(Circulation. 1997;96:3436-3442.)
© 1997 American Heart Association, Inc.
Articles |
Left Ventricular Contractile Effects of Inducible Nitric Oxide Synthase in the Human Allograft
From the Cardiovascular Center, OLV Ziekenhuis, Aalst, Belgium (W.J.P., P.P., M.V.); the Department of Cardiology, University of Wales College of Medicine, Cardiff, UK (A.M.S); and Abteilung Kardiologie, Medizinische Hochschule, Hannover, Germany (S.K., H.D.).
Correspondence to Dr Walter J. Paulus, MD, PhD, Cardiovascular Center, OLV Ziekenhuis, Moorselbaan 164, B 9300 Aalst, Belgium. E-mail Walter.Paulus{at}ping.be
Background Myocardial expression of inducible (i) nitric oxide (NO) synthase (iNOS) gene has been reported in transplant recipients and in dilated cardiomyopathy. NO derived from NO donor or from coronary endothelium has previously been shown in the human heart to reduce end-systolic left ventricular (LV) pressure, especially during ß-adrenoreceptor stimulation, because of earlier onset of LV relaxation. The present study investigated in transplant recipients whether a similar cardiodepressant effect could be attributed to NO derived from iNOS.
Methods and Results In 16 transplant recipients who were free of
rejection or graft vasculopathy, microtip LV pressure
recordings, LV angiograms, and
endomyocardial biopsies were obtained at annual
coronary angiography. In 8 transplant recipients, microtip LV
pressure recordings were obtained during
intravenous dobutamine(5 µg ·
kg-1 · min-1). Competitive reverse
transcription–polymerase chain reaction of iNOS mRNA was performed on
the endomyocardial biopsies, and the intensity of
iNOS mRNA expression was quantified on a scale ranging from 0 to 5+.
All measures of baseline LV function were comparable in transplant
recipients with low (
2+) or high myocardial iNOS mRNA. During
intravenous dobutamine infusion, there was a
significant correlation between the abbreviation of LV
electromechanical systole time (LVEST is the time from onset of QRS
to dP/dtmin) and the rise of LV dP/dtmax
(r=.79; P<.02). By use of a multiple
regression analysis, addition of the intensity of iNOS mRNA
expression as an independent variable significantly
(P<.005) improved the correlation between 
LVEST and
LV dP/dtmax (P<.001;
r=.97), implying a larger abbreviation of LV contraction
for a similar rise in LV dP/dtmax, when myocardial iNOS
mRNA was higher. The larger abbreviation of LV contraction in-patients
with high iNOS mRNA was associated with a decrease in LV
end-systolic pressure (-31±16 mm Hg).
Conclusions Myocardial iNOS gene expression in the human allograft influences the LV contractile response to ß-adrenergic stimulation through earlier onset of LV relaxation and reduction of LV end-systolic pressure. These effects are similar to the LV contractile effects of NO derived from NO donor or from coronary endothelium.
Key Words: transplantation • receptors, adrenergic, beta • endothelium-derived factors • myocardial contraction
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