Cardiac overexpression of A1-adenosine receptor protects intact mice against myocardial infarction

2002 ◽  
Vol 282 (3) ◽  
pp. H949-H955 ◽  
Author(s):  
Zequan Yang ◽  
Rachael J. Cerniway ◽  
Anne M. Byford ◽  
Stuart S. Berr ◽  
Brent A. French ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
At Risk ◽  
Infarct Size ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Blue Staining ◽  
Ventricular Ejection Fraction ◽  
High Level

Previous studies have shown that high-level (300-fold normal) cardiac overexpression of A1-adenosine receptors (A1-ARs) in transgenic (TG) mice protects isolated hearts against ischemia-reperfusion injury. However, this high level of overexpression is associated with bradycardia and increased incidence of arrhythmia during ischemia in intact mice, which interfered with studies to determine whether this line of TG mice might also be protected against myocardial infarction (MI) in vivo. For these studies, we therefore selected a line of TG mice that overexpresses the A1-AR at more moderate levels (30-fold normal), which affords cardioprotection in the isolated heart while minimizing bradycardia and arrhythmia during ischemia in intact mice. Wild-type (WT; n = 10) and moderate-level A1-AR TG ( n = 10) mice underwent 45 min of left anterior descending coronary artery occlusion, followed by 24-h reperfusion. Infarct size and region at risk were determined by triphenyltetrazolium chloride and phthalo blue staining, respectively. Infarct size (% region at risk) in WT mice was 52 ± 3%, whereas overexpression of A1-ARs in the TG mice markedly reduced infarct size to 31 ± 3% ( P < 0.05). Furthermore, contractile function (left ventricular ejection fraction) as determined by cardiac magnetic resonance imaging 24 h after MI was better preserved in TG vs. WT mice. Cardiac overexpression of A1-ARs reduces infarct size by 40% and preserves cardiac function in intact mice after MI.

Colchicine for Left Ventricular Infarct Size Reduction in Acute Myocardial Infarction: A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study Protocol – The COVERT-MI Study

Cardiology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Didier Bresson ◽  
François Roubille ◽  
Cyril Prieur ◽  
Loic Biere ◽  
Fabrice Ivanes ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Infarct Size ◽  
Phase Ii ◽  
Myocardial Injury ◽  
Ventricular Remodeling ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Controlled Study ◽  
Ventricular Ejection Fraction

Inflammatory processes have been identified as key mediators of ischemia-reperfusion injury in ST-segment elevation myocardial infarction (STEMI). They add damage to the myocardium and are associated with clinical adverse events (heart failure and cardiovascular death) and poor myocardial recovery. Colchicine is a well-known alkaloid with potent anti-inflammatory properties. In a proof-of-concept phase II trial, colchicine has been associated with a significant 50% reduction of infarct size (assessed by creatine kinase levels) in comparison to placebo in acute STEMI patients referred for primary percutaneous coronary intervention (PPCI). The Colchicine in STEMI Patients Study (COVERT-MI) is an ongoing confirmative prospective, multicenter, randomized, double-blind trial testing whether a short course oral treatment with colchicine versus placebo decreases myocardial injury in patients presenting with STEMI referred for PPCI. Adult patients, with a first STEMI episode and an initial TIMI flow ≤1, referred for PPCI, will be randomized (<i>n</i> = 194) in a 1:1 ratio to receive an oral bolus of colchicine of 2 mg followed by 0.5 mg b.i.d. treatment during 5 days or matching placebo. The primary endpoint will be the reduction in infarct size as assessed by cardiac magnetic resonance at 5 ± 2 days between both groups. The main secondary endpoints will be tested between groups in hierarchical order with left ventricular ejection fraction at 5 days, microvascular obstruction presence at 5 days, and absolute adverse left ventricular remodeling between 5 days and 3 months. This academic study is being financed by a grant from the French Ministry of Health (PHRCN-16-0357). Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present study describes the rationale, design, and methods of the trial.

Implication of anti-angiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Marcos Garces ◽  
C Rios-Navarro ◽  
L Hueso ◽  
A Diaz ◽  
C Bonanad ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Adjuvant Therapy ◽  
Ejection Fraction ◽  
Infarct Size ◽  
Systolic Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Coronary Reperfusion ◽  
Ventricular Ejection Fraction

Abstract Background Angiogenesis participates in re-establishing microcirculation after myocardial infarction (MI). Purpose In this study, we aim to further understand the role of the anti-angiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and explore its potential as a co-adjuvant therapy to coronary reperfusion. Methods Two mice MI models were formed: 1) permanent coronary ligation (non-reperfused MI), 2) transient 45-min coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. Serum and myocardial VEGF-A165b levels were determined. In both experimental MI models, functional and structural implication of VEGF-A165b blockade was assessed. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6-months and with the occurrence of adverse events (death, heart failure and/or re-infarction). Results In both models, circulating and myocardial VEGF-A165b presence was increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockage increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in non-reperfused MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. Conclusions In experimental and clinical studies, higher serum VEGF-A165b levels associates with a worse systolic function. Its blockage enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in non-reperfused MI experiments. Therefore, VEGF-A165b neutralization represents a potential co-adjuvant therapy to coronary reperfusion. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was funded by “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER” (Exp. PIE15/00013, PI17/01836, PI18/00209 and CIBERCV16/11/00486).

scholarly journals Temporal Course of Plasma Trimethylamine N-Oxide (TMAO) Levels in ST-Elevation Myocardial Infarction

2021 ◽  
Vol 10 (23) ◽  
pp. 5677
Author(s):  
Mohammad A. Almesned ◽  
Femke M. Prins ◽  
Erik Lipšic ◽  
Margery A. Connelly ◽  
Erwin Garcia ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Renal Function ◽  
Infarct Size ◽  
Impaired Renal Function ◽  
Left Ventricular ◽  
St Elevation Myocardial Infarction ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Temporal Course ◽  
St Elevation

The gut metabolite trimethylamine N-oxide (TMAO) at admission has a prognostic value in ST-elevation myocardial infarction (STEMI) patients. However, its sequential changes and relationship with long-term infarct-related outcomes after primary percutaneous coronary intervention (PCI) remain elusive. We delineated the temporal course of TMAO and its relationship with infarct size and left ventricular ejection fraction (LVEF) post-PCI, adjusting for the estimated glomerular filtration rate (eGFR). We measured TMAO levels at admission, 24 h and 4 months post-PCI in 379 STEMI patients. Infarct size and LVEF were determined by cardiac magnetic resonance 4 months after PCI. TMAO levels decreased from admission (4.13 ± 4.37 μM) to 24 h (3.41 ± 5.84 μM, p = 0.001) and increased from 24 h to 4 months (3.70 ± 3.86 μM, p = 0.026). Higher TMAO values at 24 h were correlated to smaller infarct sizes (rho = −0.16, p = 0.024). Larger declines between admission and 4 months suggestively correlated with smaller infarct size, and larger TMAO increases between 24 h and 4 months were associated with larger infarct size (rho = −0.19, p = 0.008 and rho = −0.18, p = 0.019, respectively). Upon eGFR stratification using 90 mL/min/1.73 m2 as a cut-off, significant associations between TMAO and infarct size were only noted in subjects with impaired renal function. In conclusion, TMAO levels in post-PCI STEMI patients are prone to fluctuations, and these fluctuations could be prognostic for infarct size, particularly in patients with impaired renal function.

scholarly journals Infarct Size and Left Ventricular Ejection Fraction in Acute Myocardial Infarction

1977 ◽  
Vol 41 (11) ◽  
pp. 1299-1306 ◽  
Author(s):  
MASATSUGU HORI ◽  
MICHITOSHI INOUE ◽  
MASAYOSHI MISHIMA ◽  
TAKASHI SHIMAZU ◽  
HIROSHI ABE ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Infarct Size ◽  
Left Ventricular ◽  
Ventricular Ejection ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

scholarly journals Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Ragnhild Helseth ◽  
Christian Shetelig ◽  
Geir Øystein Andersen ◽  
Miriam Sjåstad Langseth ◽  
Shanmuganathan Limalanathan ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Outcome ◽  
Infarct Size ◽  
Left Ventricular ◽  
Clinical Event ◽  
Left Ventricular Ejection ◽  
Myocardial Salvage ◽  
Area At Risk ◽  
Ventricular Ejection Fraction ◽  
Clinical Events

Background. The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients. Methods and Results. In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p≤0.02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p<0.03). Moreover, they had lower LVEF acutely and after 4 months, and larger change in LVEDVi (all p≤0.014). High day 1 dsDNA levels also associated with risk of having a large infarct size (>75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p<0.021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p=0.012). No such observations were encountered for MPO-DNA. Conclusions. High day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008)).

scholarly journals In-hospital results of rheolytic catheter thrombectomy in patients with STEMI

2016 ◽  
Vol 20 (3) ◽  
pp. 54
Author(s):  
M V Malkhasyan ◽  
V A Kuznetsov ◽  
I S Bessonov ◽  
P I Pavlov
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery ◽  
Hospital Mortality ◽  
Cardiogenic Shock ◽  
Contractile Function ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Old Myocardial Infarction ◽  
Mean Time

<p><strong>Aim.</strong> The article focuses on the evaluation of short-term efficacy of rheolytic thrombectomy (AngioJet) in patients with STEMI. <br /><strong>Methods.</strong> 188 patients (85.6% men) with STEMI underwent primary PCI by means of rheolytic catheter thrombectomy (AngioJet). The mean age was 54.1 ± 10.7 years. 32 (17 %) of patients had old myocardial infarction. 104 (55.9 %) patients were diagnosed with ST-elevated inferior myocardial infarction. 22 (12 %) patients were operated under cardiogenic shock. Mean time from the appearance of symptoms to admission was 222.5 [70, 584] min. Anterior interventricular artery (38.3 %) and right coronary artery (43.6 %) were the main infarction-related arteries. <br /><strong>Results.</strong> Complete thrombotic occlusion of the coronary artery occurred in 144 (77.4%) patients. Mean “door-to-balloon” time amounted to 41.5 [30; 60]. Coronary thrombus was fully removed in 107 (60.8%) of patients. Stents with antiproliferative effect were implanted in 48.8 % of patients. Immediate angiographic success was achieved in 177 (94.1%) cases. Mean time of PCI was 60 [50; 80] min. PCI complications were registered in 3 (1.6%) patients. Intraoperative life-threatening arrhythmias happened in 22 (11.7 %) patients. The phenomenon of "no-reflow" occurred in 6 (3.2%) PCI cases. The rate of in-hospital mortality was 5.9%, including patients with cardiogenic shock (36.4%) and those without it (1.9 %). MACCE (main adverse cardio-cerebral events) were observed in 15 (8%) cases. According to ECG data obtained postoperatively, 26 % of patients demonstrated no regional asynergy, while a decrease in myocardial contractile function occurred in just 26 % of cases, with the average left ventricular ejection fraction running to 57.5±9 %. Mean in-hospital stay was 9.5±0.6 days.<br /><strong>Conclusion.</strong> The results of this study suggest that rheolytic catheter thrombectomy (AngioJet) is a safe and effective modality. Immediate hospital results show low rate complications and low in-hospital mortality.</p><p>Received 13 April 2016. Accepted 9 June 2016.</p><p><strong>Conflict of interest:</strong> The authors declare no conflict interests.</p>

Abstract 13725: Oxidative Stress Accelerates Senescence and Reduces Life Span but Does Not Alter Cardioprotection in Mice Over-expressing H11kinase/hsp22

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Didier Morin ◽  
Romain Long ◽  
Lydie Laure ◽  
Christophe Depre ◽  
Stephen F Vatner ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Hypertrophy ◽  
Infarct Size ◽  
Life Span ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Left Ventricular Cavity ◽  
Ventricular Ejection Fraction

H11 kinase/Hsp22 (H11K) is a small heat shock protein which provides powerful cardioprotection, i.e., reduction by 80% of infarct size expressed as a fraction of area at risk following 45 min coronary occlusion/4 hr reperfusion when over-expressed in a cardiac-specific transgenic (TG) mouse model. The goal of this investigation was to determine if these protective mechanisms would also enhance longevity and be effective in protecting from age-related myocardial dysfunction. Surprisingly, TG mice showed a reduction of 48% in their mean life span as compared to wild type (WT). The mechanism of premature death was most likely cardiac as left ventricular ejection fraction was reduced in one year old TG mice (49% vs 74% in WT, p<0.01), left ventricular cavity was dilated and cardiac hypertrophy was increased by 58%, all compatible with severe dilated cardiomyopathy. At the molecular level, hearts from TG mice showed a significant increase in reactive oxygen species, oxidized/reduced glutathione ratio, NADPH and xanthine oxidase activities, Nox2 expression associated with an increase in p16, p19 mRNA, β-galactosidase positive cells and telomerase activity. Subgroups of WT and TG mice were also treated with the antioxidant tempol (100 mg/kg/d) from weaning to their sacrifice. Chronic tempol treatment abolished oxidative stress, reduced cardiac hypertrophy, extended life span (+31%) and prevented aging markers (p16, p19 mRNA, β-galactosidase positive cells) in TG mice. The marked reduction in infarct size with ischemia/reperfusion noted above, observed in 10-12 weeks old mice, remained unchanged after tempol in TG mice and was not abolished with aging. Thus, this is the first demonstration that the mechanisms mediating reduced longevity such as increased oxidative stress do not reduce cardioprotection in H11K TG mice, and conversely, the mechanisms mediating powerful cardioprotection against ischemic stress are ineffective in maintaining normal cardiac function with aging.

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