Novel drug development opportunity for relaxin in acute myocardial infarction: evidences from a swine model.
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 microg/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 201Thallium 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.
Perna
Avio-Maria
AM
Unit of Cardiac and Experimental Surgery, Careggi Hospital, Florence, Italy.
Masini
Emanuela
E
Nistri
Silvia
S
Briganti
Vittorio
V
Chiappini
Laura
L
Stefano
Pierluigi
P
Bigazzi
Mario
M
Pieroni
Cesco
C
Bani Sacchi
Tatiana
T
Bani
Daniele
D
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D004195:Disease Models, Animal; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009195:Peroxidase / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012065:Relaxin / Q000627:therapeutic use*; D013552:Swine; D015899:Tomography, Emission-Computed, Single-Photon
D011994:Recombinant Proteins; D012065:Relaxin; D009195:Peroxidase