C. Heymes et al., Endomyocardial nitric oxide synthase and left ventricular preload reserve in dilated cardiomyopathy, CIRCULATION, 99(23), 1999, pp. 3009-3016
Citations number
31
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-Patients with heart failure have modified myocardial expression
of nitric oxide synthase (NOS), as is evident from induction of calcium-ins
ensitive NOS isoforms. The functional significance of this modified NOS gen
e expression for left ventricular (LV) contractile performance was investig
ated in patients with dilated nonischemic cardiomyopathy.
Methods and Results-In patients with dilated, nonischemic cardiomyopathy. i
nvasive measures of LV contractile performance were derived from LV microti
p pressure recordings and angiograms and correlated with intensity of gene
expression of inducible (NOS2) and constitutive (NOS3) NOS isoforms in simu
ltaneously procured LV endomyocardial biopsies (n=20). LV endomyocardial ex
pression of NOS2 was linearly correlated with LV stroke Volume (P=0.001; r=
0.66), LV ejection fraction (P=0.007; r=0.58), and LV stroke work (P=0.003;
r=0.62), In patients with elevated LV end-diastolic pressure (>16 mm Hg),
a closer correlation was observed between endomyocardial expression of NOS2
and LV stroke volume (P=0.001; r=0.74), LV ejection fraction (P=0.0007; r=
0.77), and LV stroke work (r=0.82; P=0.0002). LV endomyocardial expression
of NOS3 was linearly correlated with LV stroke Volume (P=0.01; r=0.53) and
LV stroke work (P=0.01; r=0.52). To establish the role of nitric oxide (NO)
as a mediator of the observed correlations, substance P (which causes endo
thelial release of NO) was infused intracoronarily (n = 12). In patients wi
th elevated LV end-diastolic pressure, an intracoronary infusion of substan
ce P increased LV stroke volume from 72+/-13 to 91+/-16 mt (P=0.06) and LV
stroke work from 67+/-11 to 90+/-15 g.m (P=0.03) and shifted the LV end-dia
stolic pressure-volume relation to the right.
Conclusions-In patients with dilated cardiomyopathy, an increase in endomyo
cardial NOS2 or NOS3 gene expression augments LV stroke volume and LV strok
e work because of a NO-mediated rightward shift of the diastolic LV pressur
e-volume relation and a concomitant increase in LV preload reserve.