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1.
Int J Mol Sci ; 25(8)2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38673951

ABSTRACT

Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 min of reperfusion with saline with or without disodium malonate (10 mg/kg/min, 120 µL/kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p < 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p < 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion.


Subject(s)
Malonates , Myocardial Infarction , Myocardial Reperfusion Injury , Succinate Dehydrogenase , Ventricular Remodeling , Animals , Malonates/pharmacology , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Mice , Succinate Dehydrogenase/metabolism , Succinate Dehydrogenase/antagonists & inhibitors , Male , Ventricular Remodeling/drug effects , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/pathology , Cicatrix/pathology , Cicatrix/drug therapy , Mice, Inbred C57BL
2.
Front Psychol ; 14: 1216825, 2023.
Article in English | MEDLINE | ID: mdl-37560105

ABSTRACT

Preterm birth (before 37 weeks of gestational age) is associated with certain risks to child development. The aim of this systematic review was to summarize available and updated empirical evidence on prematurity as a risk factor for cognitive development in school age. Thus, we attempted to identify similarities and differences with the full-term population and to point out possible risk or protective factors among the biological, psychosocial and family variables. The conceptualization and methodology of this review followed the PRISMA recommendations. The search was carried out in Web of Science, Scopus, PsycInfo, and Dialnet databases, in May 2022. The search was limited to journal articles, published between 2012 and 2022, in English and Spanish. Research articles selected were those focused on the intelligence quotient (IQ) of preterm children aged 6-12 years. The review included studies with cross-sectional or longitudinal cohorts, compared to a control group of children born at term or to standardized scales. The quality of evidence of the selected studies was verified with the Mixed Methods Appraisal Tool (MMAT). The initial search identified 1,040 articles. Forty articles met the inclusion criteria and were finally included in this review. These studies involved 5,396 preterm children from 37 different cohorts. Despite the diversity found among the results, in general, total IQ scores were within the normative mean for premature children; however, compared to their full-term peers, these scores were lower. The most studied variables in relation to IQ are perinatal (e.g., gestational age and birth weight) and family (e.g., socioeconomic level and education level of the mother). Recent studies corroborate that premature birth affects cognitive development in school age, and identify associated perinatal and family variables. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337371; identifier: CRD42022337371.

3.
Int J Mol Sci ; 22(9)2021 Apr 23.
Article in English | MEDLINE | ID: mdl-33922534

ABSTRACT

Connexins are a family of transmembrane proteins that play a key role in cardiac physiology. Gap junctional channels put into contact the cytoplasms of connected cardiomyocytes, allowing the existence of electrical coupling. However, in addition to this fundamental role, connexins are also involved in cardiomyocyte death and survival. Thus, chemical coupling through gap junctions plays a key role in the spreading of injury between connected cells. Moreover, in addition to their involvement in cell-to-cell communication, mounting evidence indicates that connexins have additional gap junction-independent functions. Opening of unopposed hemichannels, located at the lateral surface of cardiomyocytes, may compromise cell homeostasis and may be involved in ischemia/reperfusion injury. In addition, connexins located at non-canonical cell structures, including mitochondria and the nucleus, have been demonstrated to be involved in cardioprotection and in regulation of cell growth and differentiation. In this review, we will provide, first, an overview on connexin biology, including their synthesis and degradation, their regulation and their interactions. Then, we will conduct an in-depth examination of the role of connexins in cardiac pathophysiology, including new findings regarding their involvement in myocardial ischemia/reperfusion injury, cardiac fibrosis, gene transcription or signaling regulation.


Subject(s)
Connexins/metabolism , Heart Diseases/physiopathology , Animals , Heart Diseases/metabolism , Humans
5.
Antioxidants (Basel) ; 11(1)2021 Dec 29.
Article in English | MEDLINE | ID: mdl-35052579

ABSTRACT

Lysyl oxidase (LOX) is an enzyme critically involved in collagen maturation, whose activity releases H2O2 as a by-product. Previous studies demonstrated that LOX over-expression enhances reactive oxygen species (ROS) production and exacerbates cardiac remodeling induced by pressure overload. However, whether LOX influences acute myocardial infarction and post-infarct left ventricular remodeling and the contribution of LOX to myocardial oxidative stress following ischemia-reperfusion have not been analyzed. Isolated hearts from transgenic mice over-expressing human LOX in the heart (TgLOX) and wild-type (WT) littermates were subjected to global ischemia and reperfusion. Although under basal conditions LOX transgenesis is associated with higher cardiac superoxide levels than WT mice, no differences in ROS production were detected in ischemic hearts and a comparable acute ischemia-reperfusion injury was observed (infarct size: 56.24 ± 9.44 vs. 48.63 ± 2.99% of cardiac weight in WT and TgLOX, respectively). Further, similar changes in cardiac dimensions and function were observed in TgLOX and WT mice 28 days after myocardial infarction induced by transient left anterior descending (LAD) coronary artery occlusion, and no differences in scar area were detected (20.29 ± 3.10 vs. 21.83 ± 2.83% of left ventricle). Our data evidence that, although LOX transgenesis induces baseline myocardial oxidative stress, neither ROS production, infarct size, nor post-infarction cardiac remodeling were exacerbated following myocardial ischemia-reperfusion.

6.
Biomolecules ; 10(4)2020 04 23.
Article in English | MEDLINE | ID: mdl-32340244

ABSTRACT

Previous studies demonstrated a reduction in myocardial scar size in heterozygous Cx43+/- mice subjected to permanent coronary occlusion. However, patients presenting with ST segment elevation myocardial infarction often undergo rapid coronary revascularization leading to prompt restoration of coronary flow. Therefore, we aimed to assess changes in scar size and left ventricular remodeling following transient myocardial ischemia (45 min) followed by 14 days of reperfusion using Cx43fl/fl (controls) and Cx43Cre-ER(T)/fl inducible knock-out (Cx43 content: 50%) mice treated with vehicle or 4-hydroxytamoxifen (4-OHT) to induce a Cre-ER(T)-mediated global deletion of the Cx43 floxed allele. The scar area (picrosirius red), measured 14 days after transient coronary occlusion, was similarly reduced in both vehicle and 4-OHT-treated Cx43Cre-ER(T)/fl mice, compared to Cx43fl/fl animals, having normal Cx43 levels (15.78% ± 3.42% and 16.54% ± 2.31% vs. 25.40% ± 3.14% and 22.43% ± 3.88% in vehicle and 4-OHT-treated mice, respectively, p = 0.027). Left ventricular dilatation was significantly attenuated in both Cx43-deficient groups (p = 0.037 for left ventricular end-diastolic diameter). These protective effects were correlated with an attenuated enhancement in pro-transforming growth factor beta 1 (TGFß1) expression after reperfusion. In conclusion, our data demonstrate that Cx43 deficiency induces a protective effect on scar formation after transient coronary occlusion in mice, an effect associated with reduced left ventricular remodeling and attenuated enhancement in pro-TGFß1 expression.


Subject(s)
Cicatrix/pathology , Connexin 43/deficiency , Coronary Occlusion/metabolism , Coronary Occlusion/pathology , Myocardium/pathology , Signal Transduction , Transforming Growth Factor beta1/metabolism , Animals , Biomarkers/metabolism , Connective Tissue Growth Factor/metabolism , Connexin 43/metabolism , Coronary Occlusion/diagnostic imaging , Coronary Occlusion/physiopathology , Male , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B/metabolism , Phosphorylation , Smad Proteins/metabolism , Ventricular Remodeling
7.
Cells ; 8(10)2019 10 22.
Article in English | MEDLINE | ID: mdl-31652649

ABSTRACT

Abstract: Connexin 43 (Cx43) is essential for cardiac electrical coupling, but its effects on myocardial fibrosis is controversial. Here, we analyzed the role of Cx43 in myocardial fibrosis caused by angiotensin II (AngII) using Cx43fl/fl and Cx43Cre-ER(T)/fl inducible knock-out (Cx43 content: 50%) mice treated with vehicle or 4-hydroxytamoxifen (4-OHT) to induce a Cre-ER(T)-mediated global deletion of the Cx43 floxed allele. Myocardial collagen content was enhanced by AngII in all groups (n = 8-10/group, p < 0.05). However, animals with partial Cx43 deficiency (vehicle-treated Cx43Cre-ER(T)/fl) had a significantly higher AngII-induced collagen accumulation that reverted when treated with 4-OHT, which abolished Cx43 expression. The exaggerated fibrotic response to AngII in partially deficient Cx43Cre-ER(T)/fl mice was associated with enhanced p38 MAPK activation and was not evident in Cx43 heterozygous (Cx43+/-) mice. In contrast, normalization of interstitial collagen in 4-OHT-treated Cx43Cre-ER(T)/fl animals correlated with enhanced MMP-9 activity, IL-6 and NOX2 mRNA expression, and macrophage content, and with reduced -SMA and SM22 in isolated fibroblasts. In conclusion, our data demonstrates an exaggerated, p38 MAPK-dependent, fibrotic response to AngII in partially deficient Cx43Cre-ER(T)/fl mice, and a paradoxical normalization of collagen deposition in animals with an almost complete Cx43 ablation, an effect associated with increased MMP-9 activity and inflammatory response and reduced fibroblasts differentiation.


Subject(s)
Angiotensin II/adverse effects , Cardiomyopathies/metabolism , Cell Differentiation , Connexin 43/deficiency , Fibroblasts/metabolism , Myocardium/metabolism , Angiotensin II/pharmacology , Animals , Cardiomyopathies/chemically induced , Cardiomyopathies/genetics , Cardiomyopathies/pathology , Connexin 43/metabolism , Fibrosis , Mice , Mice, Knockout , Muscle Proteins/genetics , Muscle Proteins/metabolism , Myocardium/pathology
8.
Sci Rep ; 9(1): 6395, 2019 Apr 17.
Article in English | MEDLINE | ID: mdl-30996245

ABSTRACT

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

9.
J Clin Lipidol ; 12(5): 1190-1198, 2018.
Article in English | MEDLINE | ID: mdl-30049591

ABSTRACT

BACKGROUND: High ferritin concentration is associated with hypertriglyceridemia, although it is not elucidated if iron overload has a causal role. OBJECTIVE: To evaluate the efficacy of repeated phlebotomies in patients with iron overload and hypertriglyceridemia. METHODS: Twelve weeks, 1:1 randomized, parallel-groups trial conducted at a University Hospital Lipid Clinic, including 86 subjects aged 18-70 years with serum ferritin >300 ng/mL in men or >200 ng/mL in women and triglycerides >200 mg/dL. Participants underwent: (1) three phlebotomies (every 3 weeks) and lipid-lowering dietary counseling or (2) lipid-lowering dietary counseling. The main outcome measured was the mean difference in percent change in triglyceride concentration between groups after the intervention. The mean differences in percent change of other clinical and biochemical variables (including cytokines and proinflammatory markers) after the intervention were also evaluated. RESULTS: Subjects who received phlebotomies showed a significant improvement in iron metabolism. The mean percent change in triglycerides between groups was -4.68 [-20.8, 11.4]%, P = .721. Retinol-binding protein 4 decreased by 9.98 ± 21.7% after phlebotomies, with a mean percent change between groups of -14.2 [-25.8, -2.73]%, P = .017, and correlated to gamma glutamyl transferase, alanine aminotransferase and aspartate aminotransferase change. Subjects with a large reduction in hepcidin showed a large improvement in liver enzymes and proinflammatory markers. CONCLUSIONS: A lipid-lowering diet plus a substantial reduction in iron deposits with repeated phlebotomies in subjects with hyperferritinemia and hypertriglyceridemia did not reduce triglyceride concentration in comparison with a lipid-lowering diet. Iron depletion for lipid management in these patients is not supported.


Subject(s)
Hypertriglyceridemia/complications , Hypertriglyceridemia/therapy , Iron Overload/metabolism , Phlebotomy , Adolescent , Adult , Aged , Female , Glucose/metabolism , Humans , Hypertriglyceridemia/metabolism , Lipid Metabolism , Male , Middle Aged , Young Adult
10.
Sci Rep ; 8(1): 2442, 2018 02 05.
Article in English | MEDLINE | ID: mdl-29402957

ABSTRACT

Inhibition of succinate dehydrogenase (SDH) with malonate during reperfusion reduces infarct size in isolated mice hearts submitted to global ischemia. However, malonate has toxic effects that preclude its systemic administration in animals. Here we investigated the effect of intracoronary malonate on infarct size in pigs submitted to transient coronary occlusion. Under baseline conditions, 50 mmol/L of intracoronary disodium malonate, but not lower concentrations, transiently reduced systolic segment shortening in the region perfused by the left anterior descending coronary artery (LAD) in open-chest pigs. To assess the effects of SDH inhibition on reperfusion injury, saline or malonate 10 mmol/L were selectively infused into the area at risk in 38 animals submitted to ischemia-reperfusion. Malonate improved systolic shortening in the area at risk two hours after 15 min of ischemia (0.18 ± 0.07 vs 0.00 ± 0.01 a.u., p = 0.025, n = 3). In animals submitted to 40 min of ischemia, malonate reduced reactive oxygen species production (MitoSOX staining) during initial reperfusion and limited infarct size (36.46 ± 5.35 vs 59.62 ± 4.00%, p = 0.002, n = 11), without modifying reperfusion arrhythmias. In conclusion, inhibition of SDH with intracoronary malonate during early reperfusion limits reperfusion injury and infarct size in pigs submitted to transient coronary occlusion without modifying reperfusion arrhythmias or contractile function in distant myocardium.


Subject(s)
Cardiotonic Agents/pharmacology , Hemodynamics/drug effects , Malonates/pharmacology , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Succinate Dehydrogenase/antagonists & inhibitors , Animals , Arterial Pressure/drug effects , Coronary Circulation/drug effects , Coronary Vessels/drug effects , Heart Rate/drug effects , Injections, Intravenous , Myocardial Infarction/enzymology , Myocardial Infarction/pathology , Myocardial Reperfusion Injury/enzymology , Myocardial Reperfusion Injury/pathology , Myocardium/metabolism , Myocardium/pathology , Succinate Dehydrogenase/metabolism , Swine
12.
Cardiovasc Res ; 113(1): 52-60, 2017 01.
Article in English | MEDLINE | ID: mdl-28069702

ABSTRACT

AIMS: Remote ischaemic conditioning (RIC) releases a humoural factor able to exert cross-species cardioprotection when plasma dialysate is applied to isolated hearts. However, the exact chemical nature of this factor is currently unknown. METHODS AND RESULTS: RIC (4 × 5min femoral occlusion/5min reperfusion) was applied to 10 male pigs, and blood was taken before and after the manoeuvre. Discriminant analysis of 1H-NMR spectra (n = 10-12) obtained from plasma dialysates (12-14 kDa cut-off) allowed to demonstrate a different metabolic profile between control and postRIC samples, with lactate (2.671 ± 0.294 vs. 3.666 ± 0.291 µmol/mL, P = 0.020), succinate (0.062 ± 0.005 vs. 0.082 ± 0.008 µmol/mL, P = 0.035) and glycine (0.055 ± 0.009 vs. 0.471 ± 0.151 µmol/mL, P = 0.015) being the main responsible for such differences. Plasma dialysates were then given to isolated mice hearts submitted to global ischaemia (35 min) and reperfusion (60 min), for 30 min before ischaemia or during the first 15 min of reflow. Infarct size was significantly reduced when postRIC dialysate was applied before ischaemia as compared with hearts pretreated with control dialysate (44.81 ± 3.22 vs. 55.55 ± 2.53%, P = 0.012, n = 12). Blockade of glycine receptors with strychnine 10 µM inhibited the protective effect caused by pretreatment with postRIC dialysate (52.76 ± 6.94 vs. 51.92 ± 5.78%, P-NS, n = 5), whereas pretreatment with glycine 3 mmol/L, but not succinate 100 µmol/L, mimicked RIC protection (41.90 ± 4.50% in glycine-treated vs. 61.51 ± 5.16 and 64.73 ± 4.47% in succinate-treated and control hearts, respectively, P < 0.05, n = 4-7). CONCLUSIONS: RIC releases glycine and exerts cross-species cardioprotection against infarction through glycine receptor activation.


Subject(s)
Femoral Artery/surgery , Glycine/blood , Ischemic Preconditioning/methods , Myocardial Ischemia/prevention & control , Myocardial Reperfusion Injury/prevention & control , Myocardium/metabolism , Receptors, Glycine/metabolism , Animals , Biomarkers/blood , Discriminant Analysis , Disease Models, Animal , Excitatory Amino Acid Antagonists/pharmacology , Glycine/pharmacology , Ligation , Male , Mice, Inbred C57BL , Myocardial Ischemia/blood , Myocardial Ischemia/pathology , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/blood , Myocardial Reperfusion Injury/pathology , Myocardial Reperfusion Injury/physiopathology , Myocardium/pathology , Proton Magnetic Resonance Spectroscopy , Receptors, Glycine/agonists , Receptors, Glycine/antagonists & inhibitors , Signal Transduction , Species Specificity , Sus scrofa , Time Factors
13.
Eur J Haematol ; 98(2): 142-148, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27717146

ABSTRACT

The presence of chromosomal gains other than trisomy 12 in chronic lymphocytic leukaemia (CLL) is unusual. However, some patients may show gains on several chromosomes simultaneously suggesting a hyperdiploid karyotype. OBJECTIVE: The objective of this study was to analyse by FISH the frequency and prognostic impact of hyperdiploidy in CLL. METHOD: A review of 1359 consecutive cases diagnosed with CLL referred for FISH analysis to a unique institution was carried out. Hyperdiploidy was considered when a gain of at least three of the five FISH probes used was observed. RESULTS: Seven cases (0.51%) with hyperdiploidy were found, confirming that it is a rare event in this disease. Although most patients presented with early Binet stages at diagnosis, six of seven (86%) shortly progressed. The median of time to the first therapy (TTFT) and overall survival (OS) for the patients with hyperdiploidy were short (1.4 months and 20 months, respectively). Moreover, comparing them with a control group of patients (non-hyperdiploid) with completed follow-up data, TTFT and OS of the patients with hyperdiploidy were significantly shorter than the control group. CONCLUSION: The presence of hyperdiploidy is uncommon and probably associated with poor prognostic markers in CLL.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Polyploidy , Aged , Biomarkers , Case-Control Studies , Chromosome Aberrations , Female , Humans , Immunophenotyping , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Male , Middle Aged , Mutation , Neoplasm Staging , Prognosis , Retrospective Studies , Time-to-Treatment , Treatment Outcome , Tumor Suppressor Protein p53/genetics
16.
Cardiovasc Res ; 109(3): 374-84, 2016 Mar 01.
Article in English | MEDLINE | ID: mdl-26705364

ABSTRACT

AIMS: Previous studies demonstrated that pre-treatment with malonate, a reversible inhibitor of succinate dehydrogenase, given before ischaemia, reduces infarct size. However, it is unknown whether administration of malonate may reduce reperfusion injury. METHODS AND RESULTS: Isolated mice hearts were treated, under normoxic conditions, with increasing concentrations of disodium malonate (0.03-30 mmol/L, n = 4). Malonate induced a concentration-dependent decrease in left ventricular developed pressure (LVdevP) (EC50 = 8.05 ± 2.11 mmol/L). In isolated hearts submitted to global ischaemia (35 min) followed by reperfusion (60 min), malonate 3 mmol/L given only during the first 15 min of reperfusion reduced lactate dehydrogenase release (125.41 ± 16.82 vs. 189.20 ± 13.74 U/g dry tissue/15 min in controls, P = 0.015) and infarct size (24.57 ± 2.32 vs. 39.84 ± 2.78%, P = 0.001, n = 7-8 per group) and improved recovery of LVdevP (20.06 ± 3.82 vs 7.76 ± 2.53% of baseline LVdevP, P = 0.017). (1)H NMR spectroscopy demonstrated marked changes in the metabolic profile of malonate-treated hearts, including increased accumulation of succinate. Furthermore, malonate reduced reactive oxygen species (ROS) production, as measured by MitoSOX staining in myocardial samples obtained after 5 min of reperfusion and in mitochondrial preparations from these samples, preserved mitochondrial respiration, and reduced mitochondrial permeabilization, assessed by calcein retention. Treatment with malonate did not result in activation of RISK or SAFE signalling pathways in tissue extracts obtained 5 min after reperfusion. CONCLUSION: Succinate dehydrogenase inhibition with malonate at the onset of reperfusion reduces infarct size in isolated mice hearts through reduction in ROS production and mitochondrial permeability transition pore opening.


Subject(s)
Malonates/pharmacology , Mitochondria, Heart/drug effects , Myocardial Reperfusion Injury/prevention & control , Succinate Dehydrogenase/antagonists & inhibitors , Animals , Cardiotonic Agents/pharmacology , L-Lactate Dehydrogenase/metabolism , Male , Mice, Inbred C57BL , Mitochondria, Heart/metabolism , Mitochondrial Membrane Transport Proteins/metabolism , Mitochondrial Permeability Transition Pore , Myocardial Reperfusion Injury/metabolism
17.
Cardiovasc Res ; 107(2): 246-54, 2015 Jul 15.
Article in English | MEDLINE | ID: mdl-26045476

ABSTRACT

AIMS: Remote ischaemic conditioning (RIC) has been shown to reduce myocardial infarct size in patients. Our objective was to investigate whether the combination of RIC with either exenatide or glucose-insulin-potassium (GIK) is more effective than RIC alone. METHODS AND RESULTS: Pigs were submitted to 40 min of coronary occlusion followed by reperfusion, and received (i) no treatment, (ii) one of the following treatments: RIC (5 min ischemia/5 min reperfusion × 4), GIK, or exenatide (at doses reducing infarct size in clinical trials), or (iii) a combination of two of these treatments (RIC + GIK or RIC + exenatide). After 5 min of reperfusion (n = 4/group), prominent phosphorylation of Akt and endothelial nitric oxide synthase (eNOS) was observed, both in control and reperfused myocardium, in animals receiving GIK, and mitochondria from these hearts showed reduced ADP-stimulated respiration. (1)H NMR-based metabonomics disclosed a shift towards increased glycolysis in GIK and exenatide groups. In contrast, oxidative stress (myocardial nitrotyrosine levels) and eNOS uncoupling were significantly reduced only by RIC. In additional experiments (n = 7-10/group), ANOVA demonstrated a significant effect of the number of treatments after 2 h of reperfusion on infarct size (triphenyltetrazolium, % of the area at risk; 59.21 ± 3.34, 36.64 ± 3.03, and 21.04 ± 2.38% for none, one, and two treatments, respectively), and significant differences between one and two treatments (P = 0.004) but not among individual treatments or between RIC + GIK and RIC + exenatide. CONCLUSIONS: GIK and exenatide activate cardioprotective pathways different from those of RIC, and have additive effects with RIC on infarct size reduction in pigs.


Subject(s)
Insulin/pharmacology , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Peptides/pharmacology , Venoms/pharmacology , Aging , Animals , Exenatide , Glucose/metabolism , Ischemia/drug therapy , Myocardial Infarction/metabolism , Myocardial Reperfusion/methods , Myocardial Reperfusion Injury/metabolism , Potassium/metabolism , Swine
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