Impact Of Ischemic Preconditioning Research Articles

Ischemic Preconditioning Did Not Affect Central and Peripheral Factors of Performance Fatigability After Submaximal Isometric Exercise.

The present study was designed to provide further insight into the mechanistic basis for the improved exercise tolerance following ischemic preconditioning (IPC) by investigating key-determinants of performance and perceived fatigability. Using a randomized, counterbalanced, single-blind, sham-controlled, crossover design, 16 males performed an isometric time-to-exhaustion test with the knee extensors at 20% maximal voluntary torque (MVT) after an IPC and a sham treatment (SHAM). Those who improved their time-to-exhaustion following IPC performed a time-matched IPC trial corresponding to the exercise duration of SHAM (IPCtm). Neuromuscular function was assessed before and after exercise termination during each condition (IPC, IPCtm, and SHAM) to analyze the impact of IPC on performance fatigability and its central and peripheral determinants. Muscle oxygenation (SmO2), muscle activity, and perceptual responses (effort and muscle pain) were recorded during exercise. Performance fatigability as well as its central and peripheral determinants were quantified as percentage pre-post changes in MVT (ΔMVT) as well as voluntary activation (ΔVA) and quadriceps twitch torque evoked by paired electrical stimuli at 100 and 10 Hz (ΔPS100 and ΔPS10⋅PS100–1 ratio), respectively. Time-to-exhaustion, performance fatigability, its determinants, muscle activity, SmO2, and perceptual responses during exercise were not different between IPC and SHAM. However, six participants improved their performance by >10% following IPC (299 ± 71 s) compared to SHAM (253 ± 66 s, d = 3.23). The time-matched comparisons (IPCtm vs. SHAM) indicated that performance fatigability, its determinants, and SmO2 were not affected, while effort perception seemed to be lower (ηp2 = 0.495) in those who improved their time-to-exhaustion. The longer time-to-exhaustion following IPC seemed to be associated with a lower effort perception (ηp2 = 0.380) and larger impairments in neuromuscular function, i.e., larger ΔMVT, ΔVA, and ΔPS10⋅PS100–1 ratio (d = 0.71, 1.0, 0.92, respectively). IPC did neither affect exercise tolerance, performance fatigability, as well as its central and peripheral determinants, nor muscle activity, SmO2, and perceptual responses during submaximal isometric exercise. However, IPC seemed to have an ergogenic effect in a few subjects, which might have resulted from a lower effort perception during exercise. These findings support the assumption that there are ‘responders’ and ‘non-responders’ to IPC.

Diabetic animal fed with high-fat diet prevents the protective effect of myocardial ischemic preconditioning effect in isolated rat heart perfusion model.

Diabetic heart (diabetes mellitus [DM]) has been shown to attenuate the beneficial effect of ischemic preconditioning (IPC) in rat heart. But the effect of IPC on diabetic rat heart that develops myopathy remains unclear. This study was designed to test the impact of IPC on diabetic cardiomyopathy (DCM) rat heart. Male Wistar rats were grouped as (a) normal, (b) DM (streptozotocin: 65 mg/kg; fed with normal diet), and (c) DCM (streptozotocin: 65 mg/kg; fed with high-fat diet). Isolated rat hearts from each group were randomly subjected to (a) normal perfusion, (b) ischemia-reperfusion (I/R), and (c) IPC procedure. At the end of the perfusion experiments, hearts were analyzed for injury, contractile function, mitochondrial activity, and oxidative stress. The results obtained from hemodynamics, cardiac injury markers, and caspase-3 activity showed that DCM rat displayed prominent I/R-associated cardiac abnormalities than DM rat heart. But the deteriorated physiological performance and cardiac injury were not recovered in both DM and DCM heart by IPC procedure. Unlike normal rat heart, IPC did not reverse mitochondrial dysfunction (determined by electron transport chain enzymes activity, ATP level, and membrane integrity, expression levels of genes like PGC-1ɑ, GSK3β, complex I, II, and V) in DCM and DM rat heart. The present study demonstrated that IPC failed to protect I/R-challenged DCM rat heart, and the underlying pathology was associated with deteriorated mitochondrial function.

Mechanisms underpinning protection against eccentric exercise-induced muscle damage by ischemic preconditioning

Eccentric exercise training is effective for increasing muscle mass and strength, and improving insulin sensitivity and blood lipid profiles. However, potential muscle damage symptoms such as prolonged loss of muscle function and delayed onset of muscle soreness may restrict the use of eccentric exercise, especially in clinical populations. Therefore, strategies to reduce eccentric exercise-induced muscle damage (EIMD) are necessary, and an extensive number of scientific studies have tried to identify potential intervention modalities to perform eccentric exercises without adverse effects. The present paper is based on a narrative review of current literature, and provides a novel hypothesis by which an ischemic preconditioning (IPC) of the extremities may reduce EIMD. IPC consists of an intermittent application of short-time non-lethal ischemia to an extremity (e.g. using a tourniquet) followed by reperfusion and was discovered in clinical settings in an attempt to minimize inflammatory responses induced by ischemia and ischemia-reperfusion-injury (I/R-Injury) during surgery. The present hypothesis is based on morphological and biochemical similarities in the pathophysiology of skeletal muscle damage during clinical surgery and EIMD. Even though the primary origin of stress differs between I/R-Injury and EIMD, subsequent cellular alterations characterized by an intracellular accumulation of Ca2+, an increased production of reactive oxygen species or increased apoptotic signaling are essential elements for both. Moreover, the incipient immune response appears to be similar in I/R-Injury and EIMD, which is indicated by an infiltration of leukocytes into the damaged soft-tissue. Thus far, IPC is considered as a potential intervention strategy in the area of cardiovascular or orthopedic surgery and provides significant impact on soft-tissue protection and downregulation of undesired excessive inflammation induced by I/R-Injury. Based on the known major impact of IPC on skeletal muscle physiology and immunology, the present paper aims to illustrate the potential protective effects of IPC on EIMD by discussing possible underlying mechanisms.

Protective Effect of Ischemic Preconditioning on Hepatic Ischemia-Reperfusion Injury in Rats

Aim: Ischemic preconditioning (IPC) protects tissue against ischemia and reperfusion (I/R) injury. The aim of this study was to examine the impact of IPC on protection of hepatocytes after prolonged I/R injury. Methods: Twenty-four Wistar rats were randomly divided into ischemic preconditioning group (IP), ischemia/reperfusion group (IR) and sham operation group (SO). A model of partial liver ischemia/reperfusion was used, in which rats were subjected to liver ischemia for 90 min prior to reperfusion. The animals in the IP group underwent ischemic preconditioning for 10 min prior to the ischemia/reperfusion challenge. After 3 h of reperfusion, serum and liver tissue in each group were collected to detect the level of serum ALT, AST, HA, MDA and liver histopathology. Results: Compared with IR group, IP group showed a significantly lower ALT, AST, HA and MDA level in 3 h. Proliferation index (PI) was significantly increased in IP group compared with IR group. Conclusion: Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, which may be related to cell proliferation during early ischemic reperfusion.

Complex Hepatectomy under Total Vascular Exclusion of the Liver: Impact of Ischemic Preconditioning on Clinical Outcomes

Hepatic inflow clamping during hepatectomy introduces ischemia-reperfusion (I/R) injury, and many authors regard the addition of caval occlusion as adding increased risk. Ischemic preconditioning (IPC) is one of the protective strategies employed to reduce I/R injury in animal experiments and limited clinical series. The aim of the present study was to determine the impact of systematic adoption of IPC in patients undergoing complex hepatectomy under total hepatic vascular exclusion (TVE) based on outcomes review. The records of 93 patients who underwent major hepatectomy involving TVE at our center from February 1998 to December 2008 were reviewed. These patients were divided into two groups: group 1 (n = 55, TVE alone) and group 2 (n = 38, TVE with IPC). IPC was performed by portal triad clamping for 10 min followed by 3-5 min of reperfusion prior to TVE and resection. The two groups were comparable regarding demographics, underlying liver diseases, indications for hepatectomy, duration of TVE, and preoperative liver and kidney function tests. Overall postoperative laboratory results of liver function tests were not significantly different between the two groups. Creatinine levels and prothrombin times were not significantly different between the groups. The use of IPC had no impact on the duration of the operation, blood loss, or hospital stay. The morbidity rates were 37.5 and 34.2 %, respectively. Our adoption of IPC as a protective strategy against I/R injury under TVE did not affect operative or laboratory parameters and clinical outcomes when compared to continuous clamping for comparable ischemic periods.

Ischemic preconditioning reduces endoplasmic reticulum stress and upregulates hypoxia inducible factor-1α in ischemic kidney: the role of nitric oxide

BackgroundAlthough recent studies indicate that renal ischemic preconditioning (IPC) protects the kidney from ischemia-reperfusion (I/R) injury, the precise protective mechanism remains unclear. In the current study, we investigated whether early IPC could upregulate hypoxia inducible transcription factor-1α (HIF-1α) expression and could reduce endoplasmic reticulum (ER) stress after renal I/R and whether pharmacological inhibition of nitric oxide (NO) production would abolish these protective effects.MethodsKidneys of Wistar rats were subjected to 60 min of warm ischemia followed by 120 min of reperfusion (I/R group), or to 2 preceding cycles of 5 min ischemia and 5 min reperfusion (IPC group), or to intravenously injection of NG-nitro-L-arginine methylester (L-NAME, 5 mg/kg) 5 min before IPC (L-NAME+IPC group). The results of these experimental groups were compared to those of a sham-operated group. Sodium reabsorption rate, creatinine clearance, plasma lactate dehydrogenase (LDH) activity, tissues concentrations of malonedialdehyde (MDA), HIF-1α and nitrite/nitrate were determined. In addition, Western blot analyses were performed to identify the amounts of Akt, endothelial nitric oxide synthase (eNOS) and ER stress parameters.ResultsIPC decreased cytolysis, lipid peroxidation and improved renal function. Parallely, IPC enhanced Akt phosphorylation, eNOS, nitrite/nitrate and HIF-1α levels as compared to I/R group. Moreover, our results showed that IPC increased the relative amounts of glucose-regulated protein 78 (GRP78) and decreased those of RNA activated protein kinase (PKR)-like ER kinase (PERK), activating transcription factor 4 (ATF4) and TNF-receptor-associated factor 2 (TRAF2) as judged to I/R group. However, pre treatment with L-NAME abolished these beneficial effects of IPC against renal I/R insults.ConclusionThese findings suggest that early IPC protects kidney against renal I/R injury via reducing oxidative and ER stresses. These effects are associated with phosphorylation of Akt, eNOS activation and NO production contributing thus to HIF-1α stabilization. The beneficial impact of IPC was abolished when NO production is inhibited before IPC application.

Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts

The impact of ischemic preconditioning (IPC) on contraction, Ca(2+) homeostasis, and cell survival was compared in isolated ventricular myocytes from young adult ( approximately 3 mo) and aged ( approximately 24 mo) male Fischer-344 rats. Myocytes were field stimulated at 4 Hz (37 degrees C). Contraction (edge detector) and intracellular Ca(2+) (fura-2) were measured simultaneously. Viability was assessed with trypan blue. All cells were exposed to 30 min of simulated ischemia followed by reperfusion. Some cells were preconditioned by exposure to 5 min of simulated ischemia before prolonged ischemia. Pretreatment with IPC abolished postischemic contractile depression, inhibited diastolic contracture, and increased Ca(2+) transient amplitudes in reperfusion in young adult and aged cells. IPC did not affect the modest rise in diastolic Ca(2+) in ischemia in young adult myocytes. However, IPC abolished the marked rise in diastolic Ca(2+) observed in ischemia and early reperfusion in aged myocytes. IPC also suppressed mechanical alternans in ischemia in aged cells, but younger myocytes showed little evidence of mechanical alternans whether or not cells were preconditioned. IPC markedly improved cell viability in reperfusion in young adult but not aged cells. These results suggest that IPC augments the recovery of contractile function in reperfusion by increasing Ca(2+) transient amplitudes in ventricular myocytes from young adult and aged rats. IPC reduced diastolic Ca(2+) accumulation in ischemia in aged myocytes, which may diminish the severity of mechanical alternans in aged cells. Nonetheless, the efficacy of IPC is compromised in aging, as IPC did not improve survival of aged myocytes exposed to ischemia and reperfusion.

Ischemic preconditioning enhances regenerative capacity of hepatocytes in long‐term ischemically damaged rat livers

Ischemic preconditioning (IPC) protects tissues against ischemia and reperfusion (I/R) injury. The aim of this study was to examine the impact of IPC on protection and regeneration of hepatocytes after prolonged I/R injury. A rat model of segmental (70%) hepatic ischemia was used to determine the effect of 10-min IPC preceding 40, 60, 90, or 120 min of liver ischemia. The effect was assessed by comparing cytolysis markers and necrotic areas of the liver, as well as the regenerative capacity of hepatocytes using the proliferating cell nuclear antigen labeling index (PCNA-LI) and weight of the ischemic liver lobe. Protein kinase B/Akt (Akt) and caspase-9 were investigated immunohistochemically to determine the effect of IPC on activation of survival and anti-apoptotic signals. In the model of 40 min I/R, which resulted in focal necrosis of the liver, IPC significantly protected against I/R injury by reducing the area of focal necrosis, level of PCNA-LI and immunoreactivities to Akt and caspase-9. In contrast, IPC did not prevent ischemic damage in the 90- and 120-min ischemic model with massive liver necrosis. However, IPC enhanced the regenerative capacity of the remaining hepatocytes with higher levels of PCNA-LI, number of Akt-positive cells and mean weight of the liver lobe postoperatively than in the controls. In a model of focal necrosis of the liver, IPC protected hepatocytes against I/R injury. In addition, in a model of massive necrosis, IPC maintained the regenerative capacity of the remaining hepatocytes by enhancing the survival signals.

Cardiomyocyte apoptosis and ischemic preconditioning in open heart operations

Background The aim of the present study was to ascertain the percentage of left apical myocardial apoptosis in three-vessel coronary artery bypass grafting patients quantitatively and the impact of ischemic preconditioning. Methods Twenty-one patients with three-vessel disease who had elective coronary artery bypass grafting were randomized in a ratio of 2:1 to ischemic preconditioning (n = 14) or a control group (n = 7). The ischemic preconditioning protocol was established by two cycles of ascending aorta occlusion for 2 minutes followed by 3 minutes of reperfusion. Myocardial samples from the apex of the left ventricle were taken using a Tru-Cut needle before aortic cross-clamping and immediately after declamping. The percentage of apoptosis was analyzed by TUNEL methods. Data on hemodynamics and biochemical markers were collected. Results Low levels of myocardial apoptosis were found before the operation (0.01% ± 0.00%). During the early reperfusion period, the percentage of myocardial apoptotic cells significantly increased (0.15% ± 0.05%, p = 0.008). Ischemic preconditioning significantly improved cardiac index and right ventricular ejection fraction recovery after the operation ( p = 0.036 and 0.001 respectively, repeated measure) but had no effect on myocardial apoptosis before and after the operation (0.01 ± 0.00 versus 0.01 ± 0.00, p = 0.658 and 0.12% ± 0.04% versus 0.23% ± 0.14%, p = 0.302). Conclusions Cardioplegic myocardial ischemia during open heart operation was associated with induction of cardiomyocyte apoptosis in humans. Attenuation of postoperative cardiac dysfunction by ischemic preconditioning appeared to be independent of apoptosis.