EFFECT OF APPARENT ELIMINATION HALF-LIFE ON NITROGLYCERIN-INDUCED HEMODYNAMIC REBOUND IN EXPERIMENTAL HEART-FAILURE

Hemodynamic rebound after abrupt withdrawal may be an important consid eration associated with nitroglycerin (NTG) monotherapy. This phenomen on may arise from unopposed neurohormonal vasoconstriction because of rapid elimination of NTG. The role of NTG pharmacokinetics in the deve lopment of hemodynamic rebound was examined using a rat model of conge stive heart failure. NTG was infused for 90 min, then the dose was eit her abruptly stopped (n = 8) or gradually reduced by 20% every 20 min (n = 7). Abrupt withdrawal caused rebound elevations of left ventricul ar end-diastolic pressure (LVEDP) to about 25% above baseline values, at 30-60 min after drug termination (P < 0.01), but this was completel y avoided by graded NTG withdrawal. A positive correlation was observe d (P < 0.05) between the percentage reduction in LVEDP during infusion and the maximum percentage rebound in rats after abrupt withdrawal bu t not after graded withdrawal. These results suggest that NTG-induced hemodynamic rebound is related to its short biological half-life and t hat this phenomenon is consistent with a mechanism of neurohormonal co mpensation.