Humans ; Ischemia ; metabolism ; pathology ; therapy ; Ischemic Postconditioning ; methods ; Myocardial Reperfusion Injury ; metabolism ; pathology ; therapy

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

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 observe the alteration of cardiac myocyte nuclear inositol 1,3,4,5-tetrakisphosphate receptor (IP(4)R) binding properties in rat subjected to myocardial ischemic reperfusion in order to further make it clear whether this change is involved in the molecule mechanism of cell apoptosis of rat with myocardial ischemic reperfusion.

METHODSExtracting of cardiac myocyte nucleus was accomplished by saccharose density gradient centrifugation method, the binding properties of nuclear IP(4)R in different conditions were detected by radioligand binding assay. Apoptosis index of myocardial cell was determined by using TUNEL assay.

RESULTS(1) Myocardial cell apoptosis index in rat heart underwent 30 min regional ischemia and 3 h reperfusion increased distinctly compared with that in control group (P < 0.01). (2) There were two IP(4) binding sites located to the nuclear envelope. (3) In ischemic reperfusion injury (IRI) group, Bmax from high affinity binding site of nuclear IP(4)R significantly increased compared with that in sham-operated group, whereas Bmax from low affinity binding site didn't change. Kd values of both sites were all significantly decreased by 63% and 55%, respectively. (4) Phosphorylation of nuclear IP(4)R by PKC increased markedly its binding ability both in IRI and control group (P < 0.05), which was more apparent in IRI group. (5) In sham-operated group, the binding ability of nuclear IP(4)R increased with increasing free calcium concentrations in cytoplasm, and the binding properties of IP(4)R in IRI group were also increased in the condition of calcium overloading.

CONCLUSIONThe increasing of binding properties of nuclear IP(4)R from ischemic reperfusion heart may be one of important mechanism involved in myocardial cell apoptosis, furthermore resulting in myocardial IRI.

Animals ; Apoptosis ; Cell Nucleus ; metabolism ; Male ; Myocardial Reperfusion ; Myocardial Reperfusion Injury ; metabolism ; pathology ; Myocytes, Cardiac ; metabolism ; Rats ; Rats, Wistar ; Receptors, Cytoplasmic and Nuclear ; metabolism

AIMThe observation of the relationship between the level of NO detected by ESR in the blood and the myocardial apoptosis and function caused by the recurrent, reversible myocardial ischemia/reperfusion injury.

METHODSFifteen New Zealand white rabbits were randomly divided into three groups (n = 5): (1) control group, (2) L-Arg group, (3) L-NNA group. The rabbits were anesthetized with intravenous pentobarbital. A suture ligature was passed around the left anterior descending coronary artery (LAD), so it could be snare occluded and reperfused. The LAD was occluded for 10 min three times, the first and second occlusions were followed by 10 min of reflow, after the third occlusion, the reperfusion was 120 min.

RESULTSIn all groups dp/dt(max) began to decrease at 5 min after the first ischemia. But compared with control group at 5 min after first reperfusion: in L-Arg group NO and apoptosis level were elevated but dp/dt(max) decreased significantly. In L-NNA group NO and apoptosis decreased significantly, dp/dt(max) improved significantly.

CONCLUSIONThe fact that the level of NO and apoptosis elevated suggested that they had taken part in the process of myocardial stunning.

Animals ; Apoptosis ; Female ; Male ; Myocardial Reperfusion Injury ; metabolism ; pathology ; physiopathology ; Myocytes, Cardiac ; metabolism ; Nitric Oxide ; metabolism ; Rabbits

OBJECTIVETo establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles (MVs) from myocardial ischemic preconditioning (IPC) treated rats (IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion (I/R) injury in rats.

METHODSMyocardial IPC was elicited by three.cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending (LAD) coronary artery. Platelet-free plasma (PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFR PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 µm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure (MAP), heart rate (HR) and ST-segment of electro-cardiogram (ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin (HE) staining. The activity of plasma lactate dehydrogenase (LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining.

RESULTSTotal IPC-MVs and different phenotypes, including platelet-derived MVs (PMVs), endothelial cell-derived MVs (EMVs), leucocyte-derived MVs (LMVs) and erythrocyte-derived MVs (RMVs) were all isolated which were identified membrane vesicles (<1 Vm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats (P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR (P<0.01), decreased ST-segment and LDH activity (P < 0.05, P < 0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment (P < 0.01).

CONCLUSIONThe method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.

Animals ; Cell-Derived Microparticles ; metabolism ; Coronary Vessels ; pathology ; Flow Cytometry ; Heart Rate ; Ischemic Preconditioning, Myocardial ; Myocardial Infarction ; physiopathology ; Myocardial Reperfusion Injury ; physiopathology ; Myocardium ; pathology ; Phenotype ; Rats

OBJECTIVETo investigate the effects of hydrogen sulfide preconditioning on myocardial ischemia reperfusion injury in rats.

METHODSSprague-Dawley male rats were divided into 4 groups with 10 in each group: in S group rats received sham operation; in IR group rats were given with NS (1.0 ml/kg iv) 24 h before ischemia; in H group rats were treated with NaHS (0.05 mg/kg iv) 24 h before ischemia; and in D group, NaHS-treated rats received 5-hydroxydecanoate (5-HD) 15 min before ischemia. Rats in IR group,H group and D group were subjected to ischemia by occlusion of coronary artery for 30 min followed by 2 h of reperfusion. At the end of the reperfusion,myocardial infarct size was measured. SAM-s was measured by Western blotting. Plasma SOD activity and MDA were determined at the end of reperfusion.

RESULTSThe infarct size was significantly lesser in H group (25.40 % ± 3.54%) than that in IR group (38.27% ±5.64%,P<0.05). The SAM-s protein expression in myocardium was significantly lower in H group than that in IR group. The plasma MDA content was significantly lower and SOD activity was higher in H group than those in IR group,but there was no difference between IR group and D group.

CONCLUSIONThe hydrogen sulfide preconditioning attenuates myocardial IR injury possibly through down-regulating SAM-s expression,reducing the production of oxygen free radicals and enhancing anti-oxidize effect in rats.

Animals ; Disease Models, Animal ; Hydrogen Sulfide ; pharmacology ; Ischemic Preconditioning, Myocardial ; Male ; Myocardial Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: To investigate the effect of acute cardiac injury on the activation of interleukin-1 beta (IL-1 beta) signaling in the spinal cord. METHODS: Acute cardiac injury rat model was established by intra-myocardial injection of formalin through diaphragm. IL-1 beta expression was determined by Western blot, immunohistochemistry and in situ hybridization. The DNA binding activities of 2 IL-1 beta transcription factors, activator protein (AP)-1 and nuclear factor kB (NF-kappaB) were measured by electrophoretic mobility shift assay (EMSA). RESULTS: After cardiac injury, the IL-1 beta protein level was dramatically upregulated in the spinal cord. The upregulated IL-1 beta was mainly expressed in the neurons in the lamina II approximately IV of the spinal cord. In response to cardiac injury, the DNA binding activities of NF-kappaB and AP-1 were greatly activated. CONCLUSION Acute cardiac injury could activate the spinal IL-1 beta signaling, which, in turn, may be involved in the progression of heart failure after injury.
Animals ; Interleukin-1beta ; genetics ; metabolism ; Male ; Myocardial Reperfusion Injury ; chemically induced ; metabolism ; pathology ; Myocardium ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction ; Spinal Cord ; metabolism

The effect of limb ischemic preconditioning (LIP) on ischemia-reperfused myocardium was examined in the urethane-anesthetized rats to determine whether LIP produces cardioprotection and to observe the roles of adenosine and neural reflex in this effect. The area at risk (AR) and infarct area (IA) were determined using Evans blue and nitro-blue tetrazolium staining respectively. Infarct size (IS) was defined as 100xIA/AR (%). The results obtained are as follows: (1) During 30 min myocardial ischemia and subsequent 120 min reperfusion, the myocardial infarct size occupied 51.48+/-0.82% of the area at risk. (2) LIP significantly reduced the myocardial infarct size to 35.14+/-0.88% (p<0.01 ), indicating the cardioprotective effect of such an intervention. (3) Femoral nerve section (FNS) completely abolished the cardioprotection afforded by LIP. (4) Intrafemoral artery injection of adenosine (10 nmol/kg) produced a similar effect to that of LIP, reducing the myocardial infarct size to 37.28+/-1.68%, while intrafemoral vein injection of the same dose of adenosine showed no effect. (5) Pretreatment with a selective adenosine A(1) receptor antagonist 8-cyclopentyl-1,diproylxanthine (DPCPX ) (32 nmol/kg) partially abolished the cardioprotection of LIP on myocardium. Taken together, it is concluded that LIP reduces infarct size following myocardial ischemia-reperfusion, and that the locally released adenosine and thereby the activated relevant neural pathway play an important role in the cardioprotection provided by LIP.
Adenosine ; metabolism ; Animals ; Extremities ; blood supply ; Ischemic Preconditioning ; Male ; Myocardial Infarction ; pathology ; prevention & control ; Myocardial Reperfusion Injury ; pathology ; prevention & control ; Rats ; Rats, Sprague-Dawley

OBJECTIVEIn this study, we try to find the better protocol of limb ischemia postconditioning by observing different protective effects of limb ischemic postconditioning (different strength and time windows in rabbits).

METHODS42 healthy New Zealand rabbits were randomly divided into 7 groups (n = 6): Sham; Control (CON); Skeletal muscle postconditioning (SP); 6 min-delayed skeletal muscle postconditioning (6M-DSP); 1 min-delayed skeletal muscle postconditioning (1M-DSP); Strengthen skeletal muscle postconditioning (SSP); Weakened skeletal muscle postconditioning (WSP). Acute ischemia/reperfusion (I/R) model was induced by 45 minutes occlusion on left circumflex coronary artery (LCX) and 2 hours reperfusion in all anesthetized open-chest rabbits except the Sham. Limb ischemia was induced by external iliac arteries occlusion and reperfusion through artery clamps. The extent of myocardial infarction was assessed by triphenyltetrazolium (TTC) staining. Blood serum creatine kinase (CK) activity and lactate dehydrogenase (LDH) activity were measured at baseline,the end of ischemia, after 1 hour and 2 hours of reperfusion respectively.

RESULTSCompared with the CON, the weight ratio and area ratio of myocardial infarction size were significantly decreased by 49.97% and 43.78% in SP, by 42.32% and 42.68% in 1M-DSP, by 48.36% and 48.86% in SSP (P < 0.05). But there was no significant difference between SP and 1M-DSP and SSP (P > 0.05). Otherwise, compared with the CON, myocardial infarct size was not significantly reduced in 6M-DSP or WSP (P > 0.05). The change of CK was similar to the trend of myocardial infarct size.

CONCLUSIONThe limb ischemia strength of 5 mini/1 minR x 1 cycle could significantly reduce the myocardial ischemia/ reperfusion injury in rabbits, if it was achieved before myocardial reperfusion.

Animals ; Extremities ; blood supply ; Ischemic Postconditioning ; methods ; Male ; Muscle, Skeletal ; blood supply ; Myocardial Infarction ; pathology ; Myocardial Reperfusion Injury ; pathology ; prevention & control ; Myocardium ; metabolism ; Rabbits