Role of ATP-Sensitive Potassium Channels in Remote Ischemic Preconditioning Induced Tissue Protection

2017 ◽  
Vol 22 (5) ◽  
pp. 467-475 ◽  
Author(s):  
Sapna Aggarwal ◽  
Puneet Kaur Randhawa ◽  
Nirmal Singh ◽  
Amteshwar Singh Jaggi

Remote ischemic preconditioning (RIPC) is an innovative treatment strategy that alleviates ischemia-reperfusion injury, whereby short episodes of regional ischemia and reperfusion delivered to remote organs including hind limb, kidney and intestine, and so on provide protection to the heart. The RIPC is known to reduce infarct size, serum levels of cardiac enzymes, and myocardial dysfunction in various animal species as well as in patients. There have been a large number of studies suggesting that the ATP-sensitive potassium channels (KATP channel) play a significant role as a mediator or end effector in RIPC. The present review discusses the role of KATP channels and possible mechanisms in RIPC-induced cardioprotection.

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
M S Abdelhamid ◽  
R S Mansour ◽  
A T Ebrahim ◽  
B M Elkafoury

Abstract Background Inspite of the claimed cardio-protective effects of ischemic preconditioning (IPC), it is invasive and so using remote ischemic preconditioning (RIPC) may offer an alternative. Meanwhile, RIPC cardioprotective role is controversial, with an equivocal underlying mechanism. The hypoxia inducible factor 1 alpha (HIF-1-alpha) which is increased following ischemic insults is claimed as a humoral mediator for RIPC. Objective To investigate the effect of remote ischemic pre-conditioning on myocardial ischemia/reperfusion injury in rats, and to elucidate the possible role of hypoxia inducible factor in this protection. Materials and Methods The present study was performed on 28 adult female albino rats in the same estrus cycle evaluated by vaginal smear, and they were allocated into 3 groups: Group I: control rats subjected to ischemic/reperfusion injury (I/R) only, group II: early RIPC rats (RIPC 2 hours prior to I/R), group III: acriflavine-treated early RIPC rats. Acriflavine is a drug that binds directly to HIF-1 alpha and HIF-2 alpha subunits, thus inhibiting its dimerization and transcriptional activity, and it was injected IP 10 days prior to RIPC. On sacrifice day, ECG was recorded and isolated heart studies were performed. Later, cardiac chambers weight, serum HIF-1-alpha, myocardial perfusate lactate dehydrogenase, and cardiac oxidative markers: Malonaldehyde and glutathione perioxidase were measured. Results Compared to the control group, the early RIPC group showed significant increase in the heart rate (HR), QTc interval in the ECG recording, glutathione peroxidase and the HIF 1α levels together with reduction in the percent of decrease in PT and PT/LV, in the percent of prolongation in time to peak tension (TPT), perfusate lactate dehydrogenase and MDA levels, while no significant changes were recorded in the heart chronotropic activity, in the percent of half relaxation time (HRT) prolongation, or in the percent of decrease of MFR. Following acriflavine treatment, the effects of RIPC were abolished highlighting the role of HIF-1-alpha in mediating RIPC protective effects. Conclusion The non-invasive and non-pharmological remote ischemic preconditioning technique can ameliorate the cardiac ischemic reperfusion injury with an obvious role of HIF-1α in mediating these protective effects.


2017 ◽  
Vol 32 (7) ◽  
pp. 559-567 ◽  
Author(s):  
Teresinha Regina Ribeiro de Oliveira ◽  
Geraldo Ferreira de Oliveira ◽  
Ricardo Santos Simões ◽  
Eduardo Hiroshi Tikazawa ◽  
Hugo Pequeno Monteiro ◽  
...  

2011 ◽  
Vol 300 (2) ◽  
pp. H522-H526 ◽  
Author(s):  
Michael D. Goodman ◽  
Sheryl E. Koch ◽  
Muhammad R. Afzal ◽  
Karyn L. Butler

The role of other STAT subtypes in conferring ischemic tolerance is unclear. We hypothesized that in STAT-3 deletion alternative STAT subtypes would protect myocardial function against ischemia-reperfusion injury. Wild-type (WT) male C57BL/6 mice or mice with cardiomyocyte STAT-3 knockout (KO) underwent baseline echocardiography. Langendorff-perfused hearts underwent ischemic preconditioning (IPC) or no IPC before ischemia-reperfusion. Following ex vivo perfusion, hearts were analyzed for STAT-5 and -6 phosphorylation by Western blot analysis of nuclear fractions. Echocardiography and postequilibration cardiac performance revealed no differences in cardiac function between WT and KO hearts. Phosphorylated STAT-5 and -6 expression was similar in WT and KO hearts before perfusion. Contractile function in WT and KO hearts was significantly impaired following ischemia-reperfusion in the absence of IPC. In WT hearts, IPC significantly improved the recovery of the maximum first derivative of developed pressure (+dP/d tmax) compared with that in hearts without IPC. IPC more effectively improved end-reperfusion dP/d tmax in WT hearts compared with KO hearts. Preconditioned and nonpreconditioned KO hearts exhibited increased phosphorylated STAT-5 and -6 expression compared with WT hearts. The increased subtype activation did not improve the efficacy of IPC in KO hearts. In conclusion, baseline cardiac performance is preserved in hearts with cardiac-restricted STAT-3 deletion. STAT-3 deletion attenuates preconditioning and is not associated with a compensatory upregulation of STAT-5 and -6 subtypes. The activation of STAT-5 and -6 in KO hearts following ischemic challenge does not provide functional compensation for the loss of STAT-3. JAK-STAT signaling via STAT-3 is essential for effective IPC.


2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Mehmet Balin ◽  
Tarık Kıvrak

Background/Objective. Intermittent claudication (IC) is the symptom of peripheral artery disease (PAD) and causes functional disability. Remote ischemic preconditioning (RIPC), is a phenomenon in which a short period of sub-critical ischemia, protects tissues against ischemia/reperfusion/injury. We considered to test the hypothesis that RIPC in PAD patients suffering from IC would increase muscle resistance to ischemia and thus improve walking-capacity. Materials/Methods. A total of 63 patients with proven-IC underwent two treadmill tests (graded treadmill protocol) with a 28-day interval in between. Patients were consecutively assigned for the non/RIPC-group and RIPC-group procedure one by one. Patients received 5-cycles of alternating 5-minute inflation and 5-minute deflation of blood-pressure cuffs on nondominant upper-limb every day for four weeks. Initial claudication distance (ICD), total walking distance (TWD) and time to relief of claudication (TRC) were recorded during procedure. Results. Patients receiving-RIPC exhibited a marked increase in ICD and TWD between basal and last tests: 209.1 ± 15.4 m vs. 226 ± 15.0 m and 368.8 ± 21.0 m vs. 394 ± 19.9 m, respectively (p<0.001). In addition, patients receiving-RIPC represented a significant decrease in TRC between basal and last tests: 7.8 ± 1.3 min vs. 6.4 ± 1.1 min, respectively (p<0.001). Patients not receiving-RIPC did not exhibit improvement in ICD, TWD, and TRC between basal and last tests: 205.2 ± 12.1 min vs. 207.4 ± 9.9 min, 366.5 ± 24.2 min vs. 369.4 ± 23.2 min and 7.9 ± 1.4 min vs. 7.7 ± 1.3 min, respectively (p>0.05). Conclusion. A significant increase in ICD and TWD were observed in last/treadmill test in RIPC-group. In addition, a significant decrease in TRC was observed in last/treadmill test in RIPC-group. In non/RIPC-group, no improvement was observed in ICD, TWD and TRC.


2020 ◽  
Vol 76 (3) ◽  
pp. 439-451
Author(s):  
Gabor Varga ◽  
Souleiman Ghanem ◽  
Balazs Szabo ◽  
Kitti Nagy ◽  
Noemi Pal ◽  
...  

BACKGROUND: The optimal timing of remote ischemic preconditioning (RIPC) in renal ischemia-reperfusion (I/R) injury is still unclear. We aimed to compare early- and delayed-effect RIPC with hematological, microcirculatory and histomorphological parameters. METHODS: In anesthetized male CrI:WI Control rats (n = 7) laparotomy and femoral artery cannulation were performed. In I/R group (n = 7) additionally a 45-minute unilateral renal ischemia with 120-minute reperfusion was induced. The right hind-limb was strangulated for 3×10 minutes (10-minute intermittent reperfusion) 1 hour (RIPC-1 group, n = 7) or 24 hour (RIPC-24 group, n = 6) prior to the I/R. Hemodynamic, hematological parameters and organs’ surface microcirculation were measured. RESULTS: Control and I/R group had the highest heart rate (p < 0.05 vs base), while the lowest mean arterial pressure (p < 0.05 vs RIPC-1) were found in the RIPC-24 group. The highest microcirculation values were measured in the I/R group (liver: p < 0.05 vs Control). The leukocyte count increased in I/R group (base: p < 0.05 vs Control), also this group’s histological score was the highest (p < 0.05 vs Control). The RIPC-24 group had a significantly lower score than the RIPC-1 (p = 0.0025 vs RIPC-1). CONCLUSION: Renal I/R caused significant functional and morphological, also in the RIPC groups. According to the histological examination the delayed-effect RIPC method was more effective.


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