Effects Of IPC Research Articles

Ischemic Preconditioning and Postconditioning Protect the Heart by Preserving the Mitochondrial Network.

Background Mitochondria fuse to form elongated networks which are more tolerable to stress and injury. Ischemic pre- and postconditioning (IPC and IPost, respectively) are established cardioprotective strategies in the preclinical setting. Whether IPC and IPost modulates mitochondrial morphology is unknown. We hypothesize that the protective effects of IPC and IPost may be conferred via preservation of mitochondrial network. Methods IPC and IPost were applied to the H9c2 rat myoblast cells, isolated adult primary murine cardiomyocytes, and the Langendorff-isolated perfused rat hearts. The effects of IPC and IPost on cardiac cell death following ischemia-reperfusion injury (IRI), mitochondrial morphology, and gene expression of mitochondrial-shaping proteins were investigated. Results IPC and IPost successfully reduced cardiac cell death and myocardial infarct size. IPC and IPost maintained the mitochondrial network in both H9c2 and isolated adult primary murine cardiomyocytes. 2D-length measurement of the 3 mitochondrial subpopulations showed that IPC and IPost significantly increased the length of interfibrillar mitochondria (IFM). Gene expression of the pro-fusion protein, Mfn1, was significantly increased by IPC, while the pro-fission protein, Drp1, was significantly reduced by IPost in the H9c2 cells. In the primary cardiomyocytes, gene expression of both Mfn1 and Mfn2 were significantly upregulated by IPC and IPost, while Drp1 was significantly downregulated by IPost. In the Langendorff-isolated perfused heart, gene expression of Drp1 was significantly downregulated by both IPC and IPost. Conclusion IPC and IPost-mediated upregulation of pro-fusion proteins (Mfn1 and Mfn2) and downregulation of pro-fission (Drp1) promote maintenance of the interconnected mitochondrial network, ultimately conferring cardioprotection against IRI.

Changes in Cyclin D1, cdk4, and Their Associated Molecules in Ischemic Pyramidal Neurons in Gerbil Hippocampus after Transient Ischemia and Neuroprotective Effects of Ischemic Preconditioning by Keeping the Molecules in the Ischemic Neurons.

Simple SummaryCyclin D1 and cyclin-dependent kinase 4 (cdk4) is implicated in neuronal death induced by various pathological conditions. Ischemic preconditioning (IPC) confers neuroprotective effect, but underlying mechanisms have been poorly addressed. In this study, IPC protected pyramidal neurons (cells) in gerbil hippocampus after transient ischemia. Additionally, IPC controlled expressions of cyclin D1, cdk4, phosphorylated retinoblastoma (p-Rb), and E2 promoter binding factor 1 (E2F1). In particular, the expression of p16INK4a was not different by IPC. These findings indicate that cyclin D1/cdk4-related signals may play important roles in events in neurons related to damage/death following ischemic insults. Especially, the preservation of p16INK4a by IPC may be crucial in attenuating neuronal death/damage or protecting neurons after brain ischemic insults.Inadequate activation of cell cycle proteins including cyclin D1 and cdk4 is involved in neuronal cell death induced by diverse pathological stresses, including transient global brain ischemia. The neuroprotective effect of ischemic preconditioning is well-established, but the underlying mechanism is still unknown. In this study, we examined changes in cyclin D1, cdk4, and related molecules in cells or neurons located in Cornu Ammonis 1 (CA1) of gerbil hippocampus after transient ischemia for 5 min (ischemia and reperfusion) and investigated the effects of IPC on these molecules after ischemia. Four groups were used in this study as follows: sham group, ischemia group, IPC plus (+) sham group, and IPC+ischemia group. IPC was developed by inducing 2-min ischemia at 24 h before 5-min ischemia (real ischemia). Most pyramidal cells located in CA1 of the ischemia group died five days after ischemia. CA1 pyramidal cells in the IPC+ischemia group were protected. In the ischemia group, the expressions of cyclin D1, cdk4, phosphorylated retinoblastoma (p-Rb), and E2F1 (a transcription factor regulated by p-Rb) were significantly altered in the pyramidal cells with time after ischemia; in the IPC+ischemia group, they were controlled at the level shown in the sham group. In particular, the expression of p16INK4a (an endogenous cdk inhibitor) in the ischemia group was reversely altered in the pyramidal cells; in the IPC+TI group, the expression of p16INK4a was not different from that shown in the sham group. Our current results indicate that cyclin D1/cdk4-related signals may have important roles in events in neurons related to damage/death following ischemia and reperfusion. In particular, the preservation of p16INK4a by IPC may be crucial in attenuating neuronal death/damage or protecting neurons after brain ischemic insults.

Intermittent pneumatic compression after varicose vein surgery

ObjectiveIntermittent pneumatic compression (IPC) is an established treatment option to remove tissue fluid from patients with lymphedema and chronic venous disease. The effects of IPC applied directly after varicose vein surgery performed with high volumes of tumescent local anesthesia have not been investigated. The aim of the present study was to evaluate the use of postoperative IPC concerning its effects on the leg volume and patient comfort after surgery. MethodsWe performed an investigator-initiated, single-center, open-label randomized controlled trial. A total of 186 patients indicated for saphenofemoral junction ligation and great saphenous vein or anterior accessory saphenous vein stripping or great saphenous vein redo surgery were randomly assigned 1:1 to the intervention or control group. The patients in the intervention group were treated with IPC at 40 mm Hg for 45 minutes directly after surgery. The outcome measures were the leg volume changes calculated using an optical three-dimensional scanning system (primary objective), quality of life (QoL; Freiburg Life Quality Assessment for chronic venous disease, short form), pain, and extent of ecchymosis with follow-up examinations on days 1 and 7 after surgery. ResultsThe patients in both groups had comparable mean leg volume reductions from baseline to day 1 (IPC group, 58.8 mL; control group, 37.4 mL; P = .967) and to day 7 (63.1 mL and 57.0 mL, respectively; P = .546). We also did not observe significant differences between the two groups in QoL and pain. The patients in the IPC group had developed larger areas of ecchymosis compared with the control group (16% vs 13.3% of leg surface, respectively; P = .046), with a tendency toward an increase in pain at 7 days after surgery compared with no IPC application. ConclusionsThe present randomized controlled trial was designed to evaluate the decongestive effects of a single postoperative session of IPC and its effect on QoL, pain, and ecchymosis in patients who had undergone varicose vein surgery under tumescent local anesthesia. Because no evidence for a benefit from IPC could be found in the present study and increased ecchymosis was found, its standard use after varicose vein surgery cannot be recommended.

Effects of Ischemic Preconditioning as a Warm-Up on Leg Press and Bench Press Performance.

Ischemic preconditioning (IPC) has been used to increase performance in sports. The aim of this study was to compare the acute effects of IPC with different warm-up methods on the number of repetitions and total volume in resistance exercise (RE). Sixteen healthy men recreationally trained in RE participated in this study. After the anthropometric evaluation and familiarization, a one-repetition maximum (1RM) test and retest were performed in the bench press (BP) and in the leg press 45° (LP) exercise. After these tests, participants were randomly assigned to one of the five protocols: a) IPC; b) SHAM; c) a specific warm-up (SW); d) aerobic exercise (AE), and e) active stretching (AS) prior to performing 3 sets at 80% 1RM until concentric failure. The number of repetitions was higher following IPC compared to the SW following three sets both for the BP and LP. Similarly, the number of repetitions for IPC was higher in comparison to SHAM following three sets for the LP. The number of repetitions was higher following IPC compared to AE following 1st and 2nd sets for the LP and following the 2nd set for the BP. Finally, the number of repetitions was higher following IPC compared to AS following 1st and 2nd sets for the LP. The total volume was higher following IPC compared to SHAM, SW, AE, and AS for both the BP and LP. The IPC protocol increased the number of maximum repetitions and the total volume when compared to the other tested methods, thus indicating a better utilization during the pre-work warm-up. These results indicate positive associative responses to IPC with performance maintenance, which is of importance for both athletes and coaches.

Sex differences in fatigability after ischemic preconditioning of non-exercising limbs

BackgroundIschemic preconditioning (IPC) is suggested to decrease fatigability in some individuals but not others. Sex differences in response to IPC may account for this variability and few studies systematically investigated the effects of IPC in men and women. The goal of this study was to determine if time to task failure, perception of pain, and neuromuscular mechanisms of fatigability were altered by IPC in men and women.MethodsTen women (29 ± 5 years old) and 10 men (28 ± 6 years old) performed isometric contractions with the plantar flexor muscles of the dominant leg at 20% of maximal voluntary contraction until task failure. We used a repeated measures design where each individual performed 3 randomized and counterbalanced test sessions: (A) IPC session, cuff inflation and deflation (5 min each repeated 3 times) performed before the exercise by inflating cuffs to the non-dominant leg and arm; (B) sham session, cuffs were inflated for a short period (1 min); and (C) control session, no cuffs were involved.ResultsCompared with control, IPC increased time to task failure in men (mean difference, 5 min; confidence interval (CI) of mean difference, 2.2; 7.8 min; P = 0.01) but not women (mean difference, − 0.6 min; CI of mean difference, − 3.5; 2.4 min; P = 0.51). In men, but not women, the IPC-induced increase in time to task failure was associated with lower response to pressure pain (r = − 0.79). IPC further exposed sex differences in arterial pressure during fatiguing contractions (session × sex: P < 0.05). Voluntary activation, estimated with the twitch interpolation technique, and presynaptic inhibition of leg Ia afferents were not altered after IPC for men and women. The tested variables were not altered with sham.ConclusionsThe ergogenic effect of IPC on time to task failure was observed only in men and it was associated with reductions in the perception of pain. This pilot data suggest the previously reported inter-individual variability in exercise-induced fatigability after IPC could be a consequence of the sex and individual response to pain.

P0550ISCHEMIC PRECONDITIONING ATTENUATES RENAL ISCHEMIA-REPERFUSION INJURY THROUGH ACTIVATING THE NRF2/HO-1 PATHWAY ENHANCED AUTOPHAGY

Abstract Background and Aims Ischemic preconditioning (IPC), which is a brief and nonlethal episode of ischemia, confers protection against subsequent ischemia-reperfusion (I/R) through the up-regulation of endogenous protective mechanisms. Recent studies have reported that the activation of autophagy is associated with IPC. However, the underlying mechanisms still need to be determined. In this study, we investigated the role of IPC in renal I/R injury and demonstrated that IPC could ameliorate renal I/R injury by activating the Nrf2/HO-1 pathway and induction of autophagy. Method In order to gain insights into IPC–induced alterations at the cellular level, an in vitro model for IPC was designed using the human proximal tubule epithelial cell line HK-2. In vitro I/R was induced by layering mineral oil (for 60 min) over a thinfilm of media covering the cells followed by 120 min of reperfusion in normal media. IPC was performed by a 10-min period of incubation of cells under mineral oil followed by a 30-min recovery period prior to the 120 min reperfusion. To further determine the role of autophagy in IPC-induced renoprotection, the cells were treated with bafilomycin A1 (200 nM), prior to I/R injury. In a renal I/R injury model, mice were subjected to 30 min of renal ischemia followed by 24 h of reperfusion. IPC was produced by 5 min of ischemia followed by 10 min of reperfusion prior to sustained ischemia. Results We found that IPC significantly attenuated I/R-induced kidney injury and suppressed oxidative stress and inflammatory responses. IPC also increased LC3-II and decreased SQSTM/p62 and cleaved caspase-3 during renal I/R injury, as well as increased the number of intracellular double-membrane vesicles in injured renal cells. IPC-induced renal protection was efficiently attenuated by pretreatment with Bafilomycin A1 (0.3 mg/kg, IP). Pretreatment with IPC also dynamically affected the expression of Nrf2/HO-1 signaling components. The beneficial effects of IPC were abolished by Brusatol (2 mg/kg, IP), potent inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ (50 mg/kg, IP) showed similar activity as IPC. Conclusion In summary, the present study shows that Nrf2 plays a critical role in regulating the HO-1 production induced by I/R. Also, upregulation of Nrf2 expression might represent one of the major mechanisms whereby IPC confers protection against I/R-induced kidney injury. The beneficial effects of IPC could be attributed to its antioxidative stress and anti-inflammatory properties

Haematological Effects of Intermittent Pneumatic Compression for Deep Vein Thrombosis Prophylaxis.

Intermittent pneumatic compression (IPC) is a widely used and recommended method to prevent deep vein thrombosis. While the haemodynamic effects of IPC are well understood, the objective of this systematic review was to analyse the evidence for additional haematological changes. Forty-eight studies were identified where the haematological effects of IPC were measured. The many differences between the studies prevented meta-analysis, but there was a significant amount of evidence that global fibrinolytic activity was increased by IPC, and that levels of D-dimer and tissue factor pathway inhibitor in the blood also increased. There was less consistent evidence for changes in tissue plasminogen activator, plasminogen activator inhibitor and other fibrinolytic parameters. The evidence for changes in pro-coagulant factors and many measures of platelet activation was weak, but there was evidence for increases in prostacyclin. There is sufficient evidence to conclude that IPC does produce haematological changes, but not enough data to clarify the detail of those changes or to determine if it is mediated more by direct compression of the blood vessels, or by the flow changes.

Ischemic Preconditioning Improves Strength Endurance Performance.

Carvalho, L and Barroso, R. Ischemic preconditioning improves strength endurance performance. J Strength Cond Res 33(12): 3332-3337, 2019-Ischemic preconditioning (IPC) has been used to improve performances in aerobic and anaerobic activities. However, a few studies aimed at observing the effects of IPC on resistance training. The purpose of this study is to examine the effects of IPC on the number of repetitions performed during high-load resistance training. We also aimed at investigating blood lactate concentration and muscle activation in an attempt to understand the physiological mechanisms that may be caused by IPC. Ten resistance-trained participants performed four 5-minute cycles of either IPC (250 mm Hg) or Placebo (10 mm Hg) before performing a single set to failure of knee extension exercise with 85% of 1 repetition maximum. We also assessed muscle activation during the set (EMGRMS), median power frequency (EMGMPF), and blood lactate concentration before, 3, 7, and 11 minutes after (peak value was identified and used to calculate delta to prevalues, Δlactate). Data are presented as mean, 90% confidence intervals (CIs), and were analyzed with paired t-test. The level of significance was set at p < 0.05. Participants performed on average 3.9 repetitions (90% CI = 2.4-5.4; p = 0.01), which is ∼20%, more in the IPC condition. There were no significant differences between IPC and Placebo for EMGMPF (5.0%; 90% CI = -5.2 to 15; p = 0.50), EMGRMS (4.5%; 90% CI = -8.8 to 17; p = 0.78), and Δlactate (44%; 90% CI = 11-144; p = 0.16). Our results demonstrate the effect of IPC just on the number of repetitions performed in high-load resistance exercise compared with the Placebo condition.

Macrophage migration inhibitory factor plays an essential role in ischemic preconditioning-mediated cardioprotection.

Ischemic preconditioning (IPC) is an endogenous protection strategy against myocardial ischemia-reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF) released from the myocardium subjected to brief periods of ischemia confers cardioprotection. We hypothesized that MIF plays an essential role in IPC-induced cardioprotection. I/R was induced either ex vivo or in vivo in male wild-type (WT) and MIF knockout (MIFKO) mice with or without proceeding IPC (three cycles of 5-min ischemia and 5-min reperfusion). Indices of myocardial injury, regional inflammation and cardiac function were determined to evaluate the extent of I/R injury. Activations of the reperfusion injury salvage kinase (RISK) pathway, AMP-activated protein kinase (AMPK) and their downstream components were investigated to explore the underlying mechanisms. IPC conferred prominent protection in WT hearts evidenced by reduced infarct size (by 33-35%), myocyte apoptosis and enzymatic markers of tissue injury, ROS production, inflammatory cell infiltration and MCP1/CCR2 expression (all P<0.05). IPC also ameliorated cardiac dysfunction both ex vivo and in vivo These protective effects were abolished in MIFKO hearts. Notably, IPC mediated further activations of RISK pathway, AMPK and the membrane translocation of GLUT4 in WT hearts. Deletion of MIF blunted these changes in response to IPC, which is the likely basis for the absence of protective effects of IPC against I/R injury. In conclusion, MIF plays a critical role in IPC-mediated cardioprotection under ischemic stress by activating RISK signaling pathway and AMPK. These results provide an insight for developing a novel therapeutic strategy that target MIF to protect ischemic hearts.

Ischemia postconditioning protects dermal microvascular endothelial cells of rabbit epigastric skin flaps against apoptosis via adenosine A2a receptors

Background: It has been shown that endogenous adenosine-induced by ischemia postconditioning attenuates apoptosis in recent studies; however, they focus only on parenchymal cells. The detailed mechanism has not been clearly clarified in any research and the subtype of adenosine receptors involved remains unknown. In our study, dermal microvascular endothelial cells (DMECs) are used to explore the role of adenosine A2a receptor in the anti-apoptotic effects of ischemic postconditioning.Material and methods: The epigastric skin flaps of rabbits were elevated. After 4 h of ischemia, the flaps were either abruptly reperfused or postconditioned by six cycles of brief reperfusion (15s) and re-ischemia (15s). Adenosine A2a receptor agonist (CGS-21680) and antagonist (ZM-241385) were used separately in other groups. The apoptosis-related proteins and adenosine A2a receptors were determined by immunohistochemical staining. Then apoptosis index was calculated by TUNEL.Results: Ischemia/reperfusion caused severe damages in DMECs of flaps as demonstrated by an increase in apoptosis index and an increase in expressions of apoptosis-related proteins, which can be significantly attenuated by IPC treatment or exposure to a selective adenosine A2a receptor agonist (all p values <.05). Meanwhile, the anti-apoptosis effects of IPC can be blocked by a selective adenosine A2a receptor antagonist. Statistical analysis revealed that the increase of apoptosis index closely correlated inversely with the relative increase of adenosine A2a receptors (p < .0001).Conclusions: Ischemia postconditioning protects DMECs of rabbit skin flap against apoptosis via activation of adenosine A2a receptors.

Adaptation and Effects of the Evidence-based IPC Nursing Protocol on Prevention of Postoperative Venous Thromboembolism

Adaptation and Effects of the Evidence-based IPC Nursing Protocol on Prevention of Postoperative Venous Thromboembolism

Is delayed ischemic preconditioning as effective on running performance during a 5km time trial as acute IPC?

Examine whether IPC applied 24h (24-IPC) before exercise is equally effective as IPC in improving exercise performance. Randomized, cross-over study METHODS: 12 healthy participants were randomly exposed to SHAM-session, IPC or 24-IPC before a self-paced 5km running trial on a treadmill. Subjects were blinded for time, speed and heart rate. Furthermore, heart rate, BORG, and the local tissue saturation index were measured during exercise, while lactate levels were determined after running. Using a regression model, we explored whether these parameters predicted the change in running time after IPC and 24-IPC. We found no differences in finish time after IPC (SHAM: 1400±105s, IPC: 1381±112s, 24-IPC: 1385±113s; p=0.30). However, we observed a significant positive relation between the change in finish time after IPC and 24-IPC (p=0.016; r=0.677). Using stepwise linear regression, a lower post-exercise blood lactate level after IPC or 24-IPC was significantly related to an improvement in finish time (R2=0.47, β=-0.687, p=0.007). Although no significant effect of IPC or 24-IPC on exercise performance was found, individual finish time after IPC and 24-IPC were strongly correlated. Therefore, our data suggest that, at the individual level, the effects of 24-IPC are closely related to the effects of IPC.

Steatotic livers are susceptible to normothermic ischemia-reperfusion injury from mitochondrial Complex-I dysfunction.

To assess the effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI). Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) the IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; (2) the IPC group underwent IPC prior to same standard IRI; and (3) sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function was analyzed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine aminotransferase (ALT), and histological injury were measured. Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities. Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria.

A novel chemical additive for in-situ recovery of heavy oil using waterflooding process

Abstract Chemical-assisted waterflooding is injection of specialty chemical(s) along with water to enhance the productivity through a series of mechanisms. There are several mechanisms responsible for increased ultimate recovery of such a process compared to the traditional waterflooding process including in-situ emulsification of oil, conformance control and treatment of adverse mobility ratio, reduction of Interfacial Tension (IFT) between the in-situ oil and the injecting phase, and wettability modification to facilitate recovery of oil by enhanced relative permeability values. Although chemical-assisted waterflooding has been applied since the early 20th century, it has not been until recently that applicability of this process has been tested for recovery of heavy oil using preliminary macro-scale as well as pore-scale studies. A new chemical technology (i.e. IPC Technology as referred in this paper) has been developed. A proprietary mixture of surfactants is used in several techniques associated with surface extraction as well as in-situ recovery of heavy oil and bitumen. This formulation of solvents and surfactants is reusable, low foaming, non-flammable, not acutely toxic and non-carcinogenic. A systematic study, based on a series of coreflood tests, was designed and conducted to assess efficacy of IPC in the ultimate recovery of different types of oils by use of IPC-assisted waterflooding. Effects of IPC on IFT between oil and IPC solutions at different brine salinities/hardnesses and IPC concentrations were determined. Compatibility of IPC with different brine hardnesses and salinities was determined. IPC technology was particularly effective in recovering heavy oil. The performance of IPC as an additive during waterflood at elevated temperature for recovery of heavy oil was also investigated. For this particular purpose, thermal stability tests were conducted to determine the threshold temperature below which the formulation is thermally stable. When production performance of IPC-assisted waterflood was compared with alkali flooding and a commercial surfactant, IPC gave superior ultimate recovery.

Ischemic preconditioning improves oxygen saturation and attenuates hypoxic pulmonary vasoconstriction at high altitude.

Exposure to hypoxic environments is associated with decreased arterial oxygen saturation and increased pulmonary artery pressures. Ischemic preconditioning of an extremity (IPC) is a procedure that stimulates vasoactive and inflammatory pathways that protect remote organ systems from ongoing or future ischemic injury. To test the effects of IPC on oxygen saturation and pulmonary artery pressures at high altitude, 12 healthy adult volunteers were evaluated in a randomized cross-over trial. IPC was administered utilizing a standardized protocol. IPC or placebo was administered daily for 5 days prior to ascent to altitude. All participants were evaluated twice at 4342 m altitude (placebo and IPC conditions separated by 4 weeks, randomized). The pulmonary artery systolic pressure (PASP) at 4342 m was significantly lower in the IPC condition than the placebo condition (36 ± 6.0 mmHg vs. 38.1 ± 7.6 mmHg, respectively, p = 0.035). Oxygen saturation at 4342 m was significantly higher with IPC compared to placebo (80.3 ± 8.7% vs. 75.3 ± 9.6%, respectively, p = 0.003). Prophylactic IPC treatment is associated with improved oxygen saturation and attenuation of the normal hypoxic increase in pulmonary artery pressures following ascent to high altitude.

ASSA13-03-23 Effects Caused by Postconditioning of Mouse Heart Suffering from Reperfusion Injury and Mechanisms Induced by Reperfusion Injury Salvage Kinase

Objective Explore cardioprotective mechanisms induced by reperfusion injury salvage kinase (ERK1/2) signal transduction pathways changes in isolated mouse hearts. Methods Established Langendorff perfused mouse heart model, 96 C57BL mouse hearts were divided to 4 groups: 1) I/R control: 30 min global ischemia and 2 h reperfusion; 2) IPC:IPC with 3 episodes of 10 s of ischemia and 10 s reperfusion after 30 min ischemia and before 2 h reperfusion; 3) IPC+ERK1/2 inhibitor PD98059 (10– 5 mol/L for 15 min); 4) I/R+ERK1/2 inhibitor PD98059 (10– 5 mol/L for 15 min). The effects of IPC on Ischemic size, myocardial cell apoptosis index, phospho-protein kinase (P-ERK1/2) and phospho-protein kinase B(P-Akt) were measured. Expressions of apoptosis related proteins, including Bax, Bcl-2 and Cyt.C, in cytosolic and membrane fraction were detected by Western blot. Results Following 180min reperfusion, infarct size was significantly reduced in postconditioning group (32.8 ± 3. 8)% compared with I/R group hearts [(48.1 ± 4.8)%, P Conclusions Postconditioning plays a pivotal role in reducing myocardial infarct size after ischemia/reperfusion injury. IPC right before reperfusion but not after reperfusion attenuated I/R injury of isolated mouse hearts via the upstream target, ERK1/2-MAPK signal transduction pathway which mediated the expression of Bcl-2/Bax and the release of mitochondrial Cyt.C.

The effects of ischemic preconditioning on aerobic and anaerobic variables associated with submaximal cycling performance

Acute limb ischemia induced by pressure cuffs before activity (ischemic preconditioning; IPC) has been reported to improve exercise performance at maximal efforts. The purpose of this investigation was to determine the effects of IPC during a submaximal performance test in competitive amateur level cyclists. Twelve healthy, male cyclists participated in two performance tests in which they cycled at successive relative intensities of 30, 50, and 70% of their maximal power output for 5 min each. The test culminated with an intensity of 90% of their maximal power output until exhaustion. Prior to each test, subjects randomly completed a control (CON) or IPC treatment. The IPC treatment consisted of alternating 220 mmHg of pressure applied by a cuff to the proximal portion of both thighs for 3, 5 min bouts separated by 5 min of rest. In addition to performance time to exhaustion, variables associated with aerobic performance (oxygen consumption, ventilation, respiratory exchange ratio, heart rate, and blood lactate) were measured continuously throughout the performance test. Statistical comparisons of data were made with repeated measures analyses of variance or paired T tests and significance was accepted as P < 0.05. Heart rate at the 30% relative intensity was significantly higher for the IPC treatment, but there were no other statistically significant differences between the control and IPC treatments across all variables and relative intensities. In this group of competitive amateur-level cyclists, an acute treatment of IPC did not improve performance at each submaximal intensity or increase time to exhaustion.

Abstract P077: Ischemic Preconditioning Improves Postischemic Cardiac Function by Preserving PTEN Activity

Background Ischemic preconditioning (IPC) increases post-ischemic functional recovery. Although reduced infarct size is associated with the better outcome, its underlying mechanism is not fully understood. The phosphatase and tensin homologue deleted on chromosome ten (PTEN) promotes cell death and increases myocardial contractility. We recently reported that IPC attenuates loss of PTEN activity in post-ischemic hearts. In the present study, we have investigated the hypothesis that IPC improves post-ischemic cardiac function by preserving PTEN activity. Methods and Results Isolated mouse hearts were exposed to no ischemia as control (CON) or IPC, consisting of 10-min ischemia and 5-min reperfusion (I-10/R-5), followed by I-30/R-120. bpV(phen) (10 µM), a PTEN inhibitor, or vehicle was added into the perfusion line in IPC group following reperfusion. Isolated hearts from muscle-specific PTEN knockout mice ( Pten loxp/loxp ;ckm +/− ) and control mice ( Pten loxp/loxp ;ckm −/− ) were exposed to I-30/R-30. Left ventricular (LV) pressure was monitored by a pressure catheter. Myocardial infarct size was measured by triphenyltetrazolium chloride staining. After I-30/R-120, IPC increased LV developed pressure (LVDP) and maximal +dp/dt (+dp/dtm) compared with CON. bpV blocked the effects of IPC (LVDP: 42±4 vs. 63±4 mmHg, p&lt;0.01; +dp/dtm: 1209±101 vs. 1880±155 mmHg/sec, p&lt;0.01). However, it did not increase infarct size compared with vehicle. Muscle-specific PTEN knockout modestly decreased LVDP and +dp/dtm in isolated perfused hearts under basal conditions, but it markedly impaired their recovery after I-30/R-30 compared with control (LVDP: 21±4 vs. 45±5 mmHg, p&lt;0.01; +dp/dtm: 784±146 vs. 1795±154 mmHg/sec, p&lt;0.01). Myocardial infarct size was decreased in PTEN knockout hearts after I/R. Conclusions: PTEN inhibition blocks the improvement of cardiac functional recovery induced by IPC. Loss of PTEN exacerbates post-ischemic dysfunction in isolated hearts. Therefore, our studies suggest that IPC attenuates post-ischemic cardiac dysfunction by preserving PTEN activity.

Ischemic preconditioning of the lower extremity attenuates the normal hypoxic increase in pulmonary artery systolic pressure

Ischemic pre-condition of an extremity (IPC) induces effects on local and remote tissues that are protective against ischemic injury. To test the effects of IPC on the normal hypoxic increase in pulmonary pressures and exercise performance, 8 amateur cyclists were evaluated under normoxia and hypoxia (13% F(I)O(2)) in a randomized cross-over trial. IPC was induced using an arterial occlusive cuff to one thigh for 5 min followed by deflation for 5 min for 4 cycles. In the control condition, the resting pulmonary artery systolic pressure (PASP) increased from a normoxic value of 25.6±2.3 mmHg to 41.8±7.2 mmHg following 90 min of hypoxia. In the IPC condition, the PASP increased to only 32.4±3.1 mmHg following hypoxia, representing a 72.8% attenuation (p=0.003). No significant difference was detected in cycle ergometer time trial duration between control and IPC conditions with either normoxia or hypoxia. IPC administered prior to hypoxic exposure was associated with profound attenuation of the normal hypoxic increase of pulmonary artery systolic pressure.

Bradykinin is a Mediator, but Unlikely a Trigger, of Antiarrhythmic Effects of Ischemic Preconditioning

Brief reversible ischemic episodes (ischemic preconditioning, IPC) protect the heart against arrhythmias during a subsequent prolonged low-flow ischemia. We have recently shown that this protection involves release of bradykinin, activation of bradykinin B2 receptors followed by opening of sarcolemmal, but not mitochondrial ATP-sensitive K+ channels. The goal of this study was to clarify a trigger and/or mediator role of bradykinin in the antiarrhythmic effects of IPC during low-flow ischemia. Isolated perfused rat hearts underwent 60 minutes of low-flow ischemia induced by reducing perfusion pressure followed by 60 minutes of reperfusion. Preconditioning was induced by 2 x 5 minutes episodes of zero-flow ischemia. In yet other groups, preconditioned or non-preconditioned hearts were treated either with bradykinin (10 nmol/L) or with HOE 140 (bradykinin B2 receptor antagonist, 100 nmol/L). IPC reduced the number of ventricular premature beats, as well as the incidence of ventricular tachycardia and of ventricular fibrillation during low-flow ischemia. In addition, this protection was abolished by HOE 140 given during low-flow ischemia. Pharmacological preconditioning using short bradykinin perfusion instead of IPC did not show antiarrhythmic effects. However, bradykinin administered during low-flow ischemia and reperfusion reduced the number of ventricular premature beats and the incidence of ventricular tachycardia and of ventricular fibrillation during low-flow ischemia. Bradykinin is a mediator, but unlikely a trigger, of antiarrhythmic effects of IPC during low-flow ischemia.