Basic Research in Cardiology

, Volume 91, Issue 4, pp 289–295 | Cite as

Inhibition of granulocyte-derived proteases reduces the increase in plasma endothelin associated with myocardial ischemia in the pig

  • T. Tønnessen
  • A. Ilebekk
  • P. A. Naess
  • G. Christensen
Original Contribution


Plasma endothelin (ET) is increased in association with myocardial infarction. The aim of the present study was to get insight into the mechanisms behind this ischemiainduced increase in plasma ET. Since granulocytes increase ET production in vitro, we examined to what extent inhibition of granulocyte-derived proteases could reduce the increase in plasma ET observed in association with myocardial ischemia. We infused Eglin C, a selective inhibitor of the granulocyte-derived proteases elastase, cathepsin G, and chymotrypsin, in pigs subjected to 90 min left anterior descending coronary artery occlusion followed by 210 min reperfusion (n=7). Arterial plasma ET increased in an untreated control group (n=7) from 5.0±0.6 (mean ±SEM) fmol· ml−1 before myocardial ischemia to 6.1±0.6 fmol·ml−1 at 90 min ischemia and reached a maximum of 6.8±0.9 fmol·ml−1 at 90 min reperfusion. The increase in plasma ET associated with myocardial ischemia was almost completely abolished in the Eglin C treated group (p=0.005). Plasma ET in the Eglin C treated animals was 4.7±0.4,4.7±0.4, and 4.6±0.4 fmol· ml−1 before myocardial ischemia, at 90 min ischemia, and at 90 min reperfusion, respectively. Our study suggests a role for granulocytederived proteases in the increase in plasma ET associated with myocardial ischemia. We have shown that the increase in plasma ET associated with myocardial ischemia was reduced by inhibition of granulocytederived proteases using the selective protease inhibitor Eglin C.

Key words

Endothelin Eglin C proteases ischemia granulocytes 


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Copyright information

© Steinkopff Verlag 1996

Authors and Affiliations

  • T. Tønnessen
    • 1
  • A. Ilebekk
    • 1
  • P. A. Naess
    • 1
  • G. Christensen
    • 1
  1. 1.Institute for Experimental Medical ResearchUllevål HospitalOsloNorway

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