Episodes Of Reperfusion Research Articles

Immediate Increase in the Root Mean Square of Successive Differences after Three Bouts of Remote Ischemic Preconditioning: A Randomized Controlled Trial.

(1) Background: Remote ischemic preconditioning (RIPC) is an intervention involving the application of brief episodes of ischemia and reperfusion to distant tissues to activate protective pathways in the heart. There is evidence suggesting the involvement of the autonomic nervous system (ANS) in RIPC-induced cardioprotection. This study aimed to investigate the immediate effects of RIPC on the ANS using a randomized controlled trial. (2) Methods: From March 2018 to November 2018, we conducted a single-blinded randomized controlled study involving 51 healthy volunteers (29 female, 24.9 [23.8, 26.4] years). Participants were placed in a supine position and heart rate variability was measured over 260 consecutive beats before they were randomized into either the intervention or the SHAM group. The intervention group underwent an RIPC protocol (3 cycles of 5 min of 200 mmHg ischemia followed by 5 min reperfusion) at the upper thigh. The SHAM group followed the same protocol but on the right upper arm, with just 40 mmHg of pressure inflation, resulting in no ischemic stimulus. Heart rate variability measures were reassessed afterward. (3) Results: The intervention group showed a significant increase in RMSSD, the possible marker of the parasympathetic nervous system (IG: 14.5 [5.4, 27.5] ms vs. CG: 7.0 [-4.3, 23.1 ms], p = 0.027), as well as a significant improvement in Alpha 1 levels compared to the control group (IG: -0.1 [-0.2, 0.1] vs. CG: 0.0 [-0.1, 0.2], p = 0.001). (4) Conclusions: Our results hint that RIPC increases the RMSSD and Alpha 1 parameters showing possible immediate parasympathetic modulations. RIPC could be favorable in promoting cardioprotective or/and cardiovascular effects by ameliorating ANS modulations.

Acute prevention of aheart attack : Early identification of prodromal symptoms as the Rosetta Stone in decoding the heart attack problem.

Chest discomfort before severe chest pain represents amarker of clinical ischemia and indicates live myocardium in jeopardy and often precedes cardiac arrest or acute myocardial infarction (MI). The intermittent or "stuttering" symptoms that precede MI are referred to as "prodromal symptoms." These symptoms have been shown to correlate with cyclic ST changes and repeated episodes of spontaneous reperfusion and occlusion, occurring during aperiod of hours or days before the acute ischemia proceeds to death or heart damage. These symptoms of premonitory angina have been associated with improved outcomes due to ischemic pre-conditioning or opening of collateral vascular channels around the area of ischemia. Acute prevention of an MI through recognition of prodromal symptoms represents an opportunity to significantly reduce heart attack deaths. The Early Heart Attack Care (EHAC) program puts emphasis on prodromal symptom recognition and allows for ashift in time backward to prevent the ischemic process from proceeding to MI. This strategy has been shown to detect the 15% of patients with ischemia in the low-probability group and to reduce inappropriate admissions to hospital as well as to reduce the number of patients with missed MI being sent home from the emergency department.

Adjunct remote ischemic conditioning to PCI in ST-segment elevation myocardial infraction patients: Systematic review and meta-analysis

Abstract Introduction ST-segment elevation myocardial infarction (STEMI) is the most dangerous presentation of the acute coronary syndrome (ACS). Throughout the last three decades, clinicians have been attempting to reduce the short and long-term major adverse cardiac events (MACE) associated with STEMI. Remote ischemic conditioning (RIC) is one of the new adjunctive modalities to PCI in treating STEMI patients whereby brief reversible episodes of ischemia and reperfusion are applied to the tissue (by alternative cycles of inflation and deflation of a blood pressure cuff on the upper or lower limb) confers global protection and renders remote tissues resistant to ischemia/reperfusion injury. This review aims to provide reliable evidence from published randomized controlled trials (RCTs) regarding whether RIC is beneficial for STEMI patients or not. Methods We followed the PRISMA guidelines during the preparation of this systematic review and meta-analysis. A computer literature search for (PubMed, Web of Science, Scopes, and Google Scholar) was carried out. We included RCT, comparing the remote ischemic conditioning, regardless of its timing of application to PCI, with either placebo or sham procedure, in terms of both short-term and long-term cardio protection. Outcomes of myocardial salvage index, myocardial infarction size, and left ventricular ejection fraction were pooled as the standardized mean difference between the two groups from baseline to endpoint. Results 11 RCTs (7151 patients), were included in this analysis. The overall effect on short-term outcomes, was in favor of PCI only in terms of myocardial salvage index(P value=0.04, 95% CI [0.00-0.08]), and left ventricular ejection fraction(P value=0.05, 95% CI [0.02,2.16]), while the adjunctive application of remote ischemic conditioning was beneficial in terms of: myocardial infarct size ( P value=0.004, 95% CI [-3.22,-0.62]). Regarding the long-term outcomes, the overall effect did not show any benefit in either of the two groups in terms of: major adverse cardiac and cerebrovascular events (MACCE) (P value=0.13, 95% CI [0.48,1.10]), hospitalization for heart failure (P value=1.00, 95% CI [0.83,1.20]), and cardiac death (P value=0.91, 95% CI [0.73,1.32]). Conclusion The adjunctive application of RIC to PCI during treatment of STEMI patients showed a beneficial effect only on short-term reduction of myocardial infarct size, nevertheless, it was not of benefit regarding the other short and long-term metrics of myocardial salvage and left ventricular function.

Destabilization of the Organized Structure of Ventricular Fibrillation During Reperfusion

Aim: to study the effect of reperfusion on the organized frequency-amplitude structure of ventricular fibrillation (VF) in the dog heart.Materials and methods. We conducted 4 experiments on 8 dogs. In each experiment, the isolated heart of one dog was perfused with the blood of the second (supporting) dog. In 4 experiments on an isolated artificially perfused heart, 6 episodes of 3 min ischemia and 10 min reperfusion of the heart were performed in VF (1–2 episodes of ischemia-reperfusion in one experiment). Each episode of 3 min ischemia in VF was preceded by a 10 min perfusion of the heart in VF. Ventricular electrogram was recorded during VF episodes. A frequencyamplitude (spectral) analysis of 1 sec segments of the electrogram was performed, and the proportion (in %) of 0.5–15 Hz frequency oscillations in 10 sec segments of the electrogram was determined in 6 episodes of perfusion, ischemia and reperfusion in VF (M±m, N=60). The VF frequency-amplitude structures during ischemia and reperfusion were compared with the stable VF frequency-amplitude structure during perfusion taken as the control. The nonparametric Welch criterion in the «The R Project for Statistical Computing» software environment was used to compare the VF parameters during perfusion, ischemia and reperfusion. Results. 9–10 Hz frequency oscillations dominated in the VF frequency-amplitude structure during heart perfusion, taken as the control. In the first 30 sec of ischemia, the frequency and amplitude of the dominant oscillations did not significantly change vs VF control obtained during cardiac perfusion. A decrease of dominant oscillations frequency up to 6.5–7.5 Hz, and of the proportion of oscillations — up to 26% was documented at the 3rd min of ischemia. At the 1st min of reperfusion, the frequency of dominant oscillations increased to 13.5–14.5 Hz, but the proportion of oscillations remained reduced to 26%, as at the 3rd min of ischemia. At the 2nd min of reperfusion, the frequency of dominant oscillations decreased to 9.5–10.5 Hz, and the proportion of dominant oscillations increased to 33%. The frequency and amplitude of the dominant oscillations stabilized at 3–10 min of reperfusion: oscillations at 9–10 Hz frequency accounted for 32–33% of the spectral power.Conclusion. Reperfusion in VF is characterized by transient destabilization of VF organized structure at the 1st min of the procedure. VF organized structure regains stabilization within 2–10 min of reperfusion. Cardiac perfusion in intentionally induced VF can be used instead of cardioplegia during major cardiac surgery to boost cardiac resistance to ischemia and prevent or reduce reperfusion complications.

Is Nrf2 Behind Endogenous Neuroprotection of the Hippocampal CA2-4,DG Region?

The transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is the master regulator of genes known to be involved in antioxidant, and anti-inflammatory processes, metabolic regulation, and other cellular functions. Here, we also hypothesize a core role for it in endogenous neuroprotection, i.e., the natural adaptive mechanisms protecting the brain from ischemia–reperfusion (I/R) episode. An example of endogenous neuroprotection is ischemia-resistance of the hippocampal regions comprising the CA2, CA3, CA4 and dentate gyrus subfields (here abbreviated to CA2-4,DG) which can be contrasted with the ischemia-vulnerable CA1 region. In the work detailed here, we used a gerbil model of transient cerebral ischemia to examined Nrf2 activation in CA1 and CA2-4,DG, in a control group, and post I/R episode. Data obtained indicate enhanced Nrf2 activity in CA2-4,DG as compared with CA1 in the control, with this difference seen to persist even after I/R. While I/R does indeed cause further activation of Nrf2 in CA2-4,DG, it is associated with slight and transient activation in CA1. Sub-regional differences in Nrf2 activity correlate with immunoreactivity of Keap1 (an Nrf2 suppressor) and Nrf2 target proteins, including heme oxygenase 1, the catalytic and modulatory sub-units of glutamate-cysteine ligase, and glutathione peroxidase 1. Pharmacological Nrf2 activation by sulforaphane results in protection of CA1 after I/R episode. Our results therefore suggest that high Nrf2 activity in CA2-4,DG may guarantee resistance of this region to I/R, potentially explaining the differential sensitivities of the hippocampal regions.

Ischemic preconditioning-induced protective effect for promoting angiogenesis in renal ischemia-reperfusion injury by regulating miR-376c-3p/HIF-1α/VEGF axis in male rats

ObjectiveIschemic preconditioning (IPC) is defined as a well-established phenomenon in which brief exposure to sublethal episodes of ischemia and reperfusion induces a tolerance to injurious effects of prolonged ischemia by exploiting intrinsic defence mechanisms. The present study was performed to determine the protective effect of IPC on the rat renal ischemia-reperfusion injury (IRI) via miR-376c-3p/HIF-1α/VEGF axis. MethodsIn vivo, these male Sprague-Dawley rats were treated by IRI and IPC. Meanwhile, these rats from different treatment groups were also injected subcutaneously with 2 nmol agomir-376c-3p and/or 10 nmol recombinant rat HIF-1α. At 72 h after reperfusion, serum samples were respectively collected for renal function. Besides, kidney tissues were harvested to observe renal morphology changes. Subsequently, the expression levels of CD31, HIF-1α and VEGF in the kidney tissues were measured using immunohistochemical staining, quantitative real-time PCR, as well as Western blotting analysis at the indicated time points after reperfusion. In vitro, HK-2 cells were used to detect the cell activity by CCK-8 and transfection of mir-376c-3p mimic in Hypoxia/Reoxygenation (H/R) group. ResultsIn vivo, the pathological changes were significantly relieved in the rats with IPC group, compared to the IRI group. Rats which were treated IPC significantly reduced the levels of blood urea nitrogen (BUN), serum creatinine (Scr) at 24 h after operation, compared to IRI group. After IPC treatment, the expression level of CD31 was obviously decreased, compared to IRI group. A total of differently expressed microRNAs were screened out by microRNA microarray assay in rat renal ischemia tissue, especially showing that miR-376c-3p was selected as the target miRNA. Compared to IRI group, the expression level of miR-376c-3p were obviously higher in IPC-treated group. Double-luciferase reporter assay demonstrated that miR-376c-3p directly targeted HIF-1α. In vitro, IPC significantly increased cell viability of HK-2, and promoted the angiogenesis via up-regulating miR-376c-3p/HIF-1α/VEGF axis. Furthermore, the expression level of HIF-1α was apparently decreased in HK-2 treated with H/R after miR-376c-3p mimic transfection respectively, as well as the increased expression level of VEGF. ConclusionsOur study provided a novel insight for investigating the protective effect of IPC on renal IRI. Consequently, miR-376c-3p played an important role in renal IRI by promoting angiogenesis via targeting HIF-1α/VEGF pathway in male rats.

Effects of Recurring IPC vs. rIPC Maneuvers on Exercise Performance, Pulse Wave Velocity, and Red Blood Cell Deformability: Special Consideration of Reflow Varieties.

Simple SummaryIschemia preconditioning (IPC) and remote (r) IPC consist of a sequence of blood occlusion and blood reflow to manipulate an effector organ either near (IPC) or remote (rIPC) from the occlusion site. Its benefits in medical applications are well-documented, while there is no consensus regarding its effects on exercise performance, arterial stiffness, blood pressure, and red blood cell deformability. The aim of the study was to test and compare the effects of five daily recurring IPC and rIPC maneuvers on these parameters. Additionally, different reflow protocols, low (LR) and high reflow (HR), were compared to investigate potential differences of the shear stress occurring during reflow on the outcome. Results of thirty male participants suggest improved exercise performance during IPC LR and to a lesser extent rIPC LR interventions, while HR conditions did not affect performance parameters. This might in part be related to increased red blood cell deformability and reduced lactate production, while relations to altered pulse wave velocity or blood pressures seem less likely. In conclusion, the site of occlusion and reflow conditions might influence the effectiveness of the (r)IPC intervention, which should be considered in sport-specific but also clinical settings.Beneficial effects of (remote) ischemia preconditioning ((r)IPC), short episodes of blood occlusion and reperfusion, are well-characterized, but there is no consensus regarding the effectiveness of (r)IPC on exercise performance. Additionally, direct comparisons of IPC and rIPC but also differences between reflow modes, low reflow (LR) and high reflow (HR) in particular, are lacking, which were thus the aims of this study. Thirty healthy males conducted a performance test before and after five consecutive days with either IPC or rIPC maneuvers (n = 15 per group). This procedure was repeated after a two-week wash-out phase to test for both reflow conditions in random order. Results revealed improved exercise parameters in the IPC LR and to a lesser extent in the rIPC LR intervention. RBC deformability increased during both rIPC LR and IPC LR, respectively. Pulse wave velocity (PWV) and blood pressures remained unaltered. In general, deformability and PWV positively correlated with performance parameters. In conclusion, occlusion of small areas seems insufficient to affect large remote muscle groups. The reflow condition might influence the effectiveness of the (r)IPC intervention, which might in part explain the inconsistent findings of previous investigations. Future studies should now focus on the underlying mechanisms to explain this finding.

Involvement of Estrogen Receptor and Mitochondrial KATP Channels in Cardioprotective Effect of Remote Aortic Preconditioning in Isolated Rat Heart

The present study was designed to investigate the role of estrogen receptor and KATP channel in cardioprotective effect of remote aortic preconditioning in rat heart. Remote preconditioning is a phenomenon in which brief episodes of ischemia and reperfusion to remote organs protect the target organ against sustained ischemia/ reperfusion induced injury. Protective effects of remote aortic preconditioning are well established in the heart, but their mechanisms still remain to be elucidated. Remote aortic preconditioning in rats was produced by introducing four episodes of ischemia and reperfusion, each comprising of 5 min occlusion and 5 min reperfusion, through abdominal aorta. Perfused rat heart was isolated and subjected to global ischemia for 30 min followed by reperfusion for 120 min. The degree of cardiac injury was assessed by analysing the level of lactate dehydrogenase, creatin kinase, reactive oxygen species and nitrite in coronary effluent. Myocardial infarct size was also estimated macroscopically using tetrazolium tri chloride staining. Ethylinestradiol (10 μg/kg, orally) as estrogen receptor agonist was noted to reproduce remote aortic preconditioning mediated cardioprotection in ovariectomized rat. However, administration of glibenclamide along with or prior to ethylinestradiol abolished cardioprotection. Moreover, glibenclamide a KATP channel blocker, abolish cardioprotective effect of remote aortic preconditioning with daidzein a caveolin inhibitor (0.2 mg/kg subcutaneous). Ethylinestradiol significantly increased the release of nitric oxide and restored the attenuated cardioprotective effect of remote aortic preconditioning. These data provide the evidence that estrogen receptor activation involved in cardioprotective effect of remote aortic preconditioning-mediated trough opening of KATP channels.

Pharmacological connection of Histamine-1 (H1) Receptor Mediated Neuroprotective mechanism of Ischemic preconditioning in rat

Cerebral ischemia and ischemia-reperfusion is an essential contributor to acute cerebral stroke. Ischemic preconditioning (IPC) has been proven to provide neuroprotection in ischemia-reperfusion injury in rats, but their mechanism behind neuroprotection in cerebral stroke are still unclear. Central histaminergic pathway has crucial role in the pathogenesis of cerebral stroke, but their neuroprotective role in IPC is still unidentified. This research explores the role of histamine-1 receptor in IPC induced neuroprotection against ischemia-reperfusion induced cerebral injury. Rat were subjected to 17 min of global cerebral ischemia (GCI) by occluding both carotid arteries followed by reperfusion for 24 h, to produce ischemia-reperfusion induced cerebral injury. TTC staining was used to measure cerebral infarct size. Morris water maze test was used to assess memory. Inclined beam-walk, hanging wire, lateral push and rota-rod tests were used to assess degree of motor incoordination. Brain acetylcholinesterase activity, nitrite/nitrate, glutathione, TBARS and MPO levels were also examined. GCI has produced a significant increase in cerebral infarction, brain nitrite/nitrate, MPO, TBARS and AChE activity along with a reduction in glutathione content. Impairment of memory and motor coordination were also noted in GCI induced rat. IPC was employed that consist of 3 preceding episodes of ischemia (1 min) and reperfusion (1 min) both immediately before GCI significantly decreased cerebral infarction, motor incoordination, memory impairment and biochemical impairment. Pretreatment with L-histidine mimicked the neuroprotective effects of IPC. L-histidine induced neuroprotection were significantly abolished by chlorpheniramine, a H1 receptor antagonist. We conclude that neuroprotective effects of IPC, probably occurs through the central histaminergic pathway, and histamine-1 receptor could be a new target behind the neuroprotective mechanism of IPC.

Melatonin Treatment Does Not Modify Ectopic Activity During Ischemia and Reperfusion in Rats

Introduction Ventricular tachycardia and/or ventricular fibrillation (VT/VF), a life-threatening complication of acute myocardial ischemia are based on the interaction between a vulnerable arrhythmogenic substrate and an arrhythmic trigger. Melatonin was proposed as a potential antiarrhythmic medication and was shown to ameliorate the arrhythmogenic substrate. Also, melatonin provides a sympatholytic effect and thereby can attenuate ectopic activity, which provides the triggers for VT/VF. However, little is known about a melatonin effect on the arrhythmic triggering. In the present study, we aimed at evaluation of the melatonin effects on catecholamine synthesis in normal and ischemic myocardium and heart rhythm disturbances during an episode of ischemia and reperfusion. Methods Experiments were done in 30 control and 32 melatonin-treated (10 mg/kg, daily, for 7 days) male rats. The hearts from 10 control and 10 treated animals were taken for histochemical analysis of sympathetic fibers (glyoxylic acid-induced fluorescence). Continuous ECG recording was performed in 20 control and 22 treated anesthetized animals before and during an ischemia-reperfusion episode induced by reversible 5-min occlusion of the left anterior descending coronary artery. Tyrosine hydroxylase expression in normal and ischemic myocardial regions was assessed by Western blotting analysis in 12 control and 12 melatonin-treated animals. Results No differences in the state of sympathetic innervation (density and fluorescence intensity) were observed in histochemical analysis. However, Western blotting demonstrated that melatonin treatment suppressed tyrosine hydroxylase expression in normal (p<0.05 vs control) but not in ischemic regions of myocardium. Melatonin-treated animals had longer RR-intervals in the baseline state, but this difference progressively disappeared during the period of ischemia due to tachycardic response to ischemia in the treated group (Figure). No differences in the number of extrasystoles were found between the control and treated groups during ischemia and reperfusion periods (Figure). Conclusion Chronic melatonin treatment led to the peripheral sympatholytic effect in myocardium, which was associated with decreased heart rate in preischemic conditions. However, this effect attenuated during ischemia and no differences in heart rate or extrasystolic burden were found between the control and treated animals during ischemia and reperfusion.

Non-invasive in vivo human model of post-ischaemic skin preconditioning by measurement of flow-mediated 460-nm autofluorescence.

Transient ischaemia and reperfusion (TIAR) induce early ischaemic preconditioning (IPC) in different tissues and organs, including the skin. IPC protects tissues by modifying the mitochondrial function and decreasing the amount of the reduced form of nicotinamide adenine dinucleotide (NADH). Skin 460-nm autofluorescence is proportional to the NADH content and can be non-invasively measured during TIAR. We propose a non-invasive in vivo human model of skin IPC for studying the effects of repeated TIARs on the NADH content. Fifty-one apparently healthy volunteers (36 women) underwent three 100-second forearm ischaemia episodes induced by inflation of brachial pressure cuff to the pressure of 60 mmHg above systolic blood pressure, followed by 500-second long reperfusion episodes. Changes in skin NADH content were measured using 460-nm fluorescence before and during each of the three TIARs. The first two TIARs caused a significant reduction in the skin NADH content before (P = .0065) and during the third ischaemia (P = .0011) and reperfusion (P = .0003) up to 3.0%. During the third TIAR, the increase in skin NADH was 20% lower than during the first ischaemia (P = .0474). The measurement of the 460-nm fluorescence during repeated TIARs allows for a non-invasive in vivo investigation of human skin IPC. Although IPC reduces the overall NADH skin content, the most noticeable NADH reduction appears during ischaemia after earlier TIARs. Studying the skin model of IPC may provide new avenues for in vivo physiological, clinical and pharmacological research on mitochondrial metabolism.

Hypertrophic preconditioning cardioprotection after myocardial ischaemia/reperfusion injury involves ALDH2-dependent metabolism modulation

Brief episodes of ischaemia and reperfusion render the heart resistant to subsequent prolonged ischaemic insult, termed ischaemic preconditioning. Here, we hypothesized that transient non-ischaemic stress by hypertrophic stimulation would induce endogenous cardioprotective signalling and enhance cardiac resistance to subsequent ischaemic damage. Transient transverse aortic constriction (TAC) or Ang-Ⅱ treatment was performed for 3–7 days in male mice and then withdrawn for several days by either aortic debanding or discontinuing Ang-Ⅱ treatment, followed by subsequent exposure to regional myocardial ischaemia by in situ coronary artery ligation. Following ischaemia/reperfusion (I/R) injury, myocardial infarct size and apoptosis were markedly reduced and contractile function was significantly improved in the TAC preconditioning group compared with that in the control group. Similar results were observed in mice receiving Ang-Ⅱ infusion. Mechanistically, TAC preconditioning enhanced ALDH2 activity, promoted AMPK activation and improved mitochondrial energy metabolism by increasing myocardial OXPHOS complex expression, elevating the mitochondrial ATP content and improving viable myocardium glucose uptake. Moreover, TAC preconditioning significantly mitigated I/R-induced myocardial iNOS/gp91phox activation, inhibited endoplasmic reticulum stress and ameliorated mitochondrial impairment. Using a pharmacological approach to inhibit AMPK signalling in the presence or absence of preconditioning, we demonstrated AMPK-dependent protective mechanisms of TAC preconditioning against I/R injury. Furthermore, treatment with adenovirus-encoded ALDH2 partially emulated the actions of hypertrophic preconditioning, as evidenced by improved mitochondrial metabolism, inhibited oxidative stress-induced mitochondrial damage and attenuated cell death through an AMPK-dependent mechanism, whereas genetic ablation of ALDH2 abrogated the aforementioned actions of TAC preconditioning. The present study demonstrates that preconditioning with hypertrophic stress protects the heart from I/R injury via mechanisms that improve mitochondrial metabolism, reduce oxidative/nitrative stress and inhibit apoptosis. ALDH2 is obligatorily required for the development of cardiac hypertrophic preconditioning and acts as the mediator of this process.

Evaluation of brain changes in systemic sclerosis (SSc) patients using two different techniques of MRI: Is it really worthy?

BackgroundSystemic sclerosis (SSc) is a rare chronic multi-system autoimmune disease of unknown cause and a complex pathogenesis. The hallmark of the disease is microvascular vasculopathy which results in tissue ischemia with recurrent episodes of reperfusion. Diffusion-weighted (DW) Magnetic Resonance imaging (MRI) is an excellent tool for the detection of activity of any vascular or inflammatory lesions. ObjectivesDetect brain changes in systemic sclerosis patients with asymptomatic CNS manifestations using fluid attenuation inversion recovery (FLAIR) weighted sequence and diffusion-weighted (DW) sequence MRI. MethodsFifteen systemic sclerosis female patients aged 27–60 years old with disease duration of 1–20 years with no CNS clinical manifestations were included. A controlled group of 14 clinically normal persons, age and sex matched. Both groups were subjected to brain MR examination at 1.5T; a FLAIR weighted sequence and a DW sequence. SPSS (version 20) was used for statistical analysis. Results37 white matter hyperintense lesions (≤2 to ≥ 5mm in diameter) were detected in patient group using FLAIR weighted MRI while diffusion-weighted MRI failed to detect the same lesions. A non-significant relation (P=.259) between the presence of white matter hyperintense lesions and the severity of peripheral vascular affection of the disease was observed. ConclusionsAsymptomatic central nervous system vasculopathy is detected in systemic sclerosis using FLAIR MRI, while diffusion MRI failed to detect such lesions. These findings suggest a non-inflammatory form of central nervous system microvasculopathy in SSc patients.

Risk of major cardiovascular and cerebrovascular complications after elective surgery in patients with sleep-disordered breathing: A retrospective cohort analysis.

There is limited and conflicting data on whether sleep-disordered breathing (SDB) is associated with postoperative major cardiovascular and cerebrovascular events (MACCE), and mortality. To determine whether SDB is associated with increased risks of MACCE, mortality and length of hospital stay. Retrospective cohort analysis from the Nationwide Inpatient Sample. Adults who underwent elective abdominal, orthopaedic, prostatic, gynaecological, thoracic, transplant, vascular or cardiac surgery in the United States of America between 2011 and 2014. The study cohort included 1813 974 surgical patients, of whom 185 615 (10.2%) had SDB. Emergency or urgent surgical procedures were excluded. The incidences of MACCE, respiratory and vascular complications, in-hospital mortality and mean length of hospital stay were stratified by SDB. Linear and logistic regression models were constructed to determine the independent association between SDB and outcomes of interest. The incidences of MACCE [25.3 vs. 19.8%, odds ratio (OR) 1.20, P < 0.001] and respiratory complications (11.75 vs. 8.0%, OR 1.43, P < 0.001) were significantly higher in patients with SDB than in those without SDB. SDB was associated with higher rates of atrial fibrillation (14.7 vs. 10.8%, P < 0.001), other arrhythmias (6.0 vs. 5.4%, P < 0.001) and congestive heart failure (9.8 vs. 7.1%, P < 0.001). SDB patients had a lower rate of myocardial infarction (3.1 vs. 3.4%, OR 0.69, P < 0.001), lower mortality (0.6 vs. 1.3%, P < 0.001) and shorter length of hospital stay (4.8 vs. 5.2 days, P < 0.001). SDB was associated with increased risks of MACCE, and respiratory and vascular complications, but had a lower incidence of in-hospital mortality and shorter length of hospital stay.

Exploring the role of neurogenic pathway-linked cholecystokinin release in remote preconditioning-induced cardioprotection.

Purpose:The current study explored the involvement of neurogenic pathway-linked cholecystokinin (CCK) release in RIP-induced cardioprotection in rats.Methods:Male Wistar rats were subjected to four cycles of alternate episodes of ischemia and reperfusion (five min each) to induce RIP. Thereafter, the hearts were subjected to global ischemia and reperfusion ex vivo. The myocardial damage was assessed by quantifying the levels of heartspecific biochemicals i.e. LDH-1, CK-MB and cTnT. Apoptotic cell injury was assessed by measuring the levels of caspase-3 and Bcl-2. The levels of CCK were measured in the plasma following RIP.Results:Exposure to RIP significantly increased the plasma levels of CCK and attenuated IR-induced myocardial injury. Administration of CCK antagonist, proglumide significantly attenuated RIP-induced cardioprotection. Administration of hexamethonium, a ganglion blocker, abolished RIP-induced increase in plasma CCK levels and cardioprotective effects. Exogenous delivery of CCK-8 restored the effects of RIP in hexamethonium treated animals.Conclusion:RIP activates the neurogenic pathway that may increase the plasma levels of CCK, which may act on the heart-localized CCK receptors to produce cardioprotection against I/R injury.

Remote ischemic preconditioning in patients undergoing coronary bypass grafting following acute coronary syndrome without ST elevation

Background/Aim. A protection of heart and other organs from ischemic-reperfusion injuries can be provided by remote ischemic preconditioning (RIPC) by brief episodes of ischemia and reperfusion in distant tissues. The aim of this study was to assess effects of RIPC on early outcomes in patients underwent coronary bypass surgery (CABG) following acute coronary syndrome without persistent ST segment elevation (NSTEMI ACS). Methods. This trial included 42 patients randomized into two groups: the group 1 received RIPC and the group 2 was without RIPC (control group). Pre-, intra- and postoperative parameters were compared but primary endpoint was myocardial injury reflected as value of troponin I measured preoperatively and 1, 6, 12, 24, 48 and 72 h postoperatively. The secondary endpoints were hemodynamic parameters, blood loss, intensive care unit stay, mortality etc. Results. The groups 1 and 2 were similar in preoperative characteristics including age, New York Heart Association (NYHA) class, EuroSCORE II, left ventricular ejection fraction. The only significant difference between groups was for triple vessel coronary disease with dominance in the RIPC group [20 (100%) vs. 17 (77.3%), p = 0.049]. Cardiopulmonary bypass time [mean (? standard deviation): 83.0 (22.9) vs. 67.0 (17.4) minutes, p = 0.015], cross clamp time [57.9 (15.4) vs. 44.3 (14.3) minutes, p = 0.005] and number of conduits [median (25?75th percentile): 23.5(3?4) vs. 3(2?3), p = 0.002] were different. Other intra- and postoperative variables did not differ between groups. There were no differences in C reactive protein levels and postoperative hemodynamic parameters. Average troponin values in all time points revealed no significant differences between groups (p0h = 0.740, p1h = 0.212, p6h = 0.504, p12h = 0.597, p24h = 0.562, p48h = 0.465 and p72h = 0.715, respectively). Furthermore, there were no significant differences in adverse events, hospital stay and mortality between groups. Conclusion. Treatment with RIPC during CABG following NSTEMI ACS did not provide better myocardial protection and hemodynamics characteristics but further larger randomized studies are needed t. prove its real value.

The Rise of Mitochondria in Peripheral Arterial Disease Physiopathology: Experimental and Clinical Data.

Peripheral arterial disease (PAD) is a frequent and serious condition, potentially life-threatening and leading to lower-limb amputation. Its pathophysiology is generally related to ischemia-reperfusion cycles, secondary to reduction or interruption of the arterial blood flow followed by reperfusion episodes that are necessary but also—per se—deleterious. Skeletal muscles alterations significantly participate in PAD injuries, and interestingly, muscle mitochondrial dysfunctions have been demonstrated to be key events and to have a prognosis value. Decreased oxidative capacity due to mitochondrial respiratory chain impairment is associated with increased release of reactive oxygen species and reduction of calcium retention capacity leading thus to enhanced apoptosis. Therefore, targeting mitochondria might be a promising therapeutic approach in PAD.

Evaluation of brain changes in systemic sclerosis (SSc) patients using two different techniques of MRI: Is it really worthy?

Systemic sclerosis (SSc) is a rare chronic multi-system autoimmune disease of unknown cause and a complex pathogenesis. The hallmark of the disease is microvascular vasculopathy which results in tissue ischemia with recurrent episodes of reperfusion. Diffusion-weighted (DW) Magnetic Resonance imaging (MRI) is an excellent tool for the detection of activity of any vascular or inflammatory lesions. Detect brain changes in systemic sclerosis patients with asymptomatic CNS manifestations using fluid attenuation inversion recovery (FLAIR) weighted sequence and diffusion-weighted (DW) sequence MRI. Fifteen systemic sclerosis female patients aged 27-60 years old with disease duration of 1-20 years with no CNS clinical manifestations were included. A controlled group of 14 clinically normal persons, age and sex matched. Both groups were subjected to brain MR examination at 1.5T; a FLAIR weighted sequence and a DW sequence. SPSS (version 20) was used for statistical analysis. 37 white matter hyperintense lesions (≤2 to ≥ 5mm in diameter) were detected in patient group using FLAIR weighted MRI while diffusion-weighted MRI failed to detect the same lesions. A non-significant relation (P=.259) between the presence of white matter hyperintense lesions and the severity of peripheral vascular affection of the disease was observed. Asymptomatic central nervous system vasculopathy is detected in systemic sclerosis using FLAIR MRI, while diffusion MRI failed to detect such lesions. These findings suggest a non-inflammatory form of central nervous system microvasculopathy in SSc patients.

Remote Ischemic Preconditioning Has No Short Term Effect on Blood Pressure, Heart Rate, and Arterial Stiffness in Healthy Young Adults.

ObjectiveRemote ischemic preconditioning (RIPC) are short episodes of ischemia and reperfusion applied to remote tissue to trigger responses in a specific organ or cardiovascular bed. This study investigates whether RIPC has a short-term effect on blood pressure (BP), heart rate, and arterial stiffness.Patients and MethodsFrom March 2018 to August 2018, we included 40 healthy volunteers (23 female, age 25.6 ± 2.8 years) into this single-blinded randomized-controlled crossover trial. After measuring BP, heart rate, and arterial stiffness in supine position participants were randomized into intervention or SHAM group. The intervention group then underwent a RIPC protocol (3 cycles of 5 min of 200 mmHg ischemia followed by 5 min reperfusion) at the thigh. The SHAM group followed the same protocol just on the upper arm with 40 mmHg pressure inflation. Directly after this 30-min procedure a reassessment of hemodynamic measures was conducted.ResultsThere were no significant changes in all five outcome parameters when comparing the effect of RIPC to SHAM. In peripheral systolic BP the mean difference between groups was Δ1.14 ± 6.5 mmHg (p = 0.672), and for diastolic BP Δ−0.69 ± 4.5 mmHg (p = 0.507). Heart rate shoed a Δ−0.8 ± 4.7 beats/min (p = 0.397). Regarding arterial stiffness measures, there was also no significant improvements thru RIPC. The mean difference between RIPC and SHAM for central systolic BP was Δ0.40 ± 7.2 mmHg (p = 0.951) and for PWV Δ0.01 ± 0.26 m/s (p = 0.563).ConclusionThis study could not find any short-term effects of RIPC on arterial stiffness, BP, and heart rate in a RCT in young healthy adults.

Possible involvement of Opioid like Receptor1 (ORL1) Receptor in Ischemic Preconditioning Induced Protection in Rat Brain

Opioid receptor like 1 receptor (ORL1) is a family of G-protein coupled receptor, reported to produce cardio-protection against ischemia- reperfusion induced injury in rat heart. The present study has been designed to investigate the role of ORL1 receptor in ischemic preconditioning (IPC) induced protection in rat brain. IPC was induced by giving 3 episodes of ischemia and reperfusion. Global ischemia for 17 min was given by occlusion of carotid artery followed by 24hr of reperfusion. Memory was assessed by measuring escape latency time (ELT) for consecutively 4 days and time spent in target quadrant (TSTQ) was measured on 5th day by using morrish water maze. IPC significantly decrease in infarct size and improvement in memory as compared to ischemia/reperfusion (I/R) in control group. Pretreatment with JTC-801(1mg/kg, i.p.), a selective ORL1 receptor antagonist or Glibenclamide (1mg/kg, i.p.), the KATP channel blocker significantly reduce the amplitude of IPC induced cerebroprotection measured in terms of infarct size and positively affects the memory measured in terms of time spent in target quadrant (TSTQ) at 5th day as compare to IPC group. The cerebroprotective effect of IPC was significantly attenuated in JTC-801 and Glibenclamide in combination as compare to Ischemic preconditioning (IPC) group and treated group (Glibenclamide). These results may indicate that cerebroprotective effect of IPC of brain and improvement of memory mediated through ORL1 receptor and activation of KATP channels. Keywords: Opioid receptor like1 receptor, ischemic preconditioning, JTC-801, latency time