Effects of indomethacin on systemic and coronary hemodynamics in patients with coronary artery disease
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Indomethacin increased blood pressure and decreased coronary blood flow in patients with coronary artery disease. Aspirin pretreatment attenuated these effects, suggesting prostaglandin involvement in indomethacin
Area of Science:
- Cardiovascular Pharmacology
- Hemodynamics
- Prostaglandin Inhibition
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) like indomethacin can affect cardiovascular function.
- Coronary artery disease (CAD) patients may have altered responses to vasoactive agents.
- The role of prostaglandins in regulating coronary hemodynamics is crucial.
Purpose of the Study:
- To investigate the effects of indomethacin on systemic and coronary hemodynamics in patients with CAD.
- To explore the mechanisms of indomethacin's action, particularly the role of cyclooxygenase inhibition.
- To compare indomethacin's effects with and without prior aspirin administration.
Main Methods:
- A study involving 17 patients with coronary artery disease.
- Group I: Indomethacin or placebo without cyclooxygenase inhibition.
- Group II: Indomethacin after aspirin (2600 mg) pretreatment.
- Measurements included blood pressure, coronary blood flow, coronary vascular resistance, and thromboxane B2 levels.
Main Results:
- Indomethacin increased systolic blood pressure and coronary vascular resistance, while decreasing coronary blood flow in Group I.
- Thromboxane B2 levels decreased significantly in Group I.
- In Group II, indomethacin's pressor response was attenuated, and coronary hemodynamic changes were less pronounced compared to Group I.
- Thromboxane B2 levels remained undetectable in Group II.
Conclusions:
- Indomethacin significantly impacts systemic and coronary hemodynamics in CAD patients.
- Prostaglandin synthesis, specifically thromboxane, appears to mediate indomethacin's effects on systemic blood pressure.
- Coronary vascular responses to indomethacin may be less prostaglandin-dependent than systemic responses, suggesting a dissociation.
Abstract:
The effects and possible mechanisms of actions of indomethacin on systemic and coronary hemodynamics were studied in 17 patients with coronary artery disease. Group I patients (12) were given either indomethacin or placebo in the absence of prior cyclooxygenase inhibition and group II (five) were given indomethacin after prior treatment with 2600 mg of aspirin. In group I, systolic blood pressure rose from a baseline of 136 +/- 5 mm Hg to a peak level of 158 +/- 8 mm Hg 5 minutes after drug (p less than 0.01). This was associated with a fall in coronary blood flow and a rise in coronary vascular resistance from a baseline of 1.36 +/- 0.4 mm Hg/ml/min to 1.99 +/- 0.7 mm Hg/ml/min 5 minutes after indomethacin (p less than 0.01). Immunoreactive thromboxane B2 levels fell from 191 to 1.4 ng/ml. No changes were noted in plasma renin activity, angiotensin II, or catecholamine levels. Immunoreactive thromboxane B2 levels were undetectable throughout the study period in group II patients and the blood pressure response to indomethacin was attenuated. Baseline coronary blood flow was significantly higher (p less than 0.01) and baseline coronary vascular resistance significantly lower (p less than 0.01) than in group I. At all time points after indomethacin, the fall in coronary blood flow was greater and the increase in coronary vascular resistance less in group II versus group I (p less than 0.001). These findings suggest a dissociation between the effect of indomethacin on systemic and coronary hemodynamics, the former apparently being more prostaglandin-dependent than the latter.