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The effect of monensin, a Na+-selective carboxylic ionophore, on coronary circulation
Abstract:
Carboxylic ionophores are antibiotics that selectively complex with cations and facilitate their transport across biological membranes. Monensin is a monovalent ionophore that has been reported to exhibit a high degree of in vitro selectivity to transport Na+ ions. In anesthetized dogs, intravenous injections of 5-25 micrograms/kg of monensin produce a selective coronary vasodilator action. A maximal increase in coronary blood flow (CBF) with little or no effect on other cardiovascular parameters was produced. In the 50-200-micrograms/kg dose range, additional positive inotropic and systemic vasopressor effects were elicited. In dogs with normal coronary arteries, 25 micrograms/kg i.v. of monensin increased both subendocardial (ENDO) and subepicardial (EPI) blood flows, such that the ENDO/EPI ratio was changed from 1.10 +/- 0.03 before to 0.75 +/- 0.05 after monensin. The large dose (75 micrograms/kg i.v.) of monensin produced a maximum increase in ENDO flow but the EPI flow was less than that with the small dose; the ENDO/EPI ratio was increased to 1.19 +/- .14. In dogs with 80%-90% occlusion of the left anterior descending (LAD) coronary artery, both doses of monensin increased blood flow to normal and "border" zones but not the central ischemic zone. There was no evidence of "coronary steal" after monensin. This ionophore may be useful in increasing blood pressure and cardiac output after acute myocardial infarction.
Insights
Monensin, a sodium ionophore, selectively increases coronary blood flow in dogs. This antibiotic may benefit patients with acute myocardial infarction by improving cardiac output and blood pressure.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Ion Transport
Background:
- Carboxylic ionophores are antibiotics that facilitate cation transport across membranes.
- Monensin selectively transports Na+ ions and acts as a coronary vasodilator.
- Previous studies indicated monensin's effects on cardiovascular parameters.
Purpose of the Study:
- To investigate the effects of monensin on coronary blood flow (CBF) and other cardiovascular parameters in dogs.
- To determine the dose-dependent effects of monensin on subendocardial and subepicardial blood flow.
- To assess monensin's efficacy in a canine model of myocardial infarction with coronary artery occlusion.
Main Methods:
- Intravenous administration of monensin at doses of 5-200 micrograms/kg in anesthetized dogs.
- Measurement of coronary blood flow, cardiac output, and systemic blood pressure.
- Assessment of subendocardial (ENDO) and subepicardial (EPI) blood flow, and the ENDO/EPI ratio.
- Utilized a canine model with 80%-90% occlusion of the left anterior descending (LAD) coronary artery.
Main Results:
- Low doses (5-25 micrograms/kg) of monensin selectively increased CBF without affecting other parameters.
- Higher doses (50-200 micrograms/kg) elicited positive inotropic and vasopressor effects.
- Monensin altered the ENDO/EPI ratio, indicating differential effects on myocardial layers.
- In LAD-occluded dogs, monensin increased blood flow to border zones but not the ischemic core, with no coronary steal observed.
Conclusions:
- Monensin exhibits selective coronary vasodilation and modulates myocardial blood flow distribution.
- The ionophore may be beneficial in managing acute myocardial infarction by enhancing cardiac output and blood pressure.
- Monensin's lack of coronary steal effect suggests potential safety in ischemic conditions.