Prevention of tolerance to hemodynamic effects of @entity3362 with concomitant use of XXXX in @entity1 with @entity712 .

@entity1 @entity712 @entity63 @entity3362 @entity1242 @entity2514 @entity1507 @entity358 @entity1002
OBJECTIVES: This study was designed to determine the effect of oral @entity2514 on the development of @entity1507 tolerance in @entity1 with chronic @entity712 . BACKGROUND: Early development of @entity1507 tolerance with either continuous administration of intravenous or topical @entity1507 preparations or frequent dosing of oral @entity3362 leads to significant attenuation of @entity1507 -mediated hemodynamic and anti- @entity63 effects. In recent animal experiments, prevention of @entity1242 -induced hemodynamic tolerance with a concomitant use of @entity2514 was demonstrated. This finding may have important clinical relevance. METHODS: Twenty-eight @entity1 with @entity712 due to @entity1002 were randomized to receive either a continuous infusion (24 h) of @entity1242 alone (group I, 14 @entity1 ) or concomitantly with oral @entity2514 (75 mg four times a day [group II, 14 @entity1 ]). The effect of @entity1242 in each group was evaluated by analysis of variance for repeated measures. The power of the analysis to detect a 5.4-mm Hg (20%) change in mean pulmonary artery wedge pressure was 90%. RESULTS: Baseline hemodynamic variables as well as the initial hemodynamic response to @entity1242 were comparable in both groups. Compared with the initial response to @entity1242 , a significant attenuation of effect was found in group I at 24 h in mean (+/- SE) pulmonary artery pressure (27 +/- 4% vs. 10 +/- 3%, p < 0.05) and mean pulmonary artery wedge pressure (40 +/- 4% vs. 16 +/- 4%, p < 0.05). In group II, conversely, oral @entity2514 prevented @entity1242 -induced hemodynamic tolerance and resulted in a persistent effect on mean pulmonary artery and wedge pressures throughout the study period (31 +/- 3% vs. 27 +/- 4%, p = 0.13 and 37 +/- 4% vs. 34 +/- 6%, p = 0.40, respectively). In addition, the initial effect on blood pressure was attenuated at 24 h in group I (5 +/- 2% vs. 12 +/- 3%, p < 0.05) but not in group II (15 +/- 3% vs. 17 +/- 2%, p = 0.46). CONCLUSIONS: In @entity1 with @entity712 due to @entity1002 , the concomitant use of oral @entity2514 prevents early development of @entity1507 tolerance and results in a persistent @entity1507 -mediated hemodynamic effect on @entity358 and left ventricular filling pressures. These data may support the concurrent use of @entity2514 in @entity1 with @entity712 treated with organic @entity3362 .
