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Abstract: Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family identified from human and other vertebrate tissues. Preprointermedin (preproIMD) can generate a 47 amino acid mature peptide (IMD1–47) and a shorter 40 amino acid one (IMD8–47) by proteolytic cleavage. Amino acid sequence analysis showed that cleavage sites are located between two basic amino acids at Arg93-Arg94, resulting in the production of preproIMD95–147, namely IMD1–53. The present study was designed to observe the effects of IMD1–53 on cardiac function in ischemia/reperfusion (I/R) injury in isolated rat hearts. Perfusion with high-dose IMD1–53 gave higher left ventricular systolic pressure (LVSP) and maximal rate of increase and decrease of left ventricle pressure (±LVdP/dtmax), and coronary perfusion flow (CPF) than those of controls. Cardiac I/R induced a marked inhibition of cardiac function and myocardial injury. Reperfusion with IMD1–53 significantly ameliorated the inhibited cardiac function and bradycardia induced by I/R. Compared with the I/R-treatment alone, IMD1–53 reperfusion augmented CPF, LVSP, and maximal rate of increase and decrease of left ventricle pressure (±LVdP/dtmax) and decreased LVDP. In addition, reperfusion with IMD1–53markedly attenuated the leakage of lactate dehydrogenase and malondialdehyde content in myocardia compared with I/R alone. Reperfusion with IMD1–53increased the content of cyclic adenosine monophosphate in comparison with I/R alone. Interestingly, the above IMD1–53 effects are similar to those of adrenomedullin. These results suggest that IMD1–53, like adrenomedullin, has cardioprotective effects against myocardial I/R injury. [Copyright &y& Elsevier]