Methods for preventing or treating mitochondrial permeability transition
The invention provides a method of reducing or preventing mitochondrial permeability transitioning. The method comprises administering an effective amount of an aromatic-cationic peptide having at least one net positive charge; a minimum of four amino acids; a maximum of about twenty amino acids; a relationship between the minimum number of net positive charges (p m ) and the total number of amino acid residues (r) wherein 3p m is the largest number that is less than or equal to r+1; and a relationship between the minimum number of aromatic groups (a) and the total number of net positive charges (p t ) wherein 2 a is the largest number that is less than or equal to p t +1, except that when a is 1, p t may also be 1.
1. A method for increasing cardiac contractility in a subject in need thereof, comprising administering to the subject an effective amount of the peptide D-Arg-2′6′-Dmt-Lys-Phe-NH 2 , wherein cardiac contractility is reduced due to ischemia-reperfusion injury, coronary artery disease, atherosclerosis, thrombolytic blockage, glucose deprivation, or hypoxia.
2. The method of claim 1 , wherein cardiac contractility is reduced due to ischemia-reperfusion injury.
3. The method of claim 1 , wherein the peptide is used in conjunction with a cardiac reperfusion procedure.
4. The method of claim 3 , wherein the cardiac reperfusion procedure comprises angioplasty, coronary artery bypass graft, or the use of thrombolytic drugs.
5. The method of claim 3 , wherein the peptide is applied to coronary stents.
6. The method of claim 1 , wherein the peptide is administered locally or systemically.
7. The method of claim 6 , wherein the peptide is administered intravenously, orally, topically, intranasally, intramuscularly, subcutaneously, transdermally or iontophoretically.
8. The method of claim 1 , wherein cardiac contractility is reduced due to coronary artery disease.
9. The method of claim 1 , wherein cardiac contractility is reduced due to atherosclerosis.
10. The method of claim 1 , wherein cardiac contractility is reduced due to thrombolytic blockage.
11. The method of claim 1 , wherein cardiac contractility is reduced due to glucose deprivation.
12. The method of claim 1 , wherein cardiac contractility is reduced due to hypoxia.