Jh. Traverse et al., Cyclic nucleotide phosphodiesterase type 5 activity limits blood flow to hypoperfused myocardium during exercise, CIRCULATION, 102(24), 2000, pp. 2997-3002
Citations number
25
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-Nitric oxide (NO) causes vasodilation by stimulation of guanylat
e cyclase in vascular smooth muscle to produce cGMP. The resultant vasodila
tor effect is regulated by a family of cGMP phosphodiesterases (PDEs). Sild
enafil, a selective inhibitor of PDES used for treatment of erectile dysfun
ction, has been found to cause relaxation of isolated epicardial coronary a
rtery segments. The present study examined the effects of sildenafil on cor
onary blood flow and hemodynamics during exercise in normal and ischemic he
art.
Methods and Results-In chronically instrumented normal dogs, sildenafil 2 m
g/kg PO caused a slight but significant increase in left anterior descendin
g (LAD) coronary blood flow during resting conditions, with a nonsignifican
t trend toward increased coronary flow during treadmill exercise. Exercise
in the presence of LAD stenosis that decreased distal coronary pressure to
57+/-2 mm Hg reduced LAD flow during exercise from 69+/-8 to 41+/-7 mL/min
(P<0.05), with hypoperfusion most severe in the subendocardium. At the same
distal coronary pressure, sildenafil increased LAD flow in the ischemic re
gion to 50+/-11 mL/min (P<0.05). Increase in ischemic region blood flow pro
duced by sildenafil was uniform across the LV wall, given that no change oc
curred in the transmural distribution of perfusion.
Conclusions-Inhibition of PDES with sildenafil caused vasodilation of coron
ary resistance vessels with an increase of blood flow into an ischemic myoc
ardial region during exercise in the presence of coronary artery stenosis.