Ischemia/hypoxia is one of the key clinical issues following severe burns, and ischemic/hypoxic damage of tissues and organs is still hard to be prevented or minimized by various fluid resuscitation regimens. To those who suffered severe burns, even though fluid replacement therapy is delivered promptly, ischemic/hypoxic damage of organs is still inevitable. Previously, blood flow in vital organs such as heart was considered not to be reduced because of blood redistribution under the circumstance of stress. The postburn cardiac dysfunction has been mainly attributed to the reduced blood flow returned to the heart due to decreased blood volume caused by increased capillary permeability. Therefore, postburn cardiac dysfunction has been considered to be the result of burn shock. During the past two decades, we have performed serial studies on severe burns, and found that ischemic/hypoxic myocardial damage and functional impairment of myocardium due to activation of renin angiotensin system existing in the heart itself occur immediately after severe burns even before significant reduction in blood volume secondary to an increase of capillary permeability. Such prompt myocardial damage leads to cardiac deficiency, and it is also a precipitating factor for burn shock and ischemic/hypoxic injury of systemic tissues and organs. Therefore, we called it "shock heart" in our reports. The cellular and molecular mechanisms leading to myocardial damage were systematically investigated. Strategies for prevention of early postburn myocardial damage and dysfunction, and a new effective burn shock resuscitation regimen "volume replacement" plus "dynamic support" (cardiac support and myocardial protection) have been proposed based on our previous studies.
Burns ; complications ; metabolism ; Humans ; Hypoxia ; etiology ; prevention & control ; Myocardial Reperfusion Injury ; etiology ; prevention & control ; Myocardium ; metabolism

Brain Ischemia ; metabolism ; pathology ; prevention & control ; Humans ; Ischemic Preconditioning ; methods ; Myocardial Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Reperfusion Injury ; metabolism ; pathology ; prevention & control

Cerebral ischemia-reperfusion injury(CIRI) is an important factor hindering the recovery of ischemic stroke patients after blood flow recanalization. Mitochondria, serving as the "energy chamber" of cells, have multiple important physiological functions, such as supplying energy, metabolizing reactive oxygen species, storing calcium, and mediating programmed cell death. During CIRI, oxidative stress, calcium overload, inflammatory response, and other factors can easily lead to neuronal mitochondrial dyshomeostasis, which is the key pathological link leading to secondary injury. As reported, the mitochondrial quality control(MQC) system, mainly including mitochondrial biosynthesis, kinetics, autophagy, and derived vesicles, is an important endogenous mechanism to maintain mitochondrial homeostasis and plays an important protective role in the damage of mitochondrial structure and function caused by CIRI. This paper reviewed the mechanism of MQC and the research progress on MQC-targeting therapy of CIRI in recent 10 years to provide theoretical references for exploring new strategies for the prevention and treatment of ischemic stroke with traditional Chinese medicine.
Brain Ischemia/prevention & control* ; Calcium/metabolism* ; Humans ; Ischemic Stroke ; Mitochondria/pathology* ; Reactive Oxygen Species/metabolism* ; Reperfusion Injury/prevention & control*

BACKGROUNDIt has found that ischemic postconditioning (IPO) might decrease pulmonary ischemia/reperfusion (I/R) injury, which is one of the main reasons of lung injury caused by cardiopulmonary bypass (CPB). It was found that aquaporins (AQPs) play a role in the maintenance of fluid homeostasis. But it is still unclear whether IPO influences the expression of aquaporin-1 (AQP1). This study was designed to investigate whether IPO can reduce CPB-related lung injury and affect the expression of AQP1 of lungs.

METHODSTwelve healthy dogs were divided into control group (C group) and ischemia postconditioning group (IPO group). CPB procedures were implemented. Ten minutes later, the left pulmonary artery was separated and blocked. Postconditioning consisted of two cycles of 5-minute pulmonary artery reperfusion/5-minute reocclusion starting at the beginning of reperfusion. The 2×4 cm tissues of both sides of pulmonary apex, superior, middle and inferior lobe were taken before CPB (T1), before occlusion and reopening of left pulmonary artery (T2, T3), and 2 hours after CPB (T4). Samples were used to evaluate lung injury degrees and to detect the expression of AQP1. At T1 and T4, blood was collected from femoral artery to calculate pulmonary function.

RESULTSAt T4, each pulmonary function showed significant deterioration compared with T1. Lung injury could be found at the onset of CPB. However, the expression of AQP1 decreased and wet to dry weight ratio (W/D) increased after T2. In the left lung of C group, the worst pulmonary function and structures were detected. The slightest changes were discovered in the right lung of C group. A close relationship between W/D and lung injury score was found. The lung injury score was negatively related with the expression of AQP1. It was found that the expression of AQP1 was negatively connected with W/D.

CONCLUSIONSIn dog CPB models, lung injury induced by CPB was related with down regulated expression of AQP1. AQP1 is believed to be involved in the mechanisms of lung ischemia/reperfusion (I/R) injury caused by CPB. IPO increases the expression of AQP1, provides a protective effect on lung suffering from CPB, and alleviates CPB-related lung injury.

Animals ; Aquaporin 1 ; metabolism ; Cardiopulmonary Bypass ; Dogs ; Humans ; Ischemic Postconditioning ; methods ; Lung Injury ; metabolism ; prevention & control ; Reperfusion Injury ; metabolism ; prevention & control

Animals ; Hindlimb ; blood supply ; Intestine, Small ; metabolism ; Ischemia ; metabolism ; prevention & control ; Ischemic Preconditioning ; Lung Injury ; metabolism ; Male ; Muscle, Skeletal ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism

Animals ; Isoflavones ; pharmacology ; Liver ; metabolism ; pathology ; Liver Diseases ; metabolism ; pathology ; Rats ; Rats, Wistar ; Reperfusion Injury ; pathology ; prevention & control ; Soybeans ; chemistry

BACKGROUNDIschemic postconditioning (IPost), able to significantly attenuate myocardial ischemia reperfusion injury, is dependent on RISK signaling. Studies have shown that Notch signaling repairs damaged myocardium, and this study aimed to investigate the effect of Notch signaling in myocardial IPost.

METHODSWe used H9c2 cells to establish the myocardial IPost and Hypoxia/Reoxygenation (H/R) model in vitro. which were randomly divided into control, H/R, IPost, Hepatocyte growth factor (HGF)+IPost and DAPT+IPost, N1ICD+IPost, miRNA+IPost, and Mock treatment groups. The myocardial cell viability was assessed by MTT, the cell apoptosis was detected using Annexin V/PI double staining and flow cytometry analyses. The expression of N1ICD, Hes1, PTEN Phospho-Akt/Akt, Phospho-GSK-3β/GSK-3β were detected by Western blotting. Finally, we assessed the changes in ψm using the potential-sensitive dye JC-1 and measured using flow cytometry analyses.

RESULTSThe Notch1 signaling is activated by HGF and ectopic expression of N1ICD during myocardial IPost, which increased myocardial cell viability, prevented cardiomyocyte apoptosis, and reduced loss of the mitochondrial membrane potential. However, myocardial ischemia reperfusion injury was increased in IPost when Notch1 signaling was inhibited using DAPT or with knockdown by Notch1-miRNA. Western blotting found that PTEN was down-regulated by Hes1 when Notch1 was activated, which consequently promoted Akt and GSK-3β phosphorylation.

CONCLUSIONSNotch1 crosstalk with RISK signaling may be dependent on PTEN, which plays a cardioprotective role during IPost. This mechanism could provide a promising therapeutic target for the treatment of ischemic heart disease.

Cell Line ; Humans ; Ischemic Postconditioning ; Myocardial Reperfusion Injury ; genetics ; metabolism ; prevention & control ; Receptor, Notch1 ; genetics ; metabolism ; Signal Transduction ; physiology

BACKGROUNDAscorbic acid has important antioxidant properties, and may play a role in the protective effects of ischemic preconditioning on later ischemia-reperfusion. Herein, we examined the role of endogenous extracellular ascorbic acid in ischemic preconditioning in the kidney.

METHODSWe developed a solitary rabbit kidney model where animals received ischemia-reperfusion only (ischemia-reperfusion group, n = 15) or ischemic preconditioning followed by ischemia-reperfusion (ischemic preconditioning group, n = 15). Ischemia-reperfusion was induced by occluding and loosening of the renal pedicle. The process of ischemic preconditioning included 15-minute brief ischemia and 10-minute reperfusion. In vivo microdialysis coupled with online electrochemical detection was used to determine levels of endogenous extracellular ascorbic acid in both groups. The extent of tissue damage was determined in kidney sections stained with hematoxylin and eosin. Serum creatinine and urea nitrogen were also detected to assess renal function.

RESULTSDuring ischemia-reperfusion, the extracellular ascorbic acid concentration during ischemia increased rapidly to the peak level ((130.01 +/- 9.98)%), and then decreased slowly to near basal levels. Similar changes were observed during reperfusion (peak level, (126.78 +/- 18.24)%). In the ischemic preconditioning group there was a similar pattern of extracellular ascorbic acid concentration during ischemic preconditioning. However, the ascorbic acid level was significantly lower during the ischemia and early reperfusion stage compared to the ischemia-reperfusion group. Additionally, the extent of glomerular ischemic collapse, tubular dilation, tubular denudation, and loss of brush border were markedly attenuated in the ischemic preconditioning group. Levels of serum creatinine and urea nitrogen were also decreased significantly in the ischemic preconditioning group.

CONCLUSIONSIschemic preconditioning may protect renal tissue against ischemia-reperfusion injury via use of extracellular ascorbic acid. In vivo microdialysis coupled with online electrochemical detection is effective for continuous monitoring extracellular ascorbic acid in the renal cortex.

Animals ; Ascorbic Acid ; metabolism ; Disease Models, Animal ; Ischemic Preconditioning ; methods ; Kidney ; metabolism ; pathology ; Rabbits ; Reperfusion Injury ; prevention & control

OBJECTIVEA general review was made of studies involving: (1) the concept and mechanism of the cholinergic anti-inflammatory pathway (CAP), (2) the important role of inflammatory response in myocardial ischemia reperfusion (I/R) injury and (3) the evidence and mechanisms by which CAP may provide protection against myocardial I/R injury.

DATA SOURCESThe data used in this review were mainly from manuscripts listed in PubMed that were published in English from 1987 to 2009. The search terms were "vagal nerve stimulation", "myocardial ischemia reperfusion injury", "nicotine acetylcholine receptor" and "inflammation".

STUDY SELECTION(1) Clinical and experimental evidence that the inflammatory response induced by reperfusion enhances myocardial I/R injury. (2) Clinical and laboratory evidence that the CAP inhibits the inflammation and provides protection against myocardial I/R injury.

RESULTSThe myocardial I/R injury is really an inflammatory process characterized by recruitment of neutrophils into the ischemic myocardium and excessive production of pro-inflammatory cytokines. Because the CAP can modulate the inflammatory response by decreasing the production and release of pro-inflammatory cytokines, it can provide protection against myocardial I/R injury.

CONCLUSIONSThe CAP can inhibit the inflammatory response induced by reperfusion and protect against myocardial I/R injury. It represents an exciting opportunity to develop new and novel therapeutics to attenuate the myocardial I/R injury.

Animals ; Cytokines ; metabolism ; Humans ; Inflammation ; immunology ; Models, Biological ; Myocardial Reperfusion Injury ; immunology ; metabolism ; prevention & control ; Vagus Nerve Stimulation

AIMTo study the effect of ischemic preconditioning on lung injury following ischemia/reperfusion (I/R) in the hind limbs of rats.

METHODSWistar rats were randomly divided into four groups (n=8): control group,limbs ischemia/reperfusion (LI/R) group, ischemia preconditioning (IPC) group and L-NAME group. At the end of the experiment, blood/gas analysis and the contents of serum MDA, NO, ET and lung tissue MDA, NO, ET, MPO were measured. Meanwhile, lung index and W/D) of lung were measured.

RESULTSAfter the rats' hind limbs suffered ischemia/reperfusion, the level of PaO2 decreased and the values of W/D, LI, MPO of the lung issure and MDA, NO, ET of plasma and lung all increased significantly in the LI/R group; but the ratio of NO/ET decreased. Compared with LI/R group, the contents of NO and ratio of NO/ET increased but other parameters decreased in the IPC group. Compared with IPC group, the contents of NO and ratio of NO/ET decreased, but other parameters increased in the L-NAME group.

CONCLUSIONThe IPC can attenuate lung injury following IR in the hind limbs of rats, which may correlated with the increase of NO.

Acute Lung Injury ; prevention & control ; Animals ; Extremities ; blood supply ; Ischemia ; physiopathology ; Ischemic Preconditioning ; methods ; Lung ; blood supply ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Reperfusion Injury ; metabolism ; prevention & control