High-Dose Iron-Chelator Therapy During Reperfusion with Deferoxamine-Hydroxyethyl Starch Conjugate Fails to Reduce Canine Infarct Size
| Autor: | Edward J. Lesnefsky, Philip E. Hallaway, Lawrence D. Horwitz, Bo E. Hedlund |
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| Rok vydání: | 1990 |
| Předmět: |
Male
Free Radicals medicine.medical_treatment Drug Evaluation Preclinical Myocardial Infarction Ischemia Myocardial Reperfusion Injury Deferoxamine Hydroxyethyl starch Hydroxyethyl Starch Derivatives Necrosis Random Allocation Dogs Double-Blind Method In vivo medicine Carnivora Animals Infusions Intravenous Pharmacology Analysis of Variance Chemotherapy Dose-Response Relationship Drug biology business.industry Fissipedia medicine.disease biology.organism_classification Anesthesia Cardiology and Cardiovascular Medicine business Conjugate medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology. 16:523-528 |
| ISSN: | 0160-2446 |
| Popis: | Iron catalyzes reactions during ischemia and reperfusion that contribute to myocardial injury. The iron-chelator deferoxamine blocks these reactions, but undesirable side effects limit the clinical potential of deferoxamine to decrease injury. We tested whether intravenous (i.v.) administration of high doses of a well-tolerated deferoxamine-hydroxyethyl starch (DEFHES) iron-chelator during the last 10 min of ischemia and the first 10 min of reperfusion would decrease canine infarct size. Fourteen chloralose-anesthetized mongrel dogs were randomized to therapy in a blinded fashion with deferoxamine conjugate (75 mg/kg deferoxamine) or hydroxyethyl starch (HES) vehicle alone. Nine other untreated dogs served as controls. Infarct size as a percentage of area at risk (MI/RISK) was not reduced by therapy with deferoxamine conjugate. The deferoxamine dose was five times greater than the maximally tolerated dose of free deferoxamine. Arterial deferoxamine concentrations in the deferoxamine-conjugate group were 0.69 +/- 0.09 mM at onset of reperfusion and 1.37 +/- 0.05 mM at 10 min of reperfusion. Area at risk, ischemic collateral blood flow, and heart rate-blood pressure (HR/BP) product were similar in the groups. Chelation of intravascular iron at the time of reperfusion does not reduce myocardial necrosis in an in vivo model of myocardial ischemia-reperfusion injury. |
| Databáze: | OpenAIRE |
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