HDCN Article Review/Hyperlink

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)