CLINICAL STUDIES
Bradykinin-induced preconditioning in patients undergoing coronary angioplasty
Massoud A. Leesar, MD, FACCa,
Marcus F. Stoddard, MD, FACCa,
Srinivas Manchikalapudi, MDa and
Roberto Bolli, MD, FACCa
a Division of Cardiology, University of Louisville, and the Jewish Hospital Heart and Lung Institute, Louisville, Kentucky 40292, USA
Manuscript received December 23, 1998;
revised manuscript received April 14, 1999,
accepted June 3, 1999.
Reprint requests and correspondence: Dr. Roberto Bolli, Division of Cardiology, University of Louisville, Louisville, Kentucky 40292
rbolli{at}louisville.edu
OBJECTIVES
The purpose of this study was to determine whether administration of bradykinin reproduces the cardioprotective effects of ischemic preconditioning (PC) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA).
BACKGROUND
Experimental studies suggest that activation of the bradykinin B2 receptor is an important trigger of ischemic PC. However, it is unknown whether bradykinin can precondition human myocardium against ischemia in vivo. Multicenter clinical trials have demonstrated an anti-ischemic effect of angiotensin-converting enzyme inhibitors, which has been postulated to result 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 infusion of bradykinin (2.5 µg/min) or normal saline. Ten minutes later they 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 inflation than during the second and third inflations, consistent with ischemic PC. In bradykinin-treated patients, the ST-segment shift during the first inflation 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 inflation (quantitative two-dimensional echocardiography) paralleled those of ST-segment shift. Infusion of bradykinin had no hemodynamic effects and no significant adverse effects. Thus, intracoronary infusion of bradykinin before PTCA rendered the myocardium relatively resistant to subsequent ischemia, and the degree of this cardioprotective effect was comparable to that afforded by the ischemia associated with the first balloon inflation in control subjects. In a separate cohort of seven patients given the same dose of bradykinin, coronary hyperemia resolved completely within 10 min after the end of the infusion, indicating that bradykinin-induced vasodilation cannot account for the protective effects observed during the first balloon inflation.
CONCLUSIONS
Bradykinin preconditions human myocardium against ischemia in vivo in the absence of systemic hemodynamic changes. Pretreatment with bradykinin appears to be just as effective as ischemic PC and could be used prophylactically to attenuate ischemia in selected patients undergoing PTCA.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | DCI | = digital cardiac imaging | | ECG | = electrocardiogram | | LV | = left ventricular | | PC | = preconditioning | | PKC | = protein kinase C | | PTCA | = percutaneous transluminal coronary angioplasty | | SAVE | = Survival and Ventricular Enlargement | | SOLVD | = Studies of Left Ventricular Dysfunction | | TRACE | = Trandolapril Cardiac Evaluation | | LAD | = left anterior descending coronary artery |
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