Ischemic Preconditioning Group Research Articles

Effects of ischemic pre-conditioning on electrically stimulated contractions.

Ischemic pre-conditioning (IPC) offers protection against future ischemic events and may improve sports performance due to several mechanisms at local and systemic levels. This study investigates the local effects on muscle contractility in electrically induced muscle contractions, thus effectively excluding any uncontrolled change in the motor drive. Twenty-one subjects were divided into two groups: 12 subjects in the IPC group (3 × 5/5min right arm ischemia/reperfusion; cuff pressure 250mmHg) and 9 subjects in the SHAM group (same treatment at 20mmHg). The adductor pollicis was contracted by supramaximal stimulation of the ulnar nerve with single pulses, trains of stimuli (5, 8, 10 and 12Hz, 1-s duration) and bursts (4 pulses, 25Hz), all separated by 5-s intervals. The stimulation sequence was delivered before and 15 and 30min after IPC/SHAM treatment. The isometric contraction force, the superficial electromyographic signal, and tissue oxygenation were continuously monitored. A significant force decrease in time was observed at 8, 10 (p < 0.01) and 12Hz (p < 0.05) along with a decrease in half-relaxation time in single twitches and bursts (p = 0.01), regardless of treatment. This general time-related weakening was more marked in IPC than SHAM at 5-Hz stimulation. No effects were observed on the magnitude of the superficial electromyographic signal. Data indicate that IPC does not increase muscle force during electrically stimulated contractions, supporting the idea that IPC's ergogenic effects are not due to increased muscle contractility.

Poster 191: Does Ischemic Preconditioning of the Operative Limb Reduce Pain after Hip Arthroscopy? A Prospective, Single Blind, Randomized Controlled Trial

Objectives: Improving pain control after hip arthroscopy is an important concern for surgeons and for optimizing the patient experience. Many surgeons use multimodal protocols including peripheral nerve blocks, oral medication, and intra-articular or local anesthetic. Identifying additional preoperative modalities for pain management is a promising way to improve pain and potentially decrease narcotic use. Ischemic preconditioning (IPC) involves the exposure of brief periods of circulatory occlusion and reperfusion which has protective effects on muscular and organ tissues. In addition, studies on the use of IPC prior to knee surgery have shown improvements in postoperative pain and decreased opioid consumption. The purpose of this study was to determine whether preoperative IPC of the operative limb affects postoperative pain scores or opioid consumption after hip arthroscopy. Methods: This is a prospective, single blind, randomized controlled trial. Patients were enrolled between October 2021 and April 2023. Inclusion criteria were patients age ≥ 18 years old undergoing hip arthroscopy by a single surgeon for hip pain in the setting of femoroacetabular impingement or labral tear. Exclusion criteria were history of venous thromboembolism or patients on medications known to increase the risk of blood clots. Following informed consent, patients were randomized to the IPC or control group and were blinded to their treatment group. Limb preconditioning was performed within 24 hours prior to surgery using the Delphi Personalized Tourniquet System (PTS) with the cuff placed on the proximal thigh of the operative limb. Patients in the IPC group received a 30-minute treatment consisting of 3 rounds of 5 minutes at limb occlusion pressure (LOP) alternating with 5 minutes of reperfusion. Patients in the control group received the same protocol at 20% LOP. Hip arthroscopy was then performed according to standard of care. All patients received a standardized preoperative and postoperative pain control regimen. Surveys were administered through RedCap daily from day of surgery through postoperative day 7. Patients were asked to rate their pain 0-10 according to the visual analog scale (VAS) for pain and to record pain medication utilization. Charts were reviewed for baseline characteristics and surgical procedures. Chi-square, independent t tests and paired t tests were used for statistical analysis. Results: A total of 64 patients (31 in the IPC group, 33 in the Control group) were enrolled. Demographics (age, sex, and body mass index) were similar between the IPC and Control groups. There was no significant difference in surgical procedures performed. Survey compliance was higher in the IPC group compared to the control group, 6.1 ± 2.8 days vs. 3.7 ± 3.4 days, respectively (p &lt; 0.05). Both groups reported significant reductions in their VAS for pain scores from day of surgery to postoperative day 6 or 7 (p &lt; 0.05). There was no significant difference between the IPC and control groups in VAS for pain scores at any of the time points from day of surgery to postoperative day 7 (Figure 1). There was also no significant difference between the groups in mean daily opioid consumption (expressed as morphine milligram equivalents) or in acetaminophen consumption at any time point. There were no early complications (within first 7 days postoperatively). Conclusions: Limb IPC does not appear to decrease pain or medication utilization after hip arthroscopy. It is possible that the pain modulating effects of IPC are not as effective when the surgical site is proximal to the site of occlusion. Other factors may have contributed to variability in the reported VAS scores, including differences in fluid extravasation, personal pain tolerances, and utilization of pain control regimen. [Figure: see text]

Cardioprotective Effects of Sodium-Glucose Cotransporter Subtype Inhibition on Ischemic and Pharmacological Preconditioning.

Sodium-glucose cotransporter (SGLT) 2 inhibitors partially inhibit SGLT1 expression; however, whether a clinical dose of SGLT2 inhibitor abrogates ischemic preconditioning (IPC) is unknown, and the pharmacological cardioprotective effect under SGLT1 inhibition has not been examined. In this study, we investigated whether a clinical dose of tofogliflozin abrogates IPC and whether pharmacological preconditioning with olprinone has cardioprotective effects under SGLT1 inhibition. Male Wistar rats were divided into seven groups (seven rats per group) and subjected to the following treatments before inducing ischemia/reperfusion (I/R; 30 minutes of coronary artery occlusion followed by 120 minutes of reperfusion): saline infusion control treatment (Con); ischemic preconditioning(IPC); IPC after phlorizin infusion (IPC+Phl); IPC after low-dose tofogliflozin infusion (IPC+L-Tof); IPC after high-dose tofogliflozin infusion (IPC+H-Tof); olprinone infusion (Olp); and Olp infusion after phlorizin infusion (Olp+Phl). The infarct size was significantly decreased in the IPC group, but not in the IPC+Phl group. In contrast, the infarct size decreased in the IPC+L-Tof and IPC+H-Tof groups. Additionally, Olp reduced the infarct size, and the effect was preserved in Olp+Phl groups. Phosphorylated AMP-activated protein kinase (AMPK) expression was lower in the IPC+Phl group compared to that in the IPC group. The cardioprotective effect of IPC was attenuated by strong SGLT1 inhibition, but the effect was preserved under a clinical dose of highly selective SGLT2 inhibitor. Olprinone exerts a cardioprotective effect even under strong SGLT1 inhibition.

Ischemic preconditioning affects phosphosites and accentuates myocardial stunning while reducing infarction size in rats.

Ischemic preconditioning (IPC), i.e., brief periods of ischemia, protect the heart from subsequent prolonged ischemic injury, and reduces infarction size. Myocardial stunning refers to transient loss of contractility in the heart after myocardial ischemia that recovers without permanent damage. The relationship between IPC and myocardial stunning remains incompletely understood. This study aimed primarily to examine the effects of IPC on the relationship between ischemia duration, stunning, and infarct size in an ischemia-reperfusion injury model. Secondarily, this study aimed to examine to which extent the phosphoproteomic changes induced by IPC relate to myocardial contractile function. Rats were subjected to different durations of left anterior descending artery (LAD) occlusion, with or without preceding IPC. Echocardiograms were acquired to assess cardiac contraction in the affected myocardial segment. Infarction size was evaluated using triphenyl tetrazolium chloride staining. Phosphoproteomic analysis was performed in heart tissue from preconditioned and non-preconditioned animals. In contrast to rats without IPC, reversible akinesia was observed in a majority of the rats that were subjected to IPC and subsequently exposed to ischemia of 13.5 or 15 min of ischemia. Phosphoproteomic analysis revealed significant differential regulation of 786 phosphopeptides between IPC and non-IPC groups, with significant associations with the sarcomere, Z-disc, and actin binding. IPC induces changes in phosphosites of proteins involved in myocardial contraction; and both accentuates post-ischemic myocardial stunning and reduces infarct size.

Protective effect of ischaemic preconditioning on acute and chronic renal damage following ischaemia reperfusion injury: characterisation of fibrosis development after inflammation resolution.

Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are increasingly recognised as one disease continuum, rather than distinct entities, and are associated with a huge burden to healthcare services. The leading cause of AKI worldwide is Ischaemia Reperfusion Injury (IRI), most commonly seen in clinical settings of sepsis-driven hypotension. Ischaemic Preconditioning (IPC) is a strategy aimed at reducing the deleterious effects of IRI. The objectives of this study were to demonstrate an efficacious in vivo model of Kidney IRI, and the protective influence of IPC in attenuating AKI and development of renal fibrosis. A rat model of bilateral kidney IRI was used: Male Lewis rats (n=84) were assigned to IRI, sham or IPC. In IRI, renal pedicles were clamped for 45 minutes. IPC groups underwent pulsatile IPC prior to IRI. Kidneys were retrieved at 24 hours, 48 hours, 7 days, 14 days and 28 days, and assessed histologically. IRI led to marked AKI (24-48 h) and renal fibrosis development by 28 days. IPC attenuated this damage, with 66% less fibrosis. Interestingly, at 14-days, the histological appearance of both IRI and IPC kidneys was rather similar, potentially representing an important transitional point at which kidneys commit to either fibrosis or recovery. This may provide a suitable inflexion point for introduction of novel anti-fibrotic therapies. In conclusion, we have characterised a model of kidney injury from acute to chronic phases, allowing detailed mechanistic understanding and which can be manipulated by effective treatment strategies such as IPC.

Temporal proteomic and phosphoproteomic profiling of the left ventricle in a novel rat model of ischemia/reperfusion with or without ischemic preconditioning

Abstract Background The relationship between ischemic preconditioning (IPC) and myocardial stunning is incompletely understood. Preconditioning has been shown to protect against ischemic injury, whereas myocardial stunning, i.e. transient contractile dysfunction in the setting of ischemia, can lead to severe heart failure and has been considered a deleterious process. To understand this relationship, we recently developed a novel rat model of ischemia-reperfusion (I/R) injury in the presence or absence of IPC. In the presence of IPC (2 cycles of 5 min of I/R followed by 13.5 min of ischemia), we observe a profound myocardial stunning at 4h of reperfusion which completely resolves at 48h. In the absence of IPC, we observe necrosis at 4h of reperfusion and sustained injury at 48h. Despite extensive studies on IPC and myocardial stunning in the setting of I/R, the molecular basis of the relationship between these phenomena are still unknown. Purpose To investigate alterations in protein expression after IPC and myocardial stunning in a novel rat model of I/R injury. Methods We utilized tandem mass tags and mass spectrometry to identify temporal changes in the proteomic- and phosphoproteomic-profiles in left ventricular (LV) tissue from rat hearts following 13.5 min of ischemia and 4h of reperfusion in the presence of absence of IPC. Results Proteomics analysis of the LV tissues collected at baseline showed that 115 proteins were differentially expressed between IPC and non-IPC groups. We observed abundant changes in sarcoplasmic proteins, sarcoplasmic reticulum-related proteins, and actin-based cell projection proteins. Most of these proteins are implicated in arylesterase activity, haemoglobin binding, and nitrogen metabolism. At 4h, differentially expressed proteins were predominantly related to wound healing, coagulation, and lipase activity. Phosphoproteomic analysis at baseline showed that 686 phosphosites were differentially regulated between IPC and non-IPC groups. Aberrant phosphorylation patterns mostly occurred in sarcomere proteins, Z-disc, I-band, contractile fiber associated with actin binding, and the thyroid hormone signalling pathway. At 4h, 520 phosphosites differed between IPC and non-IPC rats; these phosphosites were abundant in contractile fiber proteins, myofibril proteins, and sarcomere proteins associated with calcium signalling and cardiomyopathies. Conclusions This study demonstrates marked changes in proteins and phosphosites related to lipase activity, haemoglobin binding, calcium signalling, and the cardiac contractile apparatus in IPC versus non-IPC groups. This extensive catalogue of novel proteins and phosphosites associated with IPC and myocardial stunning in the setting of I/R injury sets the stage for future manipulation of myocardial stunning and preconditioning in both experimental and clinical settings.

Effects of Iron Nanoparticles Administration on Ischemia/Reperfusion Injury in Isolated Hearts of Male Wistar Rats.

Iron is an essential mineral participating in numerous biological processes in the organism under physiological conditions. However, it may be also involved in the pathological mechanisms activated in various cardiovascular diseases including myocardial ischemia/reperfusion (I/R) injury, due to its involvement in reactive oxygen species (ROS) production. Furthermore, iron has been reported to participate in the mechanisms of iron-dependent cell death defined as "ferroptosis". On the other hand, iron may be also involved in the adaptive processes of ischemic preconditioning (IPC). This study aimed to elucidate whether small amounts of iron may modify the cardiac response to I/R in isolated perfused rat hearts and their protection by IPC. Pretreatment of the hearts with iron nanoparticles 15 min prior to sustained ischemia (iron preconditioning, Fe-PC) did not attenuate post-I/R contractile dysfunction. Recovery of left ventricular developed pressure (LVDP) was significantly improved only in the group with combined pretreatment with iron and IPC. Similarly, the rates of contraction and relaxation [+/-(dP/dt)max] were almost completely restored in the group preconditioned with a combination of iron and IPC but not with iron alone. In addition, the severity of reperfusion arrhythmias was reduced only in the iron+IPC group. No changes in protein levels of "survival" kinases of the RISK pathway (Reperfusion Injury Salvage Kinase) were found except for reduced caspase 3 levels in both preconditioned groups. The results indicate that a failure to precondition rat hearts with iron may be associated with the absent upregulation of RISK proteins and the pro-ferroptotic effect manifested by reduced glutathione peroxidase 4 (GPX4) levels. However, combination with IPC suppressed the negative effects of iron resulting in cardioprotection.

Potential Benefits of a Single Session of Remote Ischemic Preconditioning and Walking in Sedentary Older Adults: A Pilot Study.

Ischemic preconditioning (IPC) has shown positive effects in endurance-type sports among healthy young individuals; however, its effects in endurance-type exercises in older adults have not been explored. We aimed to examine the acute effects of a single session of IPC prior to an endurance-type exercise on cardiovascular- and physical-function-related parameters in sedentary older adults. A pilot study with a time-series design was carried out. Nine participants were enrolled consecutively in the following intervention groups: (i) SHAM (sham IPC + walking) and (ii) IPC (IPC + walking) groups. The main outcomes were resting systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), peripheral oxygen saturation (SpO2), maximum isometric voluntary contraction (MIVC), endurance performance, and perceived fatigue. After the intervention, the IPC group showed a significant reduction in SBP, whereas SpO2 decreased in the SHAM group. The IPC group maintained quadriceps MIVC levels, whereas these levels dropped in the SHAM group. No changes in DBP, resting HR, endurance, or fatigue in any group were observed. These findings are of interest for the promotion of cardiovascular and physical health in older people.

The Possibility of IPC to Prevent Ischemic-Reperfusion Injury in Skeletal Muscle in a Rat

Blood removal with air tourniquets for a long time induces muscle damage after reperfusion. Ischemic preconditioning (IPC) has a protective effect against ischemia-reperfusion injury in striated muscle and myocardium. However, the mechanism of action of IPC on skeletal muscle injury is unclear. Thus, this study aimed to investigate the effect of IPC in reducing skeletal muscle damage caused by ischemia-reperfusion injury. The hindlimbs of 6-month-old rats were wounded with air tourniquets at a carminative blood pressure of 300 mmHg on the thighs. Rats were divided into the IPC (-) group and the IPC (+) group. The vascular endothelial growth factor (VEGF), 8-hydroxyguanosine (8-OHdG), and cyclooxygenase 2 (COX-2) were investigated by protein levels. Quantitative analysis of apoptosis was performed using the TUNEL method. Compared with the IPC (-) group, the IPC (+) group retained the VEGF expression, and the COX-2 and 8-OHdG expressions were suppressed. The proportion of apoptosis cells decreased in the IPC (+) group compared with the IPC (-) group. IPC in skeletal muscles proliferated VEGF and suppressed inflammatory response and oxidative DNA damage. IPC has the potential to reduce muscle damage after ischemia-reperfusion.

The effect of silymarin given before partial hepatectomy on liver regeneration in rats with ischemic preconditioning during liver resection

Background: The regeneration capacity of liver tissue after partial hepatectomy closely affects morbidity and mortality. We aimed to investigate the effect of silymarin and ischemic preconditioning (IPC) before partial hepatectomy on liver regeneration.Methods: Thirty rats were randomly divided into 5 groups (n=6). Serum AST, bilirubin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) values were studied 48 hours after hepatectomies. Mitotic count, congestion, necrosis, cytoplasmic vacuolization, and presence of neutrophils were evaluated histopathologically. Proliferating cell nuclear antigen (PCNA) antibody was studied immunohistochemically.Results: The AST value (2071.5±938.4) was the highest in the partial hepatectomy (PH) group. The Ischemic Preconditioning Partial Hepatectomy Group (IPC) (1535.5±204.8) and the Silymarin+Partial Hepatectomy Group (Silymarin group) (1192.3±526.3) had lower levels of AST values; however, the AST values were the lowest in the Silymarin+Ischemic Preconditioning+ Partial Hepatectomy Group (IPC+ Silymarin group) (1002.8±348.9). Likewise, the highest improvement in bilirubin levels was observed in the IPC+ Silymarin group (0.33±0.11). IL-6 (11.54±2.89) and TNF-α (39.2±22.73) values were the lowest in the IPC group, and interestingly, both were higher in the silymarin-treated groups. It was observed that these values increased in Silymarin group and IPC+ Silymarin group who received silymarin treatment compared to PH group and IPC group who did not receive silymarin. In histopathological analysis, it was found that the mitosis rate and PCNA percentage were higher in the Silymarin and IPC+ Silymarin groups.Conclusions: The use of silymarin before hepatectomy and IPC during partial hepatectomy increase liver regeneration.

Integrative analysis of the roles of lncRNAs and mRNAs in ischaemic preconditioning to alleviate liver ischaemia–reperfusion injury in mice

The objective of our study was to elucidate the possible underlying mechanism for the protective effect of ischaemic preconditioning (IPC) against ischaemia-reperfusion (I/R) injury and to provide new research perspectives of long non-coding RNAs (lncRNAs). In this study, serum and liver tissue samples were collected to measure indexes of liver injury from a mouse liver model in sham, I/R injury and I/R + IPC groups. Furthermore, liver samples from 5 randomly selected mice per group were extracted and subjected to the microarray and subsequent bioinformatics analysis. IPC ameliorated liver damage by lowered liver transaminase levels and pro-inflammatory cytokines. A total of 167 lncRNAs and 108 messenger RNAs (mRNAs) were significantly differentially expressed genes (DEGs) between the I/R + IPC and I/R groups. Gene Ontology (GO) analysis revealed that these genes were mainly related to unfolded proteins, responses to topologically incorrect proteins, responses to temperature stimuli, protein folding and protein refolding. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis indicated that the DEGs were enriched in the following pathways: protein processing in the endoplasmic reticulum; antigen processing and presentation; and fructose and mannose metabolism. Additionally, the 7 selected DEGs (Hspa1ab, Chka, Clec2h, Mvd, Adra1a, AK085737 and AK088966) were validated in modules of the lncRNA-mRNA weighted coexpression network, which agreed with the qRT–PCR and chip data. And the identified differentially expressed lncRNAs and mRNAs may provide new clues to understand the pivotal pathophysiological mechanism by which IPC alleviates I/R-caused liver damage.

Ischemic preconditioning upregulates Mitofusin2 and preserves muscle strength in tourniquet-induced ischemia/reperfusion.

BackgroundTourniquet-induced ischemia and reperfusion (I/R) has been related to postoperative muscle atrophy through mechanisms involving protein synthesis/breakdown, cellular metabolism, mitochondrial dysfunction, and apoptosis. Ischemic preconditioning (IPC) could protect skeletal muscle against I/R injury. This study aims to determine the underlying mechanisms of IPC and its effect on muscle strength after total knee arthroplasty (TKA).MethodsTwenty-four TKA patients were randomized to receive either sham IPC or IPC (3 cycles of 5-min ischemia followed by 5-min reperfusion). Vastus medialis muscle biopsies were collected at 30 ​min after tourniquet (TQ) inflation and the onset of reperfusion. Western blot analysis was performed in muscle protein for 4-HNE, SOD2, TNF-ɑ, IL-6, p-Drp1ser616, Drp1, Mfn1, Mfn2, Opa1, PGC-1ɑ, ETC complex I-V, cytochrome c, cleaved caspase-3, and caspase-3. Clinical outcomes including isokinetic muscle strength and quality of life were evaluated pre- and postoperatively.ResultsIPC significantly increased Mfn2 (2.0 ​± ​0.2 vs 1.2 ​± ​0.1, p ​= ​0.001) and Opa1 (2.9 ​± ​0.3 vs 1.9 ​± ​0.2, p ​= ​0.005) proteins expression at the onset of reperfusion, compared to the ischemic phase. There were no differences in 4-HNE, SOD2, TNF-ɑ, IL-6, p-Drp1ser616/Drp1, Mfn1, PGC-1ɑ, ETC complex I–V, cytochrome c, and cleaved caspase-3/caspase-3 expression between the ischemic and reperfusion periods, or between the groups. Clinically, postoperative peak torque for knee extension significantly reduced in the sham IPC group (−16.6 [-29.5, −3.6] N.m, p ​= ​0.020), while that in the IPC group was preserved (−4.7 [-25.3, 16.0] N.m, p ​= ​0.617).ConclusionIn TKA with TQ application, IPC preserved postoperative quadriceps strength and prevented TQ-induced I/R injury partly by enhancing mitochondrial fusion proteins in the skeletal muscle.The translational potential of this articleMitochondrial fusion is a potential underlying mechanism of IPC in preventing skeletal muscle I/R injury. IPC applied before TQ-induced I/R preserved postoperative quadriceps muscle strength after TKA.

Three Dimensional-Arterial Spin Labeling Evaluation of Improved Cerebral Perfusion After Limb Remote Ischemic Preconditioning in a Rat Model of Focal Ischemic Stroke.

PurposeTo investigate the application value of 3D arterial spin labeling (3D-ASL) for evaluating distal limb ischemic preconditioning to improve acute ischemic stroke (AIS) perfusion.Materials and MethodsA total of 40 patients with AISs treated in our hospital from January 2020 to December 2020 were recruited, and 15 healthy individuals who were examined in our hospital during the same period were included as the control group; all of these participants were scored on the National Institutes of Health Stroke Scale (NIHSS) and examined by MRI. Sequences included conventional sequences, diffusion-weighted imaging (DWI), magnetic resonance angiography (MRA), and 3D-ASL, and cerebral infarct volume and cerebral blood flow (CBF) in the area of the infarct lesion were measured. After 3 months of treatment, patients with AIS were scored on the modified Rankin Scale (mRS) and divided into good prognosis and poor prognosis groups. In total, 55 adult male Sprague–Dawley rats were divided randomly into three groups: 20 in the middle cerebral artery occlusion (MCAO) group, 20 in the MCAO + limb remote ischemic preconditioning (LRP) group, and 15 in the sham group. In total, 48 h after the procedures, conventional MRI, DWI, and 3D-ASL sequence data were collected, and 2,3,5-trphenyltetrazolium chloride monohydrate (TTC) staining and behavioral scoring were performed. CBF was recorded in the infarct lesion area and the corresponding contralateral area, and the affected/contralateral relative values (rCBF) were calculated to compare the differences in rCBF between different groups. The pathological changes in brain tissues were observed by HE staining, and the expression of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in brain tissues was detected by immunofluorescence and real-time quantitative polymerase chain reaction (RT-qPCR). The protein expression of VEGF was detected by western blotting.ResultsHypertension and internal carotid atherosclerosis are high-risk factors for ischemic stroke, and CBF values in the infarct area are significantly lower than those in the corresponding areas on the contralateral side. NIHSS and mRS scores and CBF values have higher specificity and sensitivity for the prognosis of patients with AIS. LRP significantly reduces the infarct area, improves behavioral deficits in rats with cerebral ischemia, reduces neurological injury and histological damage, protects vascular structures, and promotes neovascularization. In addition, 3D-ASL showed a significant increase in brain tissue perfusion in the ischemic area after LRP, and the expression of VEGF and CD31 showed a significant positive correlation with CBF values.ConclusionThree dimensional (3D) ASL can be used to evaluate LRP to improve stroke perfusion, and its protective effect may be closely related to LRP-induced vascular regeneration.

Hypercholesterolemia attenuates cardioprotection of ischemic preconditioning and postconditioning with α7 nicotinic acetylcholine receptor agonist by enhancing inflammation and inhibiting the PI3K/Akt/eNOS pathway.

The present study aimed to evaluate the effects of hypercholesterolemia on cardioprotection of ischemic preconditioning and α7 nicotinic acetylcholine receptor (α7nAChR) agonist postconditioning and explore the potential mechanisms that hypercholesterolemia affected their cardioprotection. Hypercholesterolemic and normal rats were divided into the four groups that received the following treatments: i) Hypercholesterolemic control and normal control groups; ii) hypercholesterolemic ischemia/reperfusion (HI) and normal ischemia/reperfusion (NI) groups; iii) hypercholesterolemic ischemic preconditioning (HIPC) and normal ischemic preconditioning (NIPC) groups; and iv) hypercholesterolemic PNU282987 postconditioning (HPNU) and normal PNU282987 postconditioning (NPNU) groups. Serum lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) levels after ischemia/reperfusion were assayed. Furthermore, infarct size and expression levels of Akt, phosphorylated (p)-Akt and endothelial nitric oxide synthase (eNOS) in ischemic myocardium were assessed. Compared with the NI group, serum LDH, CK-MB, cTnI, TNF-α and IL-6 levels and infarct size were significantly decreased, and myocardial p-Akt/Akt and eNOS/GAPDH ratios were significantly increased in the NIPC and NPNU groups. Compared with the HI group, serum CK-MB, cTnI, TNF-α and IL-6 levels and infarct size were significantly decreased in the HIPC group; however, myocardial p-Akt/Akt and eNOS/GAPDH ratios did not significantly change in the HIPC group. Furthermore, there were no significant difference between the HI and HPNU groups in serum LDH, CK-MB, cTnI, TNF-α and IL-6 levels, infarct size, myocardial p-Akt/Akt and eNOS/GAPDH ratios. In conclusion, hypercholesterolemia could aggravate myocardial ischemia/reperfusion injury, attenuate cardioprotection of ischemic preconditioning and eliminate cardioprotection from α7nAChR agonist postconditioning by enhancing inflammation and inhibiting PI3K/Akt/eNOS pathway.

Effects of swimming training on myocardial protection in rats.

Swimming is important for promoting and maintaining health, as it can increase the efficiency of the cardiovascular system and decrease the occurrence of cardiovascular diseases. The objective of the present study was to examine whether swimming training could decrease myocardial injury in rats caused by myocardial ischemia/reperfusion (I/R). Sprague-Dawley rats were randomized into four groups, namely the Sham, coronary artery occlusion, swimming training and ischemic preconditioning (IPC) groups. Myocardial I/R was induced in anesthetized male Sprague-Dawley rats by a 40-min occlusion followed by a 3-h reperfusion of the left anterior descending coronary artery. The rats were sacrificed after surgery and their hearts were examined. The results demonstrated that the number of TUNEL-positive nuclei and degree of caspase-3 activation were both significantly increased in the myocardium following myocardial I/R in rats, indicating increased cardiomyocyte apoptosis. On the other hand, swimming training decreased the serum levels of creatine phosphokinase, lactate dehydrogenase and cardiac troponin I, and was associated with reduced histological damage and myocardial infarct size. Furthermore, swimming training also reduced TNF-α levels, caspase-3 activation and enhanced Bcl-2 activation, which decreased the number of apoptotic cells in the myocardium. The findings of the present study showed that swimming training and IPC could similarly decrease myocardial injury following myocardial I/R, and may therefore be used as exercise training to effectively prevent myocardial injury.

Effects of myocardial fibrosis on ischemic preconditioning against myocardial ischemia-reperfusion injury in type 2 diabetic rats

Objective: To assess whether myocardial fibrosis affects the protective efficiency of ischemic preconditioning (IPC) against myocardial ischemia/reperfusion injury (MIRI) in type 2 diabetic rats. Methods: Type 2 diabetic rat model was established. Fifty-four normal and 54 diabetic spragus-dawley (SD) rats were equally divided into 6 groups (n=18) using the random number table method: (1) Control group (C group); (2) Ischemia reperfusion injury (IRI) control group (IRI group); (3) IPC group; (4) Diabetic control group (DC group); (5) Diabetic IRI group (DIRI group); (6) Diabetic IPC group (DIPC group). After the reperfusion, blood samples were obtained for measuring serum concentrations of creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) using enzyme-linked immunosorbent assay (ELISA). The myocardial infarction size (IS) was assessed by double staining method with Evan's blue and Triphenyl tetrazolium chloride (TTC), and the myocardial collagen volume fraction (CVF) and perivascular collagen area (PVCA) were assessed by Masson staining. Results: A stable and effective rat model with long-term diabetes was established in the current study. Compared with the normal rat groups, the CVF and PVCA significantly increased (all P<0.05) in the diabetic rat groups. The levels of CK-MB, cTnI and IS in the IPC group were (6.6±0.8) ng/ml, (0.5±0.1) ng/ml and (25.1±4.7) %, which showed significant decrease compared with (12.3±1.1) ng/ml, (1.2±0.3) ng/ml and (52.3±8.1) % in IRI group (all P<0.05). Among the diabetic rat groups, the CK-MB and cTnI levels in DIPC group were (11.5±0.9) and (1.1±0.1) ng/ml, apparently lower than the levels of (16.6±2.2) and (1.4±0.3) ng/ml in the DIRI group (both P<0.05). Compared with the IPC group, the IS, CK-MB and cTnI levels significantly increased in the DIPC group (all P<0.05). Conclusion: Myocardial fibrosis exists in rats with long-term type 2 diabetes, which weakens the protective effect of IPC on diabetes MIRI.

Circular RNA Microarray Analyses in Hepatic Ischemia-Reperfusion Injury With Ischemic Preconditioning Prevention.

Ischemic preconditioning (IPC) represents an effective intervention to relieve hepatic ischemia-reperfusion injury (IRI). Systematic detection of circRNA expression revealing the protection effect of IPC still remains to be elucidated. Here, we applied a microarray to detect circRNA and mRNA expression in ischemic liver with and without IPC (n = 3 in each group). Compared with the sham group, there were 39 circRNAs and 432 mRNAs increased and 38 circRNAs and 254 mRNAs decreased (fold change ≥1.5, P < 0.05) in the group of hepatic IRI. As the result of IPC intervention, 43 circRNAs and 64 mRNAs were increased, and 7 circRNAs and 31 mRNAs were decreased in the IPC group when compared with IRI. We then identified circRNA_017753 as the most possible target that may closely relate to IPC protective signaling and predicted Jade1 as the target related to circRNA_017753. Three possible circRNA–miRNA–mRNA axes were constructed that may play a vital role in protective mechanisms in IPC. The study for the first time systematically detects the dysregulated circRNAs and mRNAs in response to hepatic IRI and IPC intervention. Our profile and bioinformatic analysis provide numerous novel clues to understanding the pathophysiologic mechanism of IPC protection against hepatic IRI.

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.

Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart

Despite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats’ hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria.

Remote Ischemic Preconditioning for Prevention of Contrast-Induced Acute Kidney Injury in Patients of CKD Stage III and IV Undergoing Elective Coronary Angiography: A Randomized Controlled Trial.

Introduction:Contrast-induced acute kidney injury (CI-AKI) is a serious complication of coronary angiography (CA). The aim of this randomized, parallel group, single blind, sham-controlled trial was to assess the safety and efficacy of the remote ischemic preconditioning on the prevention of CI-AKI.Methods:Patients of 18–80 years of age with CKD 3 and 4, who were admitted for elective coronary angiography in a tertiary care hospital in eastern India were randomized in a 1:1 ratio to standard care with ischemic preconditioning (n = 45; intermittent arm ischemia through 4 cycles of 5-min inflation and 5-min deflation of a blood pressure cuff) or with standard care and sham ischemic preconditioning (n = 42). Overall, both study groups were at moderate risk of developing CI-AKI according to the Mehran risk score. The primary endpoint was the incidence of CI-AKI, defined as an increase in serum creatinine ≥25% or ≥0.5 mg/dL above baseline at 48 h after contrast medium exposure.Results:CI-AKI occurred in 8 patients (19.04%) in the control group and 2 (4.4%) in the remote ischemic preconditioning group (odds ratio, 0.198, 95% confidence interval, 0.087 to 0.452; P = 0.04). No major adverse events were related to remote ischemic preconditioning.Conclusions:This study indicates that remote ischemic preconditioning is a simple and well-tolerated procedure, which reduces the incidence of CI-AKI in CKD 3 and 4 patients undergoing coronary angiography.