Remote Ischemic Postconditioning Research Articles

Effects of remote ischemic postconditioning on HIF-1α and other markers in on-pump cardiac surgery.

There is a lack of data about the effects of remote ischemic postconditioning (RIPostC) on hypoxia-inducible factor-1α (HIF-1α) plasma levels after on-pump cardiac surgery (OPCS). This study aimed to measure the effects of RIPostC on postoperative HIF-1α plasma levels, cardiac markers and arterial oxygenation in patients undergoing OPCS. This single-centre randomized, double blind, controlled trial, enrolled 70 patients (35 control and 35 RIPostC). RIPostC was performed by 3 cycles (5min of ischemia followed by 5min of reperfusion) administered in upper arm immediately after the pump period. The primary outcome was to measure HIF-1α plasma levels: before surgery (T0), and 2h (T1), 8h (T2), 24h (T3), 36h (T4) and 48h (T5) after RIPostC. As secondary endpoint, Troponin T, CK-MB, CPK plasma levels and PaO2/FiO2 ratio were measured. HIF-1α plasma levels were increased at T1-T3 compared to T0 in both groups (P < 0.001). In the RIPostC group HIF-1α increased compared to the control group: differences between means (95% CI) were 0.034 (0.006-0.06) P = 0.019 at T1; 0.041 (0.013-0.069) P = 0.005 at T2; and 0.021 (0.001-0.042) P = 0.045 at T3. PaO2/FiO2 was higher in the RIPostC group than in the control group: at T3, T4 and T5. Moreover, Troponin T, CK-MB and CPK values decreased in the RIPostC group compared to the control group. HIF-1α plasma levels increased in control patients during for at least 36h after OPCS. RIPostC resulted in even higher HIF-1α levels during at least the first 24h and improved arterial oxygenation and cardiac markers.

Cardioprotective efficiency of pharmacological postconditioning using lactic acid in ischemia-reperfusion of the myocardium in rats with transitional hypercholesterolemia

Cardiovascular disease is the leading cause of death all over the world: for no other reason as many people die every year as from the cardiovascular disease. Taking into account the high medical and social significance of the problem of treating patients with coronary heart disease and acute myocardial infarction, the search for new effective methods of preventing or weakening ischemic myocardial damage and revealing the mechanisms of their implementation is an urgent task of modern experimental and clinical medicine. The aim of the study was to experimentally test the cardioprotective efficiency of pharmacological postconditioning with lactic acid in myocardial ischemia-reperfusion in rats with transient hypercholesterolemia.In the course of the study, it was found that remote ischemic postconditioning (RIPostC) during myocardial ischemia-reperfusion leads to an increase in the level of lactate in the blood and has an infarction-limiting effect in rats. It was revealed that lactate, after injection into the bloodstream of animals at a dose of 10 mg/kg 25 minutes after the start of reperfusion, like RIPostC, leads to a decrease in the necrosis area in the left ventricular of the myocardium. Pharmacological postconditioning with lactate is ineffective in the limiting necrosis area in the myocardium of the left ventricle of rats with transient hypercholesterolemia. The presence of such a risk factor for cardiovascular diseases as hypercholesterolemia can serve as a criterion for excluding the use of pharmacological postconditioning with lactate as a way to reduce ischemic and reperfusion damage to the myocardium in patients with acute myocardial infarction.

The hypoxia sensitive metal transcription factor MTF-1 activates NCX1 brain promoter and participates in remote postconditioning neuroprotection in stroke

Remote limb ischemic postconditioning (RLIP) is an experimental strategy in which short femoral artery ischemia reduces brain damage induced by a previous harmful ischemic insult. Ionic homeostasis maintenance in the CNS seems to play a relevant role in mediating RLIP neuroprotection and among the effectors, the sodium-calcium exchanger 1 (NCX1) may give an important contribution, being expressed in all CNS cells involved in brain ischemic pathophysiology. The aim of this work was to investigate whether the metal responsive transcription factor 1 (MTF-1), an important hypoxia sensitive transcription factor, may (i) interact and regulate NCX1, and (ii) play a role in the neuroprotective effect mediated by RLIP through NCX1 activation. Here we demonstrated that in brain ischemia induced by transient middle cerebral occlusion (tMCAO), MTF-1 is triggered by a subsequent temporary femoral artery occlusion (FAO) and represents a mediator of endogenous neuroprotection. More importantly, we showed that MTF-1 translocates to the nucleus where it binds the metal responsive element (MRE) located at −23/−17 bp of Ncx1 brain promoter thus activating its transcription and inducing an upregulation of NCX1 that has been demonstrated to be neuroprotective. Furthermore, RLIP restored MTF-1 and NCX1 protein levels in the ischemic rat brain cortex and the silencing of MTF-1 prevented the increase of NCX1 observed in RLIP protected rats, thus demonstrating a direct regulation of NCX1 by MTF-1 in the ischemic cortex of rat exposed to tMCAO followed by FAO. Moreover, silencing of MTF-1 significantly reduced the neuroprotective effect elicited by RLIP as demonstrated by the enlargement of brain infarct volume observed in rats subjected to RLIP and treated with MTF-1 silencing. Overall, MTF-dependent activation of NCX1 and their upregulation elicited by RLIP, besides unraveling a new molecular pathway of neuroprotection during brain ischemia, might represent an additional mechanism to intervene in stroke pathophysiology.

Effect of remote ischemic post conditioning on incidence of contrast induce acute kidney injury in STEMI patients undergoing primary percutaneous coronary intervention

Abstract Funding Acknowledgements Type of funding sources: None. Background Primary percutaneous coronary intervention (PPCI) is a treatment of choice in ST elevation myocardial infarction patients (STEMI). However, this approach could increase the risk of contrast induce acute kidney injury (CI-AKI) due to iodinated contrast exposure to the patient. Remote ischemic post conditioning (RIPostC) is a non-invasive and simple method that not only has cardioprotective but also renoprotective effect that could prevent the incidence of CI-AKI. Purpose The aim of this study was to investigate the effect of RIPostC to CI-AKI incident in STEMI patients undergoing PPCI. Methods This study uses pre and post-test only with control group design with experimental research designs. Data was taken at the Instalasi Pelayanan Jantung Terpadu (IPJT) RSUP Dr. M. Djamil Padang from June 2019 until March 2020, there were 66 patients with ST-segment elevation myocardial infarction (STEMI) being performed RIPostC procedure. with intermittent ischaemia and reperfusion applied to the arm through five cycles of 5-min inflation and 5-min deflation of an automated cuff device after crossing wire. Creatinine and eGFR were measured pre and 48 hours post PPCI. CI-AKI diagnosis based on increase of creatinine level &amp;gt;0,5 mg/dL or 25% from baseline value on 48 hours after PPCI. Bivariate analysis was performed to determine the effect RIPostC to incidence of CI-AKI using the Chi-square test. Result A total of 66 patients who underwent the PPCI procedure were divided into two groups RIPostC (n = 33) and without RIPostC (n = 33). The baseline characteristic in both of group was similar. The RIPostC group had a lower CI-AKI incident if we compare with the non RIPostC (15,2% vs 42,4%, p &amp;lt; 0,05). Conclusion RIPostC effectively reduced incidence of CI-AKI in STEMI patient who underwent the PPCI with statistically significant result. Effect of RIPostC in CI-AKI post PPCIPPCICI-AKI (+)(f/%)CI-AKI (-)(f/%)Total(f/%)OR (95% CI)p valueRIPostC (+)5 (15,2)28 (84,8)33 (100)0,024 (0,07-0,76)0,03*bRIPostC (-)14 (42,4)19 (57,6)33 (100)Total19 (28,8)47 (71,2)66 (100)* significant p if &amp;lt; 0,05b, chi square testAbstract Figure. Effect of RIPostC in CI-AKI post PPCI

Effect of remote ischemic post conditioning on kidney function in STEMI patients undergoing primary percutaneous coronary intervention

Abstract Funding Acknowledgements Type of funding sources: None. Background Primary percutaneous coronary intervention (PPCI) is a treatment of choice in ST elevation myocardial infarction patients (STEMI). However, this approach could affect the kidney function due to iodinated contrast exposure to the patient. Remote ischemic post conditioning (RIPostC) is a non-invasive and simple method that not only has cardioprotective but also renoprotective effect for kidney function. Purpose The aim of this study was to investigate the effect of RIPostC to kidney function in STEMI patients undergoing PPCI. Methods This study uses pre and post-test only with control group design with experimental research designs. Data was taken at an Indonesian Heart Center from June 2019 until March 2020, there were 66 patients with ST-segment elevation myocardial infarction (STEMI) being performed RIPostC procedure with intermittent ischaemia and reperfusion applied to the arm through five cycles of 5-min inflation and 5-min deflation of an automated cuff device after crossing wire. Creatinine and eGFR were measured pre and 48 hours post PPCI. Kidney function were determined by eGFR post PPCI, ΔeGFR (pre and 48 hours post PPCI), creatinine post PPCI and Δcreatinine (pre and 48 hours post PPCI). Bivariate analysis was performed to determine the effect RIPostC to kidney function using the Chi-square test. Result A total of 66 patients who underwent the PPCI procedure were divided into two groups RIPostC (n = 33) and without RIPostC (n = 33). The baseline characteristic in both of group was similar. We found that there were no differences of eGFR (70,46 ± 23,06 vs 65,88 ± 23,36, p = 0,424), ΔeGFR (0 [-34,68 - 37,32] vs 0 [-121,53 - 29,70], p value= 0,406), creatinine (1,00 [0,70 - 4,60] vs 1,20 [0,60-4,10], p value= 0,633) and Δcreatinine (0 [-1,20-1,10] vs 0 [-0,50-0,90], p value= 0,390) RIPostC group had a lower CI-AKI incident if we compare with the non RIPostC (15,2% vs 42,4%, p &amp;lt; 0,05). Conclusion Remote ischaemic conditioning does not significantly improve kidney function (eGFR, ΔeGFR, creatinine and Δcreatinine) in patients with STEMI undergoing PPCI The differences of kidney functionVariableRIPostCControlp valueeGFR post PPCI (ml/min/1,73 m2), mean70,46 ± 23,0665,88 ± 23,360,424aΔeGFR(ml/min/1,73 m2), median0 [-34,68 - 37,32]0 [-121,53 - 29,70]0,406bCreatinine post PPCI (mg/dL), median1,00 [0,70 - 4,60]1,20 [0,60-4,10]0,633bΔcreatinine (mg/dL), median0 [-1,20-1,10]0 [-0,50-0,90]0,390ba = Independent sample T testb = mann whitney testAbstract Figure. ΔeGFR and Δcreatinine pre and post PPCI

Remote Ischemic Postconditioning vs. Physical Exercise After Stroke: an Alternative Rehabilitation Strategy?

There remain debates on neuroprotection and rehabilitation techniques for acute ischemic stroke patients. Therapeutic physical exercise following stroke has shown promise but is challenging to apply clinically. Ischemic conditioning, which has several clinical advantages, is a potential neuroprotective method for stroke rehabilitation that is less understood. In the present study, the rehabilitative properties and mechanisms of physical exercise and remote ischemic postconditioning (RIPostC) after stroke were compared and determined. A total of 248 adult male Sprague-Dawley rats were divided into five groups: (1) sham, (2) stroke, (3) stroke with intense treadmill exercise, (4) stroke with mild treadmill exercise, and (5) stroke with RIPostC. Focal ischemia was evaluated by infarct volume and neurological deficit. Long-term functional outcomes were represented through neurobehavioral function tests: adhesive removal, beam balance, forelimb placing, grid walk, rota-rod, and Morris water maze. To further understand the mechanisms underlying neurorehabilitation and verify the presence thereof, we measured mRNA and protein levels of neuroplasticity factors, synaptic proteins, angiogenesis factors, and regulation molecules, including HIF-1α, BDNF, TrkB, and CREB. The key role of HIF-1α was elucidated by using the inhibitor, YC-1. Both exercise intensities and RIPostC significantly decreased infarct volumes and neurological deficits and outperformed the stroke group in the neurobehavioral function tests. All treatment groups showed significant increases in mRNA and protein expression levels of the target molecules for neurogenesis, synaptogenesis, and angiogenesis, with intermittent further increases in the RIPostC group. HIF-1α inhibition nullified most beneficial effects and indicative molecule expressions, including HIF-1α, BDNF, TrkB, and CREB, in both procedures. RIPostC is equally, or superiorly, effective in inducing neuroprotection and rehabilitation compared to exercise in ischemic rats. HIF-1α likely plays an important role in the efficacy of neuroplasticity conditioning, possibly through HIF-1α/BDNF/TrkB/CREB regulation.

Remote Limb Ischemic Postconditioning Protects against Ischemic Stroke via Modulating Microglia/Macrophage Polarization in Mice.

Aim The protection against ischemia/reperfusion injury mediated by remote limb ischemic postconditioning (RIPC) shows great clinical value in ischemic stroke therapy, but the particular mechanism of RIPC remains unclear. Methods We carried out middle cerebral artery occlusion/reperfusion (MCAO/R) surgery on C57BL/6 male mice. RIPC was generated by 10-minute occlusion followed by the same period of reperfusion of the bilateral hind limb femoral artery and repeated for 3 cycles. Infarct size and neurological score were performed to assess stroke outcomes. Ly6Chi monocytes were quantified in the blood and brain by flow cytometry. Real-time PCR, ELISA, and immunofluorescence were utilized to detect phenotype of proinflammatory M1 and anti-inflammatory M2 microglia/macrophage. Nuclear factor κB (NF-κB) and peroxisome proliferator-activated receptor γ (PPARγ) levels were detected using Western blot. Results At 24 and 72 h after MCAO, RIPC drastically attenuated infarct size and ameliorated the neurological deficits of mice and facilitated transmigration of Ly6Chi monocytes to the brain postischemia reperfusion. Furthermore, RIPC contributed to increased M2 and reduced M1 microglia/macrophage through inhibiting NF-κB and promoting PPARγ activation. Conclusion Our results reveal pharmacological effect of RIPC in promoting microglia/macrophage transferring from M1 to M2 phenotype after MCAO/R in mice, which provides theoretical support for the therapeutic effect of RIPC in ischemic stroke.

Remote Ischemic Postconditioning Inhibited Mitophagy to Achieve Neuroprotective Effects in the Rat Model of Cardiac Arrest.

Remote ischemic postconditioning (RI-postC) is an effective measure to improve nerve function after cardiac arrest. However, the brain protective mechanism of RI-postC has not been fully elucidated, and whether it is related to mitophagy is unclear. In this study, we used the rat model of cardiac arrest to study the effect of RI-postC on mitophagy and explore its possible signaling pathways. Rats were randomly divided into Sham group, CA/CPR group, Mdivi-1 group and RI-postC group. The animal model of cardiac arrest was established by asphyxia. RI-postC was performed by clamping and loosening the left femoral artery. Mdivi-1 was treated with a single intravenous injection. Levels of TOMM20, TIM23, Mfn1, PINK1 and parkin were detected by western blots. Mitochondrial membrane potential was measured by flow cytometry. Real-time PCR was used to detect relative mitochondrial DNA levels. The apoptosis of hippocampal neurons was detected by flow and TUNEL. In addition, Histopathological tests were performed. The results showed that RI-postC was similar to the mitophagy inhibitor Mdivi-1, which could inhibit the decrease of mitophagy-related protein level, improve mitochondrial membrane potential and up-regulate the ratio of mt-Atp6/Rpl13 after cardiopulmonary resuscitation (CPR). Furthermore, RI-postC could also reduce the rate of hippocampal nerve apoptosis and the damage of hippocampal neurons after CPR. Moreover, RI-postC and Mdivi-1 could reduce the protein levels of PINK1 and parkin in mitochondria after CPR, while increasing PINK1 levels in the cytoplasm. These findings suggested that RI-postC could inhibit the overactivation mitophagy through the PINK1/parkin signaling pathway, thus providing neuroprotective effects.

Serum of limb remote ischemic postconditioning inhibits fMLP-triggered activation and reactive oxygen species releasing of rat neutrophils

ABSTRACT Objectives The study explores the protective role of the peripheral serum of limb remote ischemic postconditioning (LRIP) in reducing the reactive oxygen species (ROS) levels and neutrophil activation, which are responsible for the deleterious reperfusion injury. Methods LRIP was induced in Sprague–Dawley rats by three cycles of 5 min occlusion /5 min reperfusion on the left hind limb. The blood samples were collected before LRIP or 0 and 1 h after LRIP (named SerumSham, SerumLRIP0, SerumLRIP1, respectively). The effects of LRIP serum on ROS level and neutrophils activation were determined. The expression of MyD88-TRAF6-MAPKs and PI3K/AKT pathways in neutrophils were examined. Results When compared with SerumSham, SerumLRIP0 and SerumLRIP1 significantly reduced the ROS released from neutrophils activated by fMLP. Meanwhile, the mRNA expression levels of NADPH oxidase subunit p22phox and multiple ROS-producing related key proteins, such as NADPH oxidase subunit p47phox ser 304, ser 345. MyD88, p-ERK, p-JNK and p-P38 expression of neutrophils were downregulated by SerumLRIP0 and SerumLRIP1. SerumLRIP1 also downregulated p47phox mRNA expression and tumor necrosis factor receptor-associated factor 6 (TRAF6) protein expression. Conclusion LRIP serum protects against ROS level and neutrophils activation involving the MyD88-TRAF6-MAPKs. This finding provides new insight into the understanding of LRIP mechanisms.

What's New in Shock? January 2021.

What's New in Shock? January 2021.

Remote Ischemic Post-Conditioning Therapy is Protective in Mouse Model of Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) is characterized by visual dysfunction after indirect or direct injury to the optic nerve following blunt head trauma. TON is associated with increased oxidative stress and inflammation resulting in retinal ganglion cell (RGC) death. Remote ischemic post-conditioning (RIC) has been shown to enhance endogenous protective mechanisms in diverse disease models including stroke, vascular cognitive impairment (VCI), retinal injury and optic nerve injury. However, the protective mechanisms underlying the improvement of retinal function and RGC survival after RIC treatment remain unclear. Here, we hypothesized that RIC therapy may be protective following TON by preventing RGC death, oxidative insult and inflammation in the mouse retina. To carry out the study, mice were divided in three different groups (Control, TON and TON + RIC). We harvested retinal tissue 5days after TON induction for western blotting and histochemical analysis. We observed increased TON-induced retinal cell death compared with controls by cleaved caspase-3 immunohistochemistry. Furthermore, the TON cohort demonstrated increased TUNEL positive cells which were significantly attenuated by RIC. Immunofluorescence data showed that oxidative stress markers dihydroethidium (DHE), NOX-2 and nitrotyrosine expression were elevated in the TON group relative to controls and RIC therapy significantly reduced the expression level of these markers. Next, we found that the proinflammatory cytokine TNF-α was increased and anti-inflammatory IL-10 was decreased in plasma of TON animals, and RIC therapy reversed this expression level. Interestingly, western blotting of retinal tissue showed that RGC marker Brn3a and tight junction proteins (ZO-1 and Occludin), and AMPKα1 expression were downregulated in the TON group compared to controls. However, RIC significantly increased the expression levels of these proteins. Together these data suggest that RIC therapy activates endogenous protective mechanisms which may attenuate TON-induced oxidative stress and inflammation, and improves BRB integrity.

Advances in intervention methods and brain protection mechanisms of in situ and remote ischemic postconditioning.

Ischemic postconditioning (PostC) conventionally refers to a series of brief blood vessel occlusions and reperfusions, which can induce an endogenous neuroprotective effect and reduce cerebral ischemia/reperfusion (I/R) injury. Depending on the site of adaptive ischemic intervention, PostC can be classified as in situ ischemic postconditioning (ISPostC) and remote ischemic postconditioning (RIPostC). Many studies have shown that ISPostC and RIPostC can reduce cerebral IS injury through protective mechanisms that increase cerebral blood flow after reperfusion, decrease antioxidant stress and anti-neuronal apoptosis, reduce brain edema, and regulate autophagy as well as Akt, MAPK, PKC, and KATP channel cell signaling pathways. However, few studies have compared the intervention methods, protective mechanisms, and cell signaling pathways of ISPostC and RIPostC interventions. Thus, in this article, we compare the history, common intervention methods, neuroprotective mechanisms, and cell signaling pathways of ISPostC and RIPostC.

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke.

To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT). A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated. We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score (p = 0.364) or occur-to-treatment time (p = 0.889). Favorable recovery (mRS score 0-1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54-63.16; p = 0.016). We further found significantly lower plasma S100-β (p = 0.007) and higher vascular endothelial growth factor (p = 0.003) levels in the RIPC group than in the control group. Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS. NCT03218293. This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days.

Different ischemic duration and frequency of ischemic postconditioning affect neuroprotection in focal ischemic stroke

BackgroundMany studies have confirmed that “in situ ischemia postconditioning” (ISPostC) and “remote ischemic postconditioning” (RIPostC) can reduce cerebral ischemia/reperfusion injury, but there is no comparison was made on the consistency of neuroprotection in ISPostC and RIPostC to different ischemic duration and number of cycles. New methodWe used a transient middle cerebral artery occlusion model to compare the neuroprotection of ISPostC and RIPostC. We conducted ISPostC and RIPostC via brief and repeated MCA and Femoral artery occlusion followed by different ischemic duration and number of cycles. Infarct volume, brain edema, Neurological deficit scores and Apoptosis were evaluated. ResultsFirst, the ISPostC with three cycles of 10-s occlusion/30-s release of both carotid arteries and the RIPostC with three cycles of 10-min occlusion/10-min release of the left and right femoral arteries can obviously reduce cerebral infarction size, brain edema, apoptosis, and improve behavioral deficits than other approaches. Second, three cycles of ischemia/reperfusion may be the best for RIPostC. Comparison with existing method(s)In this paper, we compared different ischemic duration and frequency of ISPostC and RIPostC models to determine the best method. This conclusion helps to unify the experimental methods. ConclusionsDifferent ischemic duration and frequency of ischemic postconditioning affect neuroprotection. three cycles of 10-s occlusion/30-s release of both carotid arteries and three cycles of 10-min occlusion/10-min release of both femoral arteries could be the first choice to study mechanisms of ischemic postconditioning and be conducive to the unification of research results.

Significance of nitrogen monoxide in the implementation of the infarctlimiting effect of remote ischemic postconditioning in myocardial ischemia-reperfusion in young and old rats

Modern medicine faces the problem of a steady growth of cardiovascular pathology. Given the high medical and social significance of the problem of treating patients with coronary heart disease and acute myocardial infarction, the search for new effective methods to prevent or mitigate ischemic myocardial damage and mechanisms for their implementation is an urgent task of modern experimental and clinical medicine. The aim of the study was to determine the significance of nitric monoxide in realizing the infarction-limiting effect of remote ischemic postconditioning (RIPostC) in myocardial ischemia-reperfusion in young and old rats. The study revealed that RIPostC has a heart attack-limiting effect in myocardial ischemia-reperfusion in both young and old rats; however, under the conditions of the systemic action of the NG-nitro-L-arginine methyl ester inhibitor at a dose of 25 mg/kg (intravenous administration 5 min before the start of reperfusion and 15 min before RIPostC), the effect remains, although not completely, in old rats but not in young rats. Apparently, the NO synthase activity and the blood level of nitric monoxide play a more significant role in the mechanisms of the cardioprotective effects of RIPostC in young rats than in old rats.

The effect of remote ischemic postconditioning on autonomic function in patients with acute ischemic stroke: A Randomized Controlled Trail

ObjectiveThe evidence for the effect of remote ischemic postconditioning(RIpostC) on autonomic function in patients with acute ischemic stroke(AIS) is lacking and the neural mechanism underlying the protection of RIpostC remains speculative. This trial was aimed to evaluated the efficiency of RIpostC on autonomic function in AIS patients. DesignOne hundred and six AIS patients were included in this prospective, randomized, placebo-controlled trial. Patients in intervention group (n = 57) received 4 cycles of alternating inflation (cuff inflation to 200 mmHg) and deflation for 5 min on healthy upper arm once a day for 30 days. The control group underwent a sham inflation and deflation cycles. Autonomic function was evaluated by heart rate variability (HRV). ResultsAll HRV parameters except for the ratio of low frequency to high frequency (P = 0.101) increased significantly with time (P < 0.001) in the two groups. The value of standard deviation of all normal R-R intervals(SDNN) and high frequency at day7 and day30 and the value of the percent of difference between adjacent normal R-R intervals (pNN50) at day 30 in RIpostC group was significantly higher than that of the sham-RIpostC group(P < 0.05). A significant time-by-group interaction was observed in SDNN、pNN50、and high frequency over time between two groups (P < 0.05). Conclusions30-day RIpostC could improve autonomic function in AIS patients through the enhancement of the total autonomic nerve activity and vagus nerve activity. The mechanism of RIpostC mediating autonomic function needs to be further investigated.

Effect of Remote Ischemic Postconditioning on miRNA-145 and Troponin I levels in STEMI patients undergoing primary percutaneous coronary intervention

Background: Primary Percutaneous Coronary Intervention Procedure (PPCI) results in reperfusion injury which will result in more extensive infarction. Remote Ischemic Postconditioning (RIPC) is a protective strategy to reduce the increase in the area of ??infarction. miRNA-145 also plays a role in the protective effect of IPC and RIPC.&#x0D; &#x0D; Research Methods: This study uses a pre and post test approach only with control group design with experimental research designs. Data is taken at the Integrated Heart Services Installation RSUP Dr. M. Djamil Padang from July to November 2019, 40 patients with ST-segment elevation myocardial infarction (STEMI) performed RIPC. Bivariate analysis was performed to determine differences in levels of miRNA-145 and troponin I in STEMI patients underwent PPCI with and without RIPC using the Wilcoxon test and the Mann Whitney test.&#x0D; &#x0D; Results:A total of 40 patients who underwent the PPCI procedure were divided into two groups PPCI + RIPC (n = 20) and PPCI without RIPC (n = 20). There were no significant differences in the basic characteristics between the two groups. There were no significant difference in escalation of median expression of miRNA-145 in PPCI+ RIPC [pre test 36.33 (27.44-52.39), post test 34.83 (27.65-65.26), p = 0.765] compared to PPCI without RIPC [pre test 31.66 (26.31-43.28), post test 33.43 (26.83-64.97), p = 0.765]. There were an increase in median troponin I levels in both groups, PPCI+ RIPC [pretest 4,104.70 (67.30-40,000.00), post test 30,448.50 (120.00-16.3192.20), p = 0.001] and PPCI without RIPC [pretest 826.50 (17.00-48.259.00), post test 42.784.50 (2,119.00-162.897.00), p = &lt;0.001].&#x0D; &#x0D; Conclusion:There were no significant difference in median expression of miRNA-145 in STEMI patients before and after (48 hours) underwent PPCI+RIPC and PPCI without RIPC. There were a significant difference in median levels of troponin I in STEMI patients before and after (48 hours) underwent PPCI+RIPC and PPCI without RIPC.&#x0D; Keywords: Remote Ischemic Postconditioning, miRNA-145, troponin I

Remote Ischemic Post-Conditioning may Improve Post-Stroke Cognitive Impairment: A Pilot Single Center Randomized Controlled Trial

Background and PurposeWe aimed to demonstrate the tolerability and feasibility and the effect of remote ischemic post-conditioning on cognitive functioning in patients with post-stroke cognitive impairment. MethodsThis was a single-center, randomized, outcome-blinded, placebo-controlled trial, randomized 1:1 to receive 4 cycles of remote ischemic post-conditioning or a sham procedure for 7 days. The primary outcome measure was tolerability and feasibility of remote ischemic post-conditioning. Secondary outcomes to measure the neurological function with national institute of health stroke scale and the cognitive impairment with Montreal Cognitive Assessment scale and Alzheimer's disease assessment scale-cognitive (at baseline, 90 days, 180 days). Results48 patients (24 RIPC and 24 Control) were recruited. remote ischemic post-conditioning was well tolerated with 90 out of 96 cycles completed in full. 4 patients experienced vascular events in the control group: 3 cerebrovascular and 1 cardiovascular event versus only 2 cerebrovascular events in the RIPC group. We showed the similar result in the neurological function with national institute of health stroke scale score with no statistically significant differences between RIPC and control group at baseline (P = 0.796) and 90 days (P = 0.401) and 180 days (P = 0.695). But compare with baseline, it was significantly difference in the control and RIPC group at 90 days (P < 0.05) and 180 days (P < 0.05). The comparison of Montreal Cognitive Assessment scale between two groups both showed that P > 0.05 at baseline which was no statistical difference, but P < 0.05 at 90 days and 180 days which were significant statistical difference. The comparison of Alzheimer's disease assessment scale-cognitive between two groups showed that P > 0.05 at baseline (P = 0.955) and 90 days (P = 0.138) was no statistical difference, but P = 0.005<0.05 at 180 days was significant statistical difference. ConclusionsThe remote ischemic post-conditioning for post-stroke cognitive impairment was well tolerated, safe and feasible. The remote ischemic post-conditioning may improve neurological and cognitive outcomes in patients with post-stroke cognitive impairment. A larger trial is warranted. (Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: ChiCTR1800015231.)

On the significance of hyperlactatemia in the implementation of the infarct-limiting effect of remote ischemic postconditioning in myocardial ischemia-reperfusion in the experiment

Modern medicine faces the problem of the growth of cardiovascular pathology. Given the high medical and social significance of the problem of treating patients with coronary heart disease and acute myocardial infarction, the search for new effective methods to prevent or weaken ischemic myocardial damage and mechanisms for their implementation is an urgent task of modern experimental and clinical medicine. The aim of the study was to determine the significance of hyperlactatemia in the realization of the infarct-limiting effect of remote ischemic postconditioning (RIPostC) in rat myocardial ischemia-reperfusion in the experiment. The study revealed that after 15-minute RIPostC, which was performed 10 minutes after 30-minute acute myocardial ischemia followed by 120-minute reperfusion, the plasma lactate level in rats increased 1.87 times (87.7 %, p &lt; 0.05) compared with intact animals. It was established that the introduction of L-lactate into the left common jugular vein at a dose of 10 μg/kg, which was carried out 25 minutes after the onset of reperfusion under the conditions of myocardial ischemia (30 minutes) and next reperfusion (120 minutes) and RIPostC (10 minutes after the onset of reperfusion), which was reproduced by ischemia of these limbs, have a heart attack-limiting effect. The increase of the level of blood lactate (hyperlactatemia) after RIPostC in myocardial ischemia-reperfusion is of significance in the implementation of its infarct-limiting effect.

No Added Neuroprotective Effect of Remote Ischemic Postconditioning and Therapeutic Hypothermia After Mild Hypoxia-Ischemia in a Piglet Model.

Introduction: Hypoxic ischemic encephalopathy (HIE) is a major cause of death and disability in children worldwide. Apart from supportive care, the only established treatment for HIE is therapeutic hypothermia (TH). As TH is only partly neuroprotective, there is a need for additional therapies. Intermittent periods of limb ischemia, called remote ischemic postconditioning (RIPC), have been shown to be neuroprotective after HIE in rats and piglets. However, it is unknown whether RIPC adds to the effect of TH. We tested the neuroprotective effect of RIPC with TH compared to TH alone using magnetic resonance imaging and spectroscopy (MRI/MRS) in a piglet HIE model.Methods: Thirty-two male and female piglets were subjected to 45-min global hypoxia-ischemia (HI). Twenty-six animals were randomized to TH or RIPC plus TH; six animals received supportive care only. TH was induced through whole-body cooling. RIPC was induced 1 h after HI by four cycles of 5 min of ischemia and 5 min of reperfusion in both hind limbs. Primary outcome was Lac/NAA ratio at 24 h measured by MRS. Secondary outcomes were NAA/Cr, diffusion-weighted imaging (DWI), arterial spin labeling, aEGG score, and blood oxygen dependent (BOLD) signal measured by MRI/MRS at 6, 12, and 24 h after the hypoxic-ischemic insult.Results: All groups were subjected to a comparable but mild insult. No difference was found between the two intervention groups in Lac/NAA ratio, NAA/Cr ratio, DWI, arterial spin labeling, or BOLD signal. NAA/Cr ratio at 24 h was higher in the two intervention groups compared to supportive care only. There was no difference in aEEG score between the three groups.Conclusion: Treatment with RIPC resulted in no additional neuroprotection when combined with TH. However, insult severity was mild and only evaluated at 24 h after HI with a short MRS echo time. In future studies more subtle neurological effects may be detected with increased MRS echo time and post mortem investigations, such as brain histology. Thus, the possible neuroprotective effect of RIPC needs further evaluation.