Hemodynamic evaluation of the addition of isosorbide-5-mononitrate to nadolol in cirrhotic patients with insufficient response to the β- blocker alone
✍ Scribed by C Merkel; D Sacerdoti; M Bolognesi; E Enzo; R Marin; G Bombonato; P Angeli; A Gatta
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 226 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
The association b-blockers plus isosorbide-5-mononitrate flow resistance is the main mechanism involved. (HEPATOL-(I5M) has been proposed for the treatment of portal hyperten-OGY 1997;26:34-39.) sion in patients with insufficient response to b-blockers alone, according to hemodynamic criteria. The mechanism of action in these patients is not clearly defined. Fifteen patients with
On the basis of several prospective evaluations, 1-3 a decirrhosis and esophageal varices were evaluated by hepatic crease in hepatic venous pressure gradient (HVPG) to 12 venous pressure gradient (HVPG) measurement and duplexmm Hg or less, or by at least 12% to 20%, is considered the Doppler ultrasonography before and after 1 month of treatbest predictor of effectiveness of treatment with b-blockers in ment with nadolol. Nine patients who did not exhibit a depatients with cirrhosis and portal hypertension. 4 Therefore, crease in HVPG to 12 mm Hg or a percent decrease greater alternative treatments are requested for patients who do not than 20% were classified as poor responders, and were studmeet these criteria. With this aim, the association with longied again with the same methodology after 3 months of acting nitrates has been proposed. 5 The association with chronic administration of nadolol / I5M 20 mg twice per long-acting nitrates was shown to decrease HVPG to a larger day. In poor responders, mean HVPG decrease after nadolol degree than b-blockers alone, 6,7 and to decrease approxiwas 8.9% { 2.8%, and after the combination, it was 25.7% mately by half the probability of being a poor responder { 1.7% (P Å .004). All patients except one became good according to hemodynamic criteria. 6,7 responders to the association. Portal blood flow (PBF) de-A few questions are still unanswered in the use of longcreased significantly after nadolol (P Å .004), and remained acting nitrates in association with b-blockers. From a clinical unchanged after the addition of nitrates. Resistance to portal point of view, it is uncertain how effective the association is blood flow (RPBF) increased after nadolol (P Å .02) and in the subgroup of patients with insufficient response to returned to baseline values during combined treatment (P Å b-blockers. From a pathophysiological point of view, the .03). In good responders, an adequate decrease in HVPG was mechanisms of action of the association are not clearly deassociated with a decrease in PBF (P Å .06) but no change fined, because nitrates may act by enhancing an insufficient in RPBF. A wide spectrum of combined changes in PBF and decrease in portal blood inflow obtained with b-blockers in RPBF after nadolol was observed in poor responders, rangalone, 8 or by contrasting a possible increase in outflow resising from no change in either parameter to a marked decrease tance induced by b-blockers. 9 in PBF counterbalanced by a marked increase in RPBF. The
In the present study, we assessed the portal hypotensive addition of I5M was followed in most cases by larger effects effect of the addition of isosorbide-5-mononitrate (I5M) to on resistance than on flow. Doppler parameters were not nadolol and the changes in portal hemodynamic variables significantly correlated with the HVPG response to nadolol determining portal pressure (i.e., portal blood flow [PBF] alone or associated with I5M. It is concluded that good hemoand resistance to portal blood flow [RPBF]) in a group of dynamic responders to nadolol differ from poor responders poor responders to nadolol, and compared them with a group in the lack of increase in RPBF after the drug. The addition of good responders. Because changes in hepatic artery blood of nitrates to nadolol is effective in decreasing portal pressure flow may influence portal hypertension, changes in hepatic artery pulsatility index (HAPI) were also assessed.
Abbreviations: HVPG, hepatic venous pressure gradient; I5M, isosorbide-5-mononi-
PATIENTS AND METHODS
trate; PBF, portal blood flow; RPBF, resistance to portal blood flow; HAPI, hepatic Fifteen patients with cirrhosis and portal hypertension who were artery pulsatility index; HR, heart rate; MAP, mean arterial pressure.