SSR69071, an elastase inhibitor, reduces myocardial infarct size following ischemia-reperfusion injury.

Abstract

Neutrophil elastase contributes to the severity of cardiac damage following coronary ischemia and reperfusion. We evaluated the effects of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyridol[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methyethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide hemihydrate (SSR69071), a novel, potent and selective inhibitor of neutrophil elastase, on infarct size in anaesthetized rabbits subjected to coronary artery occlusion for 30 min followed by reperfusion for 120 min. SSR69071 (3 mg/kg i.v.) reduced cardiac infarct size when administered before ischemia (-39%, P<0.05) or just prior to reperfusion (-37%, P<0.05). Subsequent experiments using the latter administration protocol confirmed the ability of SSR69071 (1 and 3 mg/kg i.v.) to reduce infarct size. This cardioprotective activity was associated with inhibition of cardiac elastase.

• Authors: Jean-Pierre Bidouard, Nicole Duval, Zoltan Kapui, Jean-Marc Herbert, Stephen E O'Connor, Philip Janiak
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 461 Issue 1 Pg. 49-52 (Feb 07 2003) ISSN: 0014-2999 [Print] Netherlands
• PMID: 12568915 (Publication Type: Journal Article)

Chemical References

• Cyclic S-Oxides
• SSR 69071
• Thiazoles
• Leukocyte Elastase

Topics

• Animals
• Cyclic S-Oxides (administration & dosage, therapeutic use)
• Dose-Response Relationship, Drug
• Leukocyte Elastase (antagonists & inhibitors)
• Male
• Myocardial Infarction (etiology, pathology, prevention & control)
• Myocardial Reperfusion Injury (complications, drug therapy)
• Rabbits
• Thiazoles (administration & dosage, therapeutic use)