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Novel drug development opportunity for relaxin in acute myocardial infarction: evidences from a swine model
Author(s) -
Perna AvioMaria,
Masini Emanuela,
Nistri Silvia,
Briganti Vittorio,
Chiappini Laura,
Stefano Pierluigi,
Bigazzi Mario,
Pieroni Cesco,
Sacchi Tatiana Bani,
Bani Daniele
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3664fje
Subject(s) - relaxin , medicine , myocardial infarction , cardiology , reperfusion injury , adjunctive treatment , ischemia , infarction , pharmacology , cardioprotection , hormone
The hormone relaxin has been shown to cause coronary vasodilation and to prevent ischemia/reperfusion‐induced cardiac injury in rodents. This study provides evidence that relaxin, used as an adjunctive drug to coronary reperfusion, reduces the functional, biochemical, and histopathological signs of myocardial injury in an in vivo swine model of heart ischemia/reperfusion, currently used to test cardiotropic drugs for myocardial infarction. Human recombinant relaxin, given at reperfusion at doses of 1.25, 2.5, and 5 µg/kg b.wt. after a 30‐min ischemia, caused a dose‐related reduction of key markers of myocardial damage (serum myoglobin, CK‐MB, troponin T) and cardiomyocyte apoptosis (caspase 3, TUNEL assay), as well as of cardiomyocyte contractile dysfunction (myofibril hypercontraction). Compared with the controls, relaxin also increased the uptake of the viability tracer 201 Thallium and improved ventricular performance (cardiac index). Relaxin likely acts by reducing oxygen free radical‐induced myocardial injury (malondialdehyde, tissue calcium overload) and inflammatory leukocyte recruitment (myeloperoxidase). The present findings show that human relaxin, given as a drug to counteract reperfusion‐induced cardiac injury, affords a clear‐cut protection to the heart of swine with induced myocardial infarction. The findings also provide background to future clinical trials with relaxin as adjunctive therapy to catheter‐based coronary angioplasty in patients with acute myocardial infarction.