Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function.

Pischke, Soeren E; Gustavsen, A; Orrem, H L; Egge, K H; Courivaud, F; Fontenelle, H; Despont, Alain; Bongoni, A K; Rieben, Robert; Tønnessen, T I; Nunn, M A; Scott, H; Skulstad, H; Barratt-Due, A; Mollnes, T E (2017). Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function. Basic research in cardiology, 112(3), p. 20. Springer-Medizin-Verlag 10.1007/s00395-017-0610-9

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe

UniBE Contributor:

Despont, Alain and Rieben, Robert

ISSN:

0300-8428

Publisher:

Springer-Medizin-Verlag

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

12 Jan 2018 15:42

Last Modified:

13 Mar 2021 07:36

Publisher DOI:

10.1007/s00395-017-0610-9

PubMed ID:

28258298

Uncontrolled Keywords:

C5 Complement Contractility Ischemia/reperfusion LTB4 Myocardial infarction

BORIS DOI:

10.7892/boris.109021

URI:

https://boris.unibe.ch/id/eprint/109021

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