Effect of apparent elimination half-life on nitroglycerin-induced hemodynamic rebound in experimental heart failure.
Hemodynamic rebound after abrupt withdrawal may be an important consideration associated with nitroglycerin (NTG) monotherapy. This phenomenon may arise from unopposed neurohormonal vasoconstriction because of rapid elimination of NTG. The role of NTG pharmacokinetics in the development of hemodynamic rebound was examined using a rat model of congestive heart failure. NTG was infused for 90 min, then the dose was either abruptly stopped (n = 8) or gradually reduced by 20% every 20 min (n = 7). Abrupt withdrawal caused rebound elevations of left ventricular end-diastolic pressure (LVEDP) to about 25% above baseline values, at 30-60 min after drug termination (P < 0.01), but this was completely avoided by graded NTG withdrawal. A positive correlation was observed (P < 0.05) between the percentage reduction in LVEDP during infusion and the maximum percentage rebound in rats after abrupt withdrawal but not after graded withdrawal. These results suggest that NTG-induced hemodynamic rebound is related to its short biological half-life and that this phenomenon is consistent with a mechanism of neurohormonal compensation.
Bauer
J A
JA
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo 14260.
Fung
H L
HL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007262:Infusions, Intravenous; D005996:Nitroglycerin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D016277:Ventricular Function, Left / Q000187:drug effects
D005996:Nitroglycerin