Journal article
High-Dose Iron-Chelator Therapy During Reperfusion with Deferoxamine-Hydroxyethyl Starch Conjugate Fails to Reduce Canine Infarct Size
Journal of cardiovascular pharmacology, Vol.16(4), pp.523-528
10/1990
DOI: 10.1097/00005344-199010000-00002
PMID: 1706792
Abstract
SUMMARYIron 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-chelatpr 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 percent-age 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 m M at onset of reperfusion and 1.37 ± 0.05 m M 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.
Details
- Title: Subtitle
- High-Dose Iron-Chelator Therapy During Reperfusion with Deferoxamine-Hydroxyethyl Starch Conjugate Fails to Reduce Canine Infarct Size
- Creators
- Edward LesnefskyBo HedlundPhilip HallawayLawrence Horwitz
- Resource Type
- Journal article
- Publication Details
- Journal of cardiovascular pharmacology, Vol.16(4), pp.523-528
- DOI
- 10.1097/00005344-199010000-00002
- PMID
- 1706792
- NLM abbreviation
- J Cardiovasc Pharmacol
- ISSN
- 0160-2446
- eISSN
- 1533-4023
- Publisher
- Lippincott-Raven Publishers
- Language
- English
- Date published
- 10/1990
- Academic Unit
- Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984656607202771
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