Circulation, Vol 56, 205-212, Copyright © 1977 by American Heart Association
DT Danahy and WS Aronow
In a randomized, double-blind, crossover study, 19 patients with angina
were exercised 2 min after 0.4 mg sublingual nitroglycerin and after
sublingual placebo and before and 1, 3, and 5 hours after oral isosorbide
dinitrate (ISDN) and oral placebo. After initial testing, patients took the
dose of ISDN they had had during the study (mean dose 29 mg) for a mean
period of 5.6 months before retesting using the same protocol. Compared to
placebo, exercise time after sublingual nitroglycerin increased 56% (P less
than 0.001) initially and 51% (P less than 0.001) at retest. Compared to
placebo, exercise time increased 58% (P less than 0.05) initially and 58%
(P less than 0.005) at retest 1 hour after ISDN, 38% (P less than 0.05)
initially and 27% (P less than 0.005) at retest 3 hours after ISDN, and 13%
(NS) initially and 21% (P less than 0.02) at retest five hours after ISDN.
The mean exericse times initially and at retest were not significantly
different. Hemodynamic changes (decrease in systolic blood pressure and
increase in heart rate) at 15 min persisted through 300 min after ISDN
during both initial testing and during retesting. However, these changes
were significantly less during retesting. We conclude that a partial
tolerance to the hemodynamic effects of the drug develops after chronic use
of high dose oral ISDN but that the antianginal efficacy of both sublingual
nitroglycerin and oral ISDN is unimpaired.
ARTICLES
Hemodynamics and antianginal effects of high dose oral isosorbide dinitrate after chronic use
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