HEMODYNAMIC EVALUATION OF THE ADDITION OF ISOSORBIDE-5-MONONITRATE TONADOLOL IN CIRRHOTIC-PATIENTS WITH INSUFFICIENT RESPONSE TO THE BETA-BLOCKER ALONE

The association beta-blockers plus isosorbide-5-mononitrate (15M) has been proposed for the treatment of portal hypertension in patients wit h insufficient response to beta-blockers alone, according to hemodynam ic criteria, The mechanism of action in these patients is not clearly defined, Fifteen patients with cirrhosis and esophageal varices were e valuated by hepatic venous pressure gradient (HVPG) measurement and du plex-Doppler ultrasonography before and after 1 month of treatment wit h nadolol, Nine patients who did not exhibit a decrease in HVPG to 12 mm Hg or a percent decrease greater than 20% were classified as poor r esponders, and were studied again with the same methodology after 3 mo nths of chronic administration of nadolol + 15M 20 mg twice per day, I n poor responders, mean HVPG decrease after nadolol was 8.9% +/- 2.8%, and after the combination, it was 25.7% +/- 1.7% (P =.004). All patie nts except one became good responders to the association. Portal blood flow (PBF) decreased significantly after nadolol (P =.004), and remai ned unchanged after the addition of nitrates. Resistance to portal blo od flow (RPBF) increased after nadolol (P =.02) and returned to baseli ne values during combined treatment (P = .03). In good responders, an adequate decrease in HVPG was associated with a decrease in PBF (P =.0 6) but no change in RPBF, A wide spectrum of combined changes in PBF a nd in RPBF after nadolol was observed in poor responders, ranging from no change in either parameter to a marked decrease in PBF counterbala nced by a marked increase in RPBF. The addition of 15M was followed in most cases by larger effects on resistance than on flow, Doppler para meters were not significantly correlated with the HVPG response to nad olol alone or associated with 15M. It is concluded that good hemodynam ic responders to nadolol differ from poor responders in the lack of in crease in RPBF after the drug. The addition of nitrates to nadolol is effective in decreasing portal pressure in most poor responders to nad olol alone. A decrease in outflow resistance is the main mechanism inv olved.