BACKGROUNDPlasma transfusion is a common clinical practice. Remote ischemic preconditioning (RIPC) protects organs against ischemia-reperfusion (IR) injury. Whether preconditioned plasma (PP), collected at late phase after RIPC, could protect organs against IR injury in vivo is unknown. This study explored whether transfusion of PP could reduce myocardial infarct size (IS) after IR in rat in vivo.

METHODSEighty Lewis rats were randomized to eight groups (n = 10 for each group). Two groups of plasma donor rats donated plasma at 48 h after transient limb ischemia (PP) or control protocol (nonpreconditioned plasma [NPP]). Six groups of recipient rats received normal saline (NS; NS-IR 1, and NS-IR 24 groups), NPP (NPP-IR 1 and NPP-IR 24 groups), or PP (PP-IR 1 and PP-IR 24 groups) at one or 24 h before myocardial IR. Myocardial IR consisted of 30-min left anterior descending (LAD) coronary artery occlusion and 180-min reperfusion. The area at risk (AAR) and infarct area were determined by double-staining with Evans blue and triphenyltetrazolium chloride. IS was calculated by infarct area divided by AAR. This was a 3 × 2 factorial design study, and factorial analysis was used to evaluate the data. If an interaction between the fluid and transfusion time existed, one-way analysis of variance with Bonferroni correction for multiple comparisons was used to analyze the single effects of fluid type when the transfusion time was fixed.

RESULTSIS in the NPP-IR 1 and PP-IR 1 groups was smaller than in the NS-IR 1 group (F = 6.838, P = 0.005; NPP-IR 1: 57 ± 8% vs. NS-IR1: 68 ± 6%, t = 2.843, P = 0.020; PP-IR 1: 56 ± 8% vs. NS-IR 1: 68 ± 6%, t = 3.102, P = 0.009), but no significant difference was detected between the NPP-IR 1 and PP-IR 1 groups (57 ± 8% vs. 56 ± 8%, t = 0.069, P = 1.000). IS in the NPP-IR 24 and PP-IR 24 groups was smaller than in the NS-IR 24 group (F = 24.796, P< 0.001; NPP-IR 24: 56% ± 7% vs. NS-IR 24: 68 ± 7%, t = 3.102, P = 0.026; PP-IR 24: 40 ± 9% vs. NS-IR 24: 68 ± 7%, t = 7.237, P< 0.001); IS in the PP-IR 24 group was smaller than in the NPP-IR 24 group (40 ± 9% vs. 56 ± 7%, t = 4.135, P = 0.002).

CONCLUSIONTransfusion of PP collected at late phase after remote ischemic preconditioning could reduce IS, suggesting that late-phase cardioprotection was transferable in vivo.

Animals ; Blood Component Transfusion ; methods ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Infarction ; etiology ; prevention & control ; Myocardial Reperfusion Injury ; complications ; Plasma ; Rats

To explore the protective effects of right coronary artery ischemic preconditioning and post-conditioning on myocardial ischemia reperfusion injury in rabbit heart.
 Methods: A total of 30 rabbits were randomly divided into 4 groups: a control group (n=7), an ischemia reperfusion group (IR group, n=8), an ischemic preconditioning group (IPC group, n=8) and an ischemic post-conditioning group (IPO group, n=7). Venous blood samples were taken at pre-operation, 1 and 6 h post-operation, and the concentration of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin-T (cTn-T) were measured. The infarct area of cardiac muscle was calculated.
 Results: Compared with the IR group, the levels of CK-MB and cTn-T at 1 and 6 h post-operation in the IPC group and the IPO group were reduced (all P<0.05). Compared with the IR group, the infarct size in the IPC group and the IPO group was significantly decreased, with significant difference (both P<0.05) .
 Conclusion: Right coronary artery ischemic preconditioning and post-conditioning exert significant protective effects on the myocardial ischemia reperfusion injury in New Zealand rabbits.
Animals ; Coronary Vessels ; Creatine Kinase, MB Form ; blood ; Heart ; Ischemia ; Ischemic Postconditioning ; Ischemic Preconditioning ; Ischemic Preconditioning, Myocardial ; Myocardial Infarction ; etiology ; pathology ; physiopathology ; prevention & control ; Myocardial Ischemia ; complications ; therapy ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; Rabbits ; Troponin T ; blood

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

To investigate the protective effect of preconditioning with hyperoside ( Hyp) against myocardial ischemia-reperfusion injury (MIRI) in rats and the role of PI3K/Akt signaling pathway. MIRI was established by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min in rats. Male SD rats were randomly divided into five groups: sham group,model group (MIRI),Hyp preconditioning group(Hyp), Hyp preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (Hyp + LY), and LY294002 group (LY). At the end of reperfusion, hemodynamic parameters were recorded as left ventricular systolic pressure (LVSP) , left ventricular end-diastolic pressure ( LVEDP) and maximal rate of increase and decrease of left ventricular pressure (± dP/dt(max)). Myocardial infaret size, the oxidative stress markers, myocardial enzymes indicators and inflammatory factors were also analyzed. The expressions of Akt, p-Akt, Bax and Bcl-2 proteins was detected by using Western blot method. The results showed that Hyp preconditioning remarkably improved cardiac constriction and relaxation function, reduced myocardial infarct size and enhanced the activities of oxidative stress markers about correlated to MIRI, such as superoxide dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px) and decreased the contents of malondialdehyde (MDA) as compared with MIRI group. Simultaneouly, the levels of myocardial enzymes, i. e. creatine kinase ( CK) and creatine kinase MB isoenzyme (CK-MB), and inflammatory factors, for instance tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased. Hyp pretreatment apparently restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression, increasing the levels of phosphorylation of Akt and Bcl-2 expression. These effects were inhibited by LY294002, a blocker of PI3K/Akt signaling pathway. These findings indicated that the cardioprotection of Hyp preconditioning against MIRI may be related to activating PI3K/Akt signaling pathway, upregulating the expression of BCL-2 protein and down-regulating the expression of Bax protein.
Animals ; Creatine Kinase ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Heart ; drug effects ; Humans ; Interleukin-6 ; genetics ; metabolism ; Ischemic Preconditioning, Myocardial ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; genetics ; prevention & control ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Proto-Oncogene Proteins c-akt ; genetics ; metabolism ; Quercetin ; administration & dosage ; analogs & derivatives ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; genetics ; metabolism

OBJECTIVETo study the protective effect of sufentanil preconditioning against myocardial ischemia-reperfusion (I/R) injury and the role of PI3K/Akt signaling pathway.

METHODSSixty male SD rats weighing 250-350 g were randomly divided into 5 equal groups, namely the sham-operated group, I/R group, sufentanil preconditioning group (Spc group), sufentanil preconditioning +PI3K inhibitor group (Spc+W group), and PI3K inhibitor group (W group). Myocardial I/R model was established by ligation of the anterior descending branch of the left coronary artery for 30 min followed by reperfusion for 120 min. Sufentanil was administered in 3 doses via the femoral vein before the occlusion, each at 1 µg/kg infused within 5 min at a 5-min interval. In Spc+W and W groups, PI3K inhibitor wortmannin (15 µg/kg) was given intravenously 5 min before sufentanil preconditioning and 35 min before ischemia, respectively. Heart rate and mean arterial pressure (MAP) were continuously monitored during I/R. At the end of reperfusion, blood samples were obtained to determine plasma activation of CK-MB and LDH. Acute infarct size was measured by triphenyltetrazolium chloride staining, and the myocardial tissues were obtained to detect the expression of phosphorylated Akt using Western blotting.

RESULTSPhosphorylated Akt expression was significantly up-regulated in I/R and Spc groups as compared with the sham group, and was significantly higher in Spc group than in I/R group. After reperfusion, sufentanil preconditioning significantly decreased myocardial infarct size (P<0.01) and lowered the levels of CK-MB (P<0.01) and LDH (P<0.01) compared with those in the I/R group. The I/R , Spc+W and W groups showed no significant differences in myocardial infarct size or the levels of CK-MB and LDH.

CONCLUSIONThe protective effect of sufentanil preconditioning against myocardium against I/R injury in rats may involve PI3K/Akt signaling pathway activation.

Animals ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Reperfusion Injury ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Signal Transduction ; Sufentanil ; pharmacology

OBJECTIVE: To determine the influence of stress on myocardial apoptosis in ischemic preconditioning group (IPC). METHODS: Twenty-four Japanese white rabbits were randomly divided into 4 groups (n=6): an etomidate group (the Etom group) of depressed stress established by intravenous etomidate, an IPC group, an ischemic reperfusion group (the IR group) and a methylprednisolone group (the MP group). Myocardial apoptosis was examined by DNA-laddering, in situ nick-end labeling (TUNEL) and Hoechst dyeing. RESULTS: The DNA ladder increased in the Etom group. The percentage of apoptosis by TUNEL method was 1.7%±0.2% in the IPC group, 2.3%±0.8% in the MP group, 3.8%±1.3% in the IR group and 3.0%±0.4% in the Etom group. Hoechst dying was 4.1%±0.9% in the IPC group, 3.5%±0.4% in the MP group, 6.2%±1.6% in the IR group and 7.6%±0.4% in the Etom group. There was significant difference between the IPC group and the Etom group or IR group, and also between the MP group and the IR group. CONCLUSION A depressed stress response impairs the inhibition on myocardial apoptosis in ischemic preconditioning. Methylprednisolone may inhibit myocardial apoptosis.
Animals ; Apoptosis ; Etomidate ; pharmacology ; Heart ; drug effects ; Ischemic Preconditioning ; Ischemic Preconditioning, Myocardial ; Methylprednisolone ; pharmacology ; Myocardium ; pathology ; Rabbits

OBJECTIVETo investigate the protective effect of dexmedetomidine (Dex) preconditioning against ischemia/reperfusion (I/R) injuries in isolated rat hearts and its relation to mitochondrial permeability transition pore (mPTP) and mitochondrial ATP-sensitive K(+) channel (mitoKATP).

METHODSThe hearts of male SD rats were isolated to mount on the Langendorff apparatus and subjected to 30 min global ischemia followed by 120 min reperfusion. The isolated hearts were treated with Dex (10 nmol/L) before ischemia for 15 min. The left ventricular hemodynamic parameters,coronary flow (CF) and the lactate dehydrogenase (LDH) release in the coronary effluent at 5 min reperfusion were measured. The formazan content was assayed to determine the myocardial viability at the end of reperfusion.

RESULTSCompared with normal controls, I/R markedly decreased the left ventricular developed pressure and CF during the whole reperfusion period and the formazan content; while the left ventricular end diastolic pressure and LDH release were significantly increased. Dex preconditioning markedly improved the myocardial viability and cardiac function (P<0.01), which were reversed by the treatment with both atractyloside (20 μmol/L before ischemia), an opener of mPTP, and 5-hydroxydecanoate (100 μmol/L at the beginning of reperfusion), an inhibitor of mitoKATP, for 20 min.

CONCLUSIONDex has protective effect against I/R injuries in isolated rat hearts, which may be related to inhibiting the opening of mPTP at the beginning of reperfusion and activating mitoKATP before ischemia.

Animals ; Dexmedetomidine ; pharmacology ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; Male ; Mitochondrial Membrane Transport Proteins ; drug effects ; Myocardial Reperfusion Injury ; physiopathology ; prevention & control ; Potassium Channels ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo observe the protective effect of Wufu Jingfang (WJ, containing Aconitum carmichaeli Debx, Radix Aconiti Lateralis Preparatae, Rhizoma Pinelliae, and snakegourd fruit) on myocardial ischemia-reperfusion injury (I/R) of rats, thus exploring the feasibility of recipes containing eighteen incompatible pairs for specific pathological conditions.

METHODSFifty male Wistar rats were randomly divided into five groups, i.e., the sham-operative control group (the SH group), the I/R group, the low dose WJ I/R group (the I/R +JFL group), the middle dose WJ I/R group (the I/R +JFM group), the high dose WJ I/R group (the I/R +JFH group), 10 in each group. Rats in the latter three groups were administered with WJ at 0.75 mL/100 g, 1.50 mL/100 g, and 3.00 mL/100 g body weight for 14 consecutive days by gastrogavage. All groups except the SH group received ligation of left anterior descending branch of coronary artery for 30-min ischemia followed by 120-min reperfusion. The micro-structural changes of myocardial mitochondria were observed by transmission electron microscope. The ischemic cardiomyocyte apoptosis was detected in each group using one-step terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL). The mRNA expressions of B-cell leukemia/lymphoma 2 (Bcl-2) and Bcl-2 associated x protein (Bax) were detected by RT-PCR. The activities of lactic dehydrogenase (LDH) and creatine kinase (CK) were detected using ELISA. The myocardial infarct size was detected.

RESULTSCompared with the I/R group, WJ pretreatment significantly suppressed the release of LDH and CK (Besides, the release of LDH and CK reduced along with increased dose.), reduced the myocardial infarct size, and lowered myocardial apoptosis index (P < 0.05). WJ pretreatment also modulated Bcl-2/Bax ratio by up-regulating Bcl-2 expression level while decreasing Bax expression level.

CONCLUSIONSWJ pretreatment might protect the heart from I/R injury via decreasing myocardial cell apoptosis. The results suggested that eighteen incompatible pairs is not absolute, but relative. Chinese medical preparation containing opposite Chinese herbs could be used in specific pathological states such as ischemic cardiomyopathy.

Animals ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Reperfusion Injury ; pathology ; Rats ; Rats, Wistar

Myocardial ischemic preconditioning and postconditioning can reduce myocardial infarct size, improve myocardial contractility, protect coronary endothelial and myocardial cell ultrastructure, as well as reduce the incidence of arrhythmias. Clinical practice has confirmed the safety and efficacy of these two methods of myocardial protection. This paper reviewed about ischemic preconditioning and postconditioning protection mechanisms in myocardial ischemia reperfusion injury and clinical research literatures in recent years, to provide a theoretical basis for finding new treatment strategies on the prevention and treatment of ischemic cardiomyopathy.
Animals ; Humans ; Ischemic Postconditioning ; methods ; Ischemic Preconditioning, Myocardial ; methods ; Myocardial Infarction ; therapy ; Myocardial Ischemia ; therapy ; Myocardial Reperfusion ; adverse effects ; Myocardial Reperfusion Injury ; etiology ; prevention & control ; Receptors, G-Protein-Coupled ; agonists ; Signal Transduction

Animals ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Ischemia ; prevention & control ; Myocardial Reperfusion Injury ; prevention & control ; Rabbits