic penumbra

Objective. In ischemic stroke, treatments to protect neurons from irreversible damage are urgently needed. Studies in animal models have shown that neuroprotective treatments targeting neuronal silencing improve brain recovery, but in clinical trials none of these were effective in patients. This failure of translation poses doubts on the real efficacy of treatments tested and on the validity of animal models for human stroke. Here, we established a human neuronal model of the ischemic penumbra by using human induced pluripotent stem cells and we provided an in-depth characterization of neuronal responses to hypoxia and treatment strategies at the network level.Approach. We generated neurons from induced pluripotent stem cells derived from healthy donor and we cultured them on micro-electrode arrays. We measured the electrophysiological activity of human neuronal networks under controlled hypoxic conditions. We tested the effect of different treatment strategies on neuronal network functionality.Main results. Human neuronal networks are vulnerable to hypoxia reflected by a decrease in activity and synchronicity under low oxygen conditions. We observe that full, partial or absent recovery depend on the timing of re-oxygenation and we provide a critical time threshold that, if crossed, is associated with irreversible impairments. We found that hypoxic preconditioning improves resistance to a second hypoxic insult. Finally, in contrast to previously tested, ineffective treatments, we show that stimulatory treatments counteracting neuronal silencing during hypoxia, such as optogenetic stimulation, are neuroprotective.Significance. We presented a human neuronal model of the ischemic penumbra and we provided insights that may offer the basis for novel therapeutic approaches for patients after stroke. The use of human neurons might improve drug discovery and translation of findings to patients and might open new perspectives for personalized investigations.

Effects of Hypoxic Preconditioning and Vascular Endothelial Growth Factor on the Survival of Isolated Primary Retinal Ganglion Cells.

This study aimed to investigate the effect of hypoxic preconditioning (HPC) on primary retinal ganglion cell (RGC) survival and the associated mechanism, including the role of vascular endothelial growth factor (VEGF). Retinas were separated from the enucleated eyeballs of Sprague–Dawley rats on postnatal days 1–4. RGCs were harvested using an immunopanning-magnetic separation system and maintained for 24 h in a defined medium. Hypoxic damage (0.3% O2) was inflicted on the cells using a CO₂ chamber. Anti-VEGF antibody (bevacizumab) was administered to RGCs exposed to hypoxic conditions, and RGC survival rate was compared to that of non-anti-VEGF antibody-treated RGCs. HPC lasting 4 h significantly increased RGC survival rate. In the RGCs exposed to hypoxic conditions for 4 h, VEGF mRNA and protein levels were significantly increased. Treatment with high dose bevacizumab (>1 mg/mL) countered HPC-mediated RGC survival. Protein kinase B and focal adhesion kinase levels were significantly increased in 4-h hypoxia-treated RGCs. HPC showed beneficial effects on primary RGC survival. However, only specifically controlled exposure to hypoxic conditions rendered neuroprotective effects. Strong inhibition of VEGF inhibited HPC-mediated RGC survival. These results indicate that VEGF may play an essential role in promoting cell survival under hypoxic conditions.

The effect of remote ischaemic preconditioning on postoperative cardiac and inflammatory biomarkers in pancreatic surgery: a randomized controlled trial.

BackgroundCardiac and inflammatory biomarkers have been associated with adverse outcome after major abdominal surgery. This study investigated the effect of remote ischaemic preconditioning (RIPC) on perioperative concentrations of high-sensitive cardiac troponin (hs-cTn) T and interleukin (IL) 6.MethodsAdult patients scheduled for elective pancreatic surgery between March 2017 and February 2019 were randomized to either three cycles of upper-limb ischaemia and reperfusion (each 5 min) or a sham procedure before surgery. The primary endpoint was the maximum postoperative hs-cTnT concentration within 48 h after surgery. Secondary endpoints were postoperative myocardial injury (PMI), defined as an absolute increase of hs-cTnT of at least 14 ng/l above baseline concentration, maximum concentration of IL-6 within 48 h after surgery and postoperative complications within 30 days of surgery.ResultsOf 99 eligible patients, 46 underwent RIPC and 46 a sham procedure. RIPC did not reduce the maximum hs-cTnT concentration after surgery (12.6 ng/l RIPC, 16.6 ng/l controls, P = 0.225), nor did it lessen the incidence of PMI (15/45 RIPC, 18/45 controls, P = 0.375). The maximum postoperative IL-6 concentration was 265 pg/ml after RIPC versus 385 pg/ml in controls (P = 0.108). Postoperative complications occurred in 23 RIPC and 24 control patients respectively.ConclusionsRemote ischaemic preconditioning did not reduce the maximum postoperative hs-cTnT concentration. Postoperative myocardial injury, IL-6 concentrations and postoperative complications were similar between RIPC patients and controls.Trial registrationClinicaltrials.gov identifier NCT03460938.

Effect of remote ischaemic preconditioning on mortality and morbidity after non-cardiac surgery: meta-analysis.

BackgroundRemote ischaemic preconditioning (RIPC) has been shown to have a protective role on vital organs exposed to reperfusion injury. The aim of this systematic review was to evaluate the effects of non-invasive RIPC on clinical and biochemical outcomes in patients undergoing non-cardiac surgeryMethodsA systematic literature search of PubMed, EMBASE, Scopus, and Cochrane databases was carried out in February 2020. RCTs investigating the effect of non-invasive RIPC in adults undergoing non-cardiac surgery were included. Meta-analyses and trial sequential analyses (TSAs) were performed on cardiovascular events, acute kidney injury, and short- and long-term mortality.ResultsSome 43 RCTs including 3660 patients were included. The surgical areas comprised orthopaedic, vascular, abdominal, pulmonary, neurological, and urological surgery. Meta-analysis showed RIPC to be associated with fewer cardiovascular events in non-cardiac surgery (13 trials, 1968 patients, 421 events; odds ratio (OR) 0.68, 95 per cent c.i. 0.47 to 0.96; P = 0.03). Meta-analyses of the effect of RIPC on acute kidney injury (12 trials, 1208 patients, 211 events; OR 1.14, 0.78 to 1.69; P = 0.50; I2 = 9 per cent), short-term mortality (7 trials, 1239 patients, 65 events; OR 0.65, 0.37 to 1.12; P = 0.12; I2 = 0 per cent), and long-term mortality (4 trials, 1167 patients, 9 events; OR 0.67, 0.18 to 2.55; P = 0.56; I2 = 0 per cent) showed no significant differences for RIPC compared with standard perioperative care in non-cardiac surgery. However, TSAs showed that the required information sizes have not yet been reached.ConclusionApplication of RIPC to non-cardiac surgery might reduce cardiovascular events, but not acute kidney injury or all-cause mortality, but currently available data are inadequate to confirm or reject an assumed intervention effect.

An alternative viewpoint for the cardioprotective effects of ischemic preconditioning

An alternative viewpoint for the cardioprotective effects of ischemic preconditioning

Effects of Individualized Ischemic Preconditioning on Protection Against Eccentric Exercise-Induced Muscle Damage: A Randomized Controlled Trial.

The effects of ischemic preconditioning (IPC) versus a deceptive sham protocol on indirect markers of exercise-induced muscle damage (EIMD) after the application of individualized occlusion pressure were examined. The goal of using a sham protocol is to control for the potential effect of placebo. IPC would surpass the sham protocol in protecting against EIMD. A randomized, double-blinded, clinical trial. Level 1. Thirty healthy young men were randomly assigned to an eccentric exercise for the knee extensor muscles preceded by IPC (4 × 5 minutes of individualized total occlusion pressure) or sham protocol (4 × 5 minutes using 20 mm Hg). Maximal voluntary isometric torque (MVIT), rate of torque development, muscle soreness, pressure pain threshold, knee range of motion, thigh girth, and creatine kinase (CK) activity were assessed before IPC or sham protocol and up to 72 hours after the eccentric EIMD. Affective valence and perceived exertion were also evaluated. MVIT decreased 17.1% in the IPC and 18.1% in the sham groups, with no differences between groups. Differences from baseline were observed in the sham group for muscle soreness at 48 hours (P < 0.001) and 72 hours (P = 0.02), and for CK activity at 72 hours (P = 0.04). Muscle soreness was reduced in the IPC group at 48 hours compared with the sham group (∆ = 15.8 mm; P = 0.008) but without achieving the minimal clinically important difference. IPC induced a smaller perceived exertion than the sham protocol (∆ = 1.1 a.u.; P = 0.02). The remaining outcomes were not statistically different in both groups. IPC does not surpass the sham protocol to protect against mild EIMD of the knee extensors muscles. Although IPC is a noninvasive, low-cost, and easy-to-administer intervention, the IPC effects can, in part, be explained by the placebo effect. In addition, individualized IPC promotes attenuation in perceived exertion during eccentric exercise.

Understanding parents’ decision-making on participation in clinical trials in children’s heart surgery: a qualitative study

ObjectivesFew children undergoing heart surgery are recruited to clinical trials and little is known about the views and attitudes of parents towards trials. This study explored parents’ perspectives on decision-making...

Trehalose preconditioning for transient global myocardial ischemia in rats

Autophagy is an intracellular pathway that degrades unnecessary proteins and organelles and provides energy substrates during cellular ischemic conditions. Although pharmacological myocardial preconditioning with an autophagy inducer has been reported to protect cells against ischemic reperfusion (I/R), the effects of preconditioning using naturally occurring substances are still unknown. We aimed to examine whether autophagic preconditioning with trehalose improves cardiac function after myocardial stunning by global ischemia in rats. Rat hearts were perfused by oxygenized Krebs Henseleit (KH) solution in Langendorff system. Ten rats were randomized into the following two groups according to the perfusates during the preconditioning: control (KH solution only, n = 5) and trehalose (KH + 2% trehalose, n = 5). After the 35-min preconditioning period and subsequent 20 min of global ischemia, the hearts were reperfused for 60 min. Cardiac function was assessed during the reperfusion. To evaluate autophagy, myocardial protein expression of microtubule-associated protein light chain 3 (LC3) II was evaluated by western blotting. During I/R, a systolic functional parameter, maximum dP/dt was significantly higher; meanwhile, coronary flow tended to be higher in the trehalose group than in the control group. Myocardial LC3-II expression after preconditioning was higher in the trehalose group than in the control group and decreased to the control level after I/R. In conclusion, in a rat model of global myocardial ischemia, trehalose preconditioning improved cardiac function during I/R. Further studies would be needed to identify the mechanism and effects of trehalose preconditioning.

The effect of Remote Ischemic Preconditioning (RIPC) on myocardial injury and inflammation in patients with severe aortic valve stenosis undergoing Transcatheter Aortic Valve Replacement (TAVΙ)

BackgroundRemote ischemic preconditioning (RIPC) is being evaluated as a strategy to reduce cardiac injury and inflammation in patients undergoing diverse cardiac invasive and surgical procedures. However, it is unclear whether RIPC has protective effects in patients undergoing the transfemoral- transcatheter aortic valve implantation (TF-TAVΙ) procedure. MethodsBetween September 2013 and September 2015, 55 random consecutive patients were prospectively assigned to receive SHAM preconditioning (SHAM, 22 patients) or Remote Ischemic Preconditioning (RIPC) (4 cycles of 5 min intermittent leg ischemia and 5 min reperfusion, 33 patients) prior to TF-TAVI. The primary endpoint was to determine the serum levels of: hs-cTn-I (necrosis), CK-18 (apoptosis), and IL-1b (inflammation). Quantification was performed using commercially available ELISA kits. Patients were sampled 1-day pre TF-TAVΙ and 24-hours post TF-TAVΙ. Secondary endpoints included: total mortality, incidence of periprocedural clinical acute myocardial infarction (AMI), acute kidney injury (AKI), and stroke. Results22 SHAM patients and 33 RIPC patients were finally analyzed. Our data revealed no significant difference in serum levels of hs-cTn-I and CK-18 among various groups. However, in the RIPC group, the increase in IL1b level was significantly lower for 24-h post TF-TAVΙ, (p < 0.01). There were no significant differences between groups in the secondary endpoints at the follow-up interval of one month. RIPC-related adverse events were not observed. ConclusionsOur data suggest that RIPC did not exhibit significant cardiac or kidney protective effects regarding necrosis and apoptosis in patients undergoing TF-TAVΙ. However, an important anti-inflammatory effect was detected in the RIPC group.