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CLINICAL STUDIES

Effects of bradykinin on coronary blood flow and vasomotion in transplant patients

Eduardo Aptecar, MD^* , Emmanuel Teiger, MD^* , Patrick Dupouy, MD^* , Christophe Benvenuti, MD, Morton J. Kern, MD, Javier Woscoboinik, MD, Said Sediame, MD, Jean Marc Pernes, MD, Alain Castaigne, MD^*, Daniel Loisance, MD and Jean-Luc Dubois-Randé, MD^*

^* Fédération de Cardiologie et Institut National de la Santé et de la Recherche Médicale U400, Créteil, France
Unité d’Hémodynamique et de Cardiologie Interventionnelle, Service des Explorations Fonctionnelles, Créteil, France
Service de Chirurgie Thoracique et Cardio-vasculaire et Centre National de la Recherche Scientifique URA 1431, Hôpital Henri Mondor, Créteil, France
St. Louis University Hospital, St. Louis, Missouri, USA

Manuscript received December 31, 1998; revised manuscript received November 24, 1999, accepted January 13, 2000.

Reprint requests and correspondence: Dr. Eduardo Aptecar, Fédération de Cardiologie, Service du Pr A Castaigne, Hôpital Henri Mondor, 51 Av du Maréchal de Lattre de Tassigny, 94010 Créteil, France
eaptecar{at}club-inernet.fr

OBJECTIVES

To evaluate the effects of exogenous bradykinin on coronary epicardial and microcirculatory tone in transplant patients (HTXs), and to compare them with the effects of acetylcholine.

BACKGROUND

Coronary endothelial dysfunction has been reported to occur early after heart transplantation, most notably when acetylcholine was the endothelium-function marker used. The effects of bradykinin on coronary vasomotion are unknown in HTXs.

METHODS

Sixteen HTXs were compared 3.6 ± 1.7 months after transplantation to seven control subjects. Coronary flow velocity was measured using guide-wire Doppler. Diameters (D) of three segments of the left coronary artery and coronary blood flow (CBF) were assessed at baseline, after 3-min infusions of increasing bradykinin doses (50, 150 and 250 ng/min) then of increasing acetylcholine doses (estimated blood concentrations of 10^-8, 10^-7 and 10^-6 M).

RESULTS

Bradykinin induced similar dose-dependent increases in D and CBF in both groups: D was 11 ± 12%, 19 ± 14% and 22 ± 16% (all p < 0.0001), and CBF was 50 ± 40%, 130 ± 68% and 186 ± 77% (all p < 0.0001). Acetylcholine induced significant epicardial vasodilation in control subjects and vasoconstriction in HTX, as well as a marked increase in CBF in both groups. Acute allograft rejection, present in 8 of the 16 HTXs, did not modify responses to bradykinin, but was associated with a smaller CBF increase in response to acetylcholine (p < 0.05).

CONCLUSIONS

The coronary vasodilating effects of bradykinin are preserved early after heart transplantation, even in the presence of acute allograft rejection. Although there is an abnormal vasoconstricting response to acetylcholine reflecting endothelium dysfunction, the endothelium remains a functionally active organ in heart transplant recipients.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   EDHF = endothelium-derived hyperpolarizing factor   HTX = transplant patients   Sin-1 = linsidomine

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