Faculty Collaboration Database

Effects of hydroxyethyl starch conjugated deferoxamine on myocardial functional recovery following coronary occlusion and reperfusion in dogs. J Cardiovasc Pharmacol 1991 Jan;17(1):166-75

Date

01/01/1991

Pubmed ID

1708051

DOI

10.1097/00005344-199101000-00024

Scopus ID

2-s2.0-0026007641 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

The effect of hydroxyethyl starch-conjugated deferoxamine (HES-DFO) on the recovery of regional myocardial function after 15 min of coronary artery occlusion followed by 3 h of reperfusion of the left anterior descending coronary artery (stunned myocardium) was investigated in anesthetized dogs. Regional myocardial blood flow was measured by radioactive microspheres and regional myocardial segment shortening (%SS) by sonomicrometry. HES-DFO (equivalent of 50 mg/kg DFO), iron saturated HES-DFO (HES-FO), deferoxamine (DFO, 50 mg/kg), or saline were administered by intravenous infusion starting 30 min before occlusion and throughout occlusion. Ischemic bed size and collateral blood flow were similar in all four groups. HES-DFO significantly improved %SS in the ischemic-reperfused region during reperfusion; however, HES-FO and DFO had no effect on %SS as compared to the saline-treated group. HES-DFO and HES-FO had no effect on hemodynamics; however, DFO produced a marked reduction in systemic blood pressure. Since HES-FO had no effect on the recovery of %SS, the beneficial effect of HES-DFO is thought to be due to its iron chelating characteristics. Plasma concentrations of HES-DFO not only reached a higher peak level but also had a longer half life (3 h) than that of regular DFO (20 min). Thus, high-molecular-weight HES-DFO is effective in enhancing the recovery of regional wall motion in stunned myocardium. The reason for the lack of efficacy of DFO compared to HES-DFO at this high dose may be related to the formation of a toxic deferoxamine free radical species.

Author List

Maruyama M, Pieper GM, Kalyanaraman B, Hallaway PE, Hedlund BE, Gross GJ

Author

Balaraman Kalyanaraman PhD Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Coronary Circulation
Deferoxamine
Deoxyribose
Dogs
Dose-Response Relationship, Drug
Electron Spin Resonance Spectroscopy
Female
Heart
Hemodynamics
Hydroxyethyl Starch Derivatives
Male
Reperfusion Injury