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5, 2001
© 2001 by the American College of Cardiology ISSN 0735-1097/01/$20.00
Published by Elsevier Science Inc. PII S0735-1097(01)01169-X
adjusted pairwise comparisons of treatment mean values 0.65) or an interaction between treatment and time (p ⫽
(low vs. high dose aspirin and low and high dose aspirin vs. 0.25).
placebo) were Bonferroni-corrected for multiple compari-
sons. The results are expressed as the mean values with 95% DISCUSSION
CIs in the text, and as the mean values ⫾ SD in the table,
Furosemide caused an increase in FVC in our patients with
and as the mean values ⫾ SE in figures.
CHF. Previously, venodilation has only been described in
patients with acute heart failure secondary to myocardial
infarction (4) and in salt-depleted healthy volunteers (5,15–
RESULTS 19). Our data support the hypothesis that furosemide has a
Mean arterial pressure and heart rate. Baseline mean potentially beneficial hemodynamic effect before diuresis
arterial pressure did not differ between treatments (Table 1). has time to occur, leading to an indirect hemodynamic
Similarly, heart rate did not differ between treatments change. Furthermore, we have demonstrated that the degree
(Table 1). Mean arterial pressure and heart rate did not alter of venodilation evoked by furosemide is of a similar mag-
significantly after administration of furosemide with any of nitude to that evoked by the venodilator NTG.
the three treatments or after the administration of NTG. Effect of aspirin and role of prostaglandins in
Forearm blood flow. Baseline forearm blood flow was furosemide-mediated venodilation. A daily dose of 75 mg
similar for all treatments (Table 1). Forearm blood flow was and 300 mg of the cyclooxygenase inhibitor aspirin inhib-
not changed by the administration of furosemide or NTG ited the venous effect of furosemide in our study. This
on any study day. observation provides further evidence that prostaglandins
FVC. Baseline FVC did not differ between treatments are involved in the mechanism of this vascular action of
(Table 1). In the compound symmetry mixed model, the furosemide (5,20). What is not clear, however, is precisely
effects of period (p ⫽ 0.53) and time (p ⫽ 0.84) and the how inhibition of prostaglandin synthesis inhibits venodi-
interaction of time with period (p ⫽ 0.34) were nonsignif- lation. The most obvious explanation is that aspirin inhibits
icant. In the placebo period, the mean (95% CI) response to the local production of prostaglandins, which provide the
furosemide over 20 min was a 2.2% (⫺0.9% to 5.2%) dilatory stimulus to veins. Whether these are released
increase in FVC. After pretreatment with 300 mg of aspirin,
there was a 3.7% (⫺6.8% to ⫺0.7%) fall in FVC when
furosemide was administered. After 75 mg aspirin, there
was a 1.1% (⫺4.2% to 1.9%) fall in FVC (Fig. 1). The
difference in response to furosemide between placebo,
75 mg aspirin and 300 mg aspirin was statistically significant
(p ⫽ 0.020 by the overall F test, placebo vs. 75 mg aspirin
vs. 300 mg aspirin). The response to furosemide after
pretreatment with placebo was not significantly different
from the response after pretreatment with 75 mg aspirin
(p ⫽ 0.29 after Bonferroni correction, placebo vs. 75 mg
aspirin), and was statistically different for 300 mg aspirin
(p ⫽ 0.017 after Bonferroni correction, placebo vs. 300 mg
aspirin).
Sublingual NTG caused a 2.1% (95% CI ⫺1.6% to 5.8%)
increase in FVC (Fig. 2). This was not statistically different
from the increase observed with furosemide administration Figure 1. Mean (⫾SEM) percent change in venous capacitance in re-
sponse to furosemide according to treatment group. Line with circles ⫽
after placebo pretreatment (p ⫽ 0.95, NTG vs. furosemide placebo group; line with triangles ⫽ 75-mg aspirin group; line with
and placebo), with little evidence of a trend over time (p ⫽ squares ⫽ 300-mg aspirin group.
JACC Vol. 37, No. 5, 2001 Jhund et al. 1237
April 2001:1234–8 Aspirin Inhibits Furosemide-Mediated Venodilation
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