Bradykinin-induced preconditioning in patients undergoing coronary angioplasty

OBJECTIVES The purpose of this study was to determine whether administratio n of bradykinin reproduces the cardioprotective effects of ischemic precond itioning (PC) in patients undergoing percutaneous transluminal coronary ang ioplasty (PTCA). BACKGROUND Experimental studies suggest that activation of the bradykinin B -2 receptor is an important trigger of ischemic PC. However, it is unknown whether bradykinin can precondition human myocardium against ischemia in vi vo. Multicenter clinical trials have demonstrated an anti-ischemic effect o f angiotensin-converting enzyme inhibitors, which has been postulated to re sult from potentiation of bradykinin; however, direct evidence for an anti- ischemic action of bradykinin in patients is lacking. METHODS Thirty patients were randomized to receive a 10-min intracoronary i nfusion of bradykinin (2.5 mu g/min) or normal saline. Ten minutes later th ey underwent PTCA (three 2-min balloon inflations 5 min apart). RESULTS In control patients, the ST-segment shift on the intracoronary and surface electrocardiogram was significantly greater during the first inflat ion than during the second and third inflations, consistent with ischemic P C. In bradykinin-treated patients, the ST-segment shift during the first in flation was significantly smaller than in the control group, and there were no appreciable differences in ST-segment shift during the three inflations . Measurements of chest pain score and regional wall motion during inflatio n (quantitative two-dimensional echocardiography) paralleled those of ST-se gment shift. Infusion of bradykinin had no hemodynamic effects and no signi ficant adverse effects. Thus, intracoronary infusion of bradykinin before P TCA rendered the myocardium relatively resistant to subsequent ischemia, an d the degree of this cardioprotective effect was comparable to that afforde d by the ischemia associated with the first balloon inflation in control su bjects. In a separate cohort of seven patients given the same dose of brady kinin, coronary hyperemia resolved completely within 10 min after the end o f the infusion, indicating that bradykinin-induced vasodilation cannot acco unt for the protective effects observed during the first balloon inflation. CONCLUSIONS Bradykinin preconditions human myocardium against ischemia in v ivo in the absence of systemic hemodynamic changes. Pretreatment with brady kinin appears to be just as effective as ischemic PC and could be used prop hylactically to attenuate ischemia in selected patients undergoing PTCA. (J Am Coll Cardiol 1999;34:639-50) (C) 1999 by the American College of Cardio logy.