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.