Oren S, Gossman E, Frohlich ED
Effects of calcium entry blockers on distribution blood volume
Am J Hypertens
(Jul) 9:628-632 1996

Calcium channel blockers are known to reduce preload, but although an
effect on the venous system (venodilatation) has been postulated, this
area has not been well studied. Oren et al. examined the effects of
three classes of CCBs (isradipine, diltiazem, verapamil) on the venous
system. They used indocyanine green to measure cardiac output and
also the central blood volume (CBV). Total blood volume (TBV) was
measured using RISA (I-125 tagged albumin). The ratio of CBV/TBV was
the measure of central or peripheral distribution of the blood volume,
which is a function of the peripheral venous capacity. CBV/TBW were
assessed both in the supine position and 5 min after a 45 degree
head-up tilt.
Twenty four patients with mild-to-moderate
essential hypertension were randomly divided into 3 groups and treated
with one of the above three drugs for 4-6 weeks. Invasive hemodynamic
evaluations were performed pre-drug after a placebo washout phase, and
repeated after 4-6 weeks of therapy.
Only verapamil reduced
the CBV/TBV ratio in the supine position, suggesting that it was the
most potent venodilating drug. Isradipine had an intermediate effect:
whereas it did not change CBV/TBW in the supine position, it did cause
an increased fall in the cardiac stroke volume during tilting,
suggesting attenuation of venoconstrictive reflexes. Diltiazem had no
demonstrable affect on the venous system or venoconstrictive reflexes
during tilting.
Comment: This is a very elegant study,
done using classical methodology, and focused in an area where there
has not been much investigation. It is not clear if the changes seen
with these 3 CCBs are a class effect, and if they have any
implications regarding choice of one of these agents for therapy. One
possible confounder is, that an equivalence of dosing question: the
fall in MAP with verapamil was on average 30% greater with verapamil
than with the other two agents. It would have been nice to analyze
the relationship between fall in MAP and changes in CBV/TBW or stroke
volume fall on a per patient basis to see if they correlated.
(John T. Daugirdas, M.D., University of Illinois at Chicago)