Effects of hydroxyethyl starch conjugated deferoxamine on myocardial functional recovery following coronary occlusion and reperfusion in dogs.

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.

• Authors: M Maruyama, G M Pieper, B Kalyanaraman, P E Hallaway, B E Hedlund, G J Gross
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 17 Issue 1 Pg. 166-75 (Jan 1991) ISSN: 0160-2446 [Print] United States
• PMID: 1708051 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hydroxyethyl Starch Derivatives
• hydroxyethyl starch-deferoxamine conjugate
• Deoxyribose
• Deferoxamine

Topics

• Animals
• Coronary Circulation (drug effects, physiology)
• Deferoxamine (administration & dosage, metabolism, pharmacology)
• Deoxyribose (metabolism)
• Dogs
• Dose-Response Relationship, Drug
• Electron Spin Resonance Spectroscopy (methods)
• Female
• Heart (drug effects, physiology)
• Hemodynamics (drug effects)
• Hydroxyethyl Starch Derivatives (pharmacology)
• Male
• Reperfusion Injury (drug therapy, physiopathology)