scholarly journals A Strategy for Optimizing the Combination of Active Components Based on Chinese Medicinal Formula Sheng-Mai-San for Myocardial Ischemia

2018 ◽  
Vol 45 (4) ◽  
pp. 1455-1471 ◽  
Author(s):  
Fang Li ◽  
Xiao-Xue Fan ◽  
Chun Chu ◽  
Yu Zhang ◽  
Jun-Ping Kou ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Protective Effect ◽  
Infarct Size ◽  
Troponin I ◽  
Serum Lactate Dehydrogenase ◽  
Chinese Drug ◽  
Myocardial Infarct Size ◽  
Effective Components ◽  
Creatine Kinase Mb ◽  
Further Development

Background/Aims: Traditional Chinese medicine (TCM) has been used in clinical practice for thousands of years and has accumulated considerable knowledge concerning the in vivo efficacy of targeting complicated diseases. TCM formulae are a mixture of hundreds of chemical components with multiple potential targets, essentially acting as a combination therapy of multi-component drugs. However, the obscure substances and the unclear molecular mechanisms are obstacles to their further development and internationalization. Therefore, it is necessary to develop new modern drugs based on the combination of effective components in TCM with exact clinical efficacy. In present study, we aimed to detect optimal ratio of the combination of effective components based on Sheng-Mai-San for myocardial ischemia. Methods: On the basis of preliminary studies and references of relevant literature about Sheng-Mai-San for myocardial ischemia, we chose three representative components (ginsenoside Rb1 (G), ruscogenin (R) and schisandrin (S)) for the optimization design studies. First, the proper proportion of the combination was explored in different myocardial ischemia mice induced by isoproterenol and pituitrin based on orthogonal design. Then, the different proportion combinations were further optimized through uniform design in a multi-model and multi-index mode. Finally, the protective effect of combination was verified in three models of myocardial ischemia injured by ischemia/reperfusion, chronic intermittent hypoxia and acute infarction. Results: The optimized combination GRS (G: 6 mg/kg, R: 0.75 mg/kg, S: 6 mg/kg) obtained by experimental screening exhibited a significant protective effect on myocardial ischemia injury, as evidenced by decreased myocardium infarct size, ameliorated histological features, decreased myocardial myeloperoxidase (MPO) and malondiadehyde (MDA), calcium overload, and decreased serum lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), cardiac troponin I (cTn-I) activity. In addition, the interactions of three components in combination GRS were also investigated. The combination, compared to G, R and S, could significantly reduce the concentration of serum CK-MB and cTn-I, and decrease myocardial infarct size, which demonstrated the advantages of this combination for myocardial ischemia. Conclusion: Our results demonstrated that the optimized combination GRS could exert significant cardioprotection against myocardial ischemia injury with similar effect compared to Sheng Mai preparations, which might provide some pharmacological evidences for further development of new modern Chinese drug for cardiovascular diseases basing on traditional Chinese formula with affirmative therapeutic effect.

scholarly journals STAT3 but Not STAT5 Contributes to the Protective Effect of Electroacupuncture Against Myocardial Ischemia/Reperfusion Injury in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Hui-Hui Guo ◽  
Xin-Yue Jing ◽  
Hui Chen ◽  
Hou-Xi Xu ◽  
Bing-Mei Zhu
Keyword(s):  
Myocardial Ischemia ◽  
Protective Effect ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Coronary Artery Ligation ◽  
Myocardial Infarct Size ◽  
Dependent Manner ◽  
Stat3 Signaling ◽  
Gene And Protein Expression ◽  
Myocardial Ischemia Reperfusion

Electroacupuncture (EA) can help reduce infarct size and injury resulting from myocardial ischemia/reperfusion (I/R); however, the underlying molecular mechanism remains unknown. We previously reported that STAT5 plays a critical role in the cardioprotective effect of remote ischemic preconditioning (RIPC). Here, we assessed the effects of electroacupuncture pretreatment (EAP) on myocardial I/R injury in the presence and/or absence of Stat5 in mice and investigated whether EAP exerts its cardioprotective effects in a STAT5-dependent manner. Adult Stat5fl/fl and Stat5-cKO mice were exposed to EAP at Neiguan (PC6) for 7 days before the induction of I/R injury by left anterior descending (LAD) coronary artery ligation. The myocardial infarct size (IS), area at risk, and apoptotic rate of cardiomyocytes were detected. RT-qPCR and western blotting were used to measure gene and protein expression, respectively, in homogenized heart tissues. RNA-seq was used to identify candidate genes and pathways. Our results showed that EAP decreased IS and the rate of cardiomyocyte apoptosis. We further found that STAT5 was activated by EAP in Stat5fl/fl mice but not in Stat5-cKO mice, whereas the opposite was observed for STAT3. Following EAP, the levels of the antiapoptotic proteins Bcl-xL, Bcl-2, and p-AKT were increased in the presence of Stat5, while that of interleukin 10 (IL-10) was increased in both Stat5fl/fl and Stat5-cKO. The gene expression profile in heart tissues was different between Stat5fl/fl and the Stat5-cKO mice with EAP. Importantly, the top 30 DEGs under EAP in the Stat5-cKO mice were enriched in the IL-6/STAT3 signaling pathway. Our results revealed for the first time that the protective effect of EAP following myocardial I/R injury was attributable to, but not dependent on, STAT5. Additionally, we found that EAP could activate STAT3 signaling in the absence of the Stat5 gene, and could also activate antiapoptotic, survival, and anti-inflammatory signaling pathways.

scholarly journals Sweroside Protects Against Myocardial Ischemia–Reperfusion Injury by Inhibiting Oxidative Stress and Pyroptosis Partially via Modulation of the Keap1/Nrf2 Axis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jun Li ◽  
Cuiting Zhao ◽  
Qing Zhu ◽  
Yonghuai Wang ◽  
Guangyuan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Protective Effect ◽  
Infarct Size ◽  
Cell Viability ◽  
Ischemia Reperfusion ◽  
Cell Counting ◽  
Myocardial Infarct Size ◽  
Caspase 1 ◽  
Myocardial Ischemia Reperfusion

Aims: Sweroside, a secoiridoid glucoside extracted from Swertia pseudochinensis Hara, is reported to possess antioxidant and anti-inflammatory activities. However, whether sweroside has a protective effect on myocardial ischemia–reperfusion (IR) injury is yet to be elucidated. The present study aimed to confirm the cardioprotective effect of sweroside and to identify its underlying mechanism.Methods and Results: H9c2 cells were pretreated with sweroside and then underwent hypoxia–reoxygenation. Cell Counting Kit-8, creatine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH) assays were conducted to detect cell viability and myocardial injury, respectively. The Langendorff method was used to induce myocardial IR injury ex vivo. Triphenyltetrazolium chloride staining was performed to detect myocardial infarct size, while protein expression was analyzed using western blotting. Overall, the results indicated that sweroside pretreatment dose-dependently led to a significant enhancement in cell viability, a decrease in release of CK-MB and LDH, a reduction in infarct size, and an improvement in cardiac function. Additionally, sweroside pretreatment caused a marked suppression of oxidative stress, as evidenced by the fact that sweroside decreased the accumulation of reactive oxygen species and malondialdehyde, while enhancing the activities of superoxide dismutase and glutathione peroxidase. Moreover, sweroside was found to notably repress pyroptosis, as sweroside blocked pore formation in the cell membrane, inhibited caspase-1 and interleukin (IL)-1β activity, and decreased the expression levels of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD, cleaved caspase-1, and IL-1β. Mechanistically, it was found that sweroside inhibited Kelch-like ECH-associated protein 1 (Keap1) and induced nuclear factor E2-associated factor 2 (Nrf2) nuclear translocation. Furthermore, the inhibition of oxidative stress and pyroptosis by sweroside could be abrogated via the inhibition of Nrf2 expression, which suggested that the protective effect induced by sweroside was Nrf2-dependent.Conclusions: The present study demonstrated that sweroside pretreatment could protect against myocardial IR injury by inhibiting of oxidative stress and NLRP3 inflammasome-mediated pyroptosis partially via modulation of the Keap1/Nrf2 axis.

scholarly journals Sabiporide Reduces Ischemia-Induced Arrhythmias and Myocardial Infarction and Attenuates ERK Phosphorylation and iNOS Induction in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Henri Doods ◽  
Dongmei Wu
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Troponin I ◽  
Ischemia Reperfusion ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia And Reperfusion

The aim of the present study was to investigate the effects of sabiporide, a potent and selective NHE1 inhibitor, on myocardial ischemia-induced arrhythmias and myocardial infarction and the possible pathways related to the cardioprotection afforded by sabiporide treatment. Anesthetized rats were subjected to myocardial ischemia via left main coronary artery occlusion for 30 minutes, followed by 2 hours of reperfusion. Administration of sabiporide (0.01–3.0 mg/kg) prior to coronary artery occlusion dose-dependently reduced ischemia-induced arrhythmias and infarct size with an ED50 value of 0.14 mg/kg. Administration of sabiporide (1.0 mg/kg) prior to reperfusion also reduced infarct size by 38.6%. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase and troponin I. In addition, sabiporide (1.0 mg/kg) given prior to coronary artery occlusion or immediately before reperfusion significantly reduced phosphorylation of the extracellular signal-regulated kinase (ERK1/2) and the expression of the inducible nitric oxide synthase (iNOS) following myocardial ischemia-reperfusion. This study demonstrates that sabiporide is a potent and effective cardioprotective agent during myocardial ischemia and reperfusion, by reducing serious ventricular arrhythmias and myocardial infarct size. The cardioprotection afforded by sabiporide is attributed in part to inhibition of ERK1/2 phosphorylation and suppression of iNOS expression.

Abstract 16381: Novel Thiol-activated H2S Donors Attenuate Myocardial Ischemia/Reperfusion Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Chelsea Organ ◽  
Zhen Li ◽  
Yu Zhao ◽  
Chuntao Yang ◽  
Shashi Bhushan ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Sustained Release ◽  
Murine Model ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background: Hydrogen sulfide (H2S) protects against acute myocardial ischemia/reperfusion (MI/R) injury and heart failure by ameliorating oxidative stress, improving mitochondrial function, and attenuating apoptosis. One of the major limitations of currently available H2S donors is poor pharmacokinetics profiles that result in very rapid and uncontrolled H2S release. NSHD-1 and NSHD-2 are recently developed thiol-activated H2S donors designed for sustained release of H2S upon activation by molecules containing thiol groups such as cysteine and glutathione. We hypothesized that these novel H2S donors would generate H2S for extended periods and ameliorate myocardial cell death following MI/R in an in vivo murine model. Methods and Results: C57BL6/J male mice (10-12 weeks of age) were subjected to 45 minutes of MI followed by 24 hours of R. At the time of reperfusion, animals received Vehicle (0.5% THF), NSHD-1 (50 μg/kg and 100 μg/kg), or NSHD-2 (50 μg/kg) by direct intracardiac (i.c.) injection. In addition, at 4 hours of R, plasma was collected for troponin-I measurements. In preliminary studies we observed sustained release of H2S with both of these H2S donors. Myocardial infarct size was reduced by 35% (p < 0.01 vs. Vehicle) in mice treated with NSHD-1 (100 μg/kg), 43% (p < 0.05 vs. Vehicle) in mice treated with NSHD-2 (50 μg/kg), and 54% (p < 0.01 vs. Vehicle) in mice treated with NSHD-2 (100 μg/kg). Conclusions: NSHD-1 and NSHD-2 significantly attenuate MI/R injury in a murine model. Experiments are currently underway to further define the in vivo pharmacokinetics of H2S release from these agents, mechanisms of action, and safety profile.

scholarly journals Two Benzene Rings with a Boron Atom Comprise the Core Structure of 2-APB Responsible for the Anti-Oxidative and Protective Effect on the Ischemia/Reperfusion-Induced Rat Heart Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1667
Author(s):  
Yan-Cheng Shen ◽  
Yan-Jhih Shen ◽  
Wen-Sen Lee ◽  
Michael Yu-Chih Chen ◽  
Wei-Chia Tu ◽  
...  
Keyword(s):  
Protective Effect ◽  
Infarct Size ◽  
Rat Heart ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Core Structure ◽  
Myocardial Infarct Size ◽  
The Core ◽  
Benzene Rings ◽  
Heart Injury

To identify the core structure of 2-aminoethoxydiphenyl borate (2-APB) responsible for the anti-oxidative and protective effect on the ischemia/reperfusion (I/R)-induced heart injury, various 2-APB analogues were analyzed, and several antioxidant assays were performed. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Myocardial infarct size was quantified using triphenyl tetrazolium chloride (TTC) staining. The levels of tumor necrosis factor-alpha (TNF-α) and cleaved-caspase-3 protein were evaluated as an indicator for the anti-inflammatory and anti-apoptotic effect, respectively. Our data show that 2-APB, diphenylborinic anhydride (DPBA) and 3-(diphenylphosphino)-1-propylamine (DP3A) all exerted the anti-oxidative activity, but only 2-APB and DPBA can scavenge H2O2. 2-APB and DPBA can potently inhibit hydrogen peroxide (H2O2)- and hypoxanthine/xanthine oxidase (HX/XOD)-induced increases in intracellular H2O2 and H9c2 cell death. 2-APB and DPBA were able to decrease the I/R-induced adult rat cardiomyocytes death, myocardial infarct size, and the levels of malondialdehyde (MDA) and creatine kinase-MB (CK-MB). Our results suggest that the two benzene rings with a boron atom comprise the core structure of 2-APB responsible for the anti-oxidative effect mediated through the reaction with H2O2 and generation of phenolic compounds, which in turn reduced the I/R-induced oxidative stress and injury in the rat heart.

Coronary endothelial P-selectin in pathogenesis of myocardial ischemia-reperfusion injury

1998 ◽  
Vol 275 (5) ◽  
pp. H1865-H1872 ◽  
Author(s):  
Anthony J. Palazzo ◽  
Steven P. Jones ◽  
Donald C. Anderson ◽  
D. Neil Granger ◽  
David J. Lefer
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Wild Type ◽  
Area At Risk ◽  
Myocardial Ischemia Reperfusion

We investigated in vivo coronary P-selectin expression and its pathophysiological consequences in a murine model of myocardial ischemia-reperfusion (MI/R) using wild-type and P-selectin deficient (−/−) mice. Coronary P-selectin expression [μg monoclonal antibody (MAb)/g tissue] was measured using a radiolabeled MAb method after 30 min of myocardial ischemia and 20 min of reperfusion. P-selectin expression in wild-type mice was significantly ( P< 0.01) elevated in the ischemic zone (0.070 ± 0.010) compared with the nonischemic zone (0.037 ± 0.008). Myocardial P-selectin expression was nearly undetectable in P-selectin −/− mice after MI/R. Furthermore, myocardial infarct size (% of area at risk) after 30 min of myocardial ischemia and 120 min of reperfusion was 42.5 ± 4.4 in wild-type mice and 24.4 ± 4.0 in P-selectin −/− mice ( P < 0.05). In additional experiments of prolonged myocardial ischemia (60 min) and reperfusion (120 min), myocardial infarct size was similar in P-selectin −/− mice and wild-type mice. Our results clearly demonstrate the involvement of coronary P-selectin in the development of myocardial infarction after MI/R.

Anesthetic-induced Preconditioning 

1997 ◽  
Vol 87 (5) ◽  
pp. 1182-1190 ◽  
Author(s):  
Brian A. Cason ◽  
A. Kurt Gamperl ◽  
Robert E. Slocum ◽  
Robert F. Hickey
Keyword(s):  
At Risk ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Coronary Occlusion ◽  
Myocardial Infarct ◽  
Group Analysis ◽  
Myocardial Infarct Size ◽  
Area At Risk ◽  
Myocardial Preconditioning

Background Experimental evidence suggests that ATP-sensitive potassium channels are involved in myocardial ischemic preconditioning. Because some pharmacologic effects of isoflurane are mediated by K(ATP) channels, the authors tested the hypothesis: Isoflurane administration, before myocardial ischemia, can induce or mimic myocardial preconditioning. Methods Myocardial infarct size was measured in three groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed in their pretreatment: Group 1 (control, N = 13) no pretreatment, Group 2 (ischemic preconditioning, N = 8), 5 min of coronary occlusion and 15 min of reperfusion; Group 3 (isoflurane pretreatment; N = 15), 15 min of isoflurane (1.1% end-tidal) and 15 min of washout. Hemodynamics were monitored serially. Myocardial infarct size and the area at risk were defined using triphenyltetrazolium chloride staining and fluorescent microspheres, respectively, and both were measured using computerized planimetry. Results Infarct size expressed as a percentage of area at risk was 23.4 +/- 8.5% (mean +/- SD) in the isoflurane group compared with 33.1 +/- 13.3% in controls, and 8.7 +/- 6.2% in the ischemia-preconditioned group. Analysis for coincidental regressions, followed by tests for equality of slope and elevation, showed that the linear relationship between infarct size and area at risk was significantly (P &lt; 0.05) different in all three groups because of differences in line elevation. Minor differences in hemodynamic variables were found between groups, which were unlikely to account for the significant differences in infarct size. Conclusion Preadministration of isoflurane, before myocardial ischemia, reduces myocardial infarct size, and mimics myocardial preconditioning.

scholarly journals Is postconditioning effective in prevention against long-lasting myocardial ischemia in the rabbit?

2009 ◽  
pp. 635-643
Author(s):  
R Létienne ◽  
Y Calmettes ◽  
B Le Grand
Keyword(s):  
Myocardial Infarction ◽  
At Risk ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Plasma Levels ◽  
Coronary Occlusion ◽  
Troponin I ◽  
The Other ◽  
Area At Risk ◽  
Triphenyltetrazolium Chloride

The goal of the study was to determine whether postconditioning protects against different ischemia durations in the rabbit. Rabbits were assigned to a 20-, 25-, 45- or 60-min coronary occlusion followed by 24-h of reperfusion. Rabbits received no further intervention (control) or were postconditioned with four cycles of 30-s occlusion and 30-s reperfusion after myocardial infarction. Plasma levels of troponin I were quantified throughout reperfusion. In control conditions, infarct sizes (% area at risk using triphenyltetrazolium chloride) after 20, 25, 45 and 60 min of coronary occlusions were 23±3, 51±4, 70±3 and 81±3 %, respectively. With 20 and 25 min occlusion, postconditioning reduced infarct size by 43±10 and 73±21 %, respectively. On the other hand, with 45 or 60 min occlusion, postconditioning had no significant effects on infarct size (61±3 and 80±2 % of area at risk). Preconditioning protocol was performed with 25- and 60-min coronary occlusion. As expected, preconditioning significantly reduced infarct size. In conclusion, in the rabbit, the cardioprotection afforded by postconditioning is limited to less than 45 min coronary occlusion.

scholarly journals Nitroglycerine limits infarct size through S-nitrosation of cyclophilin D: a novel mechanism for an old drug

2018 ◽  
Vol 115 (3) ◽  
pp. 625-636 ◽  
Author(s):  
Sofia-Iris Bibli ◽  
Andreas Papapetropoulos ◽  
Efstathios K Iliodromitis ◽  
Andreas Daiber ◽  
Voahanginirina Randriamboavonjy ◽  
...  
Keyword(s):  
Protective Effect ◽  
Infarct Size ◽  
Knockout Mice ◽  
Low Dose ◽  
Myocardial Infarct ◽  
Pharmacological Action ◽  
Myocardial Infarct Size ◽  
Cyclophilin D ◽  
Cardioprotective Effects

Abstract Aims Nitroglycerine (NTG) given prior to an ischaemic insult exerts cardioprotective effects. However, whether administration of an acute low dose of NTG in a clinically relevant manner following an ischaemic episode limits infarct size, has not yet been explored. Methods and results Adult mice were subjected to acute myocardial infarction in vivo and then treated with vehicle or low-dose NTG prior to reperfusion. This treatment regimen minimized myocardial infarct size without affecting haemodynamic parameters but the protective effect was absent in mice rendered tolerant to the drug. Mechanistically, NTG was shown to nitrosate and inhibit cyclophilin D (CypD), and NTG administration failed to limit infarct size in CypD knockout mice. Additional experiments revealed lack of the NTG protective effect following genetic (knockout mice) or pharmacological inhibition (L-NAME treatment) of the endothelial nitric oxide synthase (eNOS). The protective effect of NTG was attributed to preservation of the eNOS dimer. Moreover, NTG retained its cardioprotective effects in a model of endothelial dysfunction (ApoE knockout) by preserving CypD nitrosation. Human ischaemic heart biopsies revealed reduced eNOS activity and exhibited reduced CypD nitrosation. Conclusion Low-dose NTG given prior to reperfusion reduces myocardial infarct size by preserving eNOS function, and the subsequent eNOS-dependent S-nitrosation of CypD, inhibiting cardiomyocyte necrosis. This novel pharmacological action of NTG warrants confirmation in clinical studies, although our data in human biopsies provide promising preliminary results.

Growth-hormone-releasing peptide 6 (GHRP6) prevents oxidant cytotoxicity and reduces myocardial necrosis in a model of acute myocardial infarction

2007 ◽  
Vol 112 (4) ◽  
pp. 241-250 ◽  
Author(s):  
Jorge Berlanga ◽  
Danay Cibrian ◽  
Luis Guevara ◽  
Heberto Dominguez ◽  
Jose S. Alba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Hormone ◽  
Infarct Size ◽  
Myocardial Injury ◽  
Myocardial Infarct Size ◽  
Oxidative Stress Markers ◽  
Left Circumflex Artery ◽  
Stress Markers ◽  
Creatine Kinase Mb ◽  
Igf I

Therapies aimed at enhancing cardiomyocyte survival following myocardial injury are urgently required. As GHRP6 [GH (growth hormone)-releasing peptide 6] has been shown to stimulate GH secretion and has beneficial cardiovascular effects, the aim of the present study was to determine whether GHRP6 administration reduces myocardial infarct size following acute coronary occlusion in vivo. Female Cuban Creole pigs were anaesthetized, monitored and instrumented to ensure a complete sudden left circumflex artery occlusion for 1 h, followed by a 72 h reperfusion/survival period. Animals were screened clinically before surgery and assigned randomly to receive either GHRP6 (400 μg/kg of body weight) or normal saline. Hearts were processed, and the area at risk and the infarct size were determined. CK-MB (creatine kinase MB) and CRP (C-reactive protein) levels and pathological Q-wave-affected leads were analysed and compared. Evaluation of the myocardial effect of GHRP6 also included quantitative histopathology, local IGF-I (insulin-growth factor-I) expression and oxidative stress markers. GHRP6 treatment did not have any influence on mortality during surgery associated with rhythm and conductance disturbances during ischaemia. Infarct mass and thickness were reduced by 78% and 50% respectively, by GHRP6 compared with saline (P<0.01). More than 50% of the GHRP6-treated pigs did not exhibit pathogological Q waves in any of the ECG leads. Quantitative histopathology and CK-MB and CRP serum levels confirmed the reduction in GHRP6-mediated necrosis (all P<0.05). Levels of oxidative stress markers suggested that GHRP6 prevented myocardial injury via a decrease in reactive oxygen species and by the preservation of antioxidant defence systems (all P<0.05). Myocardial IGF-I transcription was not amplified by GHRP6 treatment compared with the increase induced by the ischaemic episode in relation to expression in intact hearts (P<0.01). In conclusion, GHRP6 exhibits antioxidant effects which may partially contribute to reduce myocardial ischaemic damage.

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