Nitroxyl progenitors in the treatment of heart failure
Administration of an HNO/NO − donating 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/NO − donating compound isopropylamine (IPA)/NO(Na(CH 3 ) 2 CHNHN(O)NO) surprisingly exhibited positive inotropic effects in subjects experiencing heart failure that were superior to those caused by the HNO/NO − donating compound Angeli's salt. Additionally, in contrast to the effects observed with NO − donors, administration of an HNO/NO − donor in combination with a positive inotropic agent did not impair the positive inotropic effect of the positive inotropic agent. Further, HNO/NO − exerts its positive inotropic effect independent of the adrenergic system, increasing contractility even in subjects receiving beta-antagonist therapy.
1. A method of treating systolic heart failure in a subject, comprising:
administering to the subject a therapeutically effective dose of HNO by administration of a compound that donates HNO under physiological conditions;
wherein the HNO donating compound increases the subject's myocardial contractility; and wherein the subject is in need of myocardial contractility increases caused by primary as opposed to secondary effects.
2. The method of claim 1 , wherein the subject is receiving beta-adrenergic receptor antagonist therapy.
3. The method of claim 2 , wherein the HNO donating compound comprises Angeli's salt.
4. The method of claim 2 wherein the beta-adrenergic receptor antagonist is propranolol.
5. A method of increasing myocardial contractility in a subject in need thereof, comprising:
administering to the subject a therapeutically effective dose of HNO by administration of a compound that donates HNO under physiological conditions;
wherein the nitroxyl donating compound increases the subject's myocardial contractility; and
wherein the subject's basal cardiovascular function is not amenable to a substantial decrease in blood pressure.
6. The method of claim 5 , wherein the subject is receiving beta-adrenergic receptor antagonist therapy.
7. The method of claim 1 , wherein the HNO donating compound is administered as a pharmaceutical composition suitable for infusion.
8. The method of claim 2 , wherein the HNO donating compound is administered as a pharmaceutical composition suitable for infusion.
9. The method of claim 5 , wherein the HNO donating compound is administered as a pharmaceutical composition suitable for infusion.
10. The method of claim 1 , wherein the subject is experiencing acute heart failure.
11. The method of claim 2 , wherein the subject is experiencing acute heart failure.
12. The method of claim 5 , wherein the subject is experiencing acute heart failure.
13. The method of claim 2 , wherein the subject is receiving beta-adrenergic receptor antagonist therapy that is selective for a particular receptor.
14. The method of claim 13 , wherein the subject is receiving beta-adrenergic receptor antagonist therapy that is selective for the beta-1 receptor.
15. The method of claim 2 , wherein the subject is receiving beta-adrenergic receptor antagonist therapy that is not selective for a particular receptor.
16. A method of treating systolic heart failure in a subject, comprising:
administering to the subject a therapeutically effective dose of HNO by administration of a compound that donates HNO under physiological conditions;
wherein the HNO donating compound increases the subject's myocardial contractility; and
wherein the subject is in need of a positive inotropic effect without a substantial decrease in blood pressure.
17. The method of claim 16 , wherein the subject is receiving beta-antagonist therapy and wherein the HNO donating compound exerts its positive inotropic effect independent of the adrenergic system.
18. The method of claim 1 , 5 or 16 , wherein the subject is experiencing lung congestion.