Relaxin induces mast cell inhibition and reduces ventricular arrhythmias in a swine model of acute myocardial infarction.
Resident cardiac mast cells, located mainly around coronary vessels and in the right atrium close to the sinoatrial node, are the main repository of cardiac histamine. Inflammatory activation of cardiac mast cells, as occurs upon acute myocardial infarction, causes the release of histamine and prostanoids. These substances lead to severe tachyarrhythmias, cardiodepressive effects and coronary spasm, thus contributing to myocardial damage and early, lethal outcome. Relaxin, known to inhibit mast cell activation, has been recently validated as a cardiotropic hormone, being produced by the heart and acting on specific heart receptors. In this study, we report on a swine model of heart ischemia/reperfusion, currently used to test cardiotropic drugs, in which human recombinant relaxin (2.5 and 5 microg/kg b.w.), given at reperfusion upon a 30-min ischemia, markedly reduced cardiac injury as compared with the vehicle-treated animals. Evidence is provided that relaxin, at both the assayed doses, causes a clear-cut, significant reduction of plasma histamine, increase in cardiac histamine content and decrease in cardiac mast cell degranulation. This is accompanied by a reduction of oxidative cardiac tissue injury (assessed as tissue malondialdehyde) and of the occurrence of severe ventricular arrhythmias. In conclusion, this study provides further insight into the cardioprotective effects of relaxin, which also involve mast cell inhibition, and confirms the relevance of histamine in the pathophysiology of ischemia-reperfusion-induced cardiac injury and dysfunction. It also offers additional evidence for the potential therapeutic effects of relaxin in animal models of disease involving mast cell activation.
Nistri
Silvia
S
Department of Anatomy, Histology & Forensic Medicine, viale G. Pieraccini 6, I-50139 Florence, Italy. silvia.nistri@unifi.it
Cinci
Lorenzo
L
Perna
Avio-Maria
AM
Masini
Emanuela
E
Mastroianni
Rosanna
R
Bani
Daniele
D
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D012065:Relaxin / Q000494:pharmacology* / Q000627:therapeutic use; D013552:Swine
D008315:Malondialdehyde; D006632:Histamine; D012065:Relaxin