OBJECTIVETo investigate whether adiponectin plays a role in the protection of myocardium in the rat myocardial ischemia preconditioning (IPC) model.

METHODInfarct size was measured by Masson's Trichrome staining, the expression of protein and mRNA of adiponectin at 0, 6, 12 and 24 h after IPC was examined by immunohistochemistry and quantitative real time RT-PCR, plasma levels of adiponectin at above mentioned four time points after IPC were detected by ELISA in IPC and MI rats.

RESULTInfarct size was smaller in IPC than in MI rats (20% ± 2% vs. 31% ± 3%, P < 0.05). The expression of adiponectin mRNA at 6 h and 12 h after IPC was 2.2 and 2.1 times higher than in Sham rats at respective time points (P < 0.05). Immunohistochemistry staining evidenced increased adiponectin expression in the ischemic area and weak expression of adiponectin in non-ischemic area (P < 0.05). Compared to the sham group, the plasma level of adiponectin increased significantly at 0, 6 and 12 h after IPC (0 h: 7.40 ± 0.47 vs. 10.90 ± 1.74; 6 h: 8.18 ± 1.41 vs. 10.98 ± 1.74; 12 h: 6.97 ± 1.02 vs. 9.31 ± 0.96, P < 0.05).

CONCLUSIONIPC reduced infarction size, upregulated the myocardial expression of adiponectin at mRNA and protein levels, and increased plasma adiponectin concentration, suggesting that the adiponectin may play a critical role in the protective effect of IPC.

Adiponectin ; metabolism ; Animals ; Ischemic Preconditioning, Myocardial ; Male ; Myocardial Infarction ; metabolism ; prevention & control ; Myocardial Ischemia ; metabolism ; prevention & control ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley

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

Myocardial damage and decrease in blood-pumping function, which occur immediately after severe burns, not only lead to cardiac insufficiency, but also induce or exacerbate burn shock, constituting one of the initiating factors for visceral ischemic/hypoxic damage. Therefore, prompt and effective prevention and treatment of myocardial damage are important for resuscitation of burn patients with severe burns, especially in those whose hospitalization is delayed. In this review, the potential clinical strategies including angiotensin-converting enzyme inhibitors, modulation of beta-AR-mediated signal transduction and the "molecular switch Gsalpha/Gialpha", modulation of ion channels, the control of NO donor, the use of anti-inflammatory agents, and antioxidants, and energy metabolic modulation are introduced in details.
Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Burns ; complications ; metabolism ; Humans ; Hypoxia ; etiology ; metabolism ; prevention & control ; Myocardial Ischemia ; etiology ; metabolism ; prevention & control ; Myocardium ; metabolism ; Signal Transduction

UNLABELLEDOBJECTIVE To investigate the effect of Guanxinkang (GXK) on ATP-sensitive potassium channel in myocardial cells of rat with ischemic/reperfusion injury and its possible mechanism for cardiac vascular protection and anti-myocardial ischemia.

METHODSWistar rats were established into I/R injured models by 10 min perfusion--30 min no-flow ischemia--45 min reperfusion, and divided into 5 groups: the I/R model group and 4 treatment groups treated respectively with glibenclamide, pinacidil, GXK and GXK+glibenclamide. Rats' heart were isolated for detecting Ca(2+)-Mg(2+)-ATPase, Na(+)-K(+)-ATPase activity in myocardial cells, and the changes of current in ATP-sensive potassium channel (K(ATP)) was recorded by whole patch clamp technique. Data were controlled by those taken from normal rats in a control group.

RESULTSK(ATP) in the GXK treated group were higher than that in the I/R model group; and similar to that in the pinacidil treated group (P > 0.05). As compared with the model group, activities of Ca(2+)-Mg(2+)-ATPase and Na(+)-K(+)-ATPase in the GXK treated group were increased significantly (P < 0.05).

CONCLUSIONGXK shows definite intervention effect on myocardial I/R injury; which is possibly by way of furthering the opening of K(ATP) channel, decreasing Ca2+ influx, and inhibiting Ca2+ overload.

Animals ; Calcium ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; KATP Channels ; drug effects ; Male ; Myocardial Ischemia ; metabolism ; physiopathology ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Wistar

AIMTo investigated the effect of estrogen on global myocardial ischemia/reperfusion (I/R) injury in ovariectomized (Ovx) rats.

METHODSSprague-Dawley rats were randomly repartitioned into three groups including sham-operated(Sham), ovariectomized (Ovx), or ovariectomized and then given 17beta-estradiol (Ovx + E2). Hearts were excised, mounted on the Langendorff. After the initial stabilization period, all of the three group hearts were randomly divided into normal perfusion subgroup (Control) and I/R perfusion subgroups. Control, perfused for 60 min after stabilization. I/R perfusion subgroups divided into 10 min I + 30 min R, 20 min I + 30 min R, 30 min I + 0 min R, 30 min I + 5 min R, 30 min I + 15 min R and 30 min I + 30 min R. And then, every group hearts were isolated into the single cardiomyocyte. The cardiomyocytes basal contraction and isoproterenol(ISO) stimulation contraction were measured. The viability and yield of cardiomyocytes were counted. LDH and CK concentrations in coronary effluent were assayed with assay kit.

RESULTSThe viability and yield of cardiomyocytes were significantly decreased in the conditions of 30 min ischemia followed by different times of reperfusion. The releases of LDH and CK in coronary effluent were significantly increased in the conditions of 30 min ischemia followed by different times of reperfusion. Except the 10 min and 20 min ischemia, the releases of LDH and CK were significantly increased in Ovx during I/R. Ovx + E2 could abate the heart injury through decreasing the releases of LDH and CK. Besides the control and the 10 min I + 30 min R groups, the myocardial basal and ISO stimulation contraction were higher from Ovx than Sham, and the effect was reversed by Ovx + Ez.

CONCLUSIONThe results indicate estrogen plays a cardioprotective role in global myocardial ischemia/reperfusion injury in ovariectomized (Ovx) rats.

Animals ; Estradiol ; pharmacology ; Estrogens ; pharmacology ; Female ; Myocardial Contraction ; physiology ; Myocardial Ischemia ; physiopathology ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; metabolism ; physiology ; Ovariectomy ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Cytosolic Ca2+ concentration of rat ventricular cells was measured under varying experimental conditions by using a fluorescent Ca2+ indicator, Fura-2. Resting [Ca2+]i of rat myocyte was 150 +/- 30 nM (n = 39), and this value was compatible with others. The Perfusion of cardioplegic solution significantly increased [Ca2+]i, and this effect was further augmented by hypothermia (p<0.05). Application of nifedipine (5 x 10(-7) M) to the perfusate or pretreatment of caffeine (10 mM) had no apparent effect on this cardioplegia-induced [Ca2+]i change. But Ni2+ (5 mM), an antagonist of Na+/Ca2+ exchange mechanism, prevented the [Ca2+]i change during cardioplegia (p<0.05). Magnitude of cardioplegia-induced [Ca2+]i increase was also dependent on the Ca2+ concentration of cardioplegic solution. These results suggest that Na+/Ca2+ exchange may play an important role in cardioplegia-induced [Ca2+]i change. To rule out the possibility whether the protective effect of hypothermic cardioplegia is due to the preservation of high-energy phosphate store or decreasing the transmembrane ionic fluxes by phase transition, we exhausted a energy store of cardiac cell by application of 2,4 dinitrophenol to the bath and measured its effect on [Ca2+]i change during cardioplegia. Hypothermic cardioplegia delayed the onset of [Ca2+]i increase and decreased its amplitude compared to those of normothermic cardioplegia. From the above results, hypothermic cardioplegia may protect the cardiac cells from ischemic insult by preserving a high-energy phosphate store. Application of Ni2+ to the cardioplegic solution or reduction of external Ca2+ concentration also had some protective effect, since it prevented [Ca2+]i increase during cardioplegia.
Animal ; Calcium/*metabolism ; Cytosol/metabolism ; *Heart Arrest, Induced ; Heart Ventricle/metabolism ; Hypothermia, Induced ; Myocardial Ischemia/metabolism/*prevention & control ; Myocardium/*metabolism ; Rats ; Support, Non-U.S. Gov't

OBJECTIVETo investigate whether the release of nitric oxide (NO) was involved in the cardioprotection of ethanol postconditioning in isolated rat hearts.

METHODSHearts isolated from male SD rats were subjected to 30 min of regional ischemia (occlusion of left anterior descending artery) followed by 120 min of reperfusion. Ethanol postconditioning was fulfilled through perfusion of 50 mmol/L ethanol for 15 min (at the end of cardiac ischemia for 5 min and at the beginning of reperfusion for 10 min). The rats were divided into five groups: normal, ischemia and reperfusion, ethanol postconditioning, ethanol postconditioning + L-nitro-arginine-methylester (L-NAME) and ethanol postconditioning + atractyloside. The ventricular hemodynamic parameters and lactate dehydrogenase (LDH) release during reperfusion were measured. The infarct size was measured by TTC staining method and NO content was measured by nitric acid reductase method. The expressions of Bcl-2 and Bax mRNA were detected by RT-PCR analysis.

RESULTSIn contrast to ischemia and reperfusion, ethanol postconditioning improved left ventricular developed pressure, rate pressure product during reperfusion, reduced LDH release and infarct size. NO content was decreased. The ratio of Bcl-2/Bax was increased. Administration of nitric oxide synthase inhibitor L-NAME or mitochondrial permeability transition pore opener atractyloside both attenuated the role of ethanol postconditioning, which inhibited the recovery of hemodynamic parameters, the decreases of LDH and infarct size. NO content was decreased further. The ratio of Bcl-2/Bax was decreased.

CONCLUSIONThe cardioprotection of ethanol postconditioning may be associated with reducing nitric oxide release, inhibiting the opening of mitochondrial permeability transition pore and decreasing the happening of apoptosis.

Animals ; Ethanol ; therapeutic use ; In Vitro Techniques ; Ischemic Postconditioning ; Male ; Mitochondria, Heart ; metabolism ; Myocardial Ischemia ; metabolism ; prevention & control ; Myocardial Reperfusion Injury ; metabolism ; prevention & control ; Myocardium ; metabolism ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the effects of peroxisome proliferator-activated receptor (PPAR) alpha agonist Fenofibrate (FF) on energy metabolism and histology in isoproterenol (Iso) induced acute myocardial ischemic injury model.

METHODSMale Wistar rats were randomly divided into control group, Iso group (5 mg/kg, i.p.) and FF group (80 mgxkg(-1)xd(-1) per gavage for 7 days, then Iso 5 mg/kg, i.p. n = 30 each). Twenty-four hours post Iso, heart weight/body weight ratio, myocardial histopathological changes (HE staining), serum and myocardial free fatty acids (FFA) levels, the myocardial protein expression of PPARalpha (Western blot) were determined.

RESULTCompared with the control group, pathological myocardial injuries were observed under light microscope in Iso treated hearts and FF pretreatment could significantly attenuate these changes [necrotic area: 0 vs (10.00 +/- 3.00)% vs (7.36 +/- 2.60)%], the heart weight/body weight ratio, FFA in serum (501.17 +/- 43.69 vs 939.53 +/- 69.51 vs 736.53 +/- 70.30 micromol/L) and myocardium (62.01 +/- 9.19 vs 140.59 +/- 19.34 vs 116.28 +/- 14.03 micromol/L) were significantly increased while myocardial protein expressions of PPARalpha (251.57 +/- 10.95 vs 191.97 +/- 10.74 vs 215.08 +/- 9.61) was significantly downregulated in the Iso group and FF pretreatment could significantly attenuate these changes (all P < 0.05).

CONCLUSIONOur data suggested that the FFA utilization was decreased in Iso induced acute myocardial ischemic injury and FF could attenuate Iso induced myocardial damage via activating PPARalpha signaling pathway.

Animals ; Disease Models, Animal ; Energy Metabolism ; Fenofibrate ; pharmacology ; therapeutic use ; Isoproterenol ; Male ; Myocardial Ischemia ; chemically induced ; metabolism ; prevention & control ; Myocardial Reperfusion Injury ; chemically induced ; metabolism ; prevention & control ; Myocardium ; metabolism ; PPAR alpha ; metabolism ; Rats ; Rats, Wistar

OBJECTIVETo explore the cardioprotection effect of co-treatment with ischemic postconditioning and preconditioning in ischemia/reperfusion (I/R) injury and the related mechanism.

METHODSMale Sprague-Dawley rats were used for Langendorff isolated heart perfusion. The hearts were subjected to global ischemia for 60 min followed by 120 min of reperfusion. The cardiomyocyte viability was measured by MTT-formazan method, and the cardiac injury was evaluated by the levels of lactate dehydrogenase (LDH) in the coronary effluent. Ventricular hemodynamic parameters were also measured.

RESULTIn 60 min of ischemia and 120 min of reperfusion group, ischemic postconditioning increased formazan content, reduced LDH release, but hemodynamic parameters did not improved. Co-treatment with ischemic postconditioning and preconditioning during the prolonged ischemia further improved the hemodynamic parameters. The calcium activated potassium channel antagonist paxilline attenuated the effect of co-treatment with ischemic postconditioning and preconditioning.

CONCLUSIONIschemic postconditioning and preconditioning may synergically protect myocardium from severe ischemia injury, which may be related to calcium-activated potassium channel.

Animals ; Cell Survival ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; methods ; L-Lactate Dehydrogenase ; metabolism ; Male ; Myocardial Ischemia ; pathology ; physiopathology ; Myocardial Reperfusion Injury ; metabolism ; physiopathology ; prevention & control ; Myocardium ; metabolism ; pathology ; Potassium Channels, Calcium-Activated ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the protection effects and the mechanisms of Huoxue Anxin Recipe (HAR) on acute myocardial infarction (AMI) rats.

METHODSThe AMI Wistar rat model was prepared by ligating the left anterior descending coronary artery. By taking elantan long as the positive control drug, HAR was extracted from Chinese herbs by modern pharmacological methods and composed according to theories of Chinese medicine (CM). The medication time started from the day of modeling to the 21st day of the modeling. The heart function, the morphological changes of the heart, changes in the mRNA and protein levels of toll like receptor 4 nuclear factor kappa B tumor necrosis factor alpha (TLR4-NFkappaB-TNFalpha) pathway were observed.

RESULTSCompared with the sham-operation group, the ejection fraction (EF) and left ventricular fractional shortening (FS) significantly decreased (P < 0.01), the left ventricular intemal dimension end-diastolic (LVIDd) and left ventricular internal dimension end-systolic (LVIDs) significantly increased (P < 0.01), the mRNA and protein levels of TLR4-NFkappaB-TNFalpha channel significantly increased in the model group (P < 0.01). The infarction in the front wall of the left ventricle was obviously seen, accompanied with severe inflammatory cell infiltration and collagen deposition in model group. Compared with the model group, the EF and FS significantly increased, LVIDd and LVIDs significantly decreased in the positive control group, the high and low dose HAR groups (P < 0.05, P < 0.01). The infracted area of the front wall of the left ventricle was obviously contracted. The inflammatory cell infiltration and collagen deposition were obviously alleviated. In the high and low dose HAR groups, the mRNA and protein expression levels of TLR4-NFkappaB-TNFalpha significantly decreased (P < 0.05, P < 0.01), but no inhibition was found in the positive control group.

CONCLUSIONSHAR could significantly improve the morphological structures and functional abnormality induced by myocardial ischemia in AMI rats. Its effects was correlated with inhibiting TLR4-NFkappaB-TNFalpha pathway.

Animals ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Myocardial Infarction ; drug therapy ; metabolism ; Myocardial Ischemia ; metabolism ; prevention & control ; NF-kappa B ; metabolism ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism