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- Gidlöf, Olof, et al.
(författare)
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Cardiospecific microRNA Plasma Levels Correlate with Troponin and Cardiac Function in Patients with ST Elevation Myocardial Infarction, Are Selectively Dependent on Renal Elimination, and Can Be Detected in Urine Samples.
- 2011
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Ingår i: Cardiology. - : S. Karger AG. - 1421-9751 .- 0008-6312. ; 118:4, s. 217-226
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Circulating microRNAs (miRNAs) are promising as biomarkers for various diseases. We examined the release patterns of cardiospecific miRNAs in a closed-chest, large animal ischemia-reperfusion model and in patients with ST elevation myocardial infarction (STEMI). Methods: Six anesthetized pigs were subjected to coronary occlusion-reperfusion. Plasma, urine, and clinical parameters were collected from 25 STEMI patients undergoing primary percutaneous coronary intervention. miRNA was extracted and measured with qPCR. Results: In the pig reperfusion model miR-1, miR-133a, and miR-208b increased rapidly in plasma with a peak at 120 min, while miR-499-5p remained elevated longer. In patients with STEMI all 4 miRNAs increased abruptly from 70-fold to 3,000-fold in plasma, with a peak within 12 h (p < 0.01). miR-1 and miR-133a both correlated strongly with the glomerular filtration rate (GFR), indicating renal elimination. This was confirmed by detection of miR-1 and miR-133a, but not miR-208b or miR-499-5p, in urine. Peak values of miR-208b correlated with peak troponin and the ejection fraction. Conclusion: We demonstrate a distinct and rapid increase in levels of cardiospecific miRNA in the circulation after myocardial infarction. Release of miRNAs correlated with cardiomyocyte necrosis markers, the ejection fraction, and the GFR, indicating a possible role for these molecules as biomarkers for the diagnosis of STEMI as well as the prediction of long-term complications.
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| 4. |
- Gilje, Patrik, et al.
(författare)
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Plasma Levels of Liver-Specific miR-122 is Massively Increased in a Porcine Cardiogenic Shock Model and Attenuated by Hypothermia.
- 2012
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Ingår i: Shock. - 1540-0514. ; 37, s. 234-238
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Tidskriftsartikel (refereegranskat)abstract
- AIMS:: Tissue-specific circulating microRNAs are released into the blood after organ injury. In an ischemic porcine cardiogenic shock model we investigated the release pattern of cardiacspecific miR-208b and liver-specific miR-122 and assessed the effect of therapeutic hypothermia on their respective plasma levels. METHODS AND RESULTS:: Pigs were anesthetized and cardiogenic shock was induced by inflation of a PCI-balloon in the proximal LAD for 40 minutes followed by reperfusion. After fulfillment of the predefined shock criteria, the pigs were randomized to hypothermia (33°C, n=6) or normothermia (38°C, n=6). Circulating microRNAs were extracted from plasma and measured with quantitative real-time PCR. Tissue specificity was assessed by microRNA extraction from porcine tissues followed by quantitative real-time PCR. In vitro, the release of miR-122 from a cultured hepatocyte cell line exposed to either hypoxia or acidosis was assessed by real-time PCR. miR-122 was found to be highly liver specific whereas miR-208b was expressed exclusively in the heart. In the control group ischemic cardiogenic shock induced a 460.000-fold and a 63.000-fold increase in plasma levels of miR-122 (p<0.05) and miR-208b (p<0.05), respectively. Therapeutic hypothermia significantly diminished the increase of miR-122 compared to the normothermic group (p<0.005). In our model, hypothermia was initiated after coronary reperfusion and did neither affect myocardial damage as previously assessed by magnetic resonance imaging nor the plasma level of miR-208b. CONCLUSIONS:: Our results indicate that liver-specific miR-122 is released into the circulation in the setting of cardiogenic shock and that therapeutic hypothermia significantly reduces the levels of miR-122.
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| 5. |
- Gilje, Patrik, et al.
(författare)
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The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest
- 2014
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 18:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Early prognostication after successful cardiopulmonary resuscitation is difficult, and there is a need for novel methods to estimate the extent of brain injury and predict outcome. In this study, we evaluated the impact of the cardiac arrest syndrome on the plasma levels of selected tissue-specific microRNAs (miRNAs) and assessed their ability to prognosticate death and neurological disability. Methods: We included 65 patients treated with hypothermia after cardiac arrest in the study. Blood samples were obtained at 24 hours and at 48 hours. For miRNA-screening purposes, custom quantitative polymerase chain reaction (qPCR) panels were first used. Thereafter individual miRNAs were assessed at 48 hours with qPCR. miRNAs that successfully predicted prognosis at 48 hours were further analysed at 24 hours. Outcomes were measured according to the Cerebral Performance Category (CPC) score at 6 months after cardiac arrest and stratified into good (CPC score 1 or 2) or poor (CPC scores 3 to 5). Results: At 48 hours, miR-146a, miR-122, miR-208b, miR-21, miR-9 and miR-128 did not differ between the good and poor neurological outcome groups. In contrast, miR-124 was significantly elevated in patients with poor outcomes compared with those with favourable outcomes (P < 0.0001) at 24 hours and 48 hours after cardiac arrest. Analysis of receiver operating characteristic curves at 24 and 48 hours after cardiac arrest showed areas under the curve of 0.87 (95% confidence interval (CI) = 0.79 to 0.96) and 0.89 (95% CI = 0.80 to 0.97), respectively. Conclusions: The brain-enriched miRNA miR-124 is a promising novel biomarker for prediction of neurological prognosis following cardiac arrest.
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- Ubachs, Joey, et al.
(författare)
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Myocardium at risk can be determined by ex vivo T2-weighted magnetic resonance imaging even in the presence of gadolinium: comparison to myocardial perfusion single photon emission computed tomography.
- 2013
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Ingår i: European Heart Journal-Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404. ; 14:3, s. 261-268
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Determination of the myocardium at risk (MaR) and final infarct size by cardiac magnetic resonance imaging (CMR) enables calculation of salvaged myocardium in acute infarction. T2-weighted imaging is performed prior to the administration of gadolinium, since gadolinium affects T2 tissue properties. This is, however, difficult in an ex vivo model since gadolinium must be administered for determination of infarct size by CMR. We aimed to test the ability of ex vivo T2-weighted imaging to assess MaR using myocardial perfusion single photon emission computed tomography (SPECT) as reference and to investigate whether MaR could be assessed by ex vivo T2-weighted imaging after injection of gadolinium. Materials and methods In 18 domestic pigs, the left anterior descending artery was occluded for either 30 or 40 min, followed by 4 h of reperfusion. After explantation of the hearts, myocardial perfusion SPECT and T2-weighted imaging were performed for determination of MaR, either with or without gadolinium. Infarct size was determined by T1-weighted imaging and by triphenyl tetrazolium chloride (TTC) staining. RESULTS: T2-weighted imaging agreed with myocardial perfusion SPECT, both with and without gadolinium (r(2)= 0.70, P < 0.01) with a bias of 2.6 ± 5.1% (P = 0.04). Infarct size was 15.4 ± 5.3 and 22.1 ± 5.6% with TTC and T1-weighted imaging, respectively (P = 0.008) in nine pigs who had both infarct measures. CONCLUSION: T2-weighted CMR imaging can be used to determine MaR in an ex vivo experimental model, both with and without the presence of gadolinium. Thus, CMR alone can be used to assess myocardial salvage in experimental studies.
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| 8. |
- vanderPals, Jesper, et al.
(författare)
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Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model
- 2010
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods: In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results: ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 +/- 3.4 vs control: 74.1 +/- 2.9% AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 +/- 1.2 vs control: 5.3 +/- 2.5% AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 +/- 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions: ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.
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