| Title |
Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function
|
|---|---|
| Published in |
Basic Research in Cardiology, March 2017
|
| DOI | 10.1007/s00395-017-0610-9 |
| Pubmed ID | |
| Authors |
Soeren E. Pischke, A. Gustavsen, H. L. Orrem, K. H. Egge, F. Courivaud, H. Fontenelle, A. Despont, A. K. Bongoni, R. Rieben, T. I. Tønnessen, M. A. Nunn, H. Scott, H. Skulstad, A. Barratt-Due, T. E. Mollnes |
| Abstract |
Inhibition of complement factor 5 (C5) reduced myocardial infarction in animal studies, while no benefit was found in clinical studies. Due to lack of cross-reactivity of clinically used C5 antibodies, different inhibitors were used in animal and clinical studies. Coversin (Ornithodoros moubata complement inhibitor, OmCI) blocks C5 cleavage and binds leukotriene B4 in humans and pigs. We hypothesized that inhibition of C5 before reperfusion will decrease infarct size and improve ventricular function in a porcine model of myocardial infarction. In pigs (Sus scrofa), the left anterior descending coronary artery was occluded (40 min) and reperfused (240 min). Coversin or placebo was infused 20 min after occlusion and throughout reperfusion in 16 blindly randomized pigs. Coversin significantly reduced myocardial infarction in the area at risk by 39% (p = 0.03, triphenyl tetrazolium chloride staining) and by 19% (p = 0.02) using magnetic resonance imaging. The methods correlated significantly (R = 0.92, p < 0.01). Tissue Doppler echocardiography showed increased systolic displacement (31%, p < 0.01) and increased systolic velocity (29%, p = 0.01) in coversin treated pigs. Interleukin-1β in myocardial microdialysis fluid was significantly reduced (31%, p < 0.05) and tissue E-selectin expression was significantly reduced (p = 0.01) in the non-infarcted area at risk by coversin treatment. Coversin ablated plasma C5 activation throughout the reperfusion period and decreased myocardial C5b-9 deposition, while neither plasma nor myocardial LTB4 were significantly reduced. Coversin substantially reduced the size of infarction, improved ventricular function, and attenuated interleukin-1β and E-selectin in this porcine model by inhibiting C5. We conclude that inhibition of C5 in myocardial infarction should be reconsidered. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Norway | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 7 | 19% |
| Student > Bachelor | 4 | 11% |
| Student > Ph. D. Student | 3 | 8% |
| Student > Doctoral Student | 2 | 5% |
| Professor | 2 | 5% |
| Other | 7 | 19% |
| Unknown | 12 | 32% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 11 | 30% |
| Immunology and Microbiology | 4 | 11% |
| Engineering | 3 | 8% |
| Agricultural and Biological Sciences | 3 | 8% |
| Biochemistry, Genetics and Molecular Biology | 2 | 5% |
| Other | 2 | 5% |
| Unknown | 12 | 32% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 March 2017.
All research outputs
#15,450,375
of 22,959,818 outputs
Outputs from Basic Research in Cardiology
#450
of 649 outputs
Outputs of similar age
#197,286
of 310,524 outputs
Outputs of similar age from Basic Research in Cardiology
#3
of 8 outputs
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