Effects of hydroxyethyl starch conjugated deferoxamine on myocardial functional recovery following coronary occlusion and reperfusion in dogs.
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.
Maruyama
M
M
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.
Pieper
G M
GM
Kalyanaraman
B
B
Hallaway
P E
PE
Hedlund
B E
BE
Gross
G J
GJ
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003676:Deferoxamine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D003855:Deoxyribose / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D008297:Male; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology
D006895:Hydroxyethyl Starch Derivatives; C068460:hydroxyethyl starch-deferoxamine conjugate; D003855:Deoxyribose; D003676:Deferoxamine