BENEFICIAL-EFFECTS OF BRADYKININ ON MYOCARDIAL ENERGY-METABOLISM AND INFARCT SIZE

There is growing evidence for a local kallikrein-kinin system in the h eart, In the ischemic heart the enhanced generation and release of kin ins seem to have cardioprotective actions, In isolated rat hearts with ischemia-reperfusion injuries, perfusion with bradykinin reduces the duration and incidence of ventricular fibrillations, improves cardiody namics, reduces release of cytosolic enzymes, and preserves energy-ric h phosphates and glycogen stores, In anesthetized animals, intracorona ry infusion of bradykinin is followed by comparable beneficial changes and limits infarct size, Inhibition of breakdown of bradykinin and re lated peptides induces similar beneficial cardiac effects. Treatment w ith angiotensin-converting enzyme (ACE) inhibitors such as ramipril in creases cardiac kinins and reduces postischemic reperfusion injuries i n isolated rat hearts as well as infarct size and remodeling in postin farcted animals, respectively, Blockade of B-2 kinin receptors increas es ischemia-induced effects. In isolated hearts, ischemia-reperfusion injuries intensify with the B-2 kinin receptor antagonist icatibant, w hich also abolishes the cardioprotective effects of ACE inhibitors and of exogenous bradykinin, Infarct size reduction by ACE inhibitors and bradykinin in anesthetized animals is reversed by icatibant. Kinins c ontribute to the cardioprotective effects associated with ischemic pre conditioning. Preconditioning of bradykinin-induced antiarrhythmic and infarct size-limiting effects are attenuated by icatibant. (C) 1997 b y Excerpta Medica, Inc.