Speckle tracking imaging improves in vivo assessment of EPO-induced myocardial salvage early after ischemia-reperfusion in rats

2010 ◽  
Vol 298 (6) ◽  
pp. H1679-H1686 ◽  
Author(s):  
Frederic Treguer ◽  
Erwan Donal ◽  
Sophie Tamareille ◽  
Nehmat Ghaboura ◽  
Geneviève Derumeaux ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Rat Model ◽  
Speckle Tracking ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Myocardial Salvage ◽  
Speckle Tracking Imaging ◽  
Triphenyltetrazolium Chloride ◽  
Conventional Echocardiography

A noninvasive assessment of infarct size and transmural extension of myocardial infarction (TEMI) is fundamental in experimental models of ischemia-reperfusion. Conventional echocardiography parameters are limited in this purpose. This study was designed to examine whether speckle tracking imaging can be used in a rat model of ischemia-reperfusion to accurately detect the reduction of infarct size and TEMI induced by erythropoietin (EPO) as early as 24 h after reperfusion. Rats were randomly assigned to one of three groups: myocardial infarction (MI)-control group, 45 min ischemia followed by 24 h of reperfusion; MI-EPO group, similar surgery with a single bolus of EPO administered at the onset of reperfusion; and sham-operated group. Short-axis two-dimensional echocardiography was performed after reperfusion. Global radial (GSr) and circumferential (GScir) strains were compared with infarct size and TEMI assessed after triphenyltetrazolium chloride staining. As a result, ejection fraction, shortening fraction, GSr, and GScir significantly correlated to infarct size, whereas only GSr and GScir significantly correlated to TEMI. EPO significantly decreased infarct size (30.8 ± 3.5 vs. 56.2 ± 5.7% in MI-control, P < 0.001) and TEMI (0.37 ± 0.05 vs. 0.77 ± 0.05 in MI-control, P < 0.001). None of the conventional echocardiography parameters was significantly different between the MI-EPO and MI-control groups, whereas GSr was significantly higher in the MI-EPO group (29.1 ± 4.7 vs. 16.4 ± 3.3% in MI-control; P < 0.05). Furthermore, GScir and GSr appeared to be the best parameters to identify a TEMI >0.75 24 h after reperfusion. In conclusion, these findings demonstrate the usefulness of speckle tracking imaging in the early evaluation of a cardioprotective strategy in a rat model of ischemia-reperfusion.

scholarly journals A preliminary study on the evaluation of left atrial function of rheumatoid arthritis by two dimensional speckle tracking imaging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiang Ji ◽  
Xia Zhang ◽  
Guojie Li
Keyword(s):  
Rheumatoid Arthritis ◽  
Left Atrial ◽  
Speckle Tracking ◽  
Global Longitudinal Strain ◽  
Control Group ◽  
Two Dimensional ◽  
Speckle Tracking Imaging ◽  
Group I ◽  
Group Ii ◽  
Conventional Echocardiography

AbstractTo evaluate the changes of left atrial (LA) geometry and function in patients with rheumatoid arthritis (RA) by conventional echocardiography and two-dimensional speckle tracking imaging (2D-STI). We enrolled 46 RA patients with a duration of < 5 years as Group I, 40 RA patients with a duration of ≥ 5 years as Group II, and 40 normal subjects as the control group. Conventional echocardiography was conducted to measure traditional parameters. The LA strain during reservoir phase (LASr), LA strain during conduit phase (LAScd), LA strain during contraction phase (LASct), and LA global longitudinal strain (LAGLS) were obtained from 2D-STI. Related ultrasound results were compared. The LASct was significantly higher in Group I than in control group (P < 0.05). The LASr, LAScd, and LAGLS were significantly lower in Group I than in control group (all P < 0.05). The LASr, LAScd, LASct, and LAGLS were significantly lower in Group II than in control group and Group I (all P < 0.05). The function of LA impaired in RA patients, and the impairment aggravated with the clinical course of RA patients. 2D-STI technology can early and accurately evaluate the LA function of RA patients by evaluating LASr, LAScd, LASct, and LAGLS.

Abstract 6116: Assessment of Global and Regional Left Ventricular Twist in Patients with Anterior Wall Myocardial Infarction Before and After Revascularization by 2-D Speckle Tracking Imaging

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mingxing Xie ◽  
Wei Han ◽  
Xinfang Wang ◽  
Minjuan Zheng ◽  
Shuping Ge
Keyword(s):  
Myocardial Infarction ◽  
Speckle Tracking ◽  
Anterior Wall ◽  
Left Ventricular ◽  
Control Group ◽  
Speckle Tracking Imaging ◽  
Time To Peak ◽  
Left Ventricular Twist ◽  
Before And After ◽  
Ventricular Twist

Background: Torsion of the left ventricle is related to myocardial architecture and contractility and is being evaluated as a sensitive marker of cardiac performance. New 2-D speckle tracking imaging (STI) may provide a powerful means of assessing LV torsion noninvasively. This study sought to evaluate the global and regional left ventricular twist in patients with anterior wall myocardial infarction (AMI) before and after revascularization by STI. Methods: A total of 50 subjects, including study group (n = 20) who underwent revascularization for AMI as well as 1 month after revascularization, and control group (n = 30) of normal individuals were studied using STI. LV twist was defined as apical rotation relative to the base. The peak LV twist, standard deviation of time to peak twist (Tw-SD) and maximal temporal difference of time to peak twist (Tw-diff) of 6 myocardial regions were measured. Results: Before revascularization, peak LV twist was significantly reduced while Tw-SD and Tw-diff significantly increased in patients with AMI as compared with normal control group ( P <0.001). One month after revascularization, these changes improved compared with pre- revascularization but remained diminished compared with normal controls (Table 1 ). There were significant correlations between LV peak twist and LVEF ( r =0.78, P <0.05), and LVEDD ( r =−0.63, P <0.05) in all subjects. Conclusion: LV twist measures significantly diminished and dys-synchronized in AMI patients prior to revascularization and improved after revascularization. STI measures correlate with EF and have the potential to quantify left ventricular global and segmental dysfunction in patients with AMI. Left ventricular regional and global peak twist, torsion and synchrony measures

Ceramide in the antiapoptotic effect of ischemic preconditioning

2004 ◽  
Vol 286 (1) ◽  
pp. H246-H251 ◽  
Author(s):  
Laurent Argaud ◽  
Annie-France Prigent ◽  
Lara Chalabreysse ◽  
Joseph Loufouat ◽  
Michel Lagarde ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Kinase Assay ◽  
Control Group ◽  
Blue Dye ◽  
Triphenyltetrazolium Chloride ◽  
Antiapoptotic Effect ◽  
Ceramide Production

Although the mechanism by which ischemic preconditioning (PC) inhibits myocardial apoptosis during ischemia-reperfusion is unclear, evidence indicates a role for the secondary messenger ceramide. We investigated in vivo whether PC may affect ceramide and sn-1,2-diacylglycerol (DAG) production, and attenuate apoptosis during ischemia. Rabbits underwent 30 min of ischemia, followed by 4 h of reperfusion. Before this, they received either no intervention (control group) or one episode of 5 min of ischemia, followed by 5 min of reperfusion (PC group), or an intravenous administration of the sphingomyelinase inhibitor D609. Myocardial content of ceramide and DAG was measured using the DAG kinase assay at different time points of the experiment. Apoptosis was detected and quantified by a sandwich enzyme immunoassay. Both AR and infarct size were measured using blue dye injection and triphenyltetrazolium chloride staining. Control hearts exhibited a peak of ceramide production at 5 min of the prolonged ischemia, with a mean value averaging 64 ± 5 ng/mg tissue ( P < 0.05 vs. 48 ± 4 ng/mg at baseline). In contrast, ischemic PC and D609 prevented ceramide increase during the prolonged ischemia. Myocardial DAG content was increased only in PC hearts at 30 min of ischemia. Preconditioned and D609 groups developed less apoptosis, as well as a limited infarct size, compared with the control group. These results suggest that the antiapoptotic effect of PC may be due to a reduced ceramide production during sustained ischemia in the rabbit heart.

scholarly journals Cardioprotection against Ischemia/Reperfusion by Licochalcone B in Isolated Rat Hearts

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jichun Han ◽  
Dong Wang ◽  
Bacui Yu ◽  
Yanming Wang ◽  
Huanhuan Ren ◽  
...  
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Left Ventricular Pressure ◽  
Treated Group ◽  
Left Ventricular ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Triphenyltetrazolium Chloride

The generation of reactive oxygen species (ROS) is a major cause of heart injury induced by ischemia-reperfusion. The left ventricular developed pressure (LVDP) and the maximum up/down rate of left ventricular pressure (±dp/dtmax⁡) were documented by a physiological recorder. Myocardial infarct size was estimated macroscopically using 2,3,5-triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the degree of cardiac injury. The levels of C-reactive protein (CRP), interleukin-8 (IL-8), tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) were analyzed to determine the inflammation status of the myocardial tissue. Cardiomyocyte apoptosis analysis was performed using the In Situ Cell Death Detection Kit, POD. Accordingly, licochalcone B pretreatment improved the heart rate (HR), increased LVDP, and decreased CK and LDH levels in coronary flow. SOD level and GSH/GSSG ratio increased, whereas the levels of MDA, TNF-α, and CRP and activities of IL-8 and IL-6 decreased in licochalcone B-treated groups. The infarct size and cell apoptosis in hearts from licochalcone B-treated group were lower than those in hearts from the I/R control group. Therefore, the cardioprotective effects of licochalcone B may be attributed to its antioxidant, antiapoptotic, and anti-inflammatory activities.

scholarly journals Increase in Plasma Oxidized Phosphatidylcholines (OxPCs) in Patients Presenting With ST-Elevation Myocardial Infarction (STEMI)

2021 ◽  
Vol 8 ◽  
Author(s):  
Zahra Solati ◽  
Arun Surendran ◽  
Andrea Edel ◽  
Marynia Roznik ◽  
David Allen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Plasma Levels ◽  
Ischemia Reperfusion ◽  
Biologically Active ◽  
Enzymatic Oxidation ◽  
Control Group ◽  
Myocardial Salvage ◽  
Blood Samples ◽  
Time Points

Objective: ST-segment Elevation Myocardial Infarction (STEMI) occurs as a result of acute occlusion of the coronary artery. Despite successful reperfusion using percutaneous coronary intervention (PCI), a large percentage of myocardial cells die after reperfusion which is recognized as ischemia/reperfusion injury (I/R). Oxidized phosphatidylcholines (OxPCs) are a group of oxidized lipids generated through non-enzymatic oxidation and have pro-inflammatory properties. This study aimed to examine the roles of OxPCs in a clinical setting of myocardial I/R.Methods: Blood samples were collected from STEMI patients at presentation prior to primary PCI (PPCI) (Isch) and at 4 time-points post-PPCI, including 2 h (R-2 h), 24 h (R-24 h), 48 h (R-48 h), and 30 days (R-30 d) post-PPCI. As controls, blood samples were collected from patients with non-obstructive coronary artery disease after diagnostic coronary angiography. Aspiration thrombectomy was also performed in selected STEMI patients. High-performance lipid chromatography-electrospray mass spectrometry (LC-MS/MS) was used for OxPCs analysis.Results: Twenty-two distinct OxPC species were identified and quantified in plasma samples in patients presenting with STEMI. These compounds were categorized as fragmented and non-fragmented species. Total levels of OxPCs did not significantly differ between Isch and control groups. However, total levels of fragmented OxPCs increased significantly in the ischemic period compared with controls (Isch: 4.79 ± 0.94, Control: 1.69 ± 0.19 ng/μl of plasma, P &lt; 0.05). Concentrations of non-fragmented OxPCs had significant reductions during ischemia compared to the control group (Isch: 4.84 ± 0.30, Control: 6.6 ± 0.51 ng/μl, P &lt; 0.05). Levels of total OxPCs in patients with STEMI were not significantly different during reperfusion periods. However, fragmented OxPCs levels were elevated at 48 h post-reperfusion and decreased at 30 days following MI, when compared to R-2 h and R-24 h time points (Isch: 4.79 ± 0.94, R-2 h: 5.33 ± 1.17, R-24 h: 5.20 ± 1.1, R-48 h: 4.18 ± 1.07, R-30 d: 1.87 ± 0.31 ng/μl, P &lt; 0.05). Plasma levels of two fragmented OxPCs, namely, POVPC and PONPC were significantly correlated with peak creatine kinase (CK) levels (P &lt; 0.05). As with plasma levels, the dominant OxPC species in coronary aspirated thrombus were fragmented OxPCs, which constituted 77% of total OxPC concentrations.Conclusion: Biologically active fragmented OxPC were elevated in patients presenting with STEMI when compared to controls. PONPC concentrations were subsequently increased after PPCI resulting in reperfusion. Moreover, levels of POVPC and PONPC were also associated with peak CK levels. Since these molecules are potent stimulators for cardiomyocyte cell death, therapeutics attenuating their activities can result in a novel therapeutic pathway for myocardial salvage for patients undergoing reperfusion therapy.

scholarly journals Differential Role of Pim-1 Kinase in Anesthetic-induced and Ischemic Preconditioning against Myocardial Infarction

2009 ◽  
Vol 111 (6) ◽  
pp. 1257-1264 ◽  
Author(s):  
Jan Stumpner ◽  
Andreas Redel ◽  
Anna Kellermann ◽  
Christopher A. Lotz ◽  
Christoph A. Blomeyer ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Protein Kinase ◽  
Cytochrome C ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Kinase Inhibitor ◽  
Protein Kinase B ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Area At Risk

Background Ischemic preconditioning (IPC) and anesthetic-induced preconditioning against myocardial infarction are mediated via protein kinase B. Pim-1 kinase acts downstream of protein kinase B and was recently shown to regulate cardiomyocyte survival. The authors tested the hypothesis that IPC and anesthetic-induced preconditioning are mediated by Pim-1 kinase. Methods Pentobarbital-anesthetized male C57Black/6 mice were subjected to 45 min of coronary artery occlusion and 3 h of reperfusion. Animals received no intervention, Pim-1 kinase inhibitor II (10 microg/g intraperitoneally), its vehicle dimethyl sulfoxide (10 microl/g intraperitoneally), or 1.0 minimum alveolar concentration desflurane alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). IPC was induced by three cycles of 5 min ischemia-reperfusion each, and animals received IPC either alone or in combination with Pim-1 kinase inhibitor II (10 microg/g intraperitoneally). Infarct size was determined with triphenyltetrazolium chloride, and area at risk was determined with Evans blue (Sigma-Aldrich, Taufkirchen, Germany). Protein expression of Pim-1 kinase, Bad, phospho-Bad, and cytosolic content of cytochrome c were measured using Western immunoblotting. Results Infarct size in the control group was 47 + or - 2%. Pim-1 kinase inhibitor II (44 + or - 2%) had no effect on infarct size. Desflurane (17 + or - 3%) and IPC (19 + or - 2%) significantly reduced infarct size compared with control (both P &lt; 0.05 vs. control). Blockade of Pim-1 kinase completely abrogated desflurane-induced preconditioning (43 + or - 3%), whereas IPC (35 + or - 3%) was blocked partially. Desflurane tended to reduce cytosolic content of cytochrome c, which was abrogated by Pim-1 kinase inhibitor II. Conclusion These data suggest that Pim-1 kinase mediates at least in part desflurane-induced preconditioning and IPC against myocardial infarction in mice.

Increased mitochondrial calcium coexists with decreased reperfusion injury in postconditioned (but not preconditioned) hearts

2008 ◽  
Vol 294 (1) ◽  
pp. H386-H391 ◽  
Author(s):  
Laurent Argaud ◽  
Odile Gateau-Roesch ◽  
Lionel Augeul ◽  
Elisabeth Couture-Lepetit ◽  
Joseph Loufouat ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Blue Dye ◽  
Mitochondrial Calcium ◽  
Area At Risk ◽  
Triphenyltetrazolium Chloride ◽  
Pore Opening

Ca2+ is the main trigger for mitochondrial permeability transition pore opening, which plays a key role in cardiomyocyte death after ischemia-reperfusion. We investigated whether a reduced accumulation of mitochondrial Ca2+ might explain the attenuation of lethal reperfusion injury by postconditioning. Anesthetized New Zealand White rabbits underwent 30 min of ischemia, followed by either 240 (infarct size protocol) or 60 (mitochondria protocol) min of reperfusion. They received either no intervention (control), preconditioning by 5-min ischemia and 5-min reperfusion, postconditioning by four cycles of 1-min reperfusion and 1-min ischemia at the onset of reflow, or pharmacological inhibition of the transition pore opening by N-methyl-4-isoleucine-cyclosporin (NIM811; 5 mg/kg iv) given at reperfusion. Area at risk and infarct size were assessed by blue dye injection and triphenyltetrazolium chloride staining. Mitochondria were isolated from the risk region for measurement of 1) Ca2+ retention capacity (CRC), and 2) mitochondrial content of total (atomic absorption spectrometry) and ionized (potentiometric technique) calcium concentration. CRC averaged 0.73 ± 0.16 in control vs. 4.23 ± 0.17 μg Ca2+/mg proteins in shams ( P < 0.05). Postconditioning, preconditioning, or NIM811 significantly increased CRC ( P < 0.05 vs. control). In the control group, total and free mitochondrial calcium significantly increased to 2.39 ± 0.43 and 0.61 ± 0.10, respectively, vs. 1.42 ± 0.09 and 0.16 ± 0.01 μg Ca2+/mg in sham ( P < 0.05). Surprisingly, whereas total and ionized mitochondrial Ca2+ decreased in preconditioning, it significantly increased in postconditioning and NIM811 groups. These data suggest that retention of calcium within mitochondria may explain the decreased reperfusion injury in postconditioned (but not preconditioned) hearts.

Protective mechanisms of resveratrol against ischemia-reperfusion-induced damage in hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin

2008 ◽  
Vol 294 (2) ◽  
pp. H859-H866 ◽  
Author(s):  
Istvan Lekli ◽  
Gergo Szabo ◽  
Bela Juhasz ◽  
Samarjit Das ◽  
Manika Das ◽  
...  
Keyword(s):  
Body Weight ◽  
Ventricular Fibrillation ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Serum Glucose ◽  
Control Group ◽  
Glut 4 ◽  
Reduced Body ◽  
Glucose Intake ◽  
Obese Rats

The resveratrol-induced cardiac protection was studied in Zucker obese rats. Rats were divided into five groups: group 1, lean control; group 2, obese control (OC); group 3, obese rats treated orally with 5 mg·kg−1·day−1 of resveratrol (OR) for 2 wk; group 4, obese rats received 10% glucose solution ad libitum for 3 wk (OG); and group 5, obese rats received 10% glucose for 3 wk and resveratrol (OGR) during the 2nd and 3rd wk. Body weight, serum glucose, and insulin were measured, and then hearts were isolated and subjected to 30 min of ischemia followed by 120 min of reperfusion. Heart rate, coronary flow, aortic flow, developed pressure, the incidence of reperfusion-induced ventricular fibrillation, and infarct size were measured. Resveratrol reduced body weight and serum glucose in the OR compared with the OC values (414 ± 10 g and 7.08 ± 0.41 mmol/l, respectively, to 378 ± 12 g and 6.11 ± 0.44 mmol/l), but insulin levels were unchanged. The same results were obtained for the OG vs. OGR group. Resveratrol improved postischemic cardiac function in the presence or absence of glucose intake compared with the resveratrol-free group. The incidence of ventricular fibrillation and infarct size was reduced by 83 and 20% in the OR group, and 67 and 16% in the OGR group, compared with the OC and OG groups, respectively. Resveratrol increased GLUT-4 expression and reduced endothelin expression and cardiac apoptosis in ischemic-reperfused hearts in the presence or absence of glucose intake. Thus the protective effect of resveratrol could be related to its direct effects on the heart.

Abstract 2667: Aspiration Coronary Thrombectomy for Acute Myocardial Infarction Improves Myocardial Salvage Index. Single Center Randomized Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Michal Ciszewski ◽  
Jerzy Pregowski ◽  
Anna Teresinska ◽  
Maciej Karcz ◽  
Witold Ruzyllo
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Infarct Size ◽  
Perfusion Imaging ◽  
Randomized Study ◽  
Myocardial Salvage ◽  
Aspiration Thrombectomy ◽  
Acute Stemi ◽  
Final Infarct Size ◽  
Myocardium At Risk

Primary percutaneus intervention (pPCI) is a recommended treatment strategy for acute myocardial infarction with ST segment elevation (STEMI). Adjunctive thrombectomy may add clinical benefits. The aim of our study was to compare the efficacy of aspiration thrombectomy versus standard pPCI for STEMI. The primary endpoint was salvage index assessed by sestamibi SPECT perfusion imaging. Single centre randomized study on aspiration thrombectomy in acute STEMI. 135 patients (88 males, mean age 64,3±12,4 yrs) with first acute STEMI were enrolled between Nov 2004 and Dec 2007. Inclusion criteria were: first anterior or inferior STEMI within 12 hours from pain onset with culprit lesion in left anterior descending (LAD) or right coronary artery (RCA) and TIMI flow ≤ 2. Patients were randomly assigned to thrombectomy with Rescue or Diver device followed by stent implantation (65) vs. standard pPCI with stenting (70 pts). 5 patients initially randomised to thrombectomy were finally treated with standard pPCI. Two SPECT examinations were performed: before and 5– 8 days after reperfusion therapy. Five patients died 3–7 days after the procedure, and in 3 pts second SPECT could not be performed because of patients’ severe condition. Thus two SPECT examinations were performed in 127 patients (63 treated with thrombectomy and 64 in control group). These 127 subject were the basis of the intention to treat analyses. There were 41 pts with anterior STEMI and 86 pts with inferior STEMI. Both treatment groups were similar regarding baseline demographic and clinical variables. Based on the SPECT perfusion imaging results, the final infarct size was assessed and myocardial salvage index (proportion of the myocardium at risk salvaged by reperfusion) was calculated. Baseline myocardium at risk area was 35,0%±2,8% in thrombectomy group vs 35,8%±10,9% in control patients. (p=NS). Myocardial salvage index was larger in patients treated with aspiration thrombectomy (0,33±0,27 vs. 0,20 ± 0,21 p = 0,004). Moreover, final infarct size was significantly smaller in patients treated with thrombectomy: 23,9% ± 13,1 % vs.28,3 % ±9,6% p = 0,005. Our results show that coronary thrombectomy is beneficial as an adjunctive therapy to pPCI in STEMI.

Abstract 1612: Pharmacological Postconditioning Effect of G-csf Is Mediated through Activation of Pi3k-akt-enos Pathway and Opening the Mitochondrial Katp Channels in a Rabbit Model of Myocardial Infarction

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Shohei Sumi ◽  
Masamitsu Iwasa ◽  
Hiroyuki Kobayashi ◽  
Shinji Yasuda ◽  
Takahiko Yamaki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Rabbit Model ◽  
Katp Channels ◽  
Saline Control ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Risk Area ◽  
Mitochondrial Katp Channels

It has been reported that granulocyte-colony-stimulating factor(G-CSF) improves cardiac function after myocardial infarction (MI). However, its direct effect on the myocardium and its signaling pathway remain unclear. We examined the acute beneficial effect of G-CSF on myocardial infarct size and its precise mechanisms in a rabbit model of myocardial infarction. In 80 Japanese white rabbits, MI was induced by 30 min of ischemia and 48 hours of reperfusion. Rabbits were intravenously injected with 10 μg/kg of G-CSF (G-CSF group, n=10) or saline (control group, n=10) immediately after reperfusion. The G-CSF+5HD group (n=10) was injected with 5-HD(5-hydroxydecanoate, a mitochondrial KATP channel blocker) 5 min before G-CSF injection. The G-CSF +wortmaninn group (n=10) was injected wortmaninn (0.6mg/kg) 5 min before G-CSF injection. G-CSF+L-NAME group (n=10) was injected with L-NAME (10mg/kg) 5 min before G-CSF injection. The 5HD alone (n=10), wortmannin alone (n=10), L-NAME alone (n=10) groups were respectively injected 5HD, wortmannin and L-NAME immediately after reperfusion. Myocardial infarct size was calculated as a percentage of the risk area of the left ventricle. Western blot analysis was performed to examine the Akt and phospho-Akt and phospho-eNOS in the ischemic myocardium at 48 hours of reperfusion. The infarct size was significantly smaller in the G-CSF group (26.7±2.7%) than in the control group (42.3±4.6%). The infarct size-reducing effect of G-CSF was completely blocked by 5-HD (42.5±1.66%), wortmaninn(44.7±4.81) and L-NAME (42.1±4.2%). Wortmannin, L-NAME or 5HD alone did not affect the infarct size. Western blotting showed higher expression of phospho-Akt and phosho-eNOS in the infarct area in the G-CSF group than in the control group. G-CSF administered immediately after reperfusion reduces myocardial infarct size via activation of PI3K, Akt, eNOS and opening the mitochondrial KATP channels.

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