University of California

Johns Hopkins University

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Louisiana State University and Agricultural & Mechanical College

Jon M Fukuto

David A Wink

David A Kass

Nazareno Paolocci

Katrina M Miranda

Martin Feelisch

Tatsuo Katori

Pasquale Pagliaro

Nitroxyl donating compounds are administered prior to the onset of ischemia for the prevention and/or reduction of ischemia/reperfusion injury in subjects at risk for ischemia. Nitroxyl donors also are administered to organs to be transplanted for the prevention and/or reduction of ischemia/reperfusion injury upon reperfusion in a recipient. Nitroxyl donors include any nitroxyl donating compound. In particular cases the nitroxyl donor is a nitroxyl-donating diazeniumdiolate, such as Angeli's salt or IPA/NO.

Method of treating ischemia/reperfusion injury with nitroxyl donors

Administration of an HNO/NOdonating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure. Moreover, administration of the HNO/NOdonating compound isopropylamine (IPA)/NO(Na(CH)CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NOdonating compound Angeli's salt. Additionally, in contrast to the effects observed with NOdonors, administration of an HNO/NOdonor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent. Further, HNO/NOexerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.

Nitroxyl progenitors in the treatment of heart failure

Administration of an HNO/NOdonating compound, such as Angeli's salt, increases myocardial contractility while concomitantly lowering left ventricular preload in subjects experiencing heart failure Moreover, administration of the HNO/NOdonating compound isopropylamine (IPA)/NO (Na(CH)CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NOdonating compound Angeli's salt. Additionally, in contrast to the effects observed with NOdonors, administration of an HNO/NOdonor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent Further, HNO/NOexerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy

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Agoura, CA, United States of America

Jon M Fukuto