OBJECTIVETo investigate the clinical implications of reperfusion arrhythmias during primary percutaneous coronary intervention (PCI) for patients with acute myocardial infarction (AMI).

METHODSData from 228 AMI patients in whom the infarct-related artery (IRA) were successfully recanalized by primary PCI were retrospectively analyzed. The 228 patients were divided into 2 groups: myocardial ischemia-reperfusion injury (MIRI) group (n=119) in whom MIRI events occurred within minutes after successful recanalization of IRA, and non-MIRI group (n=109). The 119 patients in MIRI group were further divided into 3 subgroups: severe bradycardia with hypotension (brady-arrhythmia subgroup), lethal ventricular arrhythmias requiring electrical cardioversion (tachy-arrhythmia subgroup), and IRA antegrade flow less than or equal to TIMI 2 grade without angiographic evidence of abrupt closure (no-reflow subgroup).

RESULTS(1) Clinical and angiographic data: Compared with non-MIRI group, MIRI group was characterized by more inferior infarct location, shorter ischemic duration, more frequently right coronary artery as IRA, more diseased vessels, more often TIMI 0 grade of initial antegrade flow in IRA, less pre-infarction angina, more renal insufficiency, and higher in-hospital mortality (13.4% vs. 4.6%, P=0.021). (2) The peak CK level was remarkably lower in brady-arrhythmia subgroup than that in non-MIRI group (2010 IU/L vs. 2521 IU/L, P=0.039). The peak CK or CK-MB level was notably higher in no-reflow subgroup than in non-MIRI group (4573 IU/L, 338 IU/L, respectively, P=0.000). (3) Left ventricular ejection fraction in no-reflow subgroup was significantly lower than in non-MIRI group (38.7% +/- 8.3% vs. 51.2% +/- 8.1%, P=0.000), left ventricular end-diastolic volume in no-reflow subgroup was greater than that in tachy-arrhythmia subgroup [(135 +/- 32) ml vs. (105 +/- 19) ml, P=0.029].

CONCLUSIONReperfusion arrhythmias may imply the existence of much survived myocardium and do not enhance myocardial damage, while no-reflow increases myocardial injury and induces permanent impairment of cardiac function.

Arrhythmias, Cardiac ; complications ; Cell Survival ; Humans ; Myocardial Infarction ; therapy ; Myocardial Reperfusion ; Myocardial Reperfusion Injury ; etiology ; Myocardium ; enzymology ; Retrospective Studies

Acute myocardial infarction is one of the major causes of mortality worldwide. Reperfusion in a timely fashion is the most effective way to limit infarct size. However, reperfusion can itself prompt further myocardial injury. This phenomenon is commonly known as myocardial ischemia-reperfusion (IR) injury. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme metabolizing acetaldehyde and toxic aldehydes. Increasing evidence has revealed a cardioprotective role of ALDH2 in myocardial IR injury. Evidence from animal studies has shown that ALDH2 diminishes acute myocardial infarct size, ameliorates cardiac dysfunction and prevents reperfusion arrhythmias. The activity of ALDH2 is severely compromised if it is encoded by the mutant ALDH2*2 gene, with an incidence of approximately 40% in Asian populations. Epidemiological surveys in the Asian population have depicted that ALDH2 polymorphism is closely associated with higher prevalence of acute myocardial infarction and coronary artery disease. Therefore, targeting ALDH2 may represent a promising avenue to protect against IR injury. This review recapitulates the underlying mechanisms involved in the protective effect of ALDH2 in cardiac IR injury. Translational potential of ALDH2 in the management of coronary heart disease is also discussed.
Aldehyde Dehydrogenase ; metabolism ; Animals ; Heart ; physiopathology ; Humans ; Mitochondria, Heart ; enzymology ; Myocardial Reperfusion Injury ; Myocardium ; pathology

OBJECTIVETo study the role of neuronal nitric oxide synthase (nNOS) in aged rats' hippocampal delayed neuronal death (DND) following brain ischemia.

METHODSModels of incomplete brain ischemia were induced by clipping common carotid artery. A total of 46 aged SD rats were divided into 8 groups: normal control group (Group A, n=5), sham-operation group (Group B, n=5), reperfusion 1, 6, 12, 24, 48, and 96 hours groups after brain ischemia for 30 minutes (Group C, D, E, F, G, and H, n=6/group). The expression of nNOS was examined by immunohistochemistry and neuronal ultrastructural changes were observed by the transmission electron microscopy (TEM) at different time points after reperfusion.

RESULTSImmunohistochemistry showed that nNOS expression in the hippocampal neurons was high in Group E, low expression in Group D, moderate expression in Group F and G. There was nearly no expression of nNOS in Group A, B, C, and H. Ultrastructure of hippocampal neurons was damaged more severely in reperfusion over 24 hours groups.

CONCLUSIONSNitric oxide (NO) may be one of the important factors in inducing DND after ischemia/reperfusion.

Animals ; Apoptosis ; Brain Ischemia ; enzymology ; Female ; Hippocampus ; enzymology ; pathology ; Immunohistochemistry ; Male ; Microscopy, Electron ; Neurons ; enzymology ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology

OBJECTIVETo observe the expression of endothelial nitric oxide synthase (eNOS)and nervous nitric oxide synthase (nNOS) in rats during cerebral ischemia/reperfusion (CI/R) and study if change will be happen in subgroup between eNOS and nNOS during earlier period of CI/R.

METHODSA total of 60 Wistar rats weighting 200-280 g, supplied by Animal Center of China Medical University, were divided into 6 groups (n=10) (sham operation group; ischemia 1 h, 2 h group; reperfusion 0.5 h, 1 h, 2 h group). Female and male was half-and-half. Cerebral ischemia/reperfusion injury was induced by a 2-hour suture occlusion of the unilateral middle cerebral artery, immediately after suture withdrawal to allow reperfusion, eNOS and nNOS expressions were examined by the method of immunohistochemistry.

RESULTSeNOS expressions increased in 1-hour during ischemia, keeping up with decreasing until reperfusion 2-hour. While nNOS expressions increased in 2-hour between ischemia and reperfusion.

CONCLUSIONChanges of expression between eNOS and nNOS in rats during cerebral ischemia/reperfusion are different. This may be related with ischemia and reperfusion injury.

Animals ; Brain ; enzymology ; Brain Ischemia ; enzymology ; Female ; Male ; Nitric Oxide Synthase Type I ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury ; enzymology ; Time Factors

Animals ; Apoptosis ; physiology ; Brain Ischemia ; enzymology ; physiopathology ; Caspase 3 ; metabolism ; Ischemic Postconditioning ; methods ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; enzymology ; pathology ; prevention & control

OBJECTIVEThe aim of the present study was designed to explore the effect of (+/-) -3-n-butylphthalide (NBP) on ATPase, anti-oxidant enzymes activities and lipid peroxidation of mitochondria and cerebral cortex in rats subjected to 24 hours of reperfusion following 2 hours of cerebral ischemia (tMCAO).

METHODSActivities of SOD (Superoxide Dismutase), GSH-Px (glutathione Peroxidase,) and CAT (Catalase), and MDA level of mitochondria or cortex were measured by using biochemical methods in tMCAO rats.

RESULTS(1) The activities of mitochondrial Na+K(+)-ATPase, Ca(2+)-ATPase and Mg2+ ATPase were found to decrease significantly in the vehicle group (ischemia + saline). Pre-treatment with NBP (5, 10, 20 mg/kg, i.p.) 10 min before tMCAO markedly enhanced the activities of Na+K(+)-ATPase and Ca(2+)-ATPase, compared with vehicle group. (2) The activities of SOD and mitochondrial GSH-Px were decreased and MDA level increased in vehicle groups as compared with that in sham group (non-ischemia + saline). NBP (20 mg/kg, i.p.) significantly enhanced total mitochondrial SOD activity, and also enhanced cerebral cortex total SOD activity (in 5, 10, 20 mg/kg groups). However, it had no obvious effect on CuZn-SOD activity. NBP (20 mg/kg i.p.) markedly increased mitochondrial (but not in cerebral cortex) GSH-Px activity; NBP 10, 20 mg/kg markedly decreased mitochondrial MDA level compared with that in vehicle group (P < 0.05). (3) The action of raceme NBP on the increase of the activities of ATPase and antioxidative enzymes seemed to be beneficial than that of (-) -NBP or (+) NBP.

CONCLUSIONThe results suggest that NBP improves energy pump and subsides oxidative injury which may contribute to its anti-neuronal apoptotic effect.

Adenosine Triphosphatases ; metabolism ; Animals ; Benzofurans ; pharmacology ; Cerebral Cortex ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; Glutathione Peroxidase ; metabolism ; Ischemic Attack, Transient ; enzymology ; Lipid Peroxidation ; Male ; Mitochondria ; enzymology ; Neuroprotective Agents ; pharmacology ; Rats ; Rats, Wistar ; Reperfusion Injury ; enzymology ; Superoxide Dismutase ; metabolism

The effects of SB203580 (SB) with different concentrations at different time points on renal function, apoptosis, P38MAPK activity and the expression, as well as the P38MAPK substrates in renal ischemia/reperfusion injury were investigated. Forty-nine rats were divided into 7 groups at random (n = 7 in each group) according to the durations of ischemia/reperfusion injury and the time of medication. Based on the orthogonal Latin side, the rats were injected, by caudal vein, with the same volume but different dosages of SB. BUN and Scr were determined. The apoptosis was detected with TUNEL kit. The protein was assayed qualitatively and semi-quantitatively by Western blot. The results showed that SB could significantly reduce the increased Scr and BUN, the apoptosis of renal tubular epithelia and the activation of P38MAPK all caused by renal ischemia/ reperfusion injury in a dose-dependent manner (P < 0.05). And the effect was most predominant when SB was given 3 h before renal ischemia. This suggested that SB could significantly alleviate renal ischemia/reperfusion injury. Administration of SB 3 h before ischemia at the concentration of 5 micromol/L could obtain an optimal effect.
Apoptosis/*drug effects ; Enzyme Inhibitors/pharmacology ; Imidazoles/*pharmacology ; Kidney/*blood supply ; Kidney/pathology ; Pyridines/*pharmacology ; Random Allocation ; Rats, Sprague-Dawley ; Reperfusion Injury/enzymology ; Reperfusion Injury/*pathology ; p38 Mitogen-Activated Protein Kinases/*metabolism

To establish rat model of lung ischemia/reperfusion (IR) in vivo, and to explore the effects of acidification pretreatment for respiratory acidosis on the expression of matrix metalloproteinase-9 (MMP-9) and the possible mechanisms.
 Methods: A total of 36 male Sprague-Dawley rats were divided into a sham group (S group), a IR group, and an experiment group (RA group) (n=12 in each group). The rat left lung hilum in the S group was dissociated, followed by perfusion without ischemia. After the left lung hilum in the IR group was blocked for 45 min, the rats were followed by reperfusion for 180 min. After left lung hilum in the RA group was dissociated, the respiratory parameters were adjusted so that pressure of end tidal carbon dioxide (PETCO2) reached 56-65 mmHg (1 mmHg=0.133 kPa) for 5 min, then the rats was subjected to IR. Lung tissue wet/dry (W/D) and lung permeability index (LPI) were calculated, while the lung histopathology was observed and the MMP-9 protein expression were measured.
 Results: Compared with the control group, the W/D and LPI in the IR group and the RA group increased after reperfusion (both P<0.05), and the levels of W/D and LPI in the group RA were lower than that in the IR group (P<0.05). LPI and pathology scores were significantly lower in the RA group than those in the IR group (both P<0.01). After IR, the expression of MMP9 in the lung tissues in the IR group and the RA group increased significantly (both P<0.01). The expression of MMP-9 protein in the RA group was significantly lower than that in the IR group (P<0.01).
 Conclusion: After lung IR injury, the expression of MMP-9 protein, vascular permeability and inflammatory exudation is increased. The acidification pretreatment for respiratory acidosis can inhibit the expression of MMP-9 protein and reduce inflammatory exudation after lung IR, showing a protective effect on lung IR injury.
Acidosis, Respiratory ; drug therapy ; prevention & control ; Animals ; Gene Expression Regulation, Enzymologic ; drug effects ; Lung ; enzymology ; Lung Injury ; enzymology ; Male ; Matrix Metalloproteinase 9 ; genetics ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; prevention & control

BACKGROUNDCaspases are important in the signaling pathway of cellular apoptosis. Caspase-3 protein expression has been shown to increase and parallel to neuronal apoptosis in retinal ischemia injury. This study was to determine whether caspase-1 is involved in neuronal cell death or in retinal ischemia and reperfusion injury.

METHODSIn twenty-one adult mice, ischemia was induced by increasing the intraocular pressure. The animals were sacrificed at 1 hour, 3 hours, 6 hours, 1 day, 3 days and 7 days after reperfusion. Frozen sections were used for caspase-1 immunostaining and TUNEL labeling.

RESULTSIn normal retina, no caspase-1 positive cells were seen. One hour after ischemia, numerous positive cells were noted in the ganglion cell layer (GCL) and inner side of inner nuclear layer (INL). At 3 hours, caspase-1 positive cells continued to increase and peaked at 6 hours, then decreased significantly at 1 day. TUNEL positive cells were detected at 3 hours and peaked at 1 day after ischemia. Double labeling of caspase-1 and TUNEL only showed few cells with co-localization after ischemia.

CONCLUSIONCaspase-1 immunoreactivity preceds to the TUNEL labeling in the GCL and INL after retinal ischemia and reperfusion injury and its early activation may play an important role in the initiation of neuronal apoptosis.

Animals ; Caspase 1 ; analysis ; metabolism ; Enzyme Activation ; Immunohistochemistry ; In Situ Nick-End Labeling ; Ischemia ; enzymology ; Male ; Mice ; Mice, Inbred C57BL ; NF-kappa B ; metabolism ; Reperfusion Injury ; enzymology ; Retinal Diseases ; enzymology

OBJECTIVETo investigate the mechanism of acupuncture at "Neiguan" (PC 6) and "Ximen" (PC 4) of the Pericardium Meridian in treatment of myocardial ischemia.

METHODSRats were randomly divided into 5 groups, sham-operation group, ischemia-reperfusion model group, Neiguan acupuncture group, Ximen acupuncture group and Zhigou acupuncture group. Electroacupuncture (EA) was given at corresponding acupoints for 20 min in the later 3 groups, followed by ligation of the left anterior descending branch of the coronary artery and 40 min later, acupuncture was given at the points for another 20 min, reperfusion for 60 min, with ECG monitoring. Then the myocardial tissue sample (below the ligation site) of the left cardiac ventricle was taken for preparation of sarcoplasmic reticulum, and determination of Ca2+-ATPase activity according to quantitative analysis of phosphorum. The relative mRNA levels were determined by Northerm Bolt analysis.

RESULTSIn the acupuncture groups, both the activities of Ca2+-ATPase and the gene expressions increased significantly as compared with the model group (all P < 0.01).

CONCLUSIONThe points of the Pericardium Meridian can obviously improve the Ca2+-ATPase activity and the gene expressions, reduce the degree of myocardial ischemia and reperfusion injury, and strength myocardial functions.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Calcium ; metabolism ; Calcium-Transporting ATPases ; genetics ; metabolism ; Male ; Myocardial Ischemia ; enzymology ; therapy ; Myocardial Reperfusion Injury ; enzymology ; therapy ; Myocardium ; enzymology ; RNA, Messenger ; analysis ; Rats ; Rats, Wistar