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Tolerance with low dose intravenous nitroglycerin therapy in acute myocardial infarction
1Department of Medicine, University of Alberta, Edmonton, Canada.
Insights
Vascular tolerance to intravenous nitroglycerin occurred in 24% of acute myocardial infarction patients, developing early and reducing therapeutic benefits. Despite this, nitroglycerin still offered advantages over placebo in this patient group.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Acute myocardial infarction (AMI) management often involves intravenous nitroglycerin.
- Vascular tolerance to nitroglycerin can limit its therapeutic efficacy.
Purpose of the Study:
- To investigate the incidence and characteristics of vascular tolerance to prolonged low-dose intravenous nitroglycerin in AMI patients.
- To assess the impact of tolerance on hemodynamic effects and clinical outcomes.
Main Methods:
- A randomized, placebo-controlled study involving 154 AMI patients treated with intravenous nitroglycerin.
- Dose titration aimed to reduce blood pressure by 10% (normotensive) or 30% (hypertensive).
- Tolerance defined as increased dose requirement to maintain hemodynamic effect; categorized as 'true' (no chest pain) or 'apparent' (chest pain present).
Main Results:
- Overall group analysis showed nitroglycerin benefits over placebo despite blood pressure equalization after 10 hours.
- Individual analysis revealed significant hemodynamic tolerance in 24% of patients, developing early (within 11 hours).
- Tolerance was associated with higher nitroglycerin doses and blunted beneficial effects on infarct size, though functional and clinical benefits persisted.
Conclusions:
- Significant hemodynamic tolerance to intravenous nitroglycerin can occur in a substantial subset of AMI patients.
- Early development of tolerance may attenuate some therapeutic advantages, but overall benefits may persist.
- Further research into managing nitroglycerin tolerance in AMI is warranted.
Abstract:
The question of vascular tolerance was examined in 154 patients with acute myocardial infarction (64 anterior, 90 inferior) who were treated with prolonged low dose intravenous nitroglycerin in a recent randomized placebo-controlled study. The dose of nitroglycerin was carefully titrated to decrease mean blood pressure by 10% in normotensive patients and 30% in hypertensive (blood pressure greater than 140/90 mm Hg) patients, but not less than 80 mm Hg. Tolerance was defined as the need to increase the dose to maintain this hemodynamic effect. It was labelled "true" if chest pain was absent and "apparent" if chest pain was present. Group analysis of dose, pain scores, hemodynamic, 2-dimensional echocardiographic and clinical parameters monitored serially before and after therapy indicated benefit with nitroglycerin over placebo despite equalizing of blood pressures after 10 hours. Reversal of blood pressures and volumes after discontinuing nitroglycerin suggested lack of significant tolerance. However, detailed individual analysis suggested significant hemodynamic tolerance in 37 patients (24%), both in the true tolerance (12%) and apparent tolerance (12%) subgroups. Tolerance appeared early, requiring the dose to be increased by 30 +/- 39 micrograms/min within 11 +/- 9 hours. The dose was greater (p less than 0.001) in the tolerance than in the no tolerance subgroup, both before (60 vs 27 micrograms/min) and after (90 vs 38 micrograms/min) 10 hours. Tolerance blunted the beneficial effect on infarct size, but positive effects on function, topography and complications persisted.